Journal articles on the topic 'Jia Pingwa Fei du'

A partir de la década de 1980, el autor de Cien años de soledad se convirtió en el gran ídolo y fuente de “angustia de las influencias” (en términos de Harold Bloom) para toda una generación de escritores chinos: Jia Pingwa, Yu Hua, Su Tong, Yan Lianke, Ma Yuan y Mo Yan, entre otros. En este artículo se propone una lectura paralela de Gabriel García Márquez y Mo Yan, el premio nobel chino, con el propósito de demostrar que el realismo mágico latinoamericano y su aventura en China ha formado parte de la historia de la literatura contemporánea del país asiático: a los escritores chinos no solo les avivó su memoria y les hizo adoptar otra actitud hacia su pasado; también les mostró el camino para escribir un nuevo tipo de novela (noveau roman).

Abstract Background: The activin type II receptor (ACVR2), which is a member of the transforming growth factor beta (TGF-β) receptor family, is frequently mutated in colorectal cancer (CRC) and gastric cancer (GC). However, the incidence of ACVR2 mutations in MSI-H patients remains unclear. The aim of this study is to evaluate ACVR2A mutation characteristics and to examine its associations between the high microsatellite instability (MSI-H) and ACVR2A mutations in CRC and GC. Materials and Methods: We analyzed data from two cohorts: a Chinese cohort and the TCGA cohort. The Chinese cohort consisted of 1960 patients with CRC and GC, including 140 MSI-H samples and 1820 MSS samples. MSI status of these patients was derived from tumor-normal paired sequence data by targeted next generation sequencing (NGS). The TCGA cohort consists of 570 patients whose MSI status was determined. NGS data and clinical information were downloaded from the cBioPortal database (https://www.cbioportal.org). The abundance of tumor immune infiltrates was estimated by the Tumor Immune Estimation Resource (TIMER) 2.0 algorithm using gene expression data. Results: In the Chinese cohort, ACVR2A mutations were identified in 204 (18.6%) of 1960 patients, including 125 (61%) MSI-H patients and 79 (39%) MSS patients. Meanwhile, in all 140 MSI-H samples, 125 (90%) samples harbored AVCR2A mutation. The main variant of ACVR2A is loss of function mutation (ACVR2ALOF), including p.K437del(65%, 132/204), p.D96del(5%, 11/204), p.Asp96ins(4%, 9/204), and etc. ACVR2ALOF were detected in 161 patients (78.9%, 161/204), of which 125 (77%) were MSI-H and 36 (22%) were MSS. In the TCGA cohort, there were 102 (102/570) MSI-H samples, and 43% (44/102) of MSI-H samples carried ACVR2A mutation. Compared to the Chinese cohort, the ACVR2A mutation frequency in MSI-H samples was significantly lower in the TCGA cohort (43% vs 90%, p<0.01). The ACVR2ALOF mutations were observed in 30 MSI-H samples and 6 MSS samples. In both cohorts, patients with ACVR2ALOF mutations exhibited higher TMB (p<0.05) and PD-L1 expression (p<0.0001) than those without ACVR2ALOF mutations. Furthermore, in the TCGA cohort, we found that the Tumor Infiltrating Lymphocytes (TILs) of CD4+ T cells and macrophage cells were significantly lower in ACVR2ALOF samples than those without ACVR2ALOF mutations (p<0.05). Conclusions: The ACVR2ALOF was strongly correlated with MSI-H in patients of CRC and GC in both cohorts, especially in the Chinese population. Patients with ACVR2ALOF mutations have similar genomic characteristics to MSI-H, with high TMB, high PD-L1 expression, and therefore can serve as a potential biomarker for selecting candidates for immunotherapy. Citation Format: Yongning Jia, Hongling Yuan, Yaqun Xin, Fei Pang, Fei Shan, Shuangxi Li, Honglin Zhu, Ziyu Li. Loss-of-function mutations in ACVR2A are correlated with microsatellite instability in gastric and colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5752.

With the increase of portable power sources demand, new technologies, e.g. wearable and flexible electronics, are projected to generate $1.25 billion market by 2022.[1] New storage energy devices are more than ever in demand which requires new specifications in order to be used in those future applications. To achieve this development, we have to minimize the environmental impact in the whole battery life cycle, from conception to degradation of the system, and reduce production costs. Polymer hydrogel electrolyte are one of the promising alternative for processing new flexible batteries.[2] A great hydrogel electrolyte should promise excellent ionic transport pathways and sufficient mechanical strength, not to cause short-circuits. As a matter of fact, hydrogel electrolytes are well-known for their good ionic conductivity. Nevertheless, the original polymers used in these systems don’t take into account the cost of the environmental impact and safety due to the processing or biodegradability of those hydrogels.[3] In this study, we report a new hydrogel-based electrolyte material made by apple pectin. This presentation will mainly focus on the interactions between pectin functional groups, water and ions using solid NMR spectroscopy. Thermal properties will be discussed based on differential scanning calorimetry analysis. Electrical and electrochemical characterisctics obtained by electrochemical impedance spectroscopy, galvanostatic cycling and cyclic voltametry will demonstrate the applicability of such hydrogel electrolyte. This study could promote a great innovation in the energy storage field, by recycling one of apple peel’s component (which is the main waste in preserves manufacturing[4]) into a hydrogel electrolyte. References [1] N. R. C. Canada in Environmentally friendly printed batteries, Vol. Boucherville, Quebec, 2021. [2] C. Y. Chan, Z. Wang, H. Jia, P. F. Ng, L. Chow and B. Fei, Journal of Materials Chemistry A 2021, 9, 2043-2069. [3] Y. Huang, M. Zhong, F. Shi, X. Liu, Z. Tang, Y. Wang, Y. Huang, H. Hou, X. Xie and C. Zhi, Angewandte Chemie International Edition 2017, 56, 9141-9145. [4] B. S. Virk and D. S. Sogi, International Journal of Food Properties 2004, 7, 693-703.

Abstract Background: Mutations in genes encoding DNA polymerase epsilon (POLE) and delta 1 (POLD1) can lead to defects in the DNA replication, resulting in a hypermutated tumor phenotype, which might help identify potential responders to immunotherapy. This study aims to comprehensively investigate the different variants of POLE/POLD1 mutants and how it related to MSI/MMR status and TMB levels within a large Chinese population. Methods:Among 15640 Chinese patients who underwent NGS testing, the prevalence of POLE/POLD1 mutants was analyzed and the high frequencies of POLE/POLD1 variants as well as their relations with MMR/MSI and TMB were explored. Results: POLE and POLD1 mutations were highly distributed in endometrial cancer (11.1% and 9.3%), colorectal cancer (5.9% and 4.5%), and gastric cancer (4.6% and 3.3%). In our study, the mutation frequency of POLE was 3.4%, including p.Ala252Val (9.2%), p.Pro286Arg (2.7%), p.Val411Leu (1.3%), p.Asp601Glu (6.0%), p.Lys425Gln (2.9%) and p.Phe1849Val (1.8%). Variants of p.Ala252Val, p.Pro286Arg and p.Val411Leu displayed high TMB levels (median 71.4 muts/Mb, 236.7 muts/Mb and 220 muts/Mb, respectively) while variants of p.Asp601Glu, p.Lys425Gln, p.Phe1849Val and p.Asn2098His had a rather low TMB, ranging from 5.2-8.1 muts/Mb. It is worth mentioning that 37.5% of p. Pro286Arg and 87.5% of Val411Leu variants had concurrent loss-of-function mutations of MMR (MMRLOF), while MMRLOF rarely occurred in the other variants.For POLD1, the mutation frequency in Chinese patients was 2.8%, including p.Arg119His (18.8%), p.Glu57del (16.5%) and p.Asp987Thrfs (3.3%). p.Arg119His variants showed a high TMB level of 65.6 muts/Mb and most occurred in lung cancer. Variants of p.Asp987Thrfs, p.Pro116Hisfs and p.Arg19His had similar TMB levels (p>0.05), while much lower TMB levels was found in p.Glu57del (3.3 muts/Mb, p<0.001) compared to p.Arg119His.Compared with POLE/POLD1 wild-type (POLDE/POLD1-WT), the percentage of MSI-H samples in POLE/POLD1 mutants was much higher (14% vs 0.7, p<0.001). About 10% of POLE/POLD1 mutations carried MMRLOF mutations while it was barely observed in POLE/POLD1-WT (0.5%). The TMB levels of POLE/POLD1 mutations were significantly higher than that of the POLE/POLD1-WT (17.7 vs 2.9 muts/Mb, p<0.001). Furthermore, POLE/POLD1 mutations was found to be a main cause leading to high levels of TMB. Among samples with TMB >10 muts/Mb, 22.6% of them were POLE/POLD1 mutations. And in samples with TMB >100 muts/Mb, as high as 82% of samples were found carrying POLE/POLD1 mutations. Conclusion: POLE/POLD1 mutations were found in Chinese patients in multiple tumors. Different POLE/POLD1 variants were associated with different MMR status and TMB levels. In addition to MMR, POLE/POLD1 mutations might be another distinct means of inducing high TMB. Citation Format: Yongning Jia, Yaqun Xin, Hongling Yuan, Fei Pang, Fei Shan, Shuangxi Li, Honglin Zhu, Ziyu Li. Comprehensive analysis of POLE/POLD1 variants, MMR deficient/MSI, and tumor mutational burden in Chinese population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5751.

Abstract Background: Although immune checkpoint inhibitors (ICI) included PD-1/PD-L1 have demonstrated durable therapeutic responses in some cases, a significant portion of patients with cancer remain nonresponsive (e.g. only ~20% with anti-PD-1 in lung cancer). Substantial limitations in the rate of response underscore the need for suitable combination therapies. SRC family kinases is overexpressed or activated in multiple human malignancies, as a candidate target in regulating antitumor immunity. Saracatinib, an orally bioavailable multi-kinase inhibitor, has demonstrated clinical efficacy in CML. Here, we proved saracatinib as SRC inhibitor that were capable of increasing the antitumor immunity in non-small lung cancer. Method: Cytotoxicity assays were used to determined antitumor activities of saracatinib in non-small lung cancer cell lines. The expression of PD-L1 expression in saracatinib 1 treated cell lines was investigated by western blots, quantitative PCR and flow cytometry. The effect of saracatinib in antitumor immunity alone or in combination with immunotherapy was also determined in vitro and in vivo. RNAi, overexpression, and gene expression analyses were used to define underlying mechanisms. Result: We found that SRC inhibitor saracatinib robustly decreased expression of PD-L1 in non-small lung cancer cells and animal models. The observed inhibitory effect was time- and concentration-dependent. Furthermore, our results showed that saracatinib and anti-PD-L1 combined to improve T-cell-mediated killing of tumor cells in vitro and in vivo, which were associated with activation of CD8+ T cytotoxic cell included expression of IFN-γ and granzyme-B. Prolonged survival was also observed in mice treated with saracatinib in combination with PD-L1 blockade. Conclusion: Our in vivo and in vitro data demonstrated that SRC inhibitor saracatinib enhance T-cell-mediated anti-tumor immune responses in non-small lung cancer. We also provide evidence that support the combination of saracatinib and anti-PD-1/PD-L1 as a potential combination therapeutic approach to increase the efficacy of immunotherapy in non-small lung cancer. Citation Format: Fei-Teng Lu, Fan Luo, Miao-Zhen Qiu, Jia-Xin Cao, Qiu-Yun Luo, Da-Jun Yang, Hong-Yun Zhao. SRC inhibitor saracatinib enhances efficacy of PD-1/PD-L1 immune checkpoint blockade in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6094.

Ever-increasing demands for energy, particularly being environmentally friendly have promoted the transition from fossil fuels to renewable energy.1 Lithium-ion batteries (LIBs), arguably the most well-studied energy storage system, have dominated the energy market since their advent in the 1990s.2 However, challenging issues regarding safety, supply of lithium, and high price of lithium resources limit the further advancement of LIBs for large-scale energy storage applications.3 Therefore, attention is being concentrated on an alternative electrochemical energy storage device that features high safety, low cost, and long cycle life. Rechargeable aqueous zinc-ion batteries (ZIBs) is considered one of the most promising alternative energy storage systems due to the high theoretical energy and power densities where the multiple electrons (Zn2+) . In addition, aqueous ZIBs are safer due to non-flammable electrolyte (e.g., typically aqueous solution) and can be manufactured since they can be assembled in ambient air conditions. 4 As an essential component in aqueous Zn-based batteries, the Zn metal anode generally suffers from the growth of dendrites, which would affect battery performance in several ways. Second, the led by the loose structure of Zn dendrite may reduce the coulombic efficiency and shorten the battery lifespan.5 Several approaches were suggested to improve the electrochemical stability of ZIBs, such as implementing an interfacial buffer layer that separates the active Zn from the bulk electrolyte.6 However, the and thick thickness of the conventional Zn metal foils remain a critical challenge in this field, which may diminish the energy density of the battery drastically. According to a theretical calculation, the thickness of a Zn metal anode with an areal capacity of 1 mAh cm-2 is about 1.7 μm. However, existing extrusion-based fabrication technologies are not capable of downscaling the thickness Zn metal foils below 20 μm. Herein, we demonstrate a thickness controllable coating approach to fabricate an ultrathin Zn metal anode as well as a thin dielectric oxide separator. First, a 1.7 μm Zn layer was uniformly thermally evaporated onto a Cu foil. Then, Al2O3 , the separator was deposited through sputtering on the Zn layer to a thickness of 10 nm. The inert and high hardness Al2O3 layer is expected to lower the polarization and restrain the growth of Zn dendrites. Atomic force microscopy was employed to evaluate the roughness of the surface of the deposited Zn and Al2O3/Zn anode structures. Long-term cycling stability was gauged under the symmetrical cells at 0.5 mA cm-2 for 1 mAh cm-2. Then the fabricated Zn anode was paired with MnO2 as a full cell for further electrochemical performance testing. To investigate the evolution of the interface between the Zn anode and the electrolyte, a home-developed in-situ optical observation battery cage was employed to record and compare the process of Zn deposition on the anodes of the Al2O3/Zn (demonstrated in this study) and the procured thick Zn anode. The surface morphology of the two Zn anodes after circulation was characterized and compared through scanning electron microscopy. The tunable ultrathin Zn metal anode with enhanced anode stability provides a pathway for future high-energy-density Zn-ion batteries. Obama, B., The irreversible momentum of clean energy. Science 2017, 355 (6321), 126-129. Goodenough, J. B.; Park, K. S., The Li-ion rechargeable battery: a perspective. J Am Chem Soc 2013, 135 (4), 1167-76. Li, C.; Xie, X.; Liang, S.; Zhou, J., Issues and Future Perspective on Zinc Metal Anode for Rechargeable Aqueous Zinc‐ion Batteries. Energy & Environmental Materials 2020, 3 (2), 146-159. Jia, H.; Wang, Z.; Tawiah, B.; Wang, Y.; Chan, C.-Y.; Fei, B.; Pan, F., Recent advances in zinc anodes for high-performance aqueous Zn-ion batteries. Nano Energy 2020, 70. Yang, J.; Yin, B.; Sun, Y.; Pan, H.; Sun, W.; Jia, B.; Zhang, S.; Ma, T., Zinc Anode for Mild Aqueous Zinc-Ion Batteries: Challenges, Strategies, and Perspectives. Nanomicro Lett 2022, 14 (1), 42. Yang, Q.; Li, Q.; Liu, Z.; Wang, D.; Guo, Y.; Li, X.; Tang, Y.; Li, H.; Dong, B.; Zhi, C., Dendrites in Zn-Based Batteries. Adv Mater 2020, 32 (48), e2001854. Acknowledgment This work was partially supported by the U.S. National Science Foundation (NSF) Award No. ECCS-1931088. S.L. and H.W.S. acknowledge the support from the Improvement of Measurement Standards and Technology for Mechanical Metrology (Grant No. 22011044) by KRISS. Figure 1

Abstract Background: The type 1/2 BRAF inhibitors (e.g., vemurafenib) have been used for patients with BRAFV600E-mutant tumors. But the application of the inhibitors was restricted to a few types of tumors (e.g., melanoma). Common adverse effects such as pruritus and skin papilloma have limited the usage. It could be attributed to the paradoxical activation of the MAPK pathway. The paradoxical activation also leads to tumor promotion in BRAF wild-type melanoma and skin toxicity in 30%-70% patients with KRAS mutations. Therefore, development of type II pan-RAF inhibitors which avoid MAPK paradoxical activation is necessary. Methods: The selective pan-RAF inhibitor QLH11906 was tested on A/B/C RAF kinases and a representative kinase panel. Both 2D and 3D proliferation studies were conducted for cell lines with BRAF and various KRAS mutations, followed by both immunoprecipitation and ERK phosphorylation assays to elucidate the mode of action. Combination studies with MEK inhibitors were implemented in both KRAS-mutant cell lines and BRAF/KRAS-mutant patient derived organoids (PDO). Single-agent and combination studies were also carried out in vivo on both BRAF/KRAS-mutant cell line-derived xenograft (CDX) and KRAS-mutant patient-derived xenograft (PDX) models. Results: QLH11906 inhibited wild-type A/B/C RAF and BRAFV600E with the IC50 of 4.9, 1.9, 0.5, and 1.1 nM, respectively, and showed no inhibition at 1 μM in a selectivity panel of 28 kinases except for DDR1 and DDR2. Under 2D culture condition, QLH11906 inhibited proliferation of various BRAF/KRAS-mutant cell lines (IC50 300-1700 nM) and suppressed ERK phosphorylation (IC50 20-600 nM). In 3D cultures, QLH11906 showed higher activity in proliferation suppression in both HCT116 (KRASG13D, IC50 24 nM 3D vs 1186 nM 2D) and Calu-6 (KRASQ61K, IC50 85 nM 3D vs 1411 nM 2D). In immunoprecipitation studies with HCT116 and Calu-6 cells, both BRAF homodimers and BRAF/CRAF heterodimers could be detected under the treatment of QLH11906. QLH11906 showed synergistic effect when combined with MEK inhibitors trametinib or cobimetinib in KRAS-mutant cell lines, including A549 (KRASG12S), Calu-6, HCT116, NCIH2122 (KRASG12C) and Panc1005 (KRASG12D), and 77%-99% tumor suppression was reached at the expected clinical Ctrough concentrations. Synergistic effects with trametinib were observed in PDO models including pancreatic cancers (KRASG12D and KRASG12V), colon cancers (KRASG12D and KRASG13D) and lung cancers (KRASG12V). QLH11906 also promoted tumor shrinkage in vivo as a single agent in Calu-6, HCT116, and Colo-205 (BRAFV600E) CDX models or combined with trametinib in PDX models (KRASG12C lung cancers and KRASG12C colon cancers) Conclusion: QLH11906 is a highly selective pan-RAF inhibitor with promising antitumor activity both in vitro and in vivo. It is hopeful to be a therapeutic agent for BRAF and KRAS-mutant tumor patients. Citation Format: Zhe Cheng, Fei Chen, Xile Liu, Cong Gao, Linchao Jia, Yuanzhi Lao. Preclinical characterization of QLH11906, a novel pan-RAF inhibitor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5460.

Abstract Background: Morpho-physiological alternations of platelets provided a rationale to harness RNA sequencing of tumor-educated platelets (TEPs) for preoperative diagnosis of cancer. Timely, accurate, and non-invasive detection of ovarian cancer in women with adnexal masses presents a significant clinical challenge. Patients and Methods: This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n=3; Netherlands, n=5; Poland, n=1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. Results: The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. Analysis of public datasets suggested that TEPs had potential to detect multiple malignancies (Table 1). Conclusions: TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, early-stage ovarian cancer as well as other malignancies. However, these observations warrant prospective validations in a larger population before clinical utilities. Table 1. Performance for TEPs in public pan-cancer datasets. Disease n Healthy Control AUC, area under the curve (95% CI) Women NSCLC (non-small-cell lung cancer) 126 77 0.758 (0.691-0.825) Breast cancer 38 77 0.817 (0.726-0.909) Colorectal cancer 18 77 0.973 (0.945-1.000) Pancreatic cancer 16 77 0.993 (0.981-1.000) Glioblastoma 10 77 0.923 (0.831-1.000) Men NSCLC 119 82 0.746 (0.677-0.815) Colorectal cancer 25 82 0.933 (0.884-0.982) Pancreatic cancer 22 82 0.993 (0.984-1.000) Glioblastoma 19 82 0.981 (0.959-1.000) All NSCLC 245 159 0.774 (0.728-0.820) Colorectal cancer 40 159 0.978 (0.961-0.996) Breast cancer 38 159 0.821 (0.736-0.906) Pancreatic cancer 35 159 0.987 (0.974-0.999) Glioblastoma 35 159 0.931 (0.890-0.972) Hepatobiliary carcinomas 14 159 0.991 (0.978-1.000) Citation Format: Yue Gao, Chun-Jie Liu, Hua-Yi Li, Xiao-Ming Xiong, Sjors G.j.g. In ‘t Veld, Gui-Ling Li, Jia-Hao Liu, Guang-Yao Cai, Gui-Yan Xie, Shao-Qing Zeng, Yuan Wu, Jian-Hua Chi, Qiong Zhang, Xiao-Fei Jiao, Lin-Li Shi, Wan-Rong Lu, Wei-Guo Lv, Xing-Sheng Yang, Jurgen M.j. Piek, Cornelis D de Kroon, C.a.r. Lok, Anna Supernat, Sylwia Łapińska-Szumczyk, Anna Łojkowska, Anna J. Żaczek, Jacek Jassem, Bakhos A. Tannous, Nik Sol, Edward Post, Myron G. Best, Bei-Hua Kong, Xing Xie, Ding Ma, Thomas Wurdinger, An-Yuan Guo, Qing-Lei Gao. Platelet RNA signature enables early and accurate detection of ovarian cancer: An intercontinental, biomarker identification study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB168.

Background:Baricitinib (BARI) is a JAK1/JAK2 inhibitor which provides improvements to clinical signs, symptoms, and patient-reported outcomes (PROs) in patients with rheumatoid arthritis [1, 2].Objectives:The effect of BARI on the relationship between disease activity and pain has been explored previously [3]. The purpose of this post hoc analysis was to determine the association between additional PROs (physical function, fatigue, and duration of morning joint stiffness) and disease activity status after 12 weeks of treatment and to evaluate whether patients with an inadequate response to methotrexate treated with BARI 4 mg experienced greater PRO improvement than patients treated with either placebo (PBO) or adalimumab (ADA) across all levels of disease activity.Methods:Data for these analyses were derived from the Phase 3 study RA-BEAM (N=1305; NCT01710358). Pain was evaluated using a 0-100 mm visual analog scale, physical function was assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI), fatigue was measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale, and duration of morning joint stiffness (MJS, minutes) was reported by the patient. Disease activity was measured using the Clinical Disease Activity Index (CDAI) and categorized as remission (REM, ≤2.8), low disease activity (LDA, >2.8 to ≤10), moderate disease activity (MDA, >10 to ≤22), or high disease activity (HDA, >22). Linear regression was used to model the relationship between change in PROs at Week 12 (response) and CDAI values at Week 12 (primary explanatory variable) to evaluate the extent of improvement in PROs with BARI relative to PBO and ADA across a spectrum of disease activity levels. Last observation carried forward was used to impute missing values.Results:At baseline, 91% of patients were classified as having HDA and 9% as having MDA by CDAI across all treatment groups. After 12 weeks of treatment, 2%, 7%, and 9% of patients achieved REM; 16%, 27%, and 33% of patients achieved LDA; and 33%, 40%, and 38% of patients achieved MDA with PBO, ADA, and BARI, respectively [3].At Week 12, the estimated changes in measures of pain and physical function, as well as duration of MJS, for BARI 4 mg were greater than both PBO and ADA at all disease activity level threshold values of CDAI (Table 1). The estimated change in fatigue for BARI 4 mg was similar to that of ADA, and greater than PBO, at all disease activity level threshold values (Table 1).Table 1.Estimate of PRO Improvement by Disease Activity Threshold Level (CDAI) at Week 12PROCDAI=2.8CDAI=10CDAI=22PBOADABARI4 mgPBOADABARI 4 mgPBOADABARI 4 mgPain VASa(mm)-28.4-37.9-40.9-24.5-32.6-36.1-18.0-23.7-28.1HAQ-DIb-0.6-0.7-0.9-0.5-0.7-0.7-0.4-0.5-0.6FACIT-Fc9.811.811.18.810.610.27.08.78.7Duration of MJS (min)-6.9-37.8-64.9-6.3-35.3-55.7-5.3-31.3-40.2aPain VAS scores range from 0 (no pain) to 100 (worst pain).bHAQ-DI scores range from 0 (no disability) to 3 (completely disabled).cFACIT-F scores range from 0 (worst fatigue) to 52 (no fatigue).Abbreviations: ADA, adalimumab; BARI, baricitinib; CDAI, Clinical Disease Activity Index; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; HAQ-DI, Health Assessment Questionnaire-Disability Index; MJS, morning joint stiffness; PBO, placebo; PRO, patient-reported outcomes; VAS, visual analog scale.Conclusion:Estimates of treatment differences suggest that patients treated with BARI 4 mg may experience greater improvements in pain, physical function, and MJS duration than patients treated with PBO or ADA regardless of their disease activity status reached after 12 weeks of treatment. Using this approach, improvements in fatigue with BARI 4 mg may be greater than with PBO and similar to ADA after 12 weeks.References:[1]Taylor, P.C., et al., N Engl J Med, 2017. 376(7): p. 652-662.[2]Keystone, E.C., et al., Ann Rheum Dis, 2017. 76(11): p. 1853-1861.[3]Taylor, P., et al., Arthritis Rheumatol, 2019. 71(S10): p. 2455-2457.Acknowledgements:The authors would like to acknowledge Catherine Lynch, with Eli Lilly and Company, for medical writing and project management support.Disclosure of Interests:Peter C. Taylor Consultant of: AbbVie, Biogen, Galapagos, Gilead, GlaxoSmithKline, Janssen, Eli Lilly, BMS, Pfizer, Roche, Celltrion, Sanofi, Nordic Pharma, Fresenius and UCB, Grant/research support from: Celgene, Galapagos, Gilead, Eli Lilly, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, BMS, Janssen, Eli Lilly and MSD, Consultant of: Abbvie, Pfizer, Roche, BMS, Janssen, Eli Lilly and MSD, Grant/research support from: Abbvie, MSD, and Roche, Kei Ikeda Speakers bureau: Eli Lilly, Abbvie, Mitsubishi-Tanabe, Novartis, Paid instructor for: Abbvie, Grant/research support from: Mitsubishi-Tanabe, Bochao Jia Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Yun-Fei Chen Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Chad Walls Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Ewa Haladyj Employee of: Eli Lilly and Company, Bruno Fautrel Speakers bureau: Eli Lilly, Consultant of: AbbVie, Biogen, Bristol-Myers Squibb, Celgene, Janssen Pharmaceuticals, Eli Lilly and Company, Medac, MSD, NORDIC Pharma, Novartis, Pfizer Inc., Roche, Sanofi-Aventis, SOBI, UCB, Grant/research support from: AbbVie, Eli Lilly and Company, MSD, Pfizer Inc

In the current study, methanolic and selective extracts from different parts of Gymnocarpos decander were screened for total phenolic, flavonoid, flavonol and condensed tannin contents. The antioxidant activity of extracts was also determined. The highest values of total contents of phenolics (156.097 ± 2.312 mg GAE/g DM), flavonoids (14.878 ± 0.275 mg CE/g DM), condensed tannins (39.388 ± 1.599 mg CE/g DM) and flavonols (6.506 ± 1.021 mg QE/g DM) were found in flowers. The most powerful antioxidant was found in the methanolic extract of flowers (32.27 ± 2.400 mg AAE/g DM). Tannins extracted from flowers showed an interesting antioxidant activity to trap the 1,1-Diphenyl- 2-picrylhydrazyl (DPPH) free radical (0.063 ± 0.000 mg/mL) and to reduce iron absorption (0.083 ± 0.004 mg/mL). The highest activity in the β-carotene test was found in the butanolic fraction of flowers (0.314 ± 0.008 mg/mL). 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