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1Special Section:SARS-CoV-2 Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19显示文摘Effective therapies are urgently needed for the SARS-CoV-2 pandemic.Chloroquine has been proved to have antiviral effect against coronavirus in vitro.In this study,we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19.In this multicenter prospective observational study,we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces.Eligible patients received chloroquinephosphate s00 mg,orally,once(half dose)or twice(full dose)daily.Patients treated with non-chloroquine therapy were included as historical controls.The primary endpoint is the time to undetectable viral RNA.Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14,hospitalization time,duration of fever,and adverse events.A total of 197 patients completed chloroquine treatment,and 176patients were included as historical controls.The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine(absolute difference in medians-6.0 days;95%CI-6.0 to—4.0).The duration of fever is shorter in chloroquine(geometric mean ratio 0.6;95%CIO.5 to 0.8).No serious adverse events were observed in the chloroquine group.Patients treated with half dose experienced lower rate of adverse events than with full dose.Although randomized trials are needed for further evaluation,this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating the COVID-19 pandemic.Mingxing Huang Man Li Fei Xiao Pengfei Pang Jiabi Liang Tiantian Tang Shaoxuan Liu Binghui Chen Jingxian Shu Yingying You Yang Li Meiwen Tang Jianhui Zhou Guanmin Jiang Jingfen Xiang Wenxin Hong Songmei He Zhaoqin Wang Jianhua Feng Changqing Lin Yinong Ye Zhilong Wu Yaocai Li Bei Zhong Ruilin Sun Zhongsi Hong Jing Liu Huili Chen Xiaohua Wang Zhonghe Li Duanqing Pei Lin Tian Jinyu Xia Shanping Jiang Nanshan Zhong Hong Shan 2020National Science Review2020,7,9:20
2FKBP23 in ER binds to BiP specifically显示文摘FKBP23 was found in mouse endoplasmic reticulum (ER) in 1998. It consists of an N-terminal peptidyl-prolyl cis-trans isomerase (PPIase) domain and a C-terminal domain with Ca2+ binding sites. The fusion protein of mouse FKBP23 and glutathione S-transferase (GST), GST-FKBP23, and the fusion protein of BiP, a member of heat shock protein 70 (Hsp 70) in ER, and GST, GST-BiP, were subcloned in E. coli, expressed and purified. The fusion proteins were restrictively digested by Factor Xa (FaXa) to obtain the free cloned proteins FKBP23 and BiP. With the assay of adsorption of free FKBP23 or BiP with GST-BiP or GST-FKBP23 attached to the Glutathione-Sepharose 4B, the adsorbed FKBP23 or BiP could be detected by Immunoblot. It means that FKBP23 binds to BiP. Furthermore, BiP in leukocyte ER-extract can be adsorbed with GST-FKBP23 attached to the glutathione-Sepharose 4B. It shows that FKBP23 binds to natural BiP in ER, too. These experiments show that a PPIase binds to a molecular chaperone of the Hsp70 family.ZHANG Wanqi, LI Hui, ZHANG Xiaobin, SHEN Ye, WANG Yinong, Ml Huaifeng & HE BinglinState Key Laboratory of Functional Polymer Materials for Adsorption and Separation, Chemical School of Nankai University, Tianjin 300071, China Hygienic School of Tianjin Medical University, Tianjin 300071, China Medical School of Nankai University, Tianjin 300071, China 2004Science China Chemistry2004,47,1:2
3Real-world effectiveness and safety of OBT/PTV/r and dasabuvir for patients with chronic HCV genotype 1b infection in China:A multicenter prospective observational study显示文摘Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicenter,prospective,real-world study of ombitasvir/paritaprevir/ritonavir(OBT/PTV/r)combined with dasabuvir(DSV)in hepatitis C virus(HCV)genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients.Materials and methods:Genotype 1b-infected patients were enrolled at eight sites in China.Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks.Sustained virological response at 12 weeks post-treatment(SVR12)and the incidence of adverse events were assessed.We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing.Intention-to-treat(ITT)and modified ITT(mITT)populations were used in the analysis.Results:One hundred forty patients were included,among whom 90.0%(126/140)were newly diagnosed,9.3%(13/140)had compensated cirrhosis,92.9%(130/140)received 12 weeks of treatment,and 7.1%(10/140)received 8 weeks of treatment.In the mITT population,the virological response rate at week 4 was 96.4%(108/112),and at the end of treatment was 100%(102/102).Among these patients,139 patients completed 12 weeks of treatment,and 73 patients were followed-up.All followed-up patients achieved SVR12.There was no adverse event-related discontinuation.Serious adverse events during treatment were reported in two(1.4%)patients,and none were considered to be drug-related.Sixty-six(47.1%)patients did not return to receive the HCV RNA test at 12 weeks post-treatment.Conclusions:The rate of SVR12 was consistent with Phase III clinical studies.OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients,and both tolerability and safety profile were favorable.However,patient compliance should be further improved in the real world.Yusheng Jie Chaoshuang Lin Jing Yuan Zhixin Zhao Yujuan Guan Yuanping Zhou Xiaohui Zhou Bihui Zhong Yinong Ye Lihua Zhang Ling Tao Jianping Li Xiaohong Zhang Yutian Chong 2020Liver Research2020,4,3:0
4SBC(Sanhuang Xiexin Tang combined with Baihu Tang plus Cangzhu)alleviates NAFLD by enhancing mitochondrial biogenesis and ameliorating inflammation in obese patients and mice显示文摘In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis—a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.REN Zhitao XIAO Gemin CHEN Yixin WANG Linli XIANG Xiaoxin YANG Yi WEN Siying XIE Zhiyong LUO Wenhui LI Guowei ZHENG Wenhua QIAN Xiaoxian HAI Rihan YANG Liansheng ZHU Yanhua CAI Mengyin YE Yinong SHI Guojun CHEN Yanming 2023Chinese Journal of Natural Medicines2023,21,11:0
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