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| 1 | The P132H mutation in the main protease of Omicron SARSCoV-2 decreases thermal stability without compromising catalysis or small-molecule drug inhibition显示文摘Dear Editor,The ongoing SARS-CoV-2 pandemic continues to be a significant threat to global health.First reported in November 2021,the Omicron variant(B.1.1.529)is more transmissible and can evade immunity better than previous SARS-CoV-2 variants,fueling an unprecedented surge in cases.To produce functional proteins from its polyprotein,SARS-CoV-2 relies on the cysteine proteases Nsp3/papain-like protease(PLpro)and Nsp5/main protease(Mpro)/3C-like protease to cleave at three and more than 11 sites,respectively.1 Therefore,Mpro and PLpro inhibitors are considered to be one of the most promising SARS-CoV-2 antivirals.On December 22,2021,the Food and Drug Administration(FDA)issued an Emergency Use Authorization(EUA)for PAXLOVID,a ritonavir-boosted formulation of nirmatrelvir.Nirmatrelvir is a first-in-class orally bioavailable SARSCoV-2 Mpro inhibitor.2 Thus,the scientific community must vigilantly monitor potential mechanisms of drug resistance,especially because SARS-CoV-2 is naïve to Mpro inhibitors.Mutations have been well identified in variants to this point.3 Notably,Omicron Mpro(OMpro)harbors a single mutation—P132H.In this study,we characterized the enzymatic activity,drug inhibition,and structure of OMpro while evaluating the past and future implications of Mpro mutations. | Michael Dominic Sacco Yanmei Hu Maura Verenice Gongora Flora Meilleur Michael Trent Kemp Xiujun Zhang Jun Wang Yu Chen | 2022 | Cell Research2022，32，5： | 3 |
| 2 | Identification of a Novel Gene on Chromosome 7q11.2 Interrupted by a Translocation Breakpoint in a Pair of Autistic Twins显示文摘 | Razia Sultana Chang-En Yu Jun Yu Jeffery Munson Donghui Chen Wenhui Hua Annette Estes Fanny Cortes Flora de la Barra Dongmei Yu Syed T. Haider Barbara J. Trask Eric D. Green Wendy H. Raskind Christine M. Disteche Ellen Wijsman Geraldine Dawson Daniel R. S | 2002 | Genomics2002，，： | 1 |
| 3 | COVID-19 Delta variants—Current status and implications as of August 2021显示文摘The SARS-CoV-2 Delta variant has evolved as the dominant strain of the current pandemic.Studies have shown that this variant has increased infectivity/viral load,and reduced neutralization by the host antibodies from convalescent patients/vaccinees.Clinically,Delta variant infection has been observed/documented in convalescent patients/vaccinees,although with less incidence of severe diseases,but can serve as reservoir to spread the infection to the unvaccinated.The current understanding(as of 18 August 2021)on the virologic aspect(including the amino acid substitutions),clinical implications,and public health implications will be discussed in this mini review,and recommendations to health authorities will be provided. | Flora Yu Lok-Ting Lau Manson Fok Johnson Yiu-Nam Lau Kang Zhang | 2021 | Precision Clinical Medicine2021，4，4： | 1 |
| 4 | 医疗保险受益人中白内障患者术后骨折风险显示文摘美国布朗大学沃伦珀特医学院眼科Tseng等学者研究发现,在美国65岁及以上人群被诊断患白内障的医疗保险受益人中,对于接受白内障手术的患者,术后一年髋关节骨折的发生率较未接受白内障手术的患者低。作者从2002—2010年医疗保险的B部分(补充性医疗保险)受益人中,随机抽取5%的样本量,在2002~2009年间65岁及以上人群被诊断患白内障的患者共有1113 640人,随访时间为1年。在研究期间接受了白内障手术的患者410 809人(占36.9%),发生髋关节骨折的患者13 976人(占1.3%)。 | Victoria L.Tseng Fei Yu Flora Lum Anne L.Coleman 王娟丽 | 2012 | 伤害医学(电子版)2012，1，3： | 0 |
| 5 | Efficacy and safety of sofosbuvir/velpatasvir with or without ribavirin in hepatitis C genotype 3 compensated cirrhosis:A meta-analysis显示文摘BACKGROUND Hepatitis C virus(HCV)is a leading cause of liver cirrhosis and hepatocellular carcinoma globally.Sofosbuvir/velpatasvir(SOF/VEL)is an effective pangenotypic direct-acting antiviral combination for treatment of chronic HCV infection.While the addition of ribavirin(RBV)to SOF/VEL improved sustained virological response(SVR12)in genotype 3(GT3)decompensated cirrhosis patients,the benefits of RBV in GT3 compensated cirrhosis patients receiving SOF/VEL remains unclear.AIM To evaluate the efficacy and safety of SOF/VEL,with or without RBV in GT3 compensated cirrhosis patients.METHODS We searched four electronic databases(PubMed/Medline,Embase,Cochrane Library and Web of Science)from inception up to June 2021 using both free text and MeSH terms.There was no restriction on language,geography,publication dates and publication status(full text or abstracts).All GT3 compensated cirrhosis patients treated with 12 wk of SOF/VEL,with or without RBV,were included,regardless of age,gender or prior treatment experience.The primary outcome was sustained virological response 12-wk posttreatment(SVR12).The secondary outcome was treatment-related adverse events,as defined by symptomatic anemia requiring transfusion or a drop in hemoglobin beyond 2 g/dL.The pooled relative risk(RR),95%CI and heterogeneity(I^(2))were estimated using Review Manager version 5.3.RESULTS From 1752 citations,a total of seven studies(2 randomized controlled trials,5 cohort studies)with 1088 subjects were identified.The SVR12 was similar in GT3 compensated cirrhosis patients,regardless of the use of RBV,for both the intention-to-treat RR 1.03,95%CI:0.99-1.07;I^(2)=0%)and the per-protocol analysis(RR:1.03,95%CI:0.99-1.07;I^(2)=48%).The overall pooled rate of treatment-related adverse events was 7.2%.Addition of RBV increased the pooled risk of treatment-related adverse events in GT3 compensated cirrhosis patients receiving SOF/VEL(RR:4.20,95%CI:1.29-13.68;I^(2)=0%).Subgroup analysis showed that RBV was associated with a higher SVR12 in GT3 compensated cirrhosis patients with baseline resistance-associated substitutions.However,addition of RBV did not significantly increase the SVR12 among treatment-experienced GT3 compensated cirrhosis patients.CONCLUSION Ribavirin was not associated with higher SVR12 in GT3 compensated cirrhosis patients receiving SOF/VEL.Our findings suggest a limited role for RBV as routine add-on therapy to SOF/VEL in GT3 compensated cirrhosis patients. | Jing Hong Loo Wen Xin Flora Xu Jun Teck Low Wei Xuan Tay Le Shaun Ang Yew Chong Tam Prem Harichander Thurairajah Rahul Kumar Yu Jun Wong | 2022 | World Journal of Hepatology2022，14，6： | 0 |
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