Zeitschriftenartikel zum Thema „Hai wan zhan zheng“

Background:TCZ is a monoclonal antibody against Interleukin-6 receptor (IL-6R) which is used for relieving inflammation and reducing mortality in COVID-19 patients. Safety and efficacy of Tocilizumab (TCZ) in Covid-19 pneumonia is uncertain yet. In this study, we aimed to determine clinical outcomes in patients treated with TCZ.Objectives:In this study we aimed to share our retrospective results which we had obtained from patients with COVID-19 diagnosis received TCZ.Methods:We performed a retrospective case control study between May and August 2020 in Turkey. We compared outcomes in patients who received TCZ with those who did not. Death in hospital and intensive care unit (ICU) requirements were evaluated as endpoints. Demographic data, comorbidities, additional treatment, treatment side effects, laboratory and clinical results were retrospectively assessed. There are no significant differences between groups according to age, gender and Charlson Comorbidity Index (CCI).Results:12 (27.3%) patients died in standard group and eight (18.6%) patients died in TCZ group (p=0.150).Days of staying in the hospital were eight days in standard treatment group and 12 days in TCZ group (p=0.03). 10 of 43 patients in TCZ group were admitted to ICU. MV support was needed in 8 of these patients. 18 of 44 patients (40.9%) within the standard group were admitted to ICU and 12 patients (27.3%) were intubated (p=0.125,p=0.480). Significant IL-6 decrease was not observed post treatment in TCZ group according to pretreatment period (p=0.60). Significant decreases were examined in CRP and ferritin values through TCZ treatment. However, D-dimer and thrombocyte values increased.Conclusion:TCZ may not be an effective treatment for reducing ICU requirement, to prevent intubation or death, for shortening period for staying in hospital. The patients should be followed up closely for possible thrombosis because of increased D-dimer and thrombocytes with TCZ treatment.References:[1]Sharma A, Tiwari S, Deb MK, Marty JL. Severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2): A global pandemic and treatment strategies. IntJ Antimicrob Agents. 2020 Aug; 56(2):106054.[2]Singhal T. A rewiev of coronavirus Disease-2019(COVID-19). Indian J Pediatr. 2020 Apr;87(4):281-286.[3]Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall R.S, Manson J.J. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-[4]Teijaro J.R. Cytokine storms in infectious diseases. SeminImmunopathol. 2017;39:501–503.[5]Zhang Y, Li J, Zhan Y, Wu L, Yu X, Zhang W et al. Analysis of Serum Cytokines in Patients with Severe Acute Respiratory Syndrome. Infect Immun 2004 Aug;72(8):4410-4415.[6]Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int J Antimicrob Agents. 2020 May; 55(5):105954.[7]Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420–2[8]Fu B, Xu X, Wei H. Why tocilizumab could be an effective treatment for severe COVID-19? J Transl Med 18,164 (2020).[9]Guaraldi G, Meschiari M, Cozzi-Lepri A, Milic J, Tonelli R, Menozzi M et al. Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol. 2020 Aug;2(8):e474-e484.[10]Gupta S, Wang W, Hayek S.S, Chan L, MathewsK.S, Melamed M.L et al. Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19. JAMA Intern Med. 2021 Jan1;181(1):41-51.[11]Campochiaro C, Della-Torre E, Cavalli G, De Luca G, Ripa M, Boffini N et al Efficacy and safety of tocilizumab in severe COVID- 19 patients: a single-centre retrospective cohort study. Eur J Intern Med. 2020 Jun;76:43-49.Disclosure of Interests:None declared

ABSTRACTThe mechanism of colistin-induced neurotoxicity is still unknown. Our recent study (L. Zhang, Y. H. Zhao, W. J. Ding, G. Z. Jiang, Z. Y. Lu, L. Li, J. L. Wang, J. Li, and J. C. Li, Antimicrob Agents Chemother 59:2189–2197, 2015,http://dx.doi.org/10.1128/AAC.04092-14; H. Jiang, J. C. Li, T. Zhou, C. H. Wang, H. Zhang, and H. Wang, Int J Mol Med 33:1298–1304, 2014,http://dx.doi.org/10.3892/ijmm.2014.1684) indicates that colistin induces autophagy and apoptosis in rat adrenal medulla PC-12 cells, and there is interplay between both cellular events. As an important cellular stress sensor, phosphoprotein p53 can trigger cell cycle arrest and apoptosis and regulate autophagy. The aim of the present study was to investigate the involvement of the p53 pathway in colistin-induced neurotoxicity in PC-12 cells. Specifically, cells were treated with colistin (125 μg/ml) in the absence and presence of a p53 inhibitor, pifithrin-α (PFT-α; 20 nM), for 12 h and 24 h, and the typical hallmarks of autophagy and apoptosis were examined by fluorescence/immunofluorescence microscopy and electron microscopy, real-time PCR, and Western blotting. The results indicate that colistin had a stimulatory effect on the expression levels of the target genes and proteins involved in autophagy and apoptosis, including LC3-II/I, p53, DRAM (damage-regulated autophagy modulator), PUMA (p53 upregulated modulator of apoptosis), Bax, p-AMPK (activated form of AMP-activated protein kinase), and caspase-3. In contrast, colistin appeared to have an inhibitory effect on the expression of p-mTOR (activated form of mammalian target of rapamycin), which is another target protein in autophagy. Importantly, analysis of the levels of p53 in the cells treated with colistin revealed an increase in nuclear p53 at 12 h and cytoplasmic p53 at 24 h. Pretreatment of colistin-treated cells with PFT-α inhibited autophagy and promoted colistin-induced apoptosis. This is the first study to demonstrate that colistin-induced autophagy and apoptosis are associated with the p53-mediated pathway.

While preparing the manuscript of Flora of Pan-Himalaya, volume 44(1) of Lamiaceae (Wang 2019), we encountered a species of the genus Premna Linnaeus (1771: 587), Premna velutina Wu (1977: 428), which was described by Wu (1977) in Flora Yunnanica, and was accepted in Flora Republicae Popularis Sinicae (Chen 1982) and Flora of China (Chen & Gilbert 1994). However, this is clearly a later homonym of Premna velutina Gürke (1895: 338). Thus, in Flora of Pan-Himalaya Vol. 44(1), a replaced name Premna wuana Wang (2019: 155) was proposed for this illegitimate name. Nonetheless, we actually made a superfluous name, since Boufford and Bartholomew (2012) had proposed Premna wui (noted as “wuii”) Boufford & Bartholomew (2012: 1) to replace the illegitimate name. We thought that all the names of Premna reported from the Pan-Himalaya region and other involved names had been dealt with in our Flora of Pan-Himalaya, volume 44(1). However, we are very sorry for ignoring the correct name Premna wui by mistake, and also for ignoring the name Premna cordiformis Li Bing Zhang & Y.F.Duan in Duan & Zhang (2014: 281), which is another superfluous name of Premna wui. We noticed that Li (2018) had reduced the superfluous name Premna cordiformis to a synonym of Premna wui.

Background: Zuotai (mainly β-HgS)-containing 70 Wei-Zhen-Zhu-Wan (70W, Rannasangpei) is a famous Tibetan medicine for treating cardiovascular and gastrointestinal diseases. We have shown that 70W protected against CCl4 hepatotoxicity. CCl4 is metabolized via cytochrome P450 (CYP) to produce reactive metabolites. Whether 70W has any effect on CYPs is unknown and such effects should be compared with mercury compounds for safety evaluation. Methods: Mice were given clinical doses of 70W (0.15-1.5 g/kg, po), Zuotai (30 mg/kg, po), and compared to HgCl2 (33.6 mg/kg, po) and MeHg (3.1 mg/kg, po) for seven days. Liver RNA and protein were isolated for qPCR and Western-blot analysis. Results: 70W and Zuotai had no effects on hepatic mRNA expression of Cyp1a2, Cyp2b10, Cyp3a11, Cyp4a10 and Cyp7a1, and corresponding nuclear receptors [aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor-α (PPARα); farnesoid X receptor (FXR)]. In comparison, HgCl2 and MeHg increased mRNA expression of Cyp1a2, Cyp2b10, Cyp4a10 and Cyp7a1 except for Cyp3a11, and corresponding nuclear receptors except for PXR. Western-blot confirmed mRNA results, showing increases in CYP1A2, CYP2B1, CYP2E1, CYP4A and CYP7A1 by HgCl2 and MeHg only, and all treatments had no effects on CYP3A. Conclusions: Zuotai and Zuotai-containing 70W at clinical doses had minimal influence on hepatic CYPs and corresponding nuclear receptors, while HgCl2 and MeHg produced significant effects. Thus, the use of total Hg content to evaluate the safety of HgS-containing 70W is inappropriate.

Background: Zuotai (mainly β-HgS)-containing 70 Wei-Zhen-Zhu-Wan (70W, Rannasangpei) is a famous Tibetan medicine for treating cardiovascular and gastrointestinal diseases. We have shown that 70W protected against CCl4 hepatotoxicity. CCl4 is metabolized via cytochrome P450 (CYP) to produce reactive metabolites. Whether 70W has any effect on CYPs is unknown and such effects should be compared with mercury compounds for safety evaluation. Methods: Mice were given clinical doses of 70W (0.15-1.5 g/kg, po), Zuotai (30 mg/kg, po), and compared to HgCl2 (33.6 mg/kg, po) and MeHg (3.1 mg/kg, po) for seven days. Liver RNA and protein were isolated for qPCR and Western-blot analysis. Results: 70W and Zuotai had no effects on hepatic mRNA expression of Cyp1a2, Cyp2b10, Cyp3a11, Cyp4a10 and Cyp7a1, and corresponding nuclear receptors [aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor-α (PPARα); farnesoid X receptor (FXR)]. In comparison, HgCl2 and MeHg increased mRNA expression of Cyp1a2, Cyp2b10, Cyp4a10 and Cyp7a1 except for Cyp3a11, and corresponding nuclear receptors except for PXR. Western-blot confirmed mRNA results, showing increases in CYP1A2, CYP2B1, CYP2E1, CYP4A and CYP7A1 by HgCl2 and MeHg only, and all treatments had no effects on CYP3A. Conclusions: Zuotai and Zuotai-containing 70W at clinical doses had minimal influence on hepatic CYPs and corresponding nuclear receptors, while HgCl2 and MeHg produced significant effects. Thus, the use of total Hg content to evaluate the safety of HgS-containing 70W is inappropriate.

While Mao Zedong might still be China's most famous communist, only scholars of the history of the Chinese Communist Party (CCP) have heard of Wang Jiaxiang and even they have never studied his career in detail. But recent Chinese publications show that there were very few CCP leaders who had such a tremendous impact on the Chinese communist movement in general and Mao Zedong's career in particular. This article will show that Wang not only supported Mao during the power struggles of the 1930s and helped convince Stalin that Mao should be acknowledged as the CCP's leader, but that Wang also played a decisive role in establishing Mao Zedong-Thought as the Party's guiding ideology. The release of numerous Party documents in the last five years also throws some light upon the relations and conflicts between Mao Zedong and other CCP leaders such as Wang Ming, Zhou Enlai, Zhang Guotao and Liu Shaoqi in the decade between the Long March and the Seventh Party Congress of 1945.

Hu, D-L., Chen, Q-Z., Zhang, C-J., Wang, Y., Zhang, B-J. and Tang, C-M. 2013. Identification of cotton SKP 1-like gene GhSKP1 and its function in seed germination and taproot growth in tobacco. Can. J. Plant Sci. 93: 817–825. The SKP1 (S-phase kinase-associated-protein1) protein, a key component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, has been reported to play many important roles in many organisms, including regulation of ubiquitin-mediated protein degradation, seed germination, taproot growth and auxin signaling, though no study of this gene in cotton has been performed. In this study, a SKP1 gene was isolated from upland cotton (Gossypium hirsutum L.) using the rapid amplification of cDNA ends (RACE) method and was named Gossypium hirsutum SKP1 (GhSKP1). The cDNA sequence of GhSKP1 was 813 bp containing a 474 bp open reading frame, encoding a protein of 156 amino acids with a predicted molecular weight of 17.63 kDa. The deduced amino acid of GhSKP1 had a conserved SKP1 domain. GhSKP1 expression was tested in all organs of cotton plants, and the strongest expression was observed in stamens and radicles that have actively dividing cells. Overexpression of the full-length GhSKP1 cDNA in tobacco caused delayed seed germination and shortened taproots. Our results suggest that the presence of functional conservation between GhSKP1 and SKP1 in plant developmental processes may exist.

Background:Polyarteritis nodosa (PAN) is a segmental, necrotizing vascular disease that primarily impacts medium-sized muscle arteries. The estimated annual incidence of PAN is still lacking in China. Digital gangrene is an ischemic manifestation of the limb. However, the causes and the treatment methods vary from case to case, and the outcome is unpredictable. These features emphasize the need to identify measurable variables that accelerate digital gangrene development in PAN patients. However, little effort has been made to identify the clinical and laboratory factors that affect PAN patients with digital gangrene to anticipate their natural history and response to therapy.Objectives:Many patients with polyarteritis nodosa (PAN) complicated with digital gangrene have poor outcomes and related research information is limited. This study was carried out to identify the associated risk and prognostic factors.Methods:We conducted a retrospective study of 148 PAN patients admitted to Peking Union Medical College Hospital (PUMCH) from September 1986 to December 2018. The characteristics, therapeutic regimens, and outcome data for patients with and without gangrene were compared. The Kaplan–Meier method and Cox hazard regression model were used to evaluate the prognostic factors.Results:Forty-seven (31.8%) PAN patients had digital gangrene complications. The average age was 40.4±17.9 years and the average disease duration was 11 (4-27) months. The presence of digital gangrene was correlated with smoking history [odds ratio (OR), 4.27; 95% confidence interval (95% CI), 1.56-11.66] and eosinophil elevation (28.12; 10.30-76.8). Thirty-two (68.1%) gangrene patients received methylprednisolone pulse therapy and all of these patients were treated with cyclophosphamide. Nine patients suffered irreversible organ injury and two died. Disease duration ≥ 24 months and elevated serum C-reactive protein (CRP) were identified as hazardous factors for poor prognosis in patients with gangrene (P=0.003, HR=8.668, 95% CI 2.11, 35.55 andP=0.042, HR=27.062, 95% CI 1.13, 648.57, respectively).Conclusion:Smoking history and eosinophil elevation in PAN patients were more prone to digital gangrene and high serum CRP level predicted poor outcomes. PAN patients with smoking history and elevated eosinophils need to be seriously evaluated by clinicians. Furthermore, the CRP level should be efficiently controlled for good prognosis.References:[1]De Virgilio A, Greco A, Magliulo G, Gallo A, Ruoppolo G, Conte M, et al. Polyarteritis nodosa: A contemporary overview. Autoimmun Rev. 2016;15:564-70.[2]Pagnoux C, Seror R, Henegar C, Mahr A, Cohen P, Le Guern V, et al. Clinical features and outcomes in 348 patients with polyarteritis nodosa: a systematic retrospective study of patients diagnosed between 1963 and 2005 and entered into the French Vasculitis Study Group Database. Arthritis Rheum. 2010;62:616-26.[3]Xu D, You X, Wang Z, Zeng Q, Xu J, Jiang L, et al. Chinese Systemic Lupus Erythematosus Treatment and Research Group Registry VI: Effect of Cigarette Smoking on the Clinical Phenotype of Chinese Patients with Systemic Lupus Erythematosus. PLoS One. 2015;10:e0134451.Acknowledgments:NoDisclosure of Interests:Dong Xu: None declared, Xinping Tian: None declared, Xiaofeng Zeng Consultant of: MSD Pharmaceuticals, Fengchun Zhang: None declared, Lin Zhao: None declared, Shangzhu Zhang: None declared, Jiaxin Zhou: None declared, Jiu-liang Zhao: None declared, Xiaodan Kong: None declared

Objectives CT-based three-column classification (TCC) has been widely used in the treatment of tibial plateau fractures (TPFs). In its updated version (updated three-column concept, uTCC), a fracture morphology-based injury mechanism was proposed for effective treatment guidance. In this study, the injury mechanism of TPFs is further explained, and its inter- and intraobserver reliability is evaluated to perfect the uTCC. Methods The radiological images of 90 consecutive TPF patients were collected. A total of 47 men (52.2%) and 43 women (47.8%) with a mean age of 49.8 years (sd 12.4; 17 to 77) were enrolled in our study. Among them, 57 fractures were on the left side (63.3%) and 33 were on the right side (36.7%); no bilateral fracture existed. Four observers were chosen to classify or estimate independently these randomized cases according to the Schatzker classification, TCC, and injury mechanism. With two rounds of evaluation, the kappa values were calculated to estimate the inter- and intrareliability. Results The overall inter- and intraobserver agreements of the injury mechanism were substantial (κinter = 0.699, κintra = 0.749, respectively). The initial position and the force direction, which are two components of the injury mechanism, had substantial agreement for both inter-reliability or intrareliability. The inter- and intraobserver agreements were lower in high-energy fractures (Schatzker types IV to VI; κinter = 0.605, κintra = 0.721) compared with low-energy fractures (Schatzker types I to III; κinter = 0.81, κintra = 0.832). The inter- and intraobserver agreements were relatively higher in one-column fractures (κinter = 0.759, κintra = 0.801) compared with two-column and three-column fractures. Conclusion The complete theory of injury mechanism of TPFs was first put forward to make the TCC consummate. It demonstrates substantial inter- and intraobserver agreement generally. Furthermore, the injury mechanism can be promoted clinically. Cite this article: B-B. Zhang, H. Sun, Y. Zhan, Q-F. He, Y. Zhu, Y-K. Wang, C-F. Luo. Reliability and repeatability of tibial plateau fracture assessment with an injury mechanism-based concept. Bone Joint Res 2019;8:357–366. DOI: 10.1302/2046-3758.88.BJR-2018-0331.R1.

Background:Ankylosing spondylitis (AS) is a chronic inflammatory disease that mainly affects the sacroiliac joints and the spine, resulting in decline in quality of life[1,2]. Poor QoL is significantly related to high disease activity[3]. However, there is no systematic report on which prognosis indicators are affected by disease activity in AS patients.Objectives:This study aimed to evaluate the patient-reported outcome measures and health-related quality of life (HR-QoL) in AS patients defined on the basis of the Bath Spondylitis Ankylosing Disease Activity Index (BASDAI).Methods:204 AS patients were involved in this study. A serious of questionnaires were used to overall assess AS patients, which include: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Bath Ankylosing Spondylitis Functional Index (BASFI), the 10 cm Visual Analog Scale (VAS), the Self-Rating Anxiety Scale (SAS), the Self-Rating Depression Scale (SDS), the Pittsburgh Sleep Quality Index (PSQI), the Health Assessment Questionnaire-Disability Index (HAQ-DI), the Fatigue Severity Scale(FSS) and the Short Form 36 Health Survey (SF-36). Independent samples t-test, Mann–Whitney U-test, Chi-square analysis and Pearson /Spearman correlation were used to analyze the data.Results:The results demonstrated 31.4% AS patients were in active disease activity stage. Active AS patients were older, unemployed, and had less exercise therapy than stable AS patients. Besides, AS patients with active disease activity presented more severe pain(P<0.001), poor physical function(P<0.001) and spinal mobility(P<0.001). They were more anxious(P<0.001), depressed(P<0.001) and had more sleep disturbance(P=0.001). Compared with active AS patients, stable AS patients had more leukocytes(P=0.040), lymphocytes(P=0.002), erythrocytes(P=0.001) and hemoglobin(P<0.001). Active disease activity had a significant impact on all dimensions of quality of life in AS patients(P<0.001).Conclusion:These findings suggested that medical personnel should pay more attention to active AS patients and make effective interventions to improve quality of life.References:[1]Exarchou S, Lindstrom U, Askling J, Eriksson JK, Forsblad-d’Elia H, Neovius M, Turesson C, Kristensen LE, Jacobsson LT (2015) The prevalence of clinically diagnosed ankylosing spondylitis and its clinical manifestations: a nationwide register study. Arthritis research & therapy 17:118. doi:10.1186/s13075-015-0627-0[2]Qian Q, Xu X, He H, Ji H, Zhang H, Ding Y, Dai SM, Zou Y, Zhu Q, Yang C, Ye S, Jiang L, Tang JP, Tong Q, He D, Zhao D, Li Y, Ma Y, Zhou J, Yuan Z, Zhang J, Jin L, Zhou X, Reveille JD, Zou H, Wang J (2017) Clinical patterns and characteristics of ankylosing spondylitis in China. Clinical rheumatology 36 (7):1561-1568. doi:10.1007/s10067-017-3660-3[3]Huang JC, Qian BP, Qiu Y, Wang B, Yu Y, Zhu ZZ, Hu J, Qu Z (2017) Quality of life and correlation with clinical and radiographic variables in patients with ankylosing spondylitis: a retrospective case series study. BMC musculoskeletal disorders 18 (1):352. doi:10.1186/s12891-017-1711-1Acknowledgments:Thanks to all the authors for their efforts and thanks to all members of the Department of Rheumatology of Affiliated Hospital of Nantong University for their helpfulness in the acquisition of data.Disclosure of Interests:None declared

This article seeks to explain periodic unrest in China’s Xinjiang Uyghur Autonomous Region in the years immediately following the Third Plenum. This unrest fractured along ethnic lines between the non-Han and the Han, and in so doing, threatened to unravel Deng Xiaoping’s modernization efforts. Simultaneously, the unrest challenged Beijing’s self-projection as a unitary multiethnic state, and singular Chinese nation. Beijing’s anxiety was evident in its response: memorializing state building on the frontier during the 1940s and 1950s; emphasizing nationalities work; and dispatching veteran revolutionaries to Xinjiang. Foremost amongst them was Wang Zhen (1908–1993), who had led the People’s Liberation Army into Xinjiang in October 1949. During four visits between 1980 and 1982, Wang admonished cadres to love Xinjiang and its people, and to settle contentedly on the frontier. In this article, I argue that in the post-1978 period, unrest in Xinjiang was local resistance to accelerated modernization after the Third Plenum. I also demonstrate how this local resistance to Deng-era modernization led to a deepening of Beijing’s appropriation of the frontier.

Background:Dermatomyositis (DM)/Polymyositis(PM) is an autoimmune disease that typically involve the striated muscle with a variable involvement of the skin and other organs1. Lymphocyte subsets disorders may contribute to the pathogenesis of DM/PM. It has been discovered that immunomodulatory drugs such as low-dose interleukin (IL)−2, rapamycin can help to regulate the lymphocyte subsets and control the disease and improve the prognosis2-4.Objectives:To investigate the levels of peripheral lymphocyte and CD4+T subsets of DM/PM patients and further to observe the regulatory effect of modulatory therapy on these cells in PM/DM at a relative large-sample size.Methods:Total 450 patients with PM/DM and 206 healthy controls (HCs) were enrolled in this study. Among these participations, 320 patients received immunomodulatory combination therapies (immunomodulatory drugs include low-dose interleukin-2, rapamycin, metformin, retinoic acid etc). The absolute numbers of T, B, NK, CD4+T, CD8+T, Th1, Th2, Th17 and Tregs in peripheral blood of these individuals were detected by flow cytometry combined with standard absolute counting beads before and after the treatment.Results:Patients with DM/PM had lower levels of total T, CD4+T, CD8+T, Th2, Th17, NK, Th1 and Tregs compared with those of HCs (P < 0.05). After immunomodulatory combination treatments, there was a dramatically increases various peripheral lymphocyte subsets such as T, B, CD4+T, CD8+T, NK, Th1, Th17 and Tregs (P < 0.05). Moreover, the increase in Tregs was much more than that in effector T cells (Teffs), resulting a rebalance of immune systems.Conclusion:The unbalance of lymphocyte cells should contribute to the pathogenesis of DM/PM patients. Immunomodulatory combination therapies could promote the proliferation and functional recovery of Tregs in patients and might help to alleviate disease activity.References:[1]Herbelet S, De Bleecker JL. Immune checkpoint failures in inflammatory myopathies: An overview. Autoimmunity reviews 2018;17(8):746-54. doi: 10.1016/j.autrev.2018.01.026 [published Online First: 2018/06/10][2]Feng M, Guo H, Zhang C, et al. Absolute reduction of regulatory T cells and regulatory effect of short-term and low-dose IL-2 in polymyositis or dermatomyositis. International immunopharmacology 2019;77:105912. doi: 10.1016/j.intimp.2019.105912 [published Online First: 2019/11/02][3]Zhang SX, Wang J, Sun HH, et al. Circulating regulatory T cells were absolutely decreased in dermatomyositis/polymyositis patients and restored by low-dose IL-2. Annals of the rheumatic diseases 2019 doi: 10.1136/annrheumdis-2019-216246 [published Online First: 2019/10/16][4]Zhao C, Chu Y, Liang Z, et al. Low dose of IL-2 combined with rapamycin restores and maintains the long-term balance of Th17/Treg cells in refractory SLE patients. BMC immunology 2019;20(1):32. doi: 10.1186/s12865-019-0305-0 [published Online First: 2019/09/06]Acknowledgments:NoneDisclosure of Interests:None declared

Computer Assisted Language Learning (CALL) has been a burgeoning industry in China, one case in point being the extensive employment of Automated Writing Evaluation (AWE) systems in college English writing instruction to reduce teachers’ workload. Nonetheless, what warrants a special mention is that most teachers include automatic scores in the formative evaluation of relevant courses with scant attention to the scoring efficacy of these systems (Bai & Wang, 2018; Wang & Zhang, 2020). To have a clearer picture of the scoring validity of two commercially available Chinese AWE systems (Pigai and iWrite), the present study sampled 486 timed CET-4 (College English Test Band-4) essays produced by second-year non-English majors from 8 intact classes. Data comprising the maximum score difference, agreement rate, Pearson’s correlation coefficient and Cohen’s Kappa were collected to showcase human-machine and machine-machine congruence. Quantitative linguistic features of the sample essays, including accuracy, lexical and syntactic complexity, and discourse features, were also gleaned to investigate the differences (or similarities) in construct representation valued by both systems and human raters. Results show that (1) Pigai and iWrite largely agreed with each other but differed a lot from human raters in essay scoring; (2) high-human-score essays were prone to be assigned low machine scores; (3) machines relied heavily on the quantifiable features, which, however, had limited impacts on human raters.

Xin, H., Wu, B., Zhang, H., Wang, C., Li, J., Yang, B. and Li, S. 2013. Characterization of volatile compounds in flowers from four groups of sweet osmanthus ( Osmanthus fragrans ) cultivars. Can. J. Plant Sci. 93: 923–931. Headspace-solid-phase microextraction (HS-SPME) and gas chromatography-mass spectroscopy (GC-MS) were used to characterize the volatiles in flowers of four cultivar groups of sweet osmanthus (Osmanthus fragrans Lour.), including Thunbergii, Latifolius, Aurantiacus and Semperflorens Groups. A total of 72 volatiles were identified. Volatile compounds and their relative contents varied among the four groups or cultivars within each group. Briefly, β-ionone, cis-linalool oxide (furan), trans-linalool oxide (furan) and linalool were the most common volatiles in tested cultivars, while (E)-2-hexenal, (Z)-3-hexen-1-ol and hexanal were abundant in several cultivars. Principal component analysis showed that the Aurantiacus Group was rich in cis- and trans-linalool oxide (furan), whereas the Latifolius group had high levels of (E)-2-hexenal and (Z)-3-hexen-1-ol. Our results contribute to our understanding of the volatile composition and content in flowers from different osmanthus groups and will facilitate development of new osmanthus cultivars to meet requirements of the food and fragrance industries.

Wang, Y., Zhang, Y., Wang, F., Liu, C. and Liu, K. 2014. Development of transgenic Brassica napus with an optimized cry1C* gene for resistance to diamondback moth (Plutella xylostella). Can. J. Plant Sci. 94: 1501–1506. Bacillus thuringiensis (Bt) cry1Ac gene has been transformed into rapeseed to control diamondback moth (DBM, Plutella xylostella), which is one of the major lepidopteran pests of rapeseed (Brassica napus). However, Cry1A-resistant DBM populations have already developed in the field. Cry1C* is a new synthetic Bt gene based on the original cry1Ca5 sequence through optimizing its codons as well as removing AT-rich sequences and inverted repeats. In our present study, the cry1C* gene was introduced into rapeseed via Agrobacterium-mediated transformation, and a total of 42 transgenic lines were recovered. The results of polymerase chain reaction (PCR) and Southern blot both confirmed the expression of the cry1C* gene in the genomes of the transformants. We also assessed the expression of this foreign gene at the mRNA level in some selected transgenic lines by real-time reverse transcription (RT) PCR analysis. Enzyme-linked immunosorbent assay (ELISA) showed that the Cry1C* expression at the protein level greatly varied among individual transgenic plants, and transgenic line 1C-8 had the highest protein level of 799.32 ng g−1. The transgenic rapeseed plants expressing cry1C* gene showed a high efficacy against DBM. Taken together, the cry1C*-transgenic rapeseed could be employed as a useful germplasm in pest management and in the broad bioinsecticidal spectrum to prevent and postpone the development of pest resistance.

The purpose of this study was to adapt to Turkish and to determine the validity and reliability of the Scale for Esports Spectator Demand (SESD), which was developed to determine the demands of the viewers who follow the esports broadcasts by Qian, Zhang, Wang and Hulland (2020). After the Turkish form equivalence test, the scale was applied to viewers who following esports broadcasts on the online broadcast network "Twitch". A total of 495 volunteers (21.43 ± 3.50), 423 men (21.71 ± 3.51), and 72 women (19.75 ± 2.95), aged between 18-32, participated in the online study. Exploratory (EFA) and confirmatory factor analysis (CFA) was performed on the data obtained. A total of 7 factors were determined with EFA, respectively, 4 overlapping items (21-11-18-29), 2 items that make up a single factor (19-20) and the 30th item that disrupted the meaning integrity of the factor to which it belongs were removed from the scale. It was seen that the model consisting of the remaining 25 items and 6 dimensions explained 67.278% variance and the 6-factor model had an acceptable fit as a result of CFA. (χ2/df=2,622; GFI=,896; AGFI=,892; CFI=,918; NFI=,902; RMR=,064; RMSEA=,071). It was determined that the internal consistency coefficients of the scale on the basis of sub-dimensions ranged between .755 and .863, and the overall internal consistency coefficient was α = .924 As a result, it was determined that the Scale for Esports Spectator Demand (SESD), adapted to Turkish, can be used as a valid and reliable measurement tool to determine the demands of esports spectator. ​Extended English summary is in the end of Full Text PDF (TURKISH) file. Özet Bu çalışma’nın amacı, Qian, Zhang, Wang ve Hulland (2020) tarafından espor yayınlarını takip eden izleyicilerin yayından taleplerini belirlemek amacıyla geliştirilmiş olan Scale for Esports Spectator Demand (SESD)’in Türkçe’ye uyarlanması, geçerlik ve güvenirliği’nin belirlenmesidir. Ölçek, Türkçe form eş-değerlik sınamasının ardından Türkiye genelinde çevrimiçi yayın ağı “Twitch” üzerinden espor yayınlarını takip eden izleyicilere uygulanmıştır. Çevrimiçi ortamda gerçekleştirilen çalışmaya yaşları 18-32 arasında değişen 423 erkek (21,71±3,51) ve 72 kadın (19,75±2,95) olmak üzere toplam 495 gönüllü birey (21,43±3,50 katılmıştır. Elde edilen veriler üzerinde açımlayıcı (AFA) ve doğrulayıcı faktör analizi (DFA) gerçekleştirilmiştir. AFA ile toplam 7 faktör belirlenmiş, sırasıyla binişik olan 4 madde (21-11-18-29), tek bir faktörü oluşturan 2 madde (19-20) ve ait olduğu faktördeki anlam bütünlüğünü bozan 30. madde ölçekten çıkarılmıştır. Kalan 25 madde ve 6 boyuttan oluşan modelin %67,278 varyansı açıkladığı ve DFA sonucunda 6 faktörlü modelin kabul edilebilir bir uyuma sahip olduğu görülmüştür (χ2/df=2,622; GFI=,896; AGFI=,892; CFI=,918; NFI=,902; RMR=,064; RMSEA=,071). Ölçeğin alt boyutlar bazında iç tutarlılık katsayılarının ,755 ile ,863 arasında değiştiği, genel iç tutarlılık katsayısının ise α= ,924 olduğu tespit edilmiştir. Sonuç olarak, Türkçe’ye uyarlama çalışması yapılmış olan Espor İzleyici Talepleri Ölçeği (ESİTÖ)’nün espor izleyicilerinin taleplerini belirlemek için geçerli ve güvenilir bir ölçüm aracı olarak kullanılabileceği belirlenmiştir.

Abstract Background Previous research has reported nontuberculous mycobacterial lung disease (NTMLD) prevalence of 47 per 100,000 among Medicare beneficiaries ≥65 years in 2007, with an average increase of 8.2% annually between 1997 and 2007. In this study, we have evaluated NTMLD incidence and prevalence in Medicare between 2008 and 2015. Methods Patients diagnosed for NTMLD with an ICD9 031.0 were identified from the Medicare database (N≈30 million yearly), not including the Part C portion. Individuals who incurred at least 2 medical claims ≥30 days apart between 2007 and 2015 were considered as a positive NTMLD case, yielding 58,294 patients. All individuals fulfilling the case definition each calendar year were considered as prevalent cases. Incident cases included those meeting case criteria and who did not have a Medicare claim for NTMLD in the prior year. Poisson regression was used to estimate yearly confidence intervals. ARIMA models were used to forecast incidence and prevalence over 2016–2025. Results Patients with NTMLD in the Medicare database had a mean age of 74 (standard deviation: ±10) years. Sixty-nine percent were women and 89% white. Yearly NTMLD incidence increased from 20.7 (95% CI: 20.2–21.3) in 2008 to 28.1 (27.5–28.7) in 2013 per 100,000 Medicare beneficiaries and leveled to 27.6 (26.9–28.2) in 2014 and 25.9 (25.3–26.5) in 2015 per 100,000. Yearly NTMLD prevalence increased throughout the observation period from 41.6 (40.9–42.3) in 2008 to 63.1 (62.2–64.0) in 2015 per 100,000 Medicare beneficiaries. Incidence was 28.1 vs. 14.7 per 100,000 in 2015 in Medicare beneficiaries ≥65 years vs. those &lt;65 years, respectively. Prevalence was 70.2 vs. 27.9 per 100,000 in 2015 in Medicare beneficiaries ≥65 years vs. those &lt;65 years, respectively. In 2015, incidence and prevalence were higher in women than men (33.9 vs. 16.0/100,000 and 86.2 vs. 34.6/100,000, respectively) and among individuals of Asian origin compared with White (41.1 vs. 27.6/100,000 and 89.4 vs. 68.7/100,000, respectively). The 10-year incidence and prevalence forecasts were presented in figures. Conclusion In US Medicare beneficiaries, NTMLD incidence increased from 2008 through 2013 and leveled off in more recent years, while NTMLD prevalence continued to rise through 2015. Disclosures K. L. Winthrop, Insmed Incorporated: Scientific Advisor, Consulting fee and Research grant. T. Marras, Insmed Incorporated: Investigator, Consulting fee and Research grant, Horizon Pharmaceuticals: Consultant, Consulting fee, Red Hill: Consultant, Consulting fee, AstraZeneca: CME, Speaker honorarium. G. Eagle, Insmed Incorporated: Employee, Salary. R. Zhang, Insmed Incorporated: Consultant, Consulting fee. P. Wang, Insmed Incorporated: Employee, Salary. E. Chou, Insmed Incorporated: Employee, Salary. Q. Zhang, Insmed Incorporated: Employee, Salary.

Historical perspectives are a means of reconstructing the sociological imagination, as classical sociologists did. There are many historical dimensions in Karl Marx’s social studies: dialectical analysis of the present as history; reconstructed narratives of historical events; and finally, evolution of family, ownership, state, and social formations. Likewise, in order to understand the reality of Chinese society, we need to examine the transformation of modern Chinese social thought and its contexts. By reinterpreting the Theory of the Three Epochs from the classic Spring and Autumn Annals, Kang Youwei proposed that the establishment of the Idea of Cosmic Unity as the universal value for world history and the building of the Confucian religion for the cultivation of mores had resulted in the successful transformation of Chinese society from the Era of War to the Era of Peace. In contrast, Zhang Taiyan upheld the tradition of ‘Six Classics are all Histories’ and furthered the academic change of focus from classics to history, which Wang Guowei and Chen Yinque carried out. Through the method of synthetical deduction in the social sciences, Wang Guowei interpreted classics historically in Institutional Change in the Yin and Zhou Dynasties, confirming the original principle of the Zhou regime and etiquette on the basis of the patriarchal clan system and its emphasis on law, mores, and institutions. On the other hand, Chen Yinque thoroughly investigated the Middle Period of Chinese history from the perspectives of concourse and inter-attestation and outlined a historical landscape of interfusion between Hu and Han nationalities, the mixing of various religions, the migrations of diverse groups, and the integration of different cultures and mores. In short, there are two waves of intellectual change in the Chinese modern transformation, which together have established the new discipline of Classical and Historical Studies as well as the subsequent institutional and spiritual sources of social and political construction.

Ba, Q. S., Zhang, G. S., Wang, J. S., Che, H. X., Liu, H. Z., Niu, N., Ma, S. C. and Wang, J. W. 2013. Relationship between metabolism of reactive oxygen species and chemically induced male sterility in wheat (Triticum aestivum L.). Can. J. Plant Sci. 93: 675–681. Chemically induced male sterility (CIMS) systems in wheat are among the male sterility types used for hybrid wheat (Triticum aestivum L.) production in China. Some studies suggested that male sterile line Xi'nong 1376-CIMS induced by chemical hybridizing agents (CHA) may suffer from oxidative stress as its cyanide-resistant respiration is lower than that of Xi'nong1376. To elucidate the metabolic mechanism of reactive oxygen species (ROS) in the CIMS anthers, the metabolism changes in the production and scavenging of ROS and gene expression related to ROS-scavenging enzymes were investigated in the anther of Xi'nong 1376-CIMS and Xi'nong1376.Anthers of Xi'nong 1376-CIMS had higher contents of [Formula: see text] and H2O2 than those of 1376, which corresponds to expression level of the NADPH oxidase (NOX) gene, and has higher contents of malondialdehyde compared with 1376. Simultaneously, there were lower activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and ascrodate peroxidase (APX) in scavenging ROS in the anthers of the Xi'nong 1376-CIMS line than in Xi'nong1376. Meanwhile, the expressions of SOD, POD, CAT and APX genes in 1376 were always higher at different levels than those in the Xi'nong 1376-CIMS line except for POD in stage 1. Therefore, it is possible that the sterility in Xi'nong 1376-CIMS is related to the abortion of microspores induced by chronic oxidative stress caused by an abnormal increase in ROS.

World Health Organization (WHO) found the number of Cesarean Section delivery in the world at 25.7% in 2004-2008 which was 27.3% in Asia, 19.0% in Europe, 29.2% in Latin America and the highest number was in China at the rate of 46.2% (Wang, Hellerstein, Hou, Zou, Ruan, & Zhang, 2017). Rates determined by WHO for each country were 10-15% (WHO, 2015). WHO (2015) stated that the causative factor that can be delivered by Cesarean section is when vaginal delivery may have a risk to the mother and baby such as taking too much time for delivery and fetal disorders. Another cause was because of abnormal position. This study aims to determine the relationship between mother’s demand and Cesarean section delivery at PKU Muhammadiyah Hospital Bantul. The type of research used in this study is quantitative research with Cross Sectional approach using secondary data, namely medical record data of PKU Muhammadiyah Hospital Bantul in 2017. Chi-Square with P value 0.05 and CI 95% was used as data analysis. The bivariate results obtained were mother’s demand associated with delivery of Cesarean section with p value of 0.000 which means that the mother's demand had a significant relationship with the section Cesarean delivery. Based on the analysis of health technology assessment (HTA), the selection efforts at Cesarean section delivery were very beneficial for the mother and family, in terms of maternal health, economy and other factors.

Показано, что фазовое превращение палладия в собственную фазу при селективном растворении сплава Ag15Pd протекает в режиме мгновенной нуклеации и лимитируется поверхностной диффузией ад-атомов Pd к растущему трехмерному зародышу новой фазы. С применением нестационарных электрохимических методов установлены кинетические закономерности процесса электроокисления муравьиной кислоты на сплаве Ag15Pd, подвергнутом предварительному селективному растворению. Найдено, что процесс анодной деструкции НСООН в кислом сульфатном растворе протекает с более высокой скоростью на анодно-модифицированном сплаве Ag15Pd, поверхность которого морфологически развита и обогащена палладием в результате потенциостатическогоселективного растворения при закритических условиях поляризации. Процесс электроокисления НСООН является нестационарным, протекает в смешанно-кинетическом режиме и ускоряется с ростом анодного потенциала. С применением метода хроноамперометрии найдены кинетические токи анодного окисления муравьиной кислоты. Обнаружена корреляция между значением электрического заряда, пропущенного при предварительной анодной модификации сплава Ag15Pd и скоростью кинетической стадии электроокисления НСООН. ЛИТЕРАТУРА 1. Бедова Е. В., Козадеров О. А. Кинетика электроокисления муравьиной кислоты на анодно-модифицированных серебряно-палладиевых сплавах. Электрохимическая энергетика. 2018;18(3): 141–154. DOI: https://doi.org/10.18500/1608-4039-2018-18-3-141-1542. Маршаков И. К, Введенский А. В., Кондрашин В. Ю., Боков Г. А. Анодное растворение и селективная коррозия сплавов. Воронеж: Изд-во Воронеж. гос. ун-та; 1988. 208 с.3. Encyclopedia of electrochemistry. Vol. 4. Corrosion and oxide fi lms. Eds. A. J. Bard, M. Stratmann, G. S. Frankel. Weinheim (Germany): Wiley-VCH; 2003. 755 p.4. Landolt D. Corrosion and Surface Chemistry of Metals. EPFL Press; 2007. 632 c.5. Кеше Г. Коррозия металлов. 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Lighting Normalization is an especially important issue in the image recognitions systems since different illumination conditions can significantly change the recognition results, and the lighting normalization allows minimizing negative effects of various illumination conditions. In this paper, we are evaluating the recognition performance of several lighting normalization methods based on the Self-Quotient ImagE(SQI) method introduced by Haitao Wang, Stan Z. Li, Yangsheng Wang, and Jianjun Zhang. For evaluation, we chose the original implementation and the most perspective latest modifications of the original SQI method, including the Gabor Quotient ImagE(GQI) method introduced by Sanun Srisuk and Amnart Petpon in 2008, and the Fast Self-Quotient ImagE(FSQI) method and its modifications proposed by authors in previous works. We are proposing an evaluation framework which uses the Cropped Extended Yale Face Database B, which allows showing the difference of the recognition results for different illumination conditions. Also, we are testing all results using two classifiers: Nearest Neighbor Classifier and Linear Support Vector Classifier. This approach allows us not only to calculate recognition accuracy for each method and select the best method but also show the importance of the proper choice of the classification method, which can have a significant influence on recognition results. We were able to show the significant decreasing of recognition accuracy for un-processed (RAW) images with increasing the angle between the lighting source and the normal to the object. From the other side, our experiments had shown the almost uniform distribution of the recognition accuracy for images processed by lighting normalization methods based on the SQI method. Another showed but expected result represented in this paper is the increasing of the recognition accuracy with the increasing of the filter kernel size. However, the large filter kernel sizes are much more computationally expensive and can produce negative effects on output images. Also, we were shown in our experiments, that the second modification of the FSQI method, called FSQI3, is better almost in all cases for all filter kernel sizes, especially, if we use Linear Support Vector Classifier for classification.

Chen, Qiu-Hong, Ri-Li Ge, Xiao-Zhen Wang, Hui-Xin Chen, Tian-Yi Wu, Toshio Kobayashi, and Kazuhiko Yoshimura. Exercise performance of Tibetan and Han adolescents at altitudes of 3,417 and 4,300 m. J. Appl. Physiol. 83(2): 661–667, 1997.—The difference was studied between O2 transport in lifelong Tibetan adolescents and in newcomer Han adolescents acclimatized to high altitude. We measured minute ventilation, maximal O2 uptake, maximal cardiac output, and arterial O2 saturation during maximal exercise, using the incremental exercise technique, at altitudes of 3,417 and 4,300 m. The groups were well matched for age, height, and nutritional status. The Tibetans had been living at the altitudes for a longer period than the Hans (14.5 ± 0.2 vs. 7.8 ± 0.8 yr at 3,417 m, P < 0.01; and 14.7 ± 0.3 vs. 5.3 ± 0.7 yr at 4,300 m, P < 0.01, respectively). At rest, Tibetans had significantly greater vital capacity and maximal voluntary ventilation than the Hans at both altitudes. At maximal exercise, Tibetans compared with Hans had higher maximal O2 uptake (42.2 ± 1.7 vs. 36.7 ± 1.2 ml ⋅ min−1 ⋅ kg−1at 3,417 m, P < 0.01; and 36.8 ± 1.9 vs. 30.0 ± 1.4 ml ⋅ min−1 ⋅ kg−1at 4,300 m, P < 0.01, respectively) and greater maximal cardiac output (12.8 ± 0.3 vs. 11.4 ± 0.2 l/min at 3,417 m, P < 0.01; 11.5 ± 0.5 vs. 10.0 ± 0.5 l/min at 4,300 m, P < 0.05, respectively). Although the differences in arterial O2saturation between Tibetans and Hans were not significant at rest and during mild exercise, the differences became greater with increases in exercise workload at both altitudes. We concluded that exposure to high altitude from birth to adolescence resulted in an efficient O2 transport and a greater aerobic exercise performance that may reflect a successful adaptation to life at high altitude.

Abstract Factors Influencing Efficacy of CD19-CAR-T cells in Children and Adults with Relapsed/Refractory B-cell Lymphoblastic Leukemia An Furun1, Liu Zhenyun2, Wu Fan1, Song Xiaotong2, Li Yingwei1, Cheng Fengwei2, Tao Qianshan1, He Weijie2, Wang Huiping1, Wang Wei2, Xu Huadong2, Zhang Jiakui1, Shen Yuanyuan1, Ruan Yanjie1, Qin Hui1, Wang Xiansheng1, Zhai Zhimin1* Author Affiliations: 1 Hematology Department of the Second Hospital and Hematologic Diseases Research Center of Anhui Medical University 2 Sinobioway Cell Therapy Co., Ltd. Fund: National Natural Science Foundation of China (No. 81670179); Sinobioway Cell Therapy Co., Ltd. *Corresponding Author: zzzm889@163.com Purpose: Using CD19-CD137-ζ CAR-T cell (named Sino19 cell) to treat patients with refractory/relapsed B-cell acute lymphoblastic leukemia (r/r B-ALL), assess the efficacy and safety, and the relationship of patients' characteristic to the response rate and long-term outcome. Method: Single-center, phase 1/2 clinical trial (NCT02735291). A total of 1-5×107/kg CD19-CD137-ζ CAR T cells manufactured by lentiviral transfection were infused to treating r/r B-ALL. Before infusion, individualized chemotherapy was given based on the tumor burden and bone marrow hyperplasity, then monitoring temperature, blood pressure etc., so as to determine and handle adverse reactions. CR, EFS, OS and their possible influencing factors were analyzed by SPSS10.01 software. Results: 1) Patients: A total of 40 patients with r/r B-ALL were enrolled, 22 males and 18 females, aged from 2 to 72. Among them, 32 patients were followed at least 2 months post infusion of CAR T-cell; 4 have not reached the minimum time requirement for efficacy assessment; 4 did not have cells infused. In the 32 patients evaluated for efficacy assessment, 2 had primary refractory B-ALL, 30 with relapsed and refractory B-ALL; 7(21.9%) previously received alloHSCT and 2 of them using blinatumomab failed; 23(71.9%) had cytogenetic aberrations relating poor prognosis; 11(34.4%) had extramedullary disease (EMD). 2) Efficacy: Up to the day cutoff, 32 patients who received a Sino19 cell infusion and had at least 2 months of follow up, the total CR rate with or without hematologic recovery was 78.1% (95% CI, 63 to 93), the rates of OS in all who had the infusion of Sino19 cells were 74% (95% CI, 57 to 91) at 6 months and 40% (95% CI, 20 to 60) at 12 months, the median of OS was not reached. Among the 25 patients with CR, 4 patients underwent allogeneic hemtologic stem-cell transplantation (alloHSCT) and alive with no relapse at the cutoff time. The rest of 21 patients had 9.6 months (2.2 to 27.4) of median following-up duration, 5 of them had relapse-free survival for more than 15 months and the longest lasted for 22 months. Except 4 who underwent alloHSCT, the rates of EFS for the other 28 patients were 66% (95% CI, 48 to 84) at 6 months and 32% (95% CI, 14 to 50) at 12 months. 3) Adverse reactions: 91% (29/32) of the patients had fever after CAR T infused. According to the NCI-CTCAE v4.03, 21.9% (7/32) had grade≥3 CRS, 6 reversed with glucocorticoid alone or plus tocilizumab and supportive care, 1 died of disease progression at the same time of CRS. Only 2 patients had transient absent-mindedness or deliration. 4) Factors influencing efficacy: ⅰ) EMD, Patients with EMD showed lower CR (54.5% vs. 90.5%, p=0.032), higher relapse (100% vs. 40%, p=0.019) and shorter OS (P=0.025) and EFS (P<0.001), compare with those without EMD; ⅱ) CAR T-cells in-vivo proliferation, CR rate in patients with no proliferation significantly lower than those with expanding (50% vs. 100%; p=0.021). OS and EFS were also significantly different. ⅲ) Regulatory T cells (Tregs), patients with higher Tregs (more than ULN) had more relapse than that with lower or normal Tregs (91% vs. 11%; p=0.001), the OS and EFS also was obviously poor. ⅳ) Cytogenetic, 4 patients with T315I mutation got CR, but 3 relapsed and all died within 6 months, other 1 undergone alloHSCT. ⅴ) CAR T-cells in vivo detected more than 6 months post-infusion, but its persistence do not show relationship to relapse and OS. C onclusion: The Sino19 cell lead to high CR rates in r/r B-ALL, with good safety profile. Some patients can achieve continuous complete remission. EMD, no in-vivo proliferation, higher Tregs and Ph+ with T315I mutation may hinder the efficacy. This is the first clinical report on the relationship between Tregs and CAR T efficacy. Disclosures No relevant conflicts of interest to declare.

Background:Rheumatoid arthritis (RA) is a common autoimmune disorder with joint destruction and synovial inflammation characterized by abnormal immune responses to autoantigens. Our previous studies have demonstrated that impaired peripheral lymphocytes especially insufficiency of regulatory T cells (Tregs) played an important role in pathogenesis of RA1 2. Interestingly, the dysbiosis of gut microbiota triggers several types of autoimmune diseases through the imbalance of T lymphocyte subsets3. However, the detailed gut microbiota of RA patients and its correlation with Tregs and helper T cells 17 (Th17) are unclear up until now.Objectives:To compare the difference of gut microbiota between RA and healthy controls (HCs), and to investigate the relevance of gut microbiota with circulating Tregs and Th17 in patients with RA.Methods:From December 2018 to August 2019, a total of 205 diagnosed patients with RA and 199 age and sex-matched HCs were enrolled in this study. Stool of Every participant was collected for bacterial DNA extraction and 16S ribosomal RNA (rRNA) gene sequencing. The absolute numbers of Tregs and Th17 in PB of these individuals were measured by Flow Cytometer (FCM) combined with standard absolute counting beads. Data were expressed as mean ± standard deviation to the distribution. Independent-samples T test and Spearman rank correlation test. P value <0.05 were considered statistically significant.Results:Patients with RA had a significantly difference of diversity and abundance of intestinal microbiota compared with those of HCs (P< 0.05). Detailedly, the abundance of Proteobacteria was significantly increased in RA patients (P< 0.05), and the abundance of Firmicutes, Fusobacteria and Verrucomicrobia were significantly reduced (P<0.05) at the level of Phylum (Figure 1). At the genus level, in the RA group, the abundance of Escherichia, Ruminococcus2 and Clostridium_sensu_stricto were significantly increased (P< 0.05), but the abundance of Lachnospiracea_incertae_sedis, Prevotella, Clostridium_XlVa, Roseburia, Dialister, Blautia, Megamonas and Gemmiger were significantly lower than the healthy controls (P< 0.05) (Figure 2). Moreover, Blautia, Anaerostipes and Ruminococcus2 have negative correlation with the absolute number of Tregs, and Cloacibacillus and Streptophyta have positive correlation with the absolute number of Th17.Conclusion:Patients with RA had a dysbiosis of the gut microbiota in both diversity and abundance, which is closely related to the impaired peripheral lymphocyte subsets, that may be related to the pathogenesis of RA, which might provide a new idea for RA treatment.References:[1]Wen HY, Wang J, Zhang SX, et al. Low-Dose Sirolimus Immunoregulation Therapy in Patients with Active Rheumatoid Arthritis: A 24-Week Follow-Up of the Randomized, Open-Label, Parallel-Controlled Trial.J Immunol Res2019;2019:7684352. doi: 10.1155/2019/7684352 [published Online First: 2019/11/30][2]Niu HQ, Li ZH, Zhao WP, et al. Sirolimus selectively increases circulating Treg cell numbers and restores the Th17/Treg balance in rheumatoid arthritis patients with low disease activity or in DAS28 remission who previously received conventional disease-modifying anti-rheumatic drugs.Clin Exp Rheumatol2019 [published Online First: 2019/05/11][3]Lee N, Kim WU. Microbiota in T-cell homeostasis and inflammatory diseases.Exp Mol Med2017;49(5):e340. doi: 10.1038/emm.2017.36 [published Online First: 2017/05/27]Acknowledgments:NoneDisclosure of Interests:None declared

Background:Little known about the roles of peripheral immune cell subsets in IgG4-related disease (IgG4-RD).Objectives:The aim of our study was to analyze the role of low-dose interleukin-2 (ld-IL2) on these cells in IgG4-RD.Methods:The percentage and absolute counts of lymphocyte subpopulations [CD3+ (T cells), CD4+, CD8+, CD19+ (B cells) and CD16+CD56+ (NK cells)] and CD4+T cell subsets (Th1, Th2, Th17, regulatory T (Treg)) using single platform flow cytometry in 25 IgG4-RD patients which were admitted and treated, as well as 24 healthy controls (HCs). Among IgG4-RD patients, 19 patients given only conventional treatments while 5 patients were were not only given conventional treatments but also received ld-IL2 (0.5 million IU/day) for 5 days.Results:We found that the absolute counts of T, CD4+T and Th1 cells were increased in the peripheral immune cells of IgG4-RD patients when compared with HCs. Meanwhile, the percentage of B, Th2, Th17 and Treg cells demonstrated significantly decreased. The ratio of Th1/Th2 and Th1/Treg in IgG4-RD patients were higher than that in HCs. After IL-2 administration, the absolute numbers of Treg cells increased dramatically, furthermore, the proportion of Treg cells had a trend towards higher values compared with those before treatment. Conversely, the ratio of Th2/Treg was downward. There were no any significant differences in the above subsets between before and after conventional treatments.Conclusion:Our findings support that the reduction of Treg cells in IgG4-RD patients, as well as ld-IL2 combined with conventional treatments were able to restore the Treg cells.References:[1]Akiyama M, Sasaki T, Kaneko Y, et al. Serum soluble interleukin-2 receptor is a useful biomarker for disease activity but not for differential diagnosis in IgG4-related disease and primary Sjögren’s syndrome adults from a defined population. Clin Exp Rheumatol, 2018.[2]Zhang SX, Wang J, Sun HH et al. Circulating regulatory T cells were absolutely decreased in dermatomyositis/polymyositis patients and restored by low-dose IL-2. Ann Rheum Dis, 2019.Disclosure of Interests:None declared

Autonomous driving has been one of the most interesting technologies in recent years with expectation of solving accidents, pollution, and traffic jams (Jo, Lee, & Kim, 2013; Schrank, Eisele, & Lomax, 2012; Singh, 2018). However, current autonomous vehicles cannot handle all driving situations. Therefore, drivers must intervene in certain situations. SAE international defined these levels of autonomous driving as partial (level 2) and conditional (level 3) autonomous driving (SAE international, 2016). In level 3 autonomous driving, drivers are not required to monitor the driving situations and they may perform non-driving related tasks (NDRTs). However, drivers must pay attention to driving situations and make an appropriate reaction when takeover request (TOR) occurs. Takeover request (TOR) is one of the major issues in autonomous driving. A human driver must be ready to transfer the control of the vehicle when TOR is given. Therefore, how and when to request the driver to transfer the control is important. In this regard, takeover lead time (TORlt) has received great attention and there are many existing scholarly works on the effect of TORlt on takeover performance (Gold et al., 2013; Gold et al., 2017; Mok, Johns, Lee, Ive et al., 2015; Mok Johns Lee, Miller et al., 2015; Payre et al., 2016; Van den Beukel & Van der Voort, 2013; Wan & Wu, 2018; Zhang et al., 2018). Besides its impact on takeover performance, TORlt also has an effect on driver workload (Eriksson & Stanton, 2017; Wan & Wu, 2018). Inappropriate TORlt makes driver overload or underload and the abnormal workload deteriorates driver performance in takeover situation (De Winter et al., 2014; Eriksson & Stanton, 2017; Hajek et al., 2013; Wan & Wu, 2018). However, these studies either did not investigate workload induced by TOR or measure driver workload in a subjective method. This study focused on workload induced by TOR. Wan & Wu (2018) stated that takeover request without sufficient time budget may increase driver workload and generate erratic driver's response. However, many researches have focused on workload while performing NDRT alone. Additionally, a few research that assessed workload induced by TOR used subjective methods. The objective of this study is to investigate the effects of TORlt on driver workload in takeover situation. This study hypothesizes that workload would increase when TORlt is too short or too long. To investigate the hypothesis, an experiment was conducted with driving simulator and workload was measured by subjective and objective methods. The experiment with driving simulator was conducted with 28 participants to investigate the effect of TORlt on the driver workload. TORlt was controlled in 7 levels (3s, 7s, 10s, 15s, 30s, 45s, 60s). Each session of the experiment was dealt with one TORlt level and was conducted in random sequence. At the beginning of the session, participants had to perform the NDRT during autonomous driving. Then, they are required to identify an obstacle in ego-lane and make a lane change to avoid the collision when TOR occurs. The dependent variables in this experiment include workload measured by subjective and physiological methods. Driving Activity Load Index (DALI; Pauzie, 2008) was conducted to measure subjective workload and physiological measures including respiration rate (RSP), heart rate (HR), and galvanic skin reponse (GSR) were conducted to evaluate objective workload. The results of this study showed that TORlt had a significant effect on subjective workload. Subjective workload was increased in short TORlt as expected. Drivers, who were given the TOR with short lead time, did not have sufficient time to perceive and comprehend the driving situation nor make an appropriate decision. As a result, drivers could not cope with the takeover situation and their workload increased. However, driver workload was not increased in excessively long TORlt. Long TORlt was expected to increase driver workload because driver could assume long TORlt to be a false alarm or feel distraction (Wan & Wu, 2018). This might be because participants did not consider that 60s of TORlt was long or there was no false alarm in the experiment. There was no significant effect of TORlt on mean RSP and mean HR. This is because each participant behaved differently or regarded driving situation after the takeover as a simple driving task. In contrast to RSP and HR, TORlt had a significant effect on mean GSR. According to Kramer (1991), Physiological signals are sensitive to different resource demands (Kramer, 1991; Ryu & Myung, 2005). In this study, excessive temporal demand because of short TORlt and distraction caused by long TORlt were demands imposed on the participants. Hence, GSR which is sensitive to emotion and frustration (Kramer, 1991) was influenced by TORlt. In conclusion, the results of the study were different from the hypothesis which expected excessive workload with too short or long TORlt. Even though subjective workload and GSR partially support the hypothesis, more complicated and controlled experiment is needed to confirm the hypothesis. In the future research, experiment including complex driving task and false alarm should be conducted and it is necessary to measure physiological signals while controlling various resource demand to investigate the effect of TORlt on physiological signals.

Background:Malignant neoplasms is the second most common non-SSc associated cause of death in SSc patients, only second to infection. And among all the neoplasms, lung cancers are the most common, which is in the urgent need of attention from clinicians.Objectives:To analyze the clinical features of patients of SSc with lung cancer.Methods:Medical records of inpatients admitted in Peking Union Medical College Hospital from March 1992 to December 2018, were collected and analyzed, including the clinical manifestation, laboratory data, radiological images, pathology. SSc patients without lung cancer during the same period, matched by age and gender, were selected as the controls.Results:Nineteen SSc patients with complete medical records were identified, with 17 (89.5%) females and 2 (10.5%) males. The mean age of SSc onset was 37.8±12.0) years old and of lung cancer diagnosis was (54.4±10.2) years old. One (5.3%) had a smoking history. Eight (42.1%) patients had family history of cancer, which was significantly higher than those without lung cancer (4 patients, 5.3%, P<0.001). The proportion of limited cutaneous SSc (lcSSc) were 63.2% among these patients, and 18 (94.7%) had interstitial lung disease (ILD), the difference between the two groups was not statistically significant (P = 0.259 and 0.051, respectively). All ILD was diagnosed before the onset of lung cancer, with a median interval of 9.2 (range 1.6-28.1) years. SSc patients with lung cancer had less myositis than control group (0% vs. 27.6%, P = 0.032), yet no significant differences were identified in Raynaud’s syndrome, esophageal involvement, digital ulcers, pulmonary hypertension, telangiectasia and arthritis. All patients developed lung cancer after the diagnosis of SSc, with a median interval 10.5 (range 2.0-36.2) years. In most of them(18, 94.7%), lung cancer happened after at least 6 years of SSc onset. Newly happened cough (9 patients), worsening decrease in activity endurance (3), chest pain (2), hemoptysis (2), nodes in lung through regular CT scans (3) were the first presentations of lung cancer. Ten(62.5%) neoplasms developed in the lower lobes of the lung, while 3 was in the upper lobes, one in the lingual lobe, and one in the left pulmonary hilum, and 3 were unknown. The median survival of the case group were 31.4 years, while the median survival of the control group was not reached. Eight patients tested EGFR gene mutation or ALK gene rearrangement, and only 2 were positive.Conclusion:It is not uncommon that SSc could be concomitant with lung cancer, especially for those with long disease duration and family history of malignancy. Due to the subtle onset of lung cancer, clinicians should pay attention to it during clinical practice.References:[1]Hu S et al. Arthritis Res Ther, 2018, 20:235.[2]Steen VD, Ann Rheum Dis, 2007, 66:940-944.[3]Tyndall AJ et al. Ann Rheum Dis, 2010, 69:1809-1815.[4]Compton CC et al. AJCC Cancer Staging Atlas [M]. 7th ed. New York:Springer, 2012:311-328.[5]Detterbeck FC et al. Chest, 2016, 1:193-203.[6]Kuo CF et al. J Rheumatol, 2012, 41:44-49.[7]Nishioka K et al. J Dermatol, 1996, 23:677-682.[8]Ling Z, et al. 2016, 10:238-241.[9]Heist RS et al. J Thorac Oncol, 2012, 7:1775-1780.[10]Kim HR et al. J Clin Oncol, 2013, 31:731-737.[11]Igusa T et al. Ann Rheum Dis, 2018, 77:1179-1186.[12]Hill CL et al. Lancet, 2001, 357:96-100.[13]Pontifex EK et al. Ann Rheum Dis, 2007, 66:551-553.[14]Thun MJ et al. N Engl J Med, 2013, 368:351-364.Disclosure of Interests:Hui Zhong: None declared, Jiaxin Zhou: None declared, Shangzhu Zhang: None declared, Yan Xu: None declared, Yong Hou: None declared, Mengtao Li: None declared, Dong Xu: None declared, Mengzhao Wang: None declared, Xiaofeng Zeng Consultant of: MSD Pharmaceuticals

Background:Only half of patients diagnosed with SLE fulfill classification criteria; the rest have “SLE-like” illnesses such as UCTD. SLE patients are known to experience impaired health-related quality of life (HRQoL) and significant anxiety, depression, and fatigue,1 yet the psychosocial aspects of UCTD are less established. In a qualitative study, we found that most UCTD patients had engaged in psychotherapy and felt additional support was needed.2Objectives:Using multiple validated instruments, this study aims to quantify the psychosocial impact of UCTD.Methods:The Hospital for Special Surgery UCTD and Overlap Registry includes UCTD patients aged ≥ 18 years with ANA ≥ 1:80 and ≥ 1 sign or symptom of rheumatic disease who do not fulfill classification criteria for a defined CTD. We administered the 36-Item Short Form Health Survey (SF-36), General Anxiety Disorder-7 (GAD-7), Beck Depression Inventory (BDI), and Fatigue Severity Scale (FSS) to all patients to assess HRQoL, anxiety, depression, and fatigue. Instruments were scored based on established algorithms and results were summarized using predefined scales and severity thresholds.Results:The composite questionnaire was administered to 85 UCTD patients and completed by 75 (97.3% female, 60% white, mean age ± SD 48.8 ± 13.6 years). The SF-36 Physical Component Summary mean score was 37.8 and Mental Component Summary mean score was 41.1. Across the 8 SF-36 subscales, mean scores were lowest for role limitations due to physical health (39.3) and vitality (39.7) and highest for physical functioning (67.2), role limitations due to emotional health (67.1), and mental health (67.1). Approximately half of UCTD patients reported anxiety (GAD-7 ≥ 6); 20% had moderate/severe anxiety (GAD-7 ≥ 10). The prevalence of depression (BDI ≥ 14) was 26.7%; 13.3% had moderate/severe depression (BDI ≥ 20). Fatigue (FSS ≥ 3) was reported by 82.8% of patients (median FSS score of 4.7) [Table 1].Table 1.Psychosocial Survey Scores of Patients with Undifferentiated Connective Tissue Disease (n=75)36-Item Short Form Health Survey (SF-36)Range 1-100 – Mean (SD)*Physical Component Summary∘Physical functioning∘Role-Physical∘Bodily PainoGeneral Health38.2 (11.2)67.2 (26.3)39.3 (46.3)49.5 (22.1)42.9 (21.5)Mental Component Summary∘Vitality∘Social Functioning∘Role-EmotionaloMental Health41.3 (10.7)39.7 (21.7)59.3 (25.9)67.1 (41.9)67.1 (18.3)Generalized Anxiety Disorder-7 (GAD-7)Range 0-21 – N (%)**None [0-5]Mild [6-10]Moderate [11-15]Severe [16-21]38 (50.7)22 (29.3)14 (18.7)1 (1.3)Beck Depression Inventory (BDI)Range 0-63 – N (%)**Minimal [0-13]Mild [14-19]Moderate [20-28]Severe [29-63]55 (73.3)10 (13.3)7 (9.3)3 (4.0)Fatigue Severity Scale (FSS) Range 1-7 – Median (IQR)**4.7 (1.5)*Higher number indicates better health state. **Higher number indicates greater severity.Conclusion:UCTD patients have significantly impaired HRQoL and a high prevalence of anxiety, depression, and fatigue, suggesting substantial psychosocial impact of UCTD comparable to that reported in SLE.3,4 Impaired HRQoL in UCTD is driven to similar degrees by aspects of physical and mental health. In future studies, we will compare age- and sex- matched UCTD to SLE patients and longitudinally evaluate psychosocial metrics alongside clinical trajectories.References:[1]Dietz B, Katz P, Dall’Era M, et al. Major depression and adverse patient-reported outcomes in systemic lupus erythematosus: Results from a prospective longitudinal cohort. Arthritis Care Res. 2021;73(1):48-54.[2]Siegel CH, Kleinman J, Barbhaiya M, et al. The psychosocial impact of undifferentiated connective tissue disease on patient health and well-being: A qualitative study. J Clin Rheumatol. In press.[3]Gu M, Cheng Q, Wang X, et al. The impact of SLE on health-related quality of life assessed with SF-36: A systemic review and meta-analysis. Lupus. 2019;28(3):371-382.[4]Zhang L, Fu T, Yin R, Zhang Q, Shen B. Prevalence of depression and anxiety in systemic lupus erythematosus: A systematic review and meta-analysis. BMC Psychiatry. 2017;17(1).Acknowledgements:This project was supported by the Barbara Volcker Center for Women and Rheumatic Diseases and the Robin J. Sillau Memorial Research Fund for Connective Tissue Disease. Dr. Barbhaiya is supported by the Rheumatology Research Foundation Investigator Award.Disclosure of Interests:None declared

Background:Idiopathic inflammatory myopathies (IIM) are featured by a series of clinical presentation such as proximal muscle weakness, increased serum levels of creatine kinase and other muscle enzymes and involvement of other organs and systems[1, 2], which results in high morbidity and early mortality[3]. We have known the changes of the level of Th17 and Treg cells in IIM in previous studies[4-6]. However, whether infection affects lymphocyte subsets or not and whether the effect of low-dose interleukin-2 (IL-2) can be influenced by the use of immunosuppressants or not are still unclear.Objectives:The study aimed to explore the changes of lymphocyte subsets in patients of IIM with or without important organ infection, and the restoration of Th17/Treg after receiving low-dose IL-2.Methods:A total of 118 IIM patients were enrolled and classified into infection group and non-infection group based on the important organ infection. Of them, 48 cases were treated with low dose IL-2 (5.0*105IU for 5 days). The absolute number of peripheral total T, B, CD4+T, CD8+T, NK, Th1, Th2, Th17 and Treg cell subsets were analyzed by flow cytometry combined with absolute counting beads. Clinical data, laboratory examinations and the levels of peripheral lymphocyte subsets were analyzed retrospectively.Results:In these patients, especially in the infection group, the absolute number of T, CD4+T, CD8+T, NK, Th1, Th2, Th17 and Treg cells were significantly decreased as compared with that in the healthy controls, which were significantly increased by low dose IL-2 (especially Treg cells) treatment. The levels of ESR, LDH and HBDH and the ratio of Th17/Treg were significantly lower than those before IL-2 treatment (Z=-2.237, -2.083, -2.140, -3.663,P=0.025, 0.037, 0.032, 0.000). The 48 cases who received IL-2 treatment were divided into 2 groups according to whether they used immunosuppressants. There was no significant difference in the absolute number of T, B, CD4+T, CD8+T, Th1, Th2, Th17 and Treg cells, the proportion of Th17 and Treg cells and the ratio of Th17/Treg between the 2 groups (P>0.05).Conclusion:Global decrease in lymphocyte subsets was found in IIM patients, especially those who had important organ infection. A significant re-balance of Th17/Treg was observed after receiving treatment with low-dose IL-2. Furthermore, the restoration of lymphocyte subsets showed similar degree after treatment with or without immunosuppressants. Low-dose IL-2 may become a potential therapy for IIM patients. The mechanism of lymphocyte decrease in IIM is required further to study.References:[1]Clark K E N, Isenberg D A. A review of inflammatory idiopathic myopathy focusing on polymyositis[J]. European Journal of Neurology, 2017.[2]Tieu J, Lundberg IE, Limaye V. Idiopathic inflammatory myositis. Best Pract Res Clin Rheumatol. 2016. 30(1): 149-68.[3]Mandel DE, Malemud CJ, Askari AD. Idiopathic Inflammatory Myopathies: A Review of the Classification and Impact of Pathogenesis. Int J Mol Sci. 2017. 18(5).[4]Zhang SX, Wang J, Sun HH, et al. Circulating regulatory T cells were absolutely decreased in dermatomyositis/polymyositis patients and restored by low-dose IL-2. Ann Rheum Dis. 2019 .[5]Espinosa-Ortega F, Gómez-Martin D, Santana-De Anda K, Romo-Tena J, Villaseñor-Ovies P, Alcocer-Varela J. Quantitative T cell subsets profile in peripheral blood from patients with idiopathic inflammatory myopathies: tilting the balance towards proinflammatory and pro-apoptotic subsets. Clin Exp Immunol. 2015. 179(3): 520-8.[6]Feng M, Guo H, Zhang C, et al. Absolute reduction of regulatory T cells and regulatory effect of short-term and low-dose IL-2 in polymyositis or dermatomyositis. Int Immunopharmacol. 2019. 77: 105912.Acknowledgments:Thanks for the support of my teachers, classmates and my family.Disclosure of Interests:None declared

Yan, Y., He, H., Zhang, X., Chen, Y., Xie, H., Bai, Z., Zhu, P., Ren, J. and Wang, L. 2012. Long-term fertilization effects on carbon and nitrogen in particle-size fractions of a Chinese Mollisol. Can. J. Soil Sci. 92: 509–519. The response of soil organic matter (SOM) dynamics to long-term fertilization may be deduced from changes in the accumulation and distribution of different soil organic carbon (SOC) and nitrogen (N) pools. The SOC and N in particle-size fractions were therefore measured to assess the influences of pig manure and synthetic fertilizer application on the characteristics of these pools. A long-term fertilization experiment, established in 1979 in the Mollisol area (Gongzhuling, China) was used for this study. Composite soil samples (0–20cm) were collected in 2005 from 12 treatment plots that had received annual applications of pig manure, synthetic fertilizers or combinations of both. Soils were fractionated into fine clay (<0.2 µm), coarse clay (0.2–2 µm), silt (2–50 µm), fine sand (50–250 µm) and coarse sand (250–2000 µm) and then SOC and N contents in each particle-size fraction were measured. Although most of the SOC and N were associated with clay and silt fractions, the large proportion of silt in the soil mass played a key role in the retention of SOC and N. The application of pig manure alone increased accumulation of SOC and N in each particle-size fraction, but preferential enrichment was found in the coarse sand fraction. This indicates that pig manure is efficient in restoring SOM in the temperate Chinese Mollisol under a tilled maize (Zea mays L.) monocropping system and having a long frozen period in winter. The application of synthetic fertilizers had no clear effect on SOC and N accumulation or their distribution in particle-size fractions. However, the combined application of pig manure and synthetic fertilizers enhanced the accumulation of SOC and N in all particle-size fractions, and led to a shift of SOC and N from fine to coarse particles. We extended the hierarchy model for SOC protection to consider a shift in SOC accumulation from fine to coarse particles, depending on the initial SOC content of the specific soil. The findings reveal a clear positive interaction between pig manure and synthetic fertilizers that may improve the quantity of SOM in the temperate Chinese Mollisol.

Science Education International ¦ Volume 32 ¦ Issue 2 149 ORIGINAL ARTICLE INTRODUCTION Science classes in elementary schools should seek to enable students to engage in scientific thinking, encourage them to perform work on basic sciences, and positively develop their attitudes toward science classes with a positive educational environment. Studies related to both the healthy construction of classroom environments and attitudes have a long history (Gardner, 1975; Ma and Bateson, 1999; Toma et al., 2019; Zhang and Campbell, 2011). Wang and Berlin (2010) indicated that attitudes toward science are effective factors in attaining goals of science education. In addition, they reported that these factors affect student motivation. According to Zhang and Campbell (2011), scientific attitudes of students also direct their interest in lessons and simultaneously affect their long-term success in courses. Attitude, as an affective domain of learning, is an element affecting learning outputs of students in science courses (Ministry of National Education, 2018). Accordingly, the importance of performing attitude studies emerges with regard to obtaining positive outputs on scientific attitude. Individuals with scientific attitudes have inquisitive and argumentative characteristics; therefore, they do not fall prey to preconceptions or dogmatic belief systems. Individuals with positive scientific attitudes are more willing to identify and solve the problems in their surroundings, as well as being willing to search for solutions. In addition, while scientific attitudes may help an individual to be successful, they also support his or her continual improvement by affecting his or her thinking (Demirbaş and Yağbasan, 2006). In this study, the effect of a different variable on attitude was examined by focusing on the relationship between scientific attitudes and intellectual risk-taking behaviors of elementary school students. Theoretical Background While an individual’s attitude cannot always be observed precisely, it largely directs love, hate, and the ideas of the individual (Morgan, 2005). Munby (1980) examined scientific attitudes in four categories as attitudes toward school science, attitudes toward science careers, attitudes toward science itself, and attitudes toward specific issues in science. This examination, indeed, emphasizes the importance of attitudes in terms of long-term learning and indifference toward science or the development of deep understandings (Hong and Lin, 2011). Gardner (1975), however, divided such attitudes into two, as attitudes toward science and scientific attitudes. Moreover, the scientific attitudes included within the context of this study were expressed as a mixture of the will to know and understand, inquiring attitudes, data collection and sense-making, and evaluation and interpretation of results (Education In this study, the relationship between scientific attitudes and intellectual risk-taking behaviors of fourth-grade students in elementary school in Turkey was examined. A total of 184 students participated in the study, which was conducted based on a survey model. For data collection, the “Scientific Attitude Inventory” and the “Intellectual Risk-Taking and Perceptions About Its Predictors Scale in Science Education” were utilized. Descriptive statistical analyses and t-test, ANOVA, simple linear regression, and multiple regression analyses were utilized for the analysis of the data. As a result of this data analysis, it was observed that these elementary school students have scientific attitudes at the “not sure” level and have intellectual risk-taking behaviors at the “mostly correct” level. Gender was not observed to have an effect on scientific attitude; however, it was effective on intellectual risk-taking behavior. In addition, the analysis results demonstrated that there is a meaningful difference between intellectual risk-taking behaviors of students and the educational levels of their fathers. Moreover, when the relations between other pairs of variables were examined, the variables of intellectual risk-taking, gender, educational level of the mother, and educational level of the father together had low-level but meaningful relations with the scientific attitudes of elementary school students. It was indicated that teachers will contribute to students’ adoption of positive scientific attitudes by introducing the lives and studies of scientists, and it was suggested that the effect of changes in educational patterns in classroom environments be examined through experimental studies on intellectual risk-taking behaviors of students. With the results obtained from this study, more light can be shed on what should be done to support students’ intellectual risk-taking behaviors.

Background:IgG4-related disease (IgG4-RD) is an autoimmune disorder and frequently involve multiple organs. The respiratory tract is one of the most frequently involved sites.Objectives:This study aimed to compare the demographic and clinical characteristics of IgG4-related respiratory disease (IgG4-RRD) and non-IgG4-RRD patients in a large cohort.Methods:We carried out a retrospective study of 452 cases of IgG4-RD (104 IgG4-RRD patients and 348 non-IgG4-RRD patients) diagnosed at Peking University People’s Hospital between 2003 and 2020.Results:IgG4-RRD patients had an elder age of disease onset and diagnosis. Multiorgan involvement and hypocomplementemia were more common in IgG4-RRD. Besides, the level of ESR, eosinophilia, IgG and IgG4 were higher in IgG4-RRD patients. In IgG4-RRD group, salivary gland, lacrimal gland, lymph nodes, biliary system and kidney were more commonly involved than those in the non-IgG4-RRD group. Also, more numbers of organ involvement and biliary involvement were independent risk factors for the development of respiratory involvement in IgG4-RD patients.Conclusion:Our study revealed demographic, clinical, laboratory and imaging features of IgG4-RRD patients and the underlying differences in pathogenesis between the two phenotypes, which have important implications for the diagnosis and treatment of the disease.References:[1]Morales AT, Cignarella AG, Jabeen IS, Barkin JS, Mirsaeidi M. An update on IgG4-related lung disease. European journal of internal medicine. 2019;66:18-24.[2]Stone JH, Zen Y, Deshpande V. IgG4-related disease. The New England journal of medicine. 2012;366(6):539-51.[3]Vasaitis L. IgG4-related disease: A relatively new concept for clinicians. European journal of internal medicine. 2016;27:1-9.[4]Matsui S, Yamamoto H, Minamoto S, Waseda Y, Mishima M, Kubo K. Proposed diagnostic criteria for IgG4-related respiratory disease. Respiratory investigation. 2016;54(2):130-2.[5]Cao L, Chen YB, Zhao DH, Shi WF, Meng S, Xie LX. Pulmonary function tests findings and their diagnostic value in patients with IgG4-related disease. Journal of thoracic disease. 2017;9(3):547-54.[6]Wallace ZS, Perugino C, Matza M, Deshpande V, Sharma A, Stone JH. Immunoglobulin G4-related Disease. Clinics in chest medicine. 2019;40(3):583-97.[7]Matsui S. IgG4-related respiratory disease. Modern rheumatology. 2019;29(2):251-6.[8]Johansson SG, Hourihane JO, Bousquet J, Bruijnzeel-Koomen C, Dreborg S, Haahtela T, et al. A revised nomenclature for allergy. An EAACI position statement from the EAACI nomenclature task force. Allergy. 2001;56(9):813-24.[9]Fei Y, Shi J, Lin W, Chen Y, Feng R, Wu Q, et al. Intrathoracic Involvements of Immunoglobulin G4-Related Sclerosing Disease. Medicine. 2015;94(50):e2150.[10]Wallace ZS, Deshpande V, Mattoo H, Mahajan VS, Kulikova M, Pillai S, et al. IgG4-Related Disease: Clinical and Laboratory Features in One Hundred Twenty-Five Patients. Arthritis & rheumatology (Hoboken, NJ). 2015;67(9):2466-75.[11]Yamada K, Yamamoto M, Saeki T, Mizushima I, Matsui S, Fujisawa Y, et al. New clues to the nature of immunoglobulin G4-related disease: a retrospective Japanese multicenter study of baseline clinical features of 334 cases. Arthritis research & therapy. 2017;19(1):262.[12]Borges T, Silva S. IgG4-related disease: How to place it in the spectrum of immune-mediated and rheumatologic disorders? Modern rheumatology. 2020;30(4):609-16.[13]Liu Y, Xue M, Wang Z, Zeng Q, Ren L, Zhang Y, et al. Salivary gland involvement disparities in clinical characteristics of IgG4-related disease: a retrospective study of 428 patients. Rheumatology (Oxford, England). 2020;59(3):634-40.[14]Matsui S, Taki H, Shinoda K, Suzuki K, Hayashi R, Tobe K, et al. Respiratory involvement in IgG4-related Mikulicz’s disease. Modern rheumatology. 2012;22(1):31-9.Disclosure of Interests:None declared

Background:SLE is an autoimmune disease characterized by the abnormal function of lymphocytes. The impairment of hematopoietic function of bone marrow participates in its pathogenesis, in which T cells play an important role. However, study on bone marrow T cells in SLE patients is very limited.Objectives:This study aims to characterize the phenotype and molecular characteristics of abnormally activated CD8+T cells in bone marrow of SLE patients and explore the mechanism of hematopoietic stem cells (HSCs) reduction caused by the abnormally activated CD8+T cells in bone marrow of patients with SLE.Methods:A total of 8 SLE patients and 5 age- and sex-matched controls were recruited in our study. Among them, 3 SLE patients and 4 donors were collected bone marrow and peripheral blood samples for Single-cell RNA sequencing (scRNA-seq) and functional studies. BM and peripheral T cell subsets were measured by flow cytometry. Plasma cytokines and secreted immunoglobulins were detected by Luminex. Disease activity of SLE patients was measured using the SLE Disease Activity Index (SLEDAI). All analyses were performed using R language and Flowjo 9.Results:In the present study, SLE patients had increased CD8+T%αβT cells and decreased CD4+T%αβT cells in bone marrow of SLE, compared to healthy controls. A large number of CD38+HLADR+CD8+T cells existed in the bone marrow and peripheral blood of SLE patients. Those patients also showed reduced number of HSCs, and with a downward trend of the numbers of peripheral red blood cells, white blood cells, neutrophils, hemoglobin, and platelets. By scRNA-seq, the CD38+HLADR+CD8+T cells contained high levels of GZMK, GZMA, PRF1, IFNG, and TNF in the bone marrow of SLE patients. the CD38+HLADR+CD8+T cells exhibited significant relationship with HSCs, white blood cells, neutrophils, and platelets.Conclusion:These findings demonstrated that the abnormally activated CD8+T cells in bone marrow can reduce the number of HSCs by the expression of killer molecules, which contributes to the impairment of hematopoietic function and the development of SLE. This project focuses on the specific bone marrow T cell subset in SLE. The completement of this project provides information for exploring the mechanism of hematopoiesis involvement.References:[1]Anderson E, Shah B, Davidson A, Furie R. Lessons learned from bone marrow failure in systemic lupus erythematosus: Case reports and review of the literature. Semin Arthritis Rheum. 2018;48(1):90-104.[2]Sun LY, Zhou KX, Feng XB, Zhang HY, Ding XQ, Jin O, Lu LW, Lau CS, Hou YY, Fan LM. Abnormal surface markers expression on bone marrow CD34+cells and correlation with disease activity in patients with systemic lupus erythematosus. Clin Rheumatol. 2007;26(12):2073-2079.Acknowledgements:We want to thank Lu Meng, Teng Li, Wei Zhou, and Jiaxin Guo for their assistance with this study.Disclosure of Interests:None declared

Abstract Abstract 2719 Poster Board II-695 Background: Rituximab directly targets CD20 positive lymphoma cells while lenalidomide targets the microenvironment. This combination was proven effective in vitro and in vivo in mantle cell lymphoma (Wu et al, Clin Cancer Res 2008; Zhang et al, Am J Hematol 2009). Clinically, lenalidomide (Habermann et al, Br J Haematol 2009) and rituximab have single-agent activity in mantle cell lymphoma (MCL) and may be an effective combination. The goal of our study was to determine the maximum tolerated dose (MTD) in phase 1 and evaluate the efficacy and safety of lenalidomide plus rituximab in patients with relapsed/refractory MCL in phase 2. Methods: Patients with relapsed/refractory MCL received lenalidomide on days 1–21 of every 28-day cycle, and rituximab (375 mg/m2) weekly during cycle 1. Dose escalation was used to determine the MTD with lenalidomide (10 mg, 15 mg, 20 mg, and 25 mg). Dose-limiting toxicity (DLT) was defined as grade 3 or 4 non-hematologic, or grade 4 hematologic adverse events in cycle 1. Phase 2 has reached targeted enrolment with 45 patients treated at MTD. Kaplan-Meier method was used to estimate progression free survival rate and response duration. Median time to event in months with 95% confidence interval was calculated. Of 45 patients treated at the MTD, the median age was 66 (46–85), 91% were males. All patients had received prior rituximab and were enrolled regardless of prior rituximab sensitivity or resistance. Results: The median follow-up time for the censored observations was 11.4 months. Two DLTs occurred at 25 mg in phase 1 (hypercalcemia, non-neutropenic fever); therefore, the MTD was 20 mg. The grade 3–4 non-hematologic events included elevated AST, elevated ALT, fatigue, myalgia, tremors, ataxia, cough, deep vein thrombosis, dyspnea, edema (facial), infection, neuropathy sensory, rash, and respiratory failure. Grade 3–4 hematologic adverse events included neutropenia (37 events), neutropenic fever (4 events), and thrombocytopenia (16 events). There were no responses in patients treated at 10 mg or 15 mg. Thirty six patients (36) were evaluable for response. Nine (9) patients are too early in their treatment and are not yet eligible for response evaluation. Among the 36 evaluable patients, 11 (31%) patients achieved CR, 8 (22%) patients achieved PR, 3 (8%) patients had minor response, 6 (17%) patients had stable disease and 8 (22%) patients had progressive mantle cell lymphoma. The overall response rate (CR + PR) was 53%. Seventy eight (78%) patients achieved stable disease or better and benefited from oral Lenalidomide plus 4 doses of rituximab. The median time to response was 2 months (2–8), and the median duration of response for the 19 patients with CR or PR was 18 months (95% CI: 10.6, NA) (range1–30 months). The median progression free survival for all patients on phase 2 was 14 months (95% CI: 9.8, NA) (ranging from 1–32 months). Conclusion: Oral lenalidomide plus rituximab resulted in durable responses in relapsed/refractory MCL with a favourable toxicity profile. Disclosures: Wang: Celgene: Honoraria, Research Funding. Hagemeister:Celgene Corporation: Consultancy. Samaniego:Celgene Corporation: Research Funding. Yi:Celgene Corporation: Research Funding. Shah:Celgene Corporation: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Elan: Consultancy; Millennium: Research Funding, Speakers Bureau. Bell:Celgene Corporation: Employment, Equity Ownership. Knight:Celgene Corporation: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Zeldis:Celgene: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.

Changes to the treatment of Coleoptera family-group names published by Bouchard et al. (2011) are given. These include necessary additions and corrections based on much-appreciated suggestions from our colleagues, as well as our own research. Our ultimate goal is to assemble a complete list of available Coleoptera family-group names published up to the end of 2010 (including information about their spelling, author, year of publication, and type genus). The following 59 available Coleoptera family-group names are based on type genera not included in Bouchard et al. (2011): Prothydrinae Guignot, 1954, Aulonogyrini Ochs, 1953 (Gyrinidae); Pogonostomini Mandl 1954, Merismoderini Wasmann, 1929, †Escheriidae Kolbe, 1880 (Carabidae); Timarchopsinae Wang, Ponomarenko &amp; Zhang, 2010 (Coptoclavidae); Stictocraniini Jakobson, 1914 (Staphylinidae); Cylindrocaulini Zang, 1905, Kaupiolinae Zang, 1905 (Passalidae); Phaeochroinae Kolbe, 1912 (Hybosoridae); Anthypnidae Chalande, 1884 (Glaphyridae); Comophorini Britton, 1957, Comophini Britton, 1978, Chasmidae Streubel, 1846, Mimelidae Theobald, 1882, Rhepsimidae Streubel, 1846, Ometidae Streubel, 1846, Jumnidae Burmeister, 1842, Evambateidae Gistel, 1856 (Scarabaeidae); Protelmidae Jeannel, 1950 (Byrrhoidea); Pseudeucinetini Csiki, 1924 (Limnichidae); Xylotrogidae Schönfeldt, 1887 (Bostrichidae); †Mesernobiinae Engel, 2010, Fabrasiinae Lawrence &amp; Reichardt, 1966 (Ptinidae); Arhinopini Kirejtshuk &amp; Bouchard, 2018 (Nitidulidae); Hypodacninae Dajoz, 1976, Ceuthocera Mannerheim, 1852 (Cerylonidae); Symbiotinae Joy, 1932 (Endomychidae); Cheilomenini Schilder &amp; Schilder, 1928, Veraniini Schilder &amp; Schilder, 1928 (Coccinellidae); Ennearthroninae Chûjô, 1939 (Ciidae); Curtimordini Odnosum, 2010, Mordellochroini Odnosum, 2010 (Mordellidae); Chanopterinae Borchmann, 1915 (Promecheilidae); Heptaphyllini Prudhomme de Borre, 1886, Olocratarii Baudi di Selve, 1875, Opatrinaires Mulsant &amp; Rey, 1853, Telacianae Poey, 1854, Ancylopominae Pascoe, 1871 (Tenebrionidae); Oxycopiini Arnett, 1984 (Oedemeridae); Eutrypteidae Gistel, 1856 (Mycteridae); Pogonocerinae Iablokoff-Khnzorian, 1985 (Pyrochroidae); Amblyderini Desbrochers des Loges, 1899 (Anthicidae); Trotommideini Pic, 1903 (Scraptiidae); Acmaeopsini Della Beffa, 1915, Trigonarthrini Villiers, 1984, Eunidiini Téocchi, Sudre &amp; Jiroux, 2010 (Cerambycidae); Macropleini Lopatin, 1977, Stenopodiides Horn, 1883, Microrhopalides Horn, 1883, Colaphidae Siegel, 1866, Lexiphanini Wilcox, 1954 (Chrysomelidae); †Medmetrioxenoidesini Legalov, 2010, †Megametrioxenoidesini Legalov, 2010 (Nemonychidae); Myrmecinae Tanner, 1966, Tapinotinae Joy, 1932, Acallinae Joy, 1932, Cycloderini Hoffmann, 1950, Sthereini Hatch, 1971 (Curculionidae). The following 21 family-group names, listed as unavailable in Bouchard et al. (2011), are determined to be available: Eohomopterinae Wasmann, 1929 (Carabidae); Prosopocoilini Benesh, 1960, Pseudodorcini Benesh, 1960, Rhyssonotini Benesh, 1960 (Lucanidae); Galbini Beaulieu, 1919 (Eucnemidae); Troglopates Mulsant &amp; Rey, 1867 (Melyridae); Hippodamiini Weise, 1885 (Coccinellidae); Micrositates Mulsant &amp; Rey, 1854, Héliopathaires Mulsant &amp; Rey, 1854 (Tenebrionidae); Hypasclerini Arnett, 1984; Oxaciini Arnett, 1984 (Oedemeridae); Stilpnonotinae Borchmann, 1936 (Mycteridae); Trogocryptinae Lawrence, 1991 (Salpingidae); Grammopterini Della Beffa, 1915, Aedilinae Perrier, 1893, Anaesthetinae Perrier, 1893 (Cerambycidae); Physonotitae Spaeth, 1942, Octotomides Horn, 1883 (Chrysomelidae); Sympiezopinorum Faust, 1886, Sueinae Murayama, 1959, Eccoptopterini Kalshoven, 1959 (Curculionidae). The following names were proposed as new without reference to family-group names based on the same type genus which had been made available at an earlier date: Dineutini Ochs, 1926 (Gyrinidae); Odonteini Shokhin, 2007 (Geotrupidae); Fornaxini Cobos, 1965 (Eucnemidae); Auletobiina Legalov, 2001 (Attelabidae). The priority of several family-group names, listed as valid in Bouchard et al. (2011), is affected by recent bibliographic discoveries or new nomenclatural interpretations. †Necronectinae Ponomarenko, 1977 is treated as permanently invalid and replaced with †Timarchopsinae Wang, Ponomarenko &amp; Zhang, 2010 (Coptoclavidae); Agathidiini Westwood, 1838 is replaced by the older name Anisotomini Horaninow, 1834 (Staphylinidae); Cyrtoscydmini Schaufuss, 1889 is replaced by the older name Stenichnini Fauvel, 1885 (Staphylinidae); Eremazinae Iablokoff-Khnzorian, 1977 is treated as unavailable and replaced with Eremazinae Stebnicka, 1977 (Scarabaeidae); Coryphocerina Burmeister, 1842 is replaced by the older name Rhomborhinina Westwood, 1842 (Scarabaeidae); Eudysantina Bouchard, Lawrence, Davies &amp; Newton, 2005 is replaced by the older name Dysantina Gebien, 1922 which is not permanently invalid (Tenebrionidae). The names Macraulacinae/-ini Fleutiaux, 1923 (Eucnemidae), Anamorphinae Strohecker, 1953 (Endomychidae), Pachycnemina Laporte, 1840 (Scarabaeidae), Thaumastodinae Champion, 1924 (Limnichidae), Eudicronychinae Girard, 1971 (Elateridae), Trogoxylini Lesne, 1921 (Bostrichidae), Laemophloeidae Ganglbauer, 1899 (Laemophloeidae); Ancitini Aurivillius, 1917 (Cerambycidae) and Tropiphorini Marseul, 1863 (Curculionidae) are threatened by the discovery of older names; Reversal of Precedence (ICZN 1999: Art. 23.9) or an application to the International Commission on Zoological Nomenclature will be necessary to retain usage of the younger synonyms. Reversal of Precedence is used herein to qualify the following family-group names as nomina protecta: Murmidiinae Jacquelin du Val, 1858 (Cerylonidae) and Chalepini Weise, 1910 (Chrysomelidae). The following 17 Coleoptera family-group names (some of which are used as valid) are homonyms of other family-group names in zoology, these cases must be referred to the Commission for a ruling to remove the homonymy: Catiniidae Ponomarenko, 1968 (Catiniidae); Homopterinae Wasmann, 1920, Glyptini Horn, 1881 (Carabidae); Tychini Raffray, 1904, Ocypodina Hatch, 1957 (Staphylinidae); Gonatinae Kuwert, 1891 (Passalidae); Aplonychidae Burmeister, 1855 (Scarabaeidae); Microchaetini Paulus, 1973 (Byrrhidae); Epiphanini Muona, 1993 (Eucnemidae); Limoniina Jakobson, 1913 (Elateridae); Ichthyurini Champion, 1915 (Cantharidae); Decamerinae Crowson, 1964 (Trogossitidae); Trichodidae Streubel, 1839 (Cleridae); Monocorynini Miyatake, 1988 (Coccinellidae); Gastrophysina Kippenberg, 2010, Chorinini Weise, 1923 (Chrysomelidae); Meconemini Pierce, 1930 (Anthribidae). The following new substitute names are proposed: Phoroschizus (to replace Schizophorus Ponomarenko, 1968) and Phoroschizidae (to replace Schizophoridae Ponomarenko, 1968); Mesostyloides (to replace Mesostylus Faust, 1894) and Mesostyloidini (to replace Mesostylini Reitter, 1913). The following new genus-group name synonyms are proposed [valid names in square brackets]: Plocastes Gistel, 1856 [Aesalus Fabricius, 1801] (Lucanidae); Evambates Gistel, 1856 [Trichius Fabricius, 1775] (Scarabaeidae); Homoeoplastus Gistel, 1856 [Byturus Latreille, 1797] (Byturidae). Two type genera previously treated as preoccupied and invalid, Heteroscelis Latreille, 1828 and Dysantes Pascoe, 1869 (Tenebrionidae), are determined to be senior homonyms based on bibliographical research. While Dysantes is treated as valid here, Reversal of Precedence (ICZN 1999: Art. 23.9) is used to conserve usage of Anomalipus Guérin-Méneville, 1831 over Heteroscelis.

This paper deals with the most salient aspects of distance education, and how it has been an issue of great relevance in the pandemic era. However, this is not a current issue, it is a situation that has affected the schooling situation in rural areas since earlier times. The positive and negative aspects of distance education from more than twenty years ago are evaluated and contrasted with the new online education methods. B-learning education and new educational paradigms are evaluated. The main results show that education can take on different effective methodologies as long as appropriate teacher training and education processes are in place. Keywords: B-learning education, distance learning, online education. References [1]V. Guichot, «Hisotria de la educación: reflexiones sobre su objeto, ubicación epistemológica, devenir histórico y tendencias actuales,» Revista Latinoamericana de Estudios Educativos, vol. 2, nº 1, pp. 11-51, 2006. [2]J.Gomera, «josegomera.com,»[Online]. Available: https://josegomera.com/academico/conoce-la-historia-de-la-educacion-a-distancia/#:~:text=La%20historia%20de%20la%20educaci%C3%B3n%20a%20distancia%20universitaria%20en%20Estados,que%20transmite%20cursos%20por%20radio.. [Last access: 30 Mar 2021]. [3]wikipedia, «Historia de internet,» [Online]. Available: https://es.wikipedia.org/wiki/Historia_de_Internet. [Last access: 2 Apr 2021]. [4]F.-J. Hinojo-Lucena, J.-M. Trujillo-Torres, J.-A. Marín-Marín y C. Rodríguez-Jiménez, «B-Learning in Basic Vocational Training Students for the Development of the Module of Applied Sciences I,» Mathematics, vol. 8, nº 1102, pp. 1-13, 2020. [5]«The objective of this research is to measure the perception that teachers had about their own Educators during the COVID-19 Pandemic: A Cross-Analysis of Different Educational Stages,» Sustainiability, vol. 12, nº 10128, pp. 1-13, 2020. [6] C. A. Gutiérrez Pérez, «Construction of Digital Identity through B-Learning Training: Resource Evaluation,» ACM International Conference Proceeding Series, pp. 930-934, 2020. [7]Y. Guo y L. Chen, «An Investigation on Online Learning for K12 in Rural Areas in China during COVID-19 Pandemic,» de 2020 9th International Conference of Educational Innovation through Technology, EITT 2020, Portugal, 2020. [8]Universidad de los Andes, «Universidad de los Andes,» [Online]. Available: https://blended.uniandes.edu.co/caracteristicas-del-blended-learning/#:~:text=Un%20elemento%20caracter%C3%ADstico%20en%20la,de%20su%20proceso%20de%20aprendizaje.. [Last access: 02 Apr 2021]. [9]M. Zhang, A. Tlili, R. Zhuang, J. Yang, T.-W. Chang, H. Wang y R. Huang, «Experiencia china de proporcionar aprendizaje remoto y flexible durante la pandemia de COVID-19: un estudio de caso sobre el mantenimiento de la educación en contextos de crisis,» Lecture Notes in Educational Technology, vol. 3, nº 2, pp. 243-253, 2021. [10]J. Carvajal, F. Suárez y X. Quiñónez, «las TIC en la educación universitaria.,» Universidad Ciencia Y Tecnología, vol. 22, nº 89, pp. 31-35, 2019.

Background:Classical lupus nephritis (LN) is characterized by glomerular immune complex(IC) deposition with glomerular proliferation, basement membrane destruction and cell infiltration. Non-IC mediated renal injury with thrombotic microangiopathy (TMA) was also reported in patients with systemic lupus erythematosus (SLE-renal TMA), but most studies were reported in patients with both LN and renal TMA.Objectives:In this study, clinical features and outcomes of SLE-renal TMA in absence of obvious IC in SLE patients were analyzed.Methods:Patients with glomerular TMA and/or vascular TMA in the absence of obvious subendothelial or epithelial immune deposits were screened out from 2332 biopsied in SLE patients who underwent first renal biopsy from January 2005 to August 2016. Their clinical, histological features and outcomes were retrospectively analyzed.Results:In 2332 renal biopsies obtained from SLE patients, 257 (11.0%) showed renal TMA, of which 237 showed both renal TMA and LN, and 20 biopsies had only renal TMA (SLE-renal TMA). There were 2 males and 18 females with an average age of (25 ± 10) years. The median course of SLE and LN were 3.0(1.0, 6.0) and 0.8(0.5, 1.9) months. All 20 patients deserved acute kidney injury, of which 11 (55%) needed renal replacement therapy (RRT) and 12 (60%) were nephrotic syndrome. Blood system involvement was found in all cases, including 13 cases (65.0%) with TMA triad (microvascular hemolytic anemia, thrombocytopenia and elevated lactate dehydrogenase).Pathological examination showed that 17 cases (85.0%) had both glomerular TMA and vascular TMA. Immunofluorescence and electron microscopy showed that 8 cases (40%) had no IC deposition in glomerulus and 12 cases (60%) had only IC deposition in mesangium. Acute tubulointerstitial lesions in patients requiring RRT were more serious than those no needing for RRT((43.6±24.9) %vs(21.7±20.1) %,P=0.047). The fusion range of foot process was positively correlated with proteinuria (r2= 0.347,P=0.006).All patients received high-dose methylprednisolone pulse therapy. Four patients received plasma exchange and three patients received gamma globulin, respectively. Eleven patients requiring RRT all stop RRT in a median time of 16.0 (9.0, 30.0) days. During a median follow-up of 58.0 (36.0, 92.3) months, complete remission (CR) was obtained in 15 cases, partial remission in 4 cases and no remission in 1 case. Six cases (30%) relapsed. No case died or progressed to end stage renal disease.Conclusion:Renal injury characterized by TMA is not uncommon in SLE renal biopsy cases. The clinical manifestation is special and the renal injury is serious. The renal outcome is good by intensive immunosuppressive therapy. It should be considered as a unique type of renal injury in SLE.References:[1]Moake JL. Thrombotic microangiopathies. N Engl J Med. 2002. 347(8): 589-600.[2]Anders HJ, Weening JJ. Kidney disease in lupus is not always ‘lupus nephritis’. Arthritis Res Ther. 2013. 15(2): 108.[3]Song D, Wu LH, Wang FM, et al. The spectrum of renal thrombotic microangiopathy in lupus nephritis. Arthritis Res Ther. 2013. 15(1): R12.[4]Hu WX, Liu ZZ, Chen HP, Zhang HT, Li LS, Liu ZH. Clinical characteristics and prognosis of diffuse proliferative lupus nephritis with thrombotic microangiopathy. Lupus. 2010. 19(14): 1591-8.[5]Tomov S, Lazarchick J, Self SE, Bruner ET, Budisavljevic MN. Kidney-limited thrombotic microangiopathy in patients with SLE treated with romiplostim. Lupus. 2013. 22(5): 504-9.[6]Li C, Yap D, Chan G, et al. Clinical Outcomes and Clinico-pathological Correlations in Lupus Nephritis with Kidney Biopsy Showing Thrombotic Microangiopathy. J Rheumatol. 2019 .[7]Chen MH, Chen MH, Chen WS, et al. Thrombotic microangiopathy in systemic lupus erythematosus: a cohort study in North Taiwan. Rheumatology (Oxford). 2011. 50(4): 768-75.[8]Park MH, AUID- Oho, Caselman N, Ulmer S, Weitz IC, AUID- Oho. Complement-mediated thrombotic microangiopathy associated with lupus nephritis. Blood Adv. 2018. 2(16): 2090-2094.Disclosure of Interests:None declared

In The Future of Human Nature, Jürgen Habermas raises the question of whether the embryonic genetic diagnosis and genetic modification threatens the foundations of the species ethics that underlies current understandings of morality. While morality, in the normative sense, is based on moral interactions enabling communicative action, justification, and reciprocal respect, the reification involved in the new technologies may preclude individuals to uphold a sense of the undisposability (Unverfügbarkeit) of human life and the inviolability (Unantastbarkeit) of human beings that is necessary for their own identity as well as for reciprocal relations. Engaging with liberal bioethics and Catholic approaches to bioethics, the article clarifies how Habermas’ position offers a radical critique of liberal autonomy while maintaining its postmetaphysical stance. The essay argues that Habermas’ approach may guide the question of rights of future generations regarding germline gene editing. But it calls for a different turn in the conversation between philosophy and theology, namely one that emphasizes the necessary attention to rights violations and injustices as a common, postmetaphysical starting point for critical theory and critical theology alike. In 2001, Jürgen Habermas published a short book on questions of biomedicine that took many by surprise.[1] To some of his students, the turn to a substantive position invoking the need to comment on a species ethics rather than outlining a public moral framework was seen as the departure from the “path of deontological virtue,”[2] and at the same time a departure from postmetaphysical reason. Habermas’ motivation to address the developments in biomedicine had certainly been sparked by the intense debate in Germany, the European Union, and internationally on human cloning, pre-implantation genetic diagnosis, embryonic stem cell research, and human enhancement. He turned to a strand of critical theory that had been pushed to the background by the younger Frankfurt School in favor of cultural theory and social critique, even though it had been an important element of its initial working programs. The relationship of instrumental reason and critical theory, examined, among others, by Max Horkheimer, Theodor W. Adorno, and Herbert Marcuse and taken up in Habermas’ own Knowledge and Interest and Theory of Communicative Action became ever-more actual with the development of the life sciences, human genome analysis, and genetic engineering of human offspring. Today, some of the fictional scenarios discussed at the end of the last century as “science fiction” have become reality: in 2018, the first “germline gene-edited” children were born in China.[3] Furthermore, the UK’s permission to create so-called “three-parent” children may create a legal and political pathway to hereditary germline interventions summarized under the name of “gene editing.”In this article, I want to explore Habermas’ “substantial” argument in the hope that (moral) philosophy and (moral) theology become allies in their struggle against an ever-more reifying lifeworld, which may create a “moral void” that would, at least from today’s perspective, be “unbearable” (73), and for upholding the conditions of human dignity, freedom, and justice. I will contextualize Habermas’ concerns in the broader discourse of bioethics, because only by doing this, his concerns are rescued from some misinterpretations.[1] Jürgen Habermas, The Future of Human Nature (Cambridge, UK: Polity, 2003).[2] Ibid., 125, fn. 58. 8[3] Up to the present, no scientific publication of the exact procedure exists, but it is known that the scientist, Jiankui He, circumvented the existing national regulatory framework and may have misled the prospective parents about existing alternatives and the unprecedented nature of his conduct. Yuanwu Ma, Lianfeng Zhang, and Chuan Qin, "The First Genetically Gene‐Edited Babies: It's “Irresponsible and Too Early”," Animal Models and Experimental Medicine (2019); Matthias Braun, Meacham, Darian, "The Trust Game: Crispr for Human Germline Editing Unsettles Scientists and Society," EMBO reports 20, no. 2 (2019).

Conyza sumatrensis (Asteraceae), an annual or biennial plant, is native to North and South America. It is an invasive, noxious weed that is widespread in southern and southeastern China. It invades farm land and causes great losses to dry land crops, including wheat, corn, and beans. It also reduces biological diversity by crowding out native plants in the infested areas (3,4). During a search for fungal pathogens that could serve as potential biological control agents of C. sumatrensis, a leaf spot disease was observed in 2010 in Chongqing, China. An isolate (SMBC22) of a highly virulent fungus was obtained from diseased leaves. Pathogenicity tests were performed by placing 6-mm-diameter mycelial disks of 7-day-old potato dextrose agar (PDA) cultures of SMBC22 on leaves of 15 healthy greenhouse-grown plants of C. sumatrensis; the same number of control plants was treated with sterile PDA disks. Treated plants were covered with plastic bags for 24 h and maintained in a growth chamber with daily average temperatures of 24 to 26°C, continuous light (3,100 lux), and high relative humidity (>90%). Lesions similar to those observed in the field were first obvious on the SMBC22-inoculated leaves 3 days after inoculation. Symptoms became severe 7 to 9 days after inoculation. Control plants remained healthy. The fungus was reisolated from inoculated and diseased leaves and it was morphologically the same as SMBC22. The pathogenicity test was conducted three times. A survey of 10 southern and southeastern Chinese provinces revealed that the disease was widespread and it attacked leaves and stems of seedlings and mature plants of C. sumatrensis. Lesions on leaves were initially small, circular, and water soaked. The typical lesion was ovoid or fusiform, dark brown, and surrounded by a yellow halo. The spots coalesced to form large lesions and plants were often completely blighted. Fungal colonies of SMBC22 on PDA plates were initially white and turned dark gray. Colonies were circular with smooth edges with obvious rings of pycnidia on the surface. Aerial hyphae were short and dense. Pycnidia, black and immersed or semi-immersed in the medium, were visible after 12 days of incubation. Pycnidia were 72 to 140 μm in diameter. Conidia were produced in the pycnidia and were hyaline, unicellular, ellipsoidal, and 4.4 to 6.1 × 1.6 to 2.2 μm. To confirm identification of the fungus, genomic DNA was extracted from mycelia of a 7-day-old culture on PDA at 25°C (2). The internal transcribed spacer (ITS) gene of rDNA was amplified using primers ITS4/ITS5. The gene sequence was 524 bp long and registered in NCBI GenBank (No. HQ645974). BLAST analysis showed that the current sequence had 99% homology to an isolate of Phoma macrostoma (DQ 404792) from Cirsium arvense (Canada thistle) in Canada and reported to cause chlorotic symptoms on that host plant (1). To our knowledge, this is the first report of P. macrostoma causing disease on C. sumatrensis in China. P. macrostoma, thought of as a biocontrol agent of broadleaf weeds in Canada, has been patented in the United States. The current isolate of P. macrostoma is considered as a potential biocontrol agent of C. sumatrensis. References: (1) P. R. Graupner et al. J. Nat. Prod. 66:1558, 2004. (2) S. Takamatsu et al. Mycoscience 42:135, 2001. (3) W. Z. Tan et al. Page 177 in: Manual of Emergency Control Technology Invasive Pests in China. G. L. Zhang, ed. Science Press, Beijing, 2010. (4) C. Wang et al. J. Wuhan Bot. Res. 28:90, 2010.

Background:Dermatomyositis (DM) is an idiopathic inflammatory myopathy with heterogeneous clinical manifestation that raise challenges regarding diagnosis and therapy1. Ferroptosis is a newly discovered form of regulated cell death that is the nexus between metabolism, redox biology, and rheumatic immune diseases2. However, how ferroptosis maintains the balance of lymphocyte T cells and affect disease activity in DM is unclear.Objectives:To investigate an ferroptosis-related multiple gene expression signature for classification by assessing the global gene expression profile, and calculate the lymphocyte T cells status in the different subsets.Methods:Gene expression profiles of skeletal muscle from DM samples were acquired from GEO database. GSE143323 (30 patients and 20 HCs) was selected as the training set. The GSE3307 contained 21 DM patients and was selected as the validation set. The 60 ferroptosis genes were obtained from previous literature3. The intersection of the global gene and ferroptosis genes was considered the set of significant G-Ferroptosis genes for further analysis. The “NMF” (R-package) was applied as an unsupervised clustering method for sample classification by using G-Ferroptosis genes expression microarray data from the training datasets. An ferroptosis score model was constructed. The performance of the ferroptosis genes-based risk score model constructed by the DM training set was validated in the batch-1 and batch-2 DM sets. Normalized ferroptosis genes training data was used to compare the ssGSEA scores of gene sets between the high risk and low risk group. The statistical software package R (version 4.0.3) was used for all analyses. P value < 0.05 were considered statistically significant.Results:We selected 54 significant G-Ferroptosis genes for further analysis in training set. There were 2 distinct subtypes (high-ferroptosis-score groups and low-ferroptosis-score groups) identified in G-Ferroptosis genes cohort which were also identified in validation datasets (Fig.1A, C, D). Metallothionein 1G (MT1G) was a characteristic gene of low-ferroptosis-score group. The characteristic genes of high-ferroptosis-score group were acyl-CoA synthetase family member 2(ACSF2) and aconitase 1(ACO1) (Fig.1B). Patients in high-ferroptosis-score group had a lower level of Tregs compared with that of low-ferroptosis-score patients in both training and validation set (P <0.05, Fig.1E).Conclusion:The biological process of ferroptosis is associated with the lever of Tregs, suggesting the process of ferroptosis may be involved in the disease progression of DM. Identificating ferroptosis-related features for DM might provide a new idea for clinical treatment.References:[1]DeWane ME, Waldman R, Lu J. Dermatomyositis: Clinical features and pathogenesis. Journal of the American Academy of Dermatology 2020;82(2):267-81. doi: 10.1016/j.jaad.2019.06.1309 [published Online First: 2019/07/08].[2]Liang C, Zhang X, Yang M, et al. Recent Progress in Ferroptosis Inducers for Cancer Therapy. Advanced materials (Deerfield Beach, Fla) 2019;31(51):e1904197. doi: 10.1002/adma.201904197 [published Online First: 2019/10/09].[3]Liang JY, Wang DS, Lin HC, et al. A Novel Ferroptosis-related Gene Signature for Overall Survival Prediction in Patients with Hepatocellular Carcinoma. International journal of biological sciences 2020;16(13):2430-41. doi: 10.7150/ijbs.45050 [published Online First: 2020/08/08].Acknowledgements:This project was supported by National Science Foundation of China (82001740).Open Fund from the Key Laboratory of Cellular Physiology (Shanxi Medical University) (KLCP2019) and Innovation Plan for Postgraduate Education in Shanxi Province (2020BY078).Disclosure of Interests:None declared

Background:COVID-19 can induce a hyperinflammatory state resulting in cytokine storm, which can lead to poor outcomes. Patients with systemic rheumatic diseases may be at increased risk for respiratory failure with COVID-19. Therefore, we investigated the relationship between rheumatic disease, hyperinflammation, and clinical outcomes among hospitalized COVID-19 patients.Objectives:To compare laboratory values, hyperinflammation, and clinical outcomes of hospitalized COVID-19 rheumatic patients and matched comparators.Methods:We performed a comparative cohort study of patients with polymerase chain reaction (PCR)-confirmed COVID-19 requiring hospitalization between 3/1/20-7/7/20 at a large health care system. We compared each systemic rheumatic disease case to up to 5 matched (by age, sex, and date of +SARS-CoV-2 PCR) comparators without systemic rheumatic disease. We extracted laboratory values from their hospitalization to compare peaks/troughs of individual laboratory results by case status and derived the COVID-19-associated hyperinflammation score (cHIS), a composite of 6 laboratory domains (0-6, ≥2 indicating hyperinflammation), as previously developed1. We used multivariable logistic regression to estimate ORs for COVID-19 outcomes by hyperinflammation and case status.Results:We identified 57 hospitalized rheumatic disease cases (mean age 67 years, 67% female) and 232 matched comparators hospitalized with PCR-confirmed COVID-19. Among cases, 26 (46%) had rheumatoid arthritis and 14 (25%) had systemic lupus erythematosus. Most cases (34, 60%) had active rheumatic disease. At baseline, 15 (27%) of cases were treated with biologic DMARDs, and 32 (56%) were using glucocorticoids. We analyzed 39,900 total laboratory results (median 85 per patient). Cases had higher peak neutrophil-to-lymphocyte ratio (9.6 vs 7.8, p=0.02), LDH (421 vs 345 U/L, p=0.04), creatinine (1.2 vs 1.0 mg/dL, p=0.01), and BUN (31 vs 23 mg/dL, p=0.03) than comparators but similar peak CRP (149 vs 116 mg/L, p=0.11, Figure 1). Cases had higher peak median cHIS (3 vs 2, p=0.01). Peak cHIS ≥2 had higher odds of intensive care unit (ICU) admission (OR 3.45, 95%CI 1.98-5.99), mechanical ventilation (OR 66.0, 95%CI 9.0-487.8), and mortality (OR 16.4, 95%CI 4.8-56.4) compared to cHIS <2 (Table 1). Cases had increased risk of ICU admission (OR 2.0, 95%CI 1.1-3.7) and mechanical ventilation (OR 2.7, 95%CI 1.4-5.2) than comparators.Table 1.Associations of peak cHIS and systemic rheumatic disease with COVID-19 hospitalization outcomesIntensive care unit admissionMechanical ventilationDeath%Adjusted OR (95%CI)%Adjusted OR (95%CI)%Adjusted OR (95%CI)Hospitalization outcomes by hyperinflammation on cHIS1cHIS <2 (n=112)21%1.0 (Ref)1%1.0 (Ref)3%1.0 (Ref)cHIS ≥2 (n=177)48%3.5 (2.0-6.0)37%66.2 (9.0-487.8)27%16.4 (4.8-56.4)Hospitalization outcomes by rheumatic disease statusComparators (n=232)30%1.0 (Ref)19%1.0 (Ref)16%1.0 (Ref)Rheumatic cases (n=57)51%1.87 (1.03-3.40)39%2.46 (1.30-4.67)21%1.32 (0.61-2.88)Matching factors: age, sex, and date of +PCR.1Adjusted for age, sex, and case status.2Adjusted for race, smoking, comorbidities, and body mass index.cHIS, COVID-19-associated hyperinflammation score; CI, confidence interval; OR, odds ratio; PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.Conclusion:Patients with systemic rheumatic disease hospitalized for COVID-19 had higher risk for hyperinflammation, kidney injury, and mechanical ventilation than non-rheumatic comparators. We validated the cHIS in our cohort, which was strongly associated with poor COVID-19 outcomes. These findings highlight that hospitalized patients with rheumatic diseases may be vulnerable to poor COVID-19 outcomes.References:[1]Webb BJ et al. Clinical criteria for COVID-19-associated hyperinflammatory syndrome. Lancet Rheumatol. 2020 Dec;2(12):e754-e763.Disclosure of Interests:Tiffany Hsu: None declared, Kristin D’Silva: None declared, Naomi Serling-Boyd: None declared, Jiaqi Wang: None declared, Alisa Mueller: None declared, Xiaoqing Fu: None declared, Lauren Prisco: None declared, Lily Martin: None declared, Kathleen Vanni: None declared, Alessandra Zaccardelli: None declared, Claire Cook: None declared, Hyon Choi Consultant of: Dr. Choi reports consultancy fees from Takeda, Selecta, GlaxoSmithKline, and Horizon, Grant/research support from: Dr. Choi reports research support from AstraZeneca., Yuqing Zhang: None declared, Ellen Gravallese: None declared, Zachary Wallace Consultant of: Dr. Wallace reports consulting fees from Viela Bio and MedPace., Grant/research support from: Dr. Wallace reports research support from Bristol-Myers Squibb and Principia., Jeffrey Sparks Consultant of: Dr. Sparks reports consultancy fees from Bristol-Myers Squibb, Gilead, Inova, Janssen, Optum, and Pfizer., Grant/research support from: Dr. Sparks reports research support from Amgen and Bristol-Myers Squibb.

Background:Interstitial lung disease (ILD) is a known extraarticular manifestation of rheumatoid arthritis (RA). Previous studies have shown variability in the prevalence of RA-ILD, as well as clinical characteristics and risk factors of RA-ILD.Objectives:To evaluate the prevalence and time to onset of ILD and compare the clinical characteristics between RA patients (pts) with or without ILD using a large US electronic medical record (EMR)-based dataset.Methods:Pts with an initial RA diagnosis (ICD-9-CM code: 714.0; ICD-10-CM codes: M05 & M06) during the study period (01JAN2009-20SEP2019) were included from the Discus Analytics JointMan database. The initial RA diagnosis date was defined as the index date. Pts with ILD were identified by ICD diagnosis codes or by provider indication in the JointMan record. Pts who developed ILD before RA were excluded from this analysis. The prevalence and time to onset of ILD were reported. Pt demographics, comorbidities, RA characteristics and disease activity scores were compared for 6 months prior to or on the index date (baseline period) for selected adult RA pts with available information.Results:Among 8,963 identified RA pts, 337 (3.8%) were diagnosed with ILD on or after RA diagnosis. The median time to ILD onset post-RA was 2.3 years, and 47% had ILD within 2 years after RA diagnosis. RA-ILD pts were significantly older than those without ILD (65.8 years vs. 59.1 years; p<0.001; Table 1). At baseline, a higher percentage of RA-ILD pts had history of chronic obstructive pulmonary disease, positive rheumatoid factor, rheumatoid nodules, erosive joint disease, positive anti-cyclic citrullinated peptide antibody, and joint swelling compared to RA-only pts (Table 2). The mean ESR and RA disease activity scores were also significantly higher for RA-ILD pts.Table 1.Patient DemographicsPatient demographicsRA-ONLY COhort(N = 5,612)RA-ild coHORT(N = 205)P-valueAge, Mean ± SD, years59.1 ± 14.265.8 ± 11.8<.001Male, N (%)1,375 (24.5%)72 (35.1%)0.001Race, N (%) White4,014 (71.5%)165 (80.5%)0.005 African American365 (6.5%)9 (4.4%)0.226 Other/Missing1,233 (22.0%)31 (15.1%)0.020Table 2.Baseline Clinical CharacteristicsClinical CharacteristicsRA-ONLY COhort(N = 3,846)RA-ild coHORT(N = 115)P-valueHistory of Chronic Obstructive Pulmonary Disease, N (%)102 (2.7%)8 (7.0%)0.006Hypertension, N (%)900 (23.4%)23 (20.0%)0.395Serious Infection, N (%)38 (1.0%)3 (2.6%)0.091Rheumatoid Factor Positive, N (%)1,388 (36.1%)69 (60.0%)<.001Joint Stiffness, N (%)1,092 (28.4%)39 (33.9%)0.197Rheumatoid Nodules, N (%)153 (4.0%)17 (14.8%)<.001Erosive Joint Disease, N (%)459 (11.9%)23 (20.0%)0.009Anti-CCP Antibody Positive, N (%)858 (22.3%)45 (39.1%)<.001Joint Swelling*, N (%)2,861 (58.0%)123 (68.0%)0.008Joint Tenderness*, N (%)3,728 (75.6%)138 (76.2%)0.851ESR**, Mean ± SD, mm/hr22.0 ± 22.630.1 ± 25.5<.001CRP**, Mean ± SD, mg/L22.5 ± 13.060.6 ± 25.00.086CDAI, Mean ± SD16.4 ± 12.318.9 ± 15.70.044DAS28-CRP, Mean ± SD2.6 ± 1.23.1 ± 1.4<.001DAS28-ESR, Mean ± SD3.3 ± 1.43.9 ± 1.5<.001SDAI, Mean ± SD20.2 ± 29.328.6 ± 40.20.048* A total of 4,929 non-ILD and 181 ILD patients had joint swelling and tenderness data.** Variables were calculated among patients who had available information.Conclusion:This large real-world RA population provides insight into the burden of ILD in RA pts. Pts with ILD had a higher proportion of comorbidities and RA-related conditions and higher RA activity. Further analysis is warranted to assess the risk factors of ILD and its prognosis.Disclosure of Interests:Joe Zhuo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Qisu Zhang Consultant of: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company., Keith Knapp Consultant of: In the last year, I was a paid consultant to Bristol Myers-Squibb Company., Employee of: I am a paid employee of Discus Analytics., Yuexi Wang Consultant of: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company., Cynthia Gutierrez Consultant of: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company., Ding He Consultant of: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company., Lin Xie Consultant of: I am a paid employee of STATinMED Research which is a paid consultant to Bristol-Myers Squibb Company., Sonie Lama Shareholder of: I own shares of Bristol-Myers Squibb Company., Employee of: I am a paid employee of Bristol-Myers Squibb Company., Gary Craig Consultant of: I have served as a consultant to Bristol-Myers Squibb Company., Employee of: I am a paid employee of Arthritis Northwest and VP of Discus Analytics., Speakers bureau: I am a member of the speakers bureau for Bristol-Myers Squibb Company.

Background:D-0120 is a novel oral selective uric acid transporter (URAT1) inhibitor being developed for the treatment of hyperuricemia and gout by blocking the reabsorption of uric acid (UA) within the renal proximal tubule, thereby reducing serum uric acid concentrations. As a novel URAT1 inhibitor, D-0120 is anticipated to have more potent serum UA reducing effect than the approved URAT1 inhibitor lesinurad, but with less toxicity and wider therapeutic window. The pharmacological potential of D-0120 for the treatment of hyperuricemia and gout was demonstrated in preclinical studies. The results of the in vitro hURAT1 expressed CHO cell model showed that the inhibitory activity of D-0120 is 150-fold more potent than lesinurad and slightly more potent than verinurad.Objectives:The purpose of this dose escalation study is to evaluate the safety and tolerability of D-0120 in multiple ascending doses in healthy volunteer, to characterize the pharmacokinetics (PK) of D-0120 and to assess pharmacodynamic (PD) effects and determine the drug-drug interaction (DDI) effect of febuxostat and D-0120 in healthy volunteers.Methods:This is a randomized, double blind, multiple ascending doses Phase I study of D-0120 in healthy volunteers conducted at one site. Thirty-two healthy eligible volunteers with serum uric acid level ≥ 4.5 mg/dL but within normal range at screening were enrolled and dosed with D-0120 within 4 different single agent cohorts for a period of 7 days. Each cohort had 8 subjects randomized at 3:1 ratio for D-0120:placebo. A fifth cohort of 8 healthy eligible volunteers were enrolled and dosed with 5 mg of D-0120 in combination with 40 mg of febuxostat over a period of 9 days. Evaluation of safety, PK and PD was conducted at various timepoints while the patients were in confinement. Further safety evaluation took place on Day 14. A Safety Review Committee reviewed safety, PK and PD data for each cohort of D-0120 dose level (2.5 mg, 5 mg, 10 mg, 20 mg) as well as when D-0120 5 mg was combined with 40 mg febuxostat. PK evaluation for multiple dose parameters included AUC0-τ, Cmax, Cmin, Tmax and Fl.Results:Dose escalation of D-0120 from 2.5 mg/day to 20 mg/day was completed without any dose limiting toxicities. Most AEs occurred during the study were mild to moderate in severity and did not require any treatment before resolution. There was no SAE and no dose reduction during the treatment period. The pharmacokinetic (PK) evaluation of ascending dose levels of D-0120 suggested a dose proportional increase in drug exposure and there was no significant change of PK profile between Day 1 and Day 7 of dosing. For pharmacodynamic (PD) evaluation, the serum uric acid (UA) levels before and after D-0120 dosing was evaluated on multiple days. The UA reduction effect achieved maximum at about 4-8 hours after dosing and the effect lasted for at least 24 hours. After the 7-day dosing period, the mean percentage of UA reduction from baseline showed an increasing trend as the dose level increased.More detailed safety, PK and PD data from multiple D-0120 dose cohorts and D-0120/febuxostat combination cohort will be presented at the meeting.Conclusion:The oral daily administration of a novel URAT1 inhibitor, D-0120, in healthy volunteers for 7 days was well tolerated at dose levels from 2.5 mg/day to 20 mg/day. The PK profile demonstrated a dose proportional increase. D-0120 administration for 7 days resulted in significant reduction of serum UA levels. Further evaluation of this novel agent in longer treatment period and in patients with hyperuricemia and/or gout is warranted.References:Not Applicable.Disclosure of Interests:Ling Zhang Employee of: INVENTISBIO, David Wyatt: None declared, Kathryn Stazzone Employee of: INVENTISBIO, Zhe Shi Employee of: INVENTISBIO, Yaolin Wang Employee of: INVENTISBIO

Background:To date, the European Alliance of Associations for Rheumatology (EULAR) guidelines recommend X-ray (XR) as first line imaging in axial Spondyloarthritis (axSpA) and magnetic resonance imaging (MR) if the diagnosis cannot be established by XR and clinical features. However, much knowledge has been gained recently strengthening the applicability of MR for the detection of structural lesions and raising the question, whether XR is still necessary. Also, several publications used low-dose computed tomography (CT) as reference standard and imaging test.Objectives:In light of this complex diagnostic situation, the aim of this study was to compare the three major modalities, XR, MR and CT of SIJ, in their diagnostic performance of axSpA and differential diagnosis in a cohort of patients with low back pain using the final judgment of the rheumatologist as standard of reference.Methods:163 patients (89 with axSpA; 74 with degenerative diseases) underwent XR, CT and MR. Three blinded experts categorized the imaging into axSpA, other diseases or normal in 5 separate reading rounds (XR, CT, MR, XR+MR, CT+MR, respectively). The results were compared to the clinical diagnosis. Sensitivity and specificity values for axSpA and interrater reliability were compared.Results:XR showed lower sensitivity and specificity (66.3%/67.6% respectively) compared to MR (82.0%/86.5%) and CT (77.5%/97.3%). Sensitivity and specificity of XR+MR was similar to MR alone (77.5% / 87.8%). However, CT+MR was superior to MR alone (75.6% / 97.3%) (see Figure). CT had the best interrater reliability (kappa = 0.875) followed by MR (0.665) and XR (0.517). CR+MR reliability was similar (0.662) compared to MR alone, while CT+MR reliability (0.732) was superior.Figure 1.Frequency of positive and negative findings in radiography (XR), computed tomography (CT), magnetic resonance imaging (MR) and combinations and resulting diagnostic accuracy values. SE: Sensitivity, SP: Specificity, LR-/+: negative/positive likelihood ratio.Conclusion:In conclusion, XR is inferior to cross-sectional imaging and should be replaced by MR or CT for differential diagnosis. While MR is the most sensitive imaging technique, it lacks specificity when compared to CT. CT alone has high diagnostic accuracy, despite being insensitive to bone marrow lesions such as fatty metaplasia or osteitis. Adding CT to MR leads to an increase in specificity at a minor expense of sensitivity.References:[1]Sieper J, Rudwaleit M, Baraliakos X, et al. The Assessment of SpondyloArthritis international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis. 2009;68 Suppl 2:ii1-44.[2]Mandl P, Navarro-Compán V, Terslev L, et al. EULAR recommendations for the use of imaging in the diagnosis and management of spondyloarthritis in clinical practice. Ann Rheum Dis. 2015;74(7):1327-39.[3]Diekhoff T, Hermann KA, Greese J, et al. Comparison of MRI with radiography for detecting structural lesions of the sacroiliac joint using CT as standard of reference: results from the SIMACT study. Ann Rheum Dis. 2017.[4]Diekhoff T, Greese J, Sieper J, Poddubnyy D, Hamm B, Hermann KA. Improved detection of erosions in the sacroiliac joints on MRI with volumetric interpolated breath-hold examination (VIBE): results from the SIMACT study. Ann Rheum Dis. 2018;77(11):1585-89.[5]Baraliakos X, Hoffmann F, Deng X, Wang YY, Huang F, Braun J. Detection of Erosions in Sacroiliac Joints of Patients with Axial Spondyloarthritis Using the Magnetic Resonance Imaging Volumetric Interpolated Breath-hold Examination. The Journal of rheumatology. 2019;46(11):1445-49.[6]Wu H, Zhang G, Shi L, et al. Axial Spondyloarthritis: Dual-Energy Virtual Noncalcium CT in the Detection of Bone Marrow Edema in the Sacroiliac Joints. Radiology. 2019;290(1):157-64.Disclosure of Interests:Torsten Diekhoff Speakers bureau: Canon MS, Roche, Novartis, MSD, Grant/research support from: Assessment of Spondyloarthritis International Society, Iris Eshed: None declared, Felix Radny: None declared, Katharina Ziegeler: None declared, Fabian Proft: None declared, Juliane Greese: None declared, Dominik Deppe: None declared, Robert Biesen: None declared, Kay-Geert Hermann: None declared, Denis Poddubnyy: None declared

Background:Donor-specific anti-HLA antibodies (DSAs) are antibodies in the recipient directed against donor class I/II HLA antigens. The existence of DSAs before allogenic hematopoietic stem cell transplantation (AHSCT) are known to cause primary graft failure. Currently there’s no established method of DSA desensitization due to the long half-life of plasma cells.Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease involving in multiple organ systems mediated by numerous autoantibodies. Recent results have shown that depletion of B cells by CD19 CAR-T cells effectively reversed some manifestations in two SLE mouse models. However, plasma cells could be spared with single CD19 CAR-T cells, and peripheral circulating anti-DNA IgG and IgM autoantibodies remain elevated or increased in treated mice.Objectives:We present the efficacy of BCMA-CD19 compound CAR (cCAR), which target on antibody- producing “root”, both B cells and plasma cells in preclinical study and in our first-in-human phase 1 clinical trial.Methods:We constructed a BCMA-CD19 cCAR composed of a complete BCMA-CAR fused to a complete CD19 CAR, separated by a self-cleaving P2A peptide. We assessed the functional activity of cCAR in co-culture assay with multiple cell lines. We also verified cCAR efficacy with two mouse models, injected with either BCMA-expressing MM.1S cells or CD19-expressing REH cells. In our phase 1 clinical trial, we enrolled patients with hematologic malignancies with antibody mediated disorders.Results:BCMA-CD19 cCAR exhibited robust cytotoxic activity against the K562 cells engineered to express either CD19 or BCMA in co-culture assays, indicating the ability of each complete CAR domain to specifically lyse target cells. In mouse model study, cCAR-T cells were able to eliminate tumor cells in mice injected with MM.1S cells and REH cells, indicating that both BCMA and CD19 are specifically and equally lysing B cells and plasma cells in vivo, making BCMA-CD19 cCAR a candidate for clinical use.In our first-in-human clinical trial, the first case is a 48-year-old female patient having resistant B-ALL with high DSA titers. She exhibited complete remission of B-ALL at day 14 post-CAR T treatment. MFI of DSA dropped from 7800 to 1400 at 8 weeks post cCAR treatment, the reduction percentage was approximately 80% (Figure 1). The patient had no CRS, and no neurotoxicity was observed.Figure 1.1. A) MFI of DSA and other HLA antibodies before and at different time points after cCAR T infusion. B) the percent reduction post-transfusion of cCAR T cells at different time points.The second case is a 41-year-old female patient having a refractory diffuse large B cell lymphoma with bone marrow (BM) involvement. Furthermore, she has a 20 years of SLE, with manifestation of fever dependent of corticosteroids. On day 28 after cCAR treatment, PET/CT scan showed CR, and BM turned negative. In addition, she is independent of steroids, has no fever and other manifestations, C3/C4 are within normal ranges, and all the ANA dropped significantly, especially the nuclear type ANA, which turned from> 1:1000 to be negative at day 64. She had Grade 1 CRS but with no neurotoxicity observed. The absence of B cells and plasma cells persisted more than 5 months post CAR therapy.Conclusion:Our first in human clinical trial on BCMA-CD19 cCAR demonstrated profound efficacy in reducing DSA levels in an AHSCT candidate and ANA titer in a SLE patient. There was strong clinical evidence of depletion of antibody-producing roots, B-cells and plasma cells in both patients. Our results further suggested that BCMA-CD19 cCAR has the potential to benefit patients receiving solid organ transplants or those with other antibody-mediated diseases.Figure 2.Reduction of different type of ANA titer at different time points.Acknowledgments:patients and their familiesDisclosure of Interests:Fang liu: None declared, Hongyu Zhang: None declared, Xiao Wang: None declared, Jia Feng: None declared, Yuanzhen cao Employee of: Employee of iCell Gene Therapeutics LLC, Yi Su: None declared, Masayuki Wada Employee of: employee of iCell Gene Therapeutics LLC, Yu Ma Employee of: employee of iCAR Bio Therapeutics Ltd, Yupo Ma Shareholder of: shareholder of iCell Gene Therapeutics LLC

Abstract Introduction: Attaining complete remission (CR) prior to HSCT is associated with better outcomes post-HSCT. Inotuzumab ozogamicin (INO), an anti-CD22 antibody conjugated to calicheamicin, has shown significantly higher remission rates (CR/CRi and MRD negativity) compared with standard chemotherapy (SC) in patients (pts) with R/R ALL (Kantarjian et al. N Engl J Med. 2016). Pts treated with INO were more likely to proceed to HSCT than SC, which allowed for a higher 2-yr probability of overall survival (OS) than patients receiving SC (39% vs 29%). We investigated the role of prior transplant and proceeding directly to HSCT after attaining remission from INO administration as potential factors in determining post-HSCT survival to inform when best to use INO in R/R ALL patients. Methods: The analysis population consisted of R/R ALL pts who were enrolled and treated with INO and proceeded to allogeneic HSCT as part of two clinical trials: Study 1010 is a Phase 1/2 trial (NCT01363297), while Study 1022 is the pivotal randomized Phase 3 (NCT01564784) trial. Full details of methods for both studies have been previously published (DeAngelo et al. Blood Adv. 2017). All reference to OS pertains to post-HSCT survival defined as time from HSCT to death from any cause. Results: As of March 2016, out of 236 pts administered INO in the two studies (Study 1010, n=72; Study 1022, n=164), 101 (43%) proceeded to allogeneic HSCT and were included in this analysis. Median age was 37 y (range 20-71) with 55% males. The majority of pts received INO as first salvage treatment (62%) and 85% had no prior SCT. Most pts received matched HSCTs (related = 25%; unrelated = 45%) with peripheral blood as the predominant cell source (62%). The conditioning regimens were mainly myeloablative regimens (60%) and predominantly TBI-based (62%). Dual alkylators were used in 13% of pts, while thiotepa was used in 8%. The Figure shows post-transplant survival in the different INO populations: The median OS post-HSCT for all pts (n=101) who received INO and proceeded to HSCT was 9.2 mos with a 2-yr survival probability of 41% (95% confidence interval [CI] 31-51%). In patients with first HSCT (n=86) the median OS post-HSCT was 11.8 mos with a 2-yr survival probability of 46% (95% CI 35-56%). Of note, some patients lost CR while waiting for HSCT and had to receive additional treatments before proceeding to HSCT (n=28). Those pts who went directly to first HSCT after attaining remission with no intervening additional treatment (n=73) fared best, with median OS post-HSCT not reached with a 2-yr survival probability of 51% (95% CI 39-62%). In the latter group, 59/73 (80%) attained MRD negativity, and 49/73 (67%) were in first salvage therapy. Of note, the post-HSCT 100-day survival probability was similar among the 3 groups, as shown in the Table. Multivariate analyses using Cox regression modelling confirmed that MRD negativity during INO treatment and no prior HSCT were associated with lower risk of mortality post-HSCT. Other prognostic factors associated with worse OS included older age, higher baseline LDH, higher last bilirubin measurement prior to HSCT, and use of thiotepa. Veno-occlusive disease post-transplant was noted in 19 of the 101 pts who received INO. Conclusion: Administration of INO in R/R ALL pts followed with allogeneic HSCT provided the best long-term survival benefit among those who went directly to HSCT after attaining remission and had no prior HSCT. Disclosures DeAngelo: Glycomimetics: Research Funding; Incyte: Consultancy, Honoraria; Blueprint Medicines: Honoraria, Research Funding; Takeda Pharmaceuticals U.S.A., Inc.: Honoraria; Shire: Honoraria; Pfizer Inc.: Consultancy, Honoraria, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Research Funding; BMS: Consultancy; ARIAD: Consultancy, Research Funding; Immunogen: Honoraria, Research Funding; Celgene: Research Funding; Amgen: Consultancy, Research Funding. Kantarjian: Novartis: Research Funding; Amgen: Research Funding; Delta-Fly Pharma: Research Funding; Bristol-Meyers Squibb: Research Funding; Pfizer: Research Funding; ARIAD: Research Funding. Advani: Takeda/ Millenium: Research Funding; Pfizer: Consultancy. Merchant: Pfizer: Consultancy, Research Funding. Stock: Amgen: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wang: Pfizer: Employment, Equity Ownership. Zhang: Pfizer: Employment, Equity Ownership. Loberiza: Pfizer: Employment, Equity Ownership. Vandendries: Pfizer: Employment, Equity Ownership. Marks: Pfizer: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau.

Rapid urbanization rates impact significantly on the nature of Land Cover patterns of the environment, which has been evident in the depletion of vegetal reserves and in general modifying the human climatic systems (Henderson, et al., 2017; Kumar, Masago, Mishra, & Fukushi, 2018; Luo and Lau, 2017). This study explores remote sensing classification technique and other auxiliary data to determine LULCC for a period of 50 years (1967-2016). The LULCC types identified were quantitatively evaluated using the change detection approach from results of maximum likelihood classification algorithm in GIS. Accuracy assessment results were evaluated and found to be between 56 to 98 percent of the LULC classification. The change detection analysis revealed change in the LULC types in Minna from 1976 to 2016. Built-up area increases from 74.82ha in 1976 to 116.58ha in 2016. Farmlands increased from 2.23 ha to 46.45ha and bared surface increases from 120.00ha to 161.31ha between 1976 to 2016 resulting to decline in vegetation, water body, and wetlands. The Decade of rapid urbanization was found to coincide with the period of increased Public Private Partnership Agreement (PPPA). Increase in farmlands was due to the adoption of urban agriculture which has influence on food security and the environmental sustainability. The observed increase in built up areas, farmlands and bare surfaces has substantially led to reduction in vegetation and water bodies. The oscillatory nature of water bodies LULCC which was not particularly consistent with the rates of urbanization also suggests that beyond the urbanization process, other factors may influence the LULCC of water bodies in urban settlements. Keywords: Minna, Niger State, Remote Sensing, Land Surface Characteristics References Akinrinmade, A., Ibrahim, K., & Abdurrahman, A. (2012). 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