Academic literature on the topic 'Nong yi shi'

ABSTRACTWe explore the meaning of parochialism (xiao nong yi shi, 小农意识) to explain certain paradoxical Chinese managerial behaviors. We discuss how cultural, political, and economic traditions in China formed a salient context to cultivate parochialism. Qualitative data from Chinese and American managers reveal that the conceptual framework of parochialism includes a cognitive dimension of closed-mindedness, a behavioral dimension of self-protection, and a relational dimension of in-group focused social relationship. Parochialism hampers effective globalization of Chinese firms because it negatively impacts key facets of organizational culture: employee development, communication, customer orientation, social responsibility, strategic planning, and innovation. The study offers theoretical and practical implications for Chinese management research and the development of global competence.

Abstract Background: KRASG12C mutation acts as an oncogenic driver and occurs in ~15% of NSCLC. D-1553 is a novel and potent small molecule inhibitor of KRASG12C. Here we present the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of D-1553 in KRASG12C mutated NSCLC. Methods: Key inclusion criteria: KRASG12C identified by molecular testing, and after progression of standard therapy. Oral daily (QD) doses of 600, 800 and 1200 mg, and twice daily (BID) doses of 400 and 600 mg were assessed in dose escalation part; 600 mg BID was assessed in dose expansion part. Endpoints included safety, PK parameters, objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and duration of response (DOR), evaluated by RECIST 1.1. Efficacy results included 6 NSCLC pts from dose escalation part of another Phase I study of D-1553 [NCT04585035] with similar inclusion/exclusion criteria as this study. Results: As of Dec 27, 2021, 16 pts with NSCLC (15 [93.8%] male, median age 61 [range: 30-74]) were enrolled in dose escalation part and 8 pts were evaluated in dose expansion part. D-1553 was well absorbed, with a median time to reach tmax in 1-4 hours. The Cmax and AUC of each dose group tested (400 mg and 600 mg, BID) increased linearly as the dose increased. However, the changes of Cmax and AUC in 600, 800 and 1200 mg (QD) group were not dose-dependent. No DLTs had been reported in dose escalation part. 15 pts (93.8%) had treatment-related adverse events (TRAEs), most of which were grade 1-2. The most frequently reported TRAEs (frequency ≥ 15%) were elevated alanine aminotransferase, aspartate aminotransferase and conjugated bilirubin, rash, anemia, asthenia, decreased appetite, hyperuricemia, and increased γ-glutamyltransferase. Among the 28 pts (including 14 pts from dose escalation, 8 pts from dose expansion, and 6 pts with NSCLC from another D-1553 study) evaluable for tumor response, 12 pts had partial response (PR), and 14 had stable disease (SD). ORR and DCR were 42.9% (12/28) and 92.9% (26/28), respectively. Among the 11 pts in 600 mg BID group, 6 pts had PR, and 3 had SD. ORR and DCR were 54.5% (6/11,) and 81.8% (9/11), respectively. Most of the patients with PR or SD were continuing on study at the time of the data cut-off. Conclusion: D-1553 is well tolerated with no DLTs at studied doses. Early results demonstrate significant anti-tumor activity of single-agent D-1553 in pts with KRASG12C mutated NSCLC. This study is ongoing. More results will be presented at the meeting. Citation Format: Hong Jian, Zhenbo Song, Yiping Zhang, Kunyan Li, Nong Yang, Melissa Moore, Pingli Wang, Yanqiu Zhao, Yi Gong, Craig Underhill, Sang-We Kim, Cheng-Ta Yang, Ziyong Xiang, Zhe Shi, Ling Zhang, Yaolin Wang, Shun Lu. Phase I study of D-1553 to assess safety and efficacy in patients with non-small cell lung cancer (NSCLC) harboring KRASG12C mutation [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 CT505.

e16117 Combining radiation therapy with anti-PD-1 for patients with advanced hepatocellular carcinoma: an open-label, single-center, single-arm clinical study Jian-Xu Li, Ting-Shi Su, Xiao-Feng Lin, Yi-Tian Chen, Shi-Xiong Liang, Bang-De Xiang; Guangxi Medical University Cancer Hospital, Nanning, China Abstract Research Funding: Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China. Guangxi Medical and Health Appropriate Technology Development and Application Project (No. S2019039), Guangxi, China. Background: Based on the results of recent studies, the PD-1 monoclonal antibodies have been approved to treat the patients with advanced hepatocellular carcinoma (HCC) by the FDA. Radiation therapy (RT) can enhance responsiveness to PD-1 monoclonal antibody by potential mechanisms. A phase Ⅱa study was conducted to assess the safety and the efficacy of combining RT with anti-PD-1 for patients with advanced hepatocellular carcinoma. Methods: Patients with advanced HCC were eligible. Stereotactic body radiation therapy (SBRT) were adopted, and the dose of radiation were Dt-PGTV 30-50 Gy/10fractions. Camrelizumab (200mg) were given intravenously every 3 weeks since the first day of RT until disease progression, or intolerable toxicity. Adverse events (AEs) and objective response rate (ORR) were summarized to assess the safety and efficacy. Results: From April 2020 to November 2020, 17 patients were enrolled (median age 54, range 32-69). 15 (88%) patients were male. 14 (82%) had ECOG performance score of 0. All the patients had Child-Pugh score A. 16 patients staged as Barcelona Clinic Liver Cancer staging C or China Liver Cancer staging Ⅲ. Extrahepatic metastases were identified in 11 (65%) patients. 13 (77%) patients were Hepatitis B virus infected. 15 (88%) patients had previously 2 lines or more chemotherapy. 9 (53%) patients had Alpha-fetoprotein level≥400 ng/ml. The ORR was 47%. The best response assessed by RECIST 1.1 was partial response (8 patients). Four patients had grade 3 immune-related adverse events (irAEs), including increased aspartate aminotransferase and alanine transaminase (n =1)，decreased hemoglobin (n =1)，decreased platelet count (n =1)，decreased neutrophil count (n =1). All grade 3 irAEs were mitigated with proper treatment. None treatment-related deaths occurred. Conclusions: In this study, RT combined with anti-PD-1 had an acceptable safety profile and indicated an effective treatment option in patients with unresectable HCC. Clinical trial information: NCT04193696. Clinical trial information: NCT04193696.

BackgroundSome studies demonstrated that withdrawal of low-dose glucocorticoids in clinically quiescent systemic lupus erythematosus (SLE) patients increased the risk of flare [1]. An international survey of 130 clinicians showed that persistent abnormal serology led to a reluctance to reduce or discontinue medications [2].ObjectivesTo assess the risk of flare and damage accrual after tapering glucocorticoids in serologically active clinically quiescent (SACQ) patients with SLE. Association of other medications with flare in SACQ patients was also analyzed.MethodsWe used data from the Asia Pacific Lupus Collaboration cohort, prospectively collected from SLE patients (ACR/SLICC criteria) observed for at least 2 visits between 2013 and 2020. Disease activity and medication details were captured at enrolment and at routine visits. SACQ was defined at any visit as the state with serological activity (increased anti-dsDNA or hypocomplementemia) but without clinical activity as measured by SLEDAI-2K. Patients treated with 0 to 7.5 mg/day of prednisolone at a SACQ visit were analyzed after stratification according to the initial dosages of prednisolone. Cox proportional hazard models were used to assess the time-dependent relationship between decreasing prednisolone in SACQ patients and disease flares captured with the SELENA flare index at each subsequent visit, as well as subsequent damage accrual (≥1-point increase in SLICC/ACR damage index [SDI]). Each patient was observed for up to 2 years or until each outcome event occurred.ResultsFrom a total of 4,106 patients, 1,850 patients with SACQ and 8,905 visits were analyzed: 742, 271, and 180 patients experienced overall flare, severe flare, and increase in SDI, respectively. Tapering prednisolone was not associated with subsequent overall or severe flare: Each unit decrease in prednisolone dosage (1 mg/day) resulted in adjusted HRs 1.02 (95%CI, 0.99–1.05) and 0.98 (95%CI, 0.96–1.00) for overall and severe flare, respectively, in the group with initial prednisolone dosages of 0–7.5 mg/day. However, among SACQ patients, antimalarial use was significantly associated with reduced overall and severe flare in the groups with initial prednisolone of 0–7.5 or 0–5 mg/day. In addition, immunosuppressive use was significantly associated with reduced severe flare but not overall flare in these groups. Decreasing the dosage of prednisolone was significantly negatively associated with damage accrual in the groups with initial prednisolone dosages of 0–7.5 mg/day (adjusted HR [95%CI], 0.97 [0.96–0.99]) and 5–7.5 mg/day (adjusted HR [95%CI], 0.96 [0.94–0.99]) but not 0–5 mg/day (adjusted HR [95%CI], 0.98 [0.95–1.01]).Table 1.Summary results of association between decreasing the prednisolone dosages and disease flares or damage accrual in SLE patients with SACQInitial prednisolone dosage (mg/day)Overall disease flareSevere disease flareIncrease in SDI0 ≤ prednisolone ≤7.51.02 (0.99–1.05),p= 0.270.98 (0.96–1.00),p= 0.110.97 (0.96–0.99),p< 0.010 ≤ prednisolone ≤51.02 (0.98–1.06),p= 0.410.98 (0.96–1.01),p= 0.280.98 (0.95–1.01),p= 0.145 < prednisolone ≤7.51.01 (0.96–1.06),p= 0.840.98 (0.92–1.03),p= 0.410.97 (0.96–0.99),p< 0.01* HRs (95% CIs) per unit decrease in prednisolone dosages (1 mg/day) were calculated using Cox proportional hazard models and adjusted by initial prednisolone dosage, antimalarial, immunosuppressive, disease duration, SLEDAI-2K, age at visit, gender, and ethnicity.ConclusionTapering prednisolone was not significantly associated with subsequent flare in SLE patients who were SACQ. Antimalarial and immunosuppressive use were associated with reduced risk of flares in SACQ patients. Tapering prednisolone was associated with reduced risk of damage accrual in SACQ patients treated with more than 5 mg/day of prednisolone. These findings suggest glucocorticoid tapering is safe and protective in SLE patients in SACQ.References[1]Rheumatology (Oxford). 2021;60:5517[2]Lupus Sci Med. 2017;4:e000173AcknowledgementsWe acknowledge the unrestricted project grants received from AstraZeneca, BMS, Eli Lilly, GSK, Janssen, Merck Serono, and UCB to support data collection and project management contributing to this work.Disclosure of InterestsYasuhiro Katsumata Speakers bureau: GlaxoSmithKline K.K., AstraZeneca K.K., Sanofi K.K., Pfizer Japan Inc., Janssen Pharmaceutical K.K., Chugai Pharmaceutical Co., Ltd.Asahi Kasei Pharma, Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Eisuke Inoue Speakers bureau: Bristol-Myers Squibb K.K., Eisai Co., Ltd., Consultant of: Nippontect Systems co., Ltd., Masayoshi Harigai Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., Teijin Pharma Ltd., Consultant of: AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. Teijin Pharma, Grant/research support from: AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei.Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi & Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Teijin.Pharma Ltd., Rangi Kandane-Rathnayake: None declared, Worawit Louthrenoo: None declared, Alberta Hoi Speakers bureau: UCB, Janssen, Sandoz, Eli Lilly, Consultant of: Abbvie, GSK, Grant/research support from: AstraZeneca, GSK, BMS, Janssen, Merck Serono, Vera Golder: None declared, C.S. Lau Speakers bureau: AstraZeneca UK Ltd., Consultant of: AstraZeneca Pharmaceuticals LP, Jiacai Cho: None declared, Aisha Lateef: None declared, Yi-Hsing Chen: None declared, Shue Fen Luo: None declared, Yeong-Jian Jan Wu: None declared, Laniyati Hamijoyo: None declared, Zhanguo Li Consultant of: Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma, Grant/research support from: Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma, Sargunan Sockalingam Consultant of: Pfizer, AstraZeneca, ZP Therapeutics, Grant/research support from: Pfizer, AstraZeneca, ZP Therapeutics, Sandra Navarra Consultant of: Biogen, Boehringer Ingelheim, Astra Zeneca, Grant/research support from: Jannsen, Novartis, Pfizer, Glaxo Smith Kline, Leonid Zamora: None declared, Yanjie Hao: None declared, Zhuoli Zhang: None declared, Madelynn Chan: None declared, Shereen Oon: None declared, Kristine Ng Consultant of: AbbVie, Jun Kikuchi: None declared, Tsutomu Takeuchi Consultant of: AbbVie, Chugai, Mitsubishi-Tanabe, Grant/research support from: AbbVie, Mitsubishi-Tanabe, Eli Lilly Japan, Fiona Goldblatt: None declared, Sean O’Neill: None declared, Nicola Tugnet: None declared, Annie Law: None declared, Sang-Cheol Bae: None declared, Yoshiya Tanaka Speakers bureau: Behringer-Ingelheim, Eli Lilly, Abbvie, Gilead, AstraZeneca, Bristol-Myers, Chugai, Daiichi-Sankyo, Eisai, Pfizer, Mitsubishi-Tanabe, GlaxoSmithKline, Grant/research support from: Asahi-Kasei, Abbvie, Chugai, Eisai, Takeda, Daiichi-Sankyo, Behringer-Ingelheim, Naoaki Ohkubo: None declared, Sunil Kumar: None declared, Mandana Nikpour Speakers bureau: Actelion, GSK, Janssen, Pfizer, UCB, Paid instructor for: UCB, Consultant of: Boehringer Ingelheim, Certa Therapeutics, Eli.Lilly, GSK, Janssen, Pfizer, UCB, Grant/research support from: Actelion, Astra Zeneca, BMS, GSK, Janssen, UCB, Eric F. Morand Speakers bureau: AstraZeneca, EMD Serono, Gilead, Consultant of: AstraZeneca, BristolMyersSquibb, Biogen, Eli Lilly, EMD Serono, Novartis, Grant/research support from: AbbVie, Amgen, AstraZeneca, BristolMyersSquibb, Biogen, Eli Lilly, EMD Serono, Genentech, GSK, Janssen, UCB.

BackgroundSystemic sclerosis (SSc) patients often become refractory to proton pump inhibitor (PPI)—a standard treatment for gastroesophageal reflux disease (GERD)—and intolerant to PPI in combination with domperidone. PPI with alginic acid is an alternative treatment option, but alginic acid is costly.ObjectivesWe compared the costs and effectiveness of alginic acid plus proton pump inhibitor (PPI) versus standard treatments (PPI with/without antacids as needed and lifestyle modifications) for gastroesophageal reflux disease (GERD) in systemic sclerosis (SSc) patients unsuitable for, or intolerant to, domperidone.MethodsAn economic evaluation using the Markov model was conducted among SSc patients between 40 and 65 with GERD, having a partial or non-response to 4 weeks of standard-dose omeprazole (40 mg/d) and being unsuitable for or intolerance to domperidone. Using a societal perspective, we computed the incremental cost-effectiveness ratios (ICERs) in terms of Thai baht (THB) per quality-adjusted life-years (QALY) between a combination of alginic acid plus PPI and standard treatment for GERD. The lifetime time horizon was used.ResultsThe ICER for alginic acid plus PPI versus standard treatments was 377,101THB/QALY. According to the one-way sensitivity analysis, the cost of alginic acid was the most impactful parameter. If the market prices of alginic acid plus PPI were reduced by 61%, this treatment option would become cost-effective at the willingness-to-pay threshold of 160,000THB/QALY (34.71 THB/USD data on 3 December 2022). Furthermore, if alginic acid were included in the public health insurance program, the national budget would be increased by 66,313THB per patient resulting in an overall budget increase of 5,106,101 to 8,885,942THB compared to the standard treatment.ConclusionAlginic acid plus PPI does not represent good value for money compared to the standard treatment among such SSc patients in Thailand unless its price is reduced significantly.References[1]Foocharoen C, Peansukwech U, Mahakkanukrauh A, Suwannaroj S, Pongkulkiat P, Khamphiw P, et al. Clinical characteristics and outcomes of 566 Thais with systemic sclerosis: A cohort study. Int J Rheum Dis 2020;23:945–57.[2]Chunlertrith K, Noiprasit A, Foocharoen C, Mairiang P, Sukeepaisarnjaroen W, Sangchan A, et al. GERD questionnaire for diagnosis of gastroesophageal reflux disease in systemic sclerosis. Clin. Exp. Rheumatol. 2014;32:S-98-102.[3]Foocharoen C, Chunlertrith K, Mairiang P, Mahakkanukrauh A, Suwannaroj S, Namvijit S, et al. Prevalence and predictors of proton pump inhibitor partial response in gastroesophageal reflux disease in systemic sclerosis: a prospective study. Sci Rep 2020;10:769.[4] Foocharoen C, Chunlertrith K, Mairiang P, Mahakkanukrauh A, Suwannaroj S, Namvijit S, et al. Effectiveness of add-on therapy with domperidone vs alginic acid in proton pump inhibitor partial response gastro-oesophageal reflux disease in systemic sclerosis: randomized placebo-controlled trial. Rheumatology (Oxford) 2017;56:214–22.[5] Lei WY, Chang WC, Wen SH, Yi CH, Liu TT, Hung JS, et al. Predicting factors of recurrence in patients with gastroesophageal reflux disease: a prospective follow-up analysis. Therap Adv Gastroenterol 2019;12:1756284819864549.[6] Teerawattananon Y, Chaikledkaew U. Thai health technology assessment guideline development. J Med Assoc Thai 2008;91 Suppl 2:S11-15.[7] BOI: The Board of Investment of Thailand [Internet]. [cited 2022 Apr 19];Available from:https://www.boi.go.th/index.php?page=demographic.[8] Nimdet K, Ngorsuraches S. Willingness to pay per quality-adjusted life year for life-saving treatments in Thailand. BMJ Open 2015;5:e008123.Acknowledgements:NIL.Disclosure of InterestsChingching Foocharoen Speakers bureau: Boehringer Ingelheim, Norvatis, Janssen, Pritaporn Kingkaew: None declared, Yot Teerawattananon: None declared, Ajanee Mahakkanukrauh: None declared, Siraphop Suwannaroj: None declared, Witsarut Manasirisuk: None declared, Jitjira Chaiyarit: None declared, Apichat Sangchan: None declared.

Background:The recent prospectively validated definition of the lupus low disease activity state (LLDAS) allows characterisation of patients not achieving a treatment goal, providing impetus for an analysis of unmet needs in SLE using formal definitions. Other recently described definitions of high disease burden include disease activity over time, high disease activity status (HDAS) episodes, and the combination of high disease activity, serological activity and glucocorticoid (GC) use (HDAS+SA+GC).Objectives:To determine the prevalence of formal categories of unmet need, and the association of these with adverse outcomes, in SLE.Methods:Data from a 13-country longitudinal SLE cohort (ACR/SLICC criteria) were collected between 2013 and 19 using standard templates. Unmet need was defined as (i) patients never attaining LLDAS defined as in Golder et al., 2019 [1], (ii) having persistently active disease (time adjusted mean SLEDAI-2K (AMS) > 4), (iii) ever exhibiting high disease activity status (HDAS; SLEDAI-2K ≥10[2]), or (iv) ever exhibiting all of SLEDAI≥10, serological activity, and glucocorticoid use (HDAS+SA+GC)[3]. Health-related quality of life (HRQoL) was assessed using SF36 (v2) surveys and damage accrual using SLE Damage Index (SDI).Results:3,384 SLE patients were followed for 30,313 visits over median [IQR] 2.4 [0.4, 4.3] years. 53% of all visits were not in LLDAS; 813 patients (24%) never achieved LLDAS during observation. Median AMS was 3.0 [1.4, 4.9] and 34% of patients had AMS > 4 throughout the study. 25% of patients had at least one episode of HDAS, representing 8% of visits. 702 patients (21%) had at least one episode of HDAS+SA+GC, representing 8% of visits. Each of never-LLDAS, AMS>4, ever-HDAS, and ever-HDAS+SA+GC were associated with significantly greater number of physician visits, higher mean glucocorticoid dose, lower HRQoL and higher mortality. 31%, 58% and 83% of never-LLDAS, AMS>4, and ever-HDAS patients respectively were also HDAS+SA+GC on at least one occasion.Conclusion:Data from a multinational longitudinal SLE cohort indicate that unmet need, defined by LLDAS-never, AMS>4, HDAS, or HDAS+SA+GC, is prevalent in SLE, and that these definitions are associated with poor outcomes.References:[1]Golder, V., et al., Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study. The Lancet Rheumatology, 2019. 1(2): p. e95-e102.[2]Koelmeyer, R., et al., High disease activity status suggests more severe disease and damage accrual in systemic lupus erythematosus. Lupus Sci Med, 2020. 7(1).[3]van Vollenhoven, R.F., et al., Belimumab in the treatment of systemic lupus erythematosus: high disease activity predictors of response. Annals of the Rheumatic Diseases, 2012. 71(8): p. 1343-1349.Acknowledgements:The APLC acknowledges all the Data Collectors and Patients for their valuable contributions to research.Disclosure of Interests:Rangi Kandane-Rathnayake: None declared, Worawit Louthrenoo: None declared, Alberta Hoi Consultant of: Abbvie and GSK, Grant/research support from: AstraZeneca, GSK, BMS, Janssen, and Merck Serono, Vera Golder: None declared, Yi-Hsing Chen Speakers bureau: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, AstraZeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Consultant of: Pfizer, Novartis, Abbvie, Johnson & Johnson, BMS, Roche, Lilly, AstraZeneca, Sanofi, MSD, Guigai, Astellas, Inova Diagnostics, UCB, Agnitio Science Technology, United Biopharma, Thermo Fisher, Gilead, Grant/research support from: Pfizer, Norvatis, BMS, Abbevie, Johnson & Johnson, Roche, Sanofi, Guigai, Roche, Boehringer Ingelheim, UCB, MSD, Astra-Zeneca, Astellas, Gilead, Shue Fen Luo: None declared, Yeong-Jian Jan Wu Speakers bureau: Pfizer, Lilly, Novartis, Abbvie, Aisha Lateef: None declared, Jiacai Cho: None declared, Laniyati Hamijoyo Speakers bureau: Pfizer, Novartis, Abbot, Chak Sing Lau Shareholder of: Pfizer, Sanofi, and Janssen, Sandra Navarra Speakers bureau: Pfizer, Johnson & Johnson, Novartis, Astellas, Grant/research support from: Astellas, Johnson & Johnson, Leonid Zamora: None declared, Zhanguo Li Speakers bureau: Eli, Lilly, Novartis, GSK, AbbVie, Paid instructor for: Pfizer, Roche, Johnson., Consultant of: Lilly, Pfizer, Grant/research support from: Pfizer, Yuan An: None declared, Sargunan Sockalingam Speakers bureau: Pfizer, Roche, Novartis, Grant/research support from: Roche and Novartis, Yasuhiro Katsumata Speakers bureau: Chugai Pharmaceutical Co., Ltd., Glaxo-Smithkline K.K., and Sanofi K.K., masayoshi harigai Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Consultant of: AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma., Grant/research support from: AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi & Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Yanjie Hao: None declared, Zhuoli Zhang Speakers bureau: Norvatis, GSK, Pfizer, Jun Kikuchi: None declared, Tsutomu Takeuchi Speakers bureau: AbbVie AYUMI Pharmaceutical Corp. Bristol-Myers Squibb Chugai Pharmaceutical Co, Ltd. Daiichi Sankyo Co., Ltd. Eisai Co., Ltd. Eli Lilly Japan, Gilead Sciences, Inc. Mitsubishi-Tanabe Pharma Corp. Pfizer Japan Inc. Sanofi K.K., Consultant of: Astellas Pharma, Inc. Chugai Pharmaceutical Co, Ltd. Eli Lilly Japan, Mitsubishi-Tanabe Pharma Corp., Grant/research support from: AbbVie, Asahikasei Pharma Corp. Chugai Pharmaceutical Co, Ltd. Mitsubishi-Tanabe Pharma Corp. Sanofi K.K., BMDB Basnayake: None declared, Fiona Goldblatt: None declared, Madelynn Chan Speakers bureau: AbbVie, Novartis, Consultant of: Pfizer, Eli-Lilly, Kristine Ng Speakers bureau: Abbvie, Novartis, Janssen, Sang-Cheol Bae: None declared, Shereen Oon: None declared, Sean O’Neill Consultant of: GSK, Kathryn Gibson Speakers bureau: UCB, Consultant of: Novartis, Janssen, Grant/research support from: Novartis, Sunil Kumar: None declared, Nicola Tugnet: None declared, Yoshiya Tanaka Speakers bureau: Daiichi-Sankyo, Eli Lilly, Novartis, YL Biologics, Bristol-Myers, Eisai, Chugai, Abbvie, Astellas, Pfizer, Sanofi, Asahi-kasei, GSK, Mitsubishi-Tanabe, Gilead, Janssen, Grant/research support from: Abbvie, Mitsubishi-Tanabe, Chugai, Asahi-Kasei, Eisai, Takeda, Daiichi-Sankyo, Mandana Nikpour Speakers bureau: Actelion, GSK, Janssen, Pfizer, UCB, Paid instructor for: UCB, Consultant of: Actelion, Boehringer Ingelheim, Certa Therapeutics, Eli Lilly, GSK, Janssen, Pfizer, UCB, Grant/research support from: Actelion, Astra Zeneca, BMS, GSK, Janssen, UCB, Eric F. Morand Speakers bureau: AstraZeneca, Paid instructor for: Eli Lilly, Consultant of: AstraZeneca, Amgen, Biogen, BristolMyersSquibb, Eli Lilly, EMD Serono, Genentech, Janssen, Grant/research support from: AstraZeneca, BristolMyersSquibb, Eli Lilly, EMD Serono, Janssen.

BackgroundThe lupus low disease activity state (LLDAS) treat-to-target definition sets a ceiling for acceptable disease and treatment burden in SLE. Definition of Remission in SLE (DORIS) is a more stringent state, but as it is concentric with LLDAS many patients in LLDAS also meet the DORIS remission definition. Studies in cohorts with a majority of patients in remission poorly separate LLDAS and remission, leading to debate about the independent effects of LLDAS on SLE outcomes.ObjectivesWe examined whether being in LLDAS but not remission provided protection against adverse outcomes of flare, irreversible organ damage accrual and mortality in patients with SLE.MethodsData from a 13-country longitudinal SLE cohort (ACR/SLICC criteria), collected prospectively between 2013 and 2020, were analysed. Organ damage and flare were captured using SLICC Damage Index and SELENA-SLEDAI Flare Index, respectively. LLDAS was defined as Golderet al., 2019 [1] (SLEDAI<4, no new activity, PGA<1, prednisolone (PNL)<7.5 mg/d, antimalarials (AM) and immunosuppressants (IS) allowed). Remission was defined as Vollenhovenet al, 2021 [2] (clinical SLEDAI=0, PGA <0.5, PNL<5 mg/d, AM/IS allowed).Results3,811 patients with ≥ 2 visits followed over a median of 2.8 years [IQR: 1.0 to 5.3] were studied. 80 (2.1%) patients died; 717 (21%) accrued organ damage, and 2,142 (56%) experienced mild-moderate or severe flare during the study period. 55% (n=2,099) attained LLDAS but not remission (LLDAS+REM-) at least once, with a median (IQR) cumulative percent-time spent in LLDAS+REM- of 21.5% [9.8, 42.9]. Overall, 63% attained both LLDAS and remission (LLDAS+REM+) with median (IQR) cumulative time 45% [22, 71]; 18% attained LLDAS+REM-., and 19% of patients never attained LLDAS or REM.Compared to patients who never attained LLDAS or remission (LLDAS-REM-), LLDAS+REM- attainment at any time during the study observation period provided significant protection against subsequent flare and damage accrual, and protection against mortality with borderline statistical significance, after adjusting for potential confounding factors (Table 1). Similarly, ≥50% of cumulative observed time in LLDAS+REM- provided significant protection against flare and damage accrual but not mortality, possibly due to lack of power (Table 1). Protective effects of LLDAS+REM+ were also confirmed.Table 1.Longitudinal associations of LLDAS+REM- attainment with flare, organ damage accrual and mortalityFlaretDamage accrualtMortalitytHR1(95%CI)p-valueHR2(95%CI)p-valueHR3(95%CI)p-valueNot in LLDAS or REMt-11.001.001.00LLDAS+REM-t-10.66 (0.60, 073)p<0.00010.63 (0.52, 0.77)p<0.00010.14 (0.02, 1.07)p=0.059LLDAS+REM+t-10.57 (0.52, 0.61)p<0.00010.46 (0.39, 0.54)p<0.00010.22 (0.08, 0.65)P=0.006<50%T in LLDAS+REM-t-11.001.001.00≥50%T in LLDAS+REM-t-10.71 (0.62, 0.81)p<0.00010.72 (0.56, 0.92)p=0.0100.39 (0.14, 1.10)p=0.08<50%T in LLDAS+REM+t-11.001.001.00≥50%T in LLDAS+REM+t-10.62 (0.56, 0.67)P<0.00010.64 (0.53, 0.76)P<0.00010.53 (0.19, 1.43)p=0.21Hazard ratios adjusted for1age and national gross domestic product (GDP);2age, GDP and baseline organ damage, and3GDP and SDI score. T=time.ConclusionAttainment of LLDAS provides significant protection against flare and organ damage accrual even when excluding patients who are also meet the definition of remission. LLDAS is an independent predictor of improved outcomes in SLE.References[1]Golder V, Kandane-Rathnayake R, Huq M, Nim H, Louthrenoo W, Luo SF, et al. Lupus low disease activity state as a treatment endpoint for systemic lupus erythematosus: a prospective validation study. The Lancet Rheumatology. 2019; 1(2):e95–e102.[2]van Vollenhoven RF, Bertsias G, Doria A, Isenberg D, Morand E, Petri MA, et al. 2021 DORIS definition of remission in SLE: final recommendations from an international task force. Lupus science & medicine. 2021 Nov; 8[1].AcknowledgementsWe acknowledge the unrestricted project grants received from AstraZeneca, BMS, Eli Lilly, GSK, Janssen, Merck Serono, and UCB to support data collection and project management contributing to this work.Disclosure of InterestsRangi Kandane-Rathnayake: None declared, Vera Golder: None declared, Worawit Louthrenoo: None declared, Yi-Hsing Chen: None declared, Jiacai Cho: None declared, Aisha Lateef: None declared, Laniyati Hamijoyo: None declared, Shue Fen Luo: None declared, Yeong-Jian Jan Wu: None declared, Sandra Navarra Consultant of: Biogen, Boehringer Ingelheim, Astra Zeneca, Grant/research support from: Jannsen, Novartis, Pfizer, Glaxo Smith Kline, Pfizer, Leonid Zamora: None declared, Zhanguo Li Consultant of: Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma, Grant/research support from: Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma, Sargunan Sockalingam Consultant of: Pfizer, AstraZeneca, ZP Therapeutics, Grant/research support from: Pfizer, AstraZeneca, ZP Therapeutics, Yasuhiro Katsumata Grant/research support from: GlaxoSmithKline K.K. AstraZeneca K.K. Sanofi K.K. Pfizer Japan Inc., Janssen Pharmaceutical K.K., Chugai Pharmaceutical Co., Ltd., Asahi Kasei Pharma, Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Masayoshi Harigai Speakers bureau: AbbVie Japan GK, Ayumi Pharmaceutical Co., Boehringer Ingelheim Japan, Inc.,Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd, Consultant of: AbbVie, Boehringer-ingelheim, Bristol Myers Squibb Co., Kissei Pharmaceutical Co.,Ltd. and Teijin Pharma, Grant/research support from: AbbVie Japan GK, Asahi Kasei Corp., Astellas Pharma Inc., Ayumi Pharmaceutical Co., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Daiichi-Sankyo, Inc.,Eisai Co., Ltd., Kissei Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Nippon Kayaku Co., Ltd., Sekiui Medical, Shionogi & Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Teijin Pharma Ltd., Yanjie Hao: None declared, Zhuoli Zhang: None declared, BMDB Basnayake: None declared, Madelynn Chan: None declared, Jun Kikuchi: None declared, Tsutomu Takeuchi Consultant of: AbbVie, Chugai, Mitsubishi-Tanabe, Grant/research support from: AbbVie, Mitsubishi-Tanabe, Eli Lilly Japan, Shereen Oon: None declared, Sang-Cheol Bae: None declared, Sean O’Neill: None declared, Fiona Goldblatt: None declared, Kristine Ng Consultant of: AbbVie, Annie Law: None declared, Nicola Tugnet: None declared, Sunil Kumar: None declared, Michael Tee: None declared, Cherica Tee: None declared, Yoshiya Tanaka Speakers bureau: Behringer-Ingelheim, Eli Lilly, Abbvie, Gilead, AstraZeneca, Bristol-Myers, Chugai, Daiichi-Sankyo, Eisai, Pfizer, Mitsubishi-Tanabe, GlaxoSmithKline, Grant/research support from: Asahi-Kasei, Abbvie, Chugai, Eisai, Takeda, Daiichi-Sankyo, Behringer-Ingelheim, C.S. Lau Speakers bureau: AstraZeneca UK Ltd, Consultant of: AstraZeneca Pharmaceuticals LP, Mandana Nikpour Speakers bureau: Actelion, GSK, Janssen, Pfizer, UCB, Paid instructor for: UCB, Consultant of: Boehringer Ingelheim, Certa Therapeutics, Eli Lilly, GSK, Janssen, Pfizer, UCB, Grant/research support from: Actelion, Astra Zeneca, BMS, GSK, Janssen, UCB, Alberta Hoi Speakers bureau: UCB, Janssen, Sandoz, Eli Lilly, Consultant of: Abbvie, GSK, Grant/research support from: AstraZeneca, GSK, BMS, Janssen, and Merck Serono, Eric F. Morand Speakers bureau: AstraZeneca, EMD Serono, Gilead, Consultant of: AstraZeneca, BristolMyersSquibb, Biogen, Eli Lilly, EMD Serono, Novartis, Grant/research support from: AbbVie, Amgen, AstraZeneca, BristolMyersSquibb, Biogen, Eli Lilly, EMD Serono, Genentech, GSK, Janssen, UCB.

Barley cultivation for drought areas requires reliable assessment of drought tolerance variability among the breeding germplasms. Hence, 121 barley landraces, advanced breeding lines and varieties were evaluated under both moisture non-stress and stress field conditions using a lattice square (11×11) design with two replications for each set of trials. Twelve drought tolerance indices (SSI, TOL, MP, GMP, STI, YI, YSI, HM, SDI, DI, RDI and SSPI) were used based on grain yield under normal (Yp) and drought (Ys) conditions. Analysis of variance showed a significant genetic variation among genotypes for all indices with the exception of TOL and SSPI indices. Yp had a very strong association with Ys (r=0.92**) that indicates high yield potential under non-stress can predict better yield under stress conditions. Yp and Ys were positively and significantly correlated with MP, GMP, STI, YI, HM and DI indices, whereas they were negatively correlated with SSI and SDI. In principal component analysis (PCA), the first PC explained 64% of total variation with Yp, Ys, MP, GMP, STI, YI, HM and DI. The second PC explained 35.6% of the total variation and had positive correlation with SSI, TOL, SDI and SSPI. It can be concluded that MP, GMP, STI, YI, HM and DI indices with the most positive and significant correlation with yield at both non-stress and stress environments would be better indices to screen barley genotypes, although none of the indices could undoubtedly identify high yield genotypes under both conditions.

Type 2 diabetes is a fairly common chronic disease. α-glucosidase and protein tyrosine phosphatase, as enzymes, play an important role in type 2 diabetes. This study evaluates the inhibitory effect of the two enzymes in vitro of ethanol extract and fractions of Vietnam Psidium guajava’s leaves. The leaves were collected, dried and extracted with 96% ethanol and successively fractionated with n-hexane, ethyl acetate and butanol solvents. The results show that the EtOH extract, n-nexan, EtOAc and BuOH fractions had high α-glucosidase inhibitory effect with IC50 values ​​of 2.20; 2.53; 2.24 and 2.16 µg/mL, respectively. In addition, EtOAc and BuOH fractions also show strong inhibitory PTP1B effect with IC50 at 120.22 mg/mL and 97.72 mg/mL, respectively. The study results show that Psidium guajava leaves are a potential source of material to inhibit α-glucosidase and PTP1B in the treatment of diabetes. Keywords Psidium guajava, α-glucosidase, protein tyrosine phosphatase 1B, diabetes, extraction. References [1] A. Chaudhury, C. Duvoor, R. Dendi, V. Sena, S. Kraleti, A. Chada, et al. Clinical review of antidiabetic drugs: Implications for type 2 diabetes mellitus management, Frontiers in endocrinology. 8 (2017) 6.[2] F.A. Van de Laar, P.L. Lucassen, R.P. Akkermans, E. H. Van de Lisdonk, G.E. Rutten,C. Van, Alpha - glucosidase inhibitors for type 2 diabetes mellitus. The Cochrane Library (2005).[3] J. Montalibet, B.P. Kennedy. Therapeutic strategies for targeting PTP1B in diabetes. Drug Discovery Today: Therapeutic Strategies 2(2) (2005) 129.[4] S.M. Barbalho, Farinazzi-Machado, R. De Alvares Goulart, A.C.S. Brunnati, A. Otoboni, B. Ottoboni. Psidium guajava (Guava): A plant of multipurpose medicinal applications, Med Aromat Plants. 1(104) (2012) 2167.[5] R.M.P. Gutiérrez, S. Mitchell, Solis R. V. Psidium guajava: a review of its traditional uses, phytochemistry and pharmacology. Journal of ethnopharmacology 117(1) (2008) 1.[6] B. T. Tùng, Đ.K. Thu, P.T. Hải, N.T. Hải. Đánh giá tác dụng ức chế enzym α-glucosidase của các phân đoạn dịch chiết quả Lựu (Punica granatum Linn), Tạp chí Y Dược cổ truyền Việt Nam. 5(18) (2018) 59.[7] P.H. Nguyen, J.L. Yang, M.N. Uddin, S.L. Park, S.I. Lim, D.W. Jung, et al. Protein tyrosine phosphatase 1B (PTP1B) inhibitors from Morinda citrifolia (Noni) and their insulin mimetic activity, Journal of natural products. 76(11) (2013) 2080.[8] H.B.H. Khan, D. Rajendran, M.R. Bai, Sorimuthu S. Protective effect of Psidium guajava leaf extract on altered carbohydrate metabolism in streptozotocin-induced diabetic rats, Journal of dietary supplements. 10(4) (2013) 335.[9] H. Mukhtar, S. Ansari, M. Ali, T. Naved, Z. Bhat Effect of water extract of Psidium guajava leaves on alloxan-induced diabetic rats. Die Pharmazie-An International Journal of Pharmaceutical Sciences. 59(9) (2004) 734.[10] W. K. Oh, C. H. Lee, M. S. Lee, E. Y. Bae, C. B. Sohn, H. Oh, et al. Antidiabetic effects of extracts from Psidium guajava, Journal of ethnopharmacology. 96(3) (2005) 411.[11] B. Wang, H. Liu, J. Hong, H. Li, C. Huang, Effect of Psidium guajava leaf extract on alpha-glucosidase activity in small intestine of diabetic mouse. Sichuan da xue xue bao Yi xue ban, Journal of Sichuan University Medical science edition. 38(2) (2007) 298.[12] S. C. Shen, F. C. Cheng, N. J. Wu. Effect of guava (Psidium guajava Linn.) leaf soluble solids on glucose metabolism in type 2 diabetic rats, Phytotherapy Research. 22(11) (2008) 1458.

The intellectual development in the Tang Dynasty (618-907) could be generally divided into two phases, with the first one inherited from the Han Wei period focusing on the meaning of words, while the second phase focuses on the teaching of the Confucian classics. Among the various scholars during the course of this transformation, Dan Zhu (啖助,724-770) has been recognized as a non-mainstream but yet very influential character. To avoid the An-Shi Rebellion, Dan Zhu resided in the south-eastern part of the country where he taught Lu Chun (陸淳) the Chun Qiu (春秋) classic. Many famous Tang political reformers including Lu Wen (呂溫) and Liu Zong Yuan (柳宗元) are considered by historians as Dan Zhu’s students and followers. This has made Dan Zhu even more influential than other Confucius scholars in that period. Nevertheless, due to the controversial nature of his teachings, Dan Zhu was heavily criticized by Ouyang Xiu (歐陽修) as being specious and at the same time appraised by Cheng Yi (程頤) to be one of the fore-runners who founded the Song Confucianism. This research reveals that Dan Zhu abandons the approach of focusing on the meaning wording and goes directly into the teachings of the classics. He considers that there are large amount of mistakes in the then contemporary explanation of Chun Qiu, he also considers that Tang scholars have not just worked in isolation without much view sharing, but also misinterpreted Confucius’ teachings. Moreover, the Tang scholars are treating Chun Qiu as history or even as literature, rather than Confucius’ teaching on how the society should be run. From Dan Zhu’s perspective, Confucius was trying to make use of histories to set proper behavioural standards and protocols for running the country, with an objective of saving the imperial control of Zhou (周). During the mid-Tang period, China was undergoing major social changes from a feudal to a modern society. Tang imperials whose ancestors carried a nomadic blood stream tried to strengthen their control by adopting Confucianism; and placing more emphasis on the south-eastern region where the Han Chinese of the Southern Dynasty was concentrated. Coupling with the civil examination (科舉) reform and the impacts of Zen Buddhism, the Tang society was undergoing major social-political transformation which Dan Zhu was situated right on its course. The research concludes that Dan Zhu’s ideas fit well with Xuan-zong’s (唐玄宗) appeal for revival of Confucius teachings and the social-political setting in Mid-Tang. Although Dan Zhu is considered a non-mainstream scholar, his teachings have brought about significant impacts on later development of the Neo-Confucianism. Nonetheless, Dan Zhu has not deviated from the fundamental principles of a Confucian whose destiny is to serve the people and the country, and of course for Dan Zhu, the Tang Dynasty.
published_or_final_version
Chinese
Master
Master of Philosophy