Azvudine(FNC)is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase(RdRp).Recently,we discovered FNC an agent against SARS-CoV-2,and have taken it into Phase III trial for COVID-19 patients.FNC monoph...Azvudine(FNC)is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase(RdRp).Recently,we discovered FNC an agent against SARS-CoV-2,and have taken it into Phase III trial for COVID-19 patients.FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC_(50) between 1.2 and 4.3 μM,depending on viruses or cells,and selective index(SI)in 15-83 range.Oral administration of FNC in rats revealed a substantial thymus-homing feature,with FNC triphosphate(the active form)concentrated in the thymus and peripheral blood mononuclear cells(PBMC).Treating SARS-CoV-2 infected rhesus macaques with FNC(0.07 mg/kg, qd,orally)reduced viral load,recuperated the thymus,improved lymphocyte profiles,alleviated in flammation and orga n damage,and lessened grou nd・glass opacities in chest X-ray.Sin gle-cell seque ncing suggested the promotion of thymus function by FNC.A randomized,single-arm clinical trial of FNC on compassionate use(n=31)showed that oral FNC(5 mg,qd)cured all COVID-19 patients,with 100%viral ribonucleic acid negative conversion in 3.29±2.22 days(range:1-9 days)and 100%hospital discharge rate in 9.00±4.93 days(range:2-25 days).The side-effect of FNC is minor and transient dizziness and nausea in 16.12%(5/31)patients.Thus,FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus,followed by promoted immunity.展开更多
Si-Miao-Wan(SMW), a tradiational Chinese medicinal formula consisting of Atractylodis Rhizoma, Phellodendri Chinensis Cortex, Coicis Semen, and Achyranthis Bidentatae Radix, has been used for the treatment of gout and...Si-Miao-Wan(SMW), a tradiational Chinese medicinal formula consisting of Atractylodis Rhizoma, Phellodendri Chinensis Cortex, Coicis Semen, and Achyranthis Bidentatae Radix, has been used for the treatment of gout and gouty arthritis for many years. In the present study, a liquid chromatography quadrupole-time-of-flight mass spectrometry(LC-Q-TOF/MS) method was established to identify the multiple constituents of SMW and its metabolites in rat biological samples after oral administration. A total of 48 compounds in SMW, including 21 alkaloids, 12 organic acids, 2 terpenes, 3 lactones, 2 phytosterols, and 8 other compounds, were tentatively characterized with the diagnostic-ion filtering strategy. Based on the diagnostic ions applied to identify compounds in SMW, 28 prototype compounds and 10 metabolic compounds were detected in the biological samples. This was the first comprehensive drug metabolism investigation of SMW in rats. The developed method could be a useful means for identifying the multi-components in SMW and the metabolic components. The results may help explore the possible metabolic processes and mechanism of action for SMW in vivo.展开更多
Objective：To exam the effect and safety of conventional acupuncture（CA） on cardiac arrhythmia.Methods：Nine medical databases were searched until February 2016 for randomized controlled trials.Heterogeneity was mea...Objective：To exam the effect and safety of conventional acupuncture（CA） on cardiac arrhythmia.Methods：Nine medical databases were searched until February 2016 for randomized controlled trials.Heterogeneity was measured by Cochran Q test.Meta-analysis was conducted if I2 was less than 85% and the characteristics of included trials were similar.Results：Nine qualified studies involving 638 patients were included.Only 1 study had definitely low risk of bias,while 7 trials were rated as unclear and 1 as high.Meta-analysis of CA alone did not have a significant benefit on response rate compared to amiodarone in patients with atrial fibrillation（Af） and atrial flutter（AF） [relative risk（RR）：1.09;95% confidence interval（CI）：0.79–1.49;P=0.61;I2=61%,P=0.11].However,1 study with higher methodological quality detected a lower recurrence rate of Af in CA alone as compared with sham acupuncture plus no treatment,and benefits on ventricular rate and time of conversion to normal sinus rhythm were found in CA alone group by 1 study,as well as the response rate in CA plus deslanoside group by another study.Meta-analysis of CA plus anti-arrhythmia drug（AAD） was associated with a significant benefit on the response rate when compared with AAD alone in ventricular premature beat（VPB） patients（RR,1.19,95% CI：1.05–1.34;P=0.005;I2=13%,P=0.32）,and an improvement in quality-of-life score（QOLS） of VPB also showed in 1 individual study.Besides,a lower heart rate was detected in the CA alone group by 1 individual study when compared with no treatment in sinus tachycardia patients（MD –21.84 [–27.21,–16.47]） and lower adverse events of CA alone were reported than amiodarone.Conclusions：CA may be a useful and safe alternative or additive approach to AADs for cardiac arrhythmia,especially in VPB and Af patients,which mainly based on a pooled estimate and result from 1 study with higher methodological quality.However,we could not reach a robust conclusion due to low quality of overal展开更多
Acute coronary syndrome(ACS)is one of the leading causes of death in cardiovascular disease.Percutaneous coronary intervention(PCI)is an important method for the treatment of coronary heart disease(CHD),and it has gre...Acute coronary syndrome(ACS)is one of the leading causes of death in cardiovascular disease.Percutaneous coronary intervention(PCI)is an important method for the treatment of coronary heart disease(CHD),and it has greatly reduced the mortality of ACS patients since its application.However,a series of new problems may occur after PCI,such as in-stent restenosis,no-reflow phenomenon,in-stent neoatherosclerosis,late stent thrombosis,myocardial ischemia-reperfusion injury,and malignant ventricular arrhythmias,which result in the occurrence of major adverse cardiac events(MACE)that seriously reduce the postoperative benefit for patients.The inflammatory response is a key mechanism of MACE after PCI.Therefore,examining effective anti-inflammatory therapies after PCI in patients with ACS is a current research focus to reduce the incidence of MACE.The pharmacological mechanism and clinical efficacy of routine Western medicine treatment for the anti-inflammatory treatment of CHD have been verified.Many Chinese medicine(CM)preparations have been widely used in the treatment of CHD.Basic and clinical studies showed that effectiveness of the combination of CM and Western medicine treatments in reducing incidence of MACE after PCI was better than Western medicine treatment alone.The current paper reviewed the potential mechanism of the inflammatory response and occurrence of MACE after PCI in patients with ACS and the research progress of combined Chinese and Western medicine treatments in reducing incidence of MACE.The results provide a theoretical basis for further research and clinical treatment.展开更多
滴灌技术结合节水灌溉制度可显著提高作物水分利用效率,但针对滴灌条件下冬小麦节水灌溉制度的优化研究相对较少,利用作物模型优化节水灌溉制度可以弥补田间试验的不足,对于作物精确灌溉具有重要的指导意义。本研究利用胶东冬小麦滴灌...滴灌技术结合节水灌溉制度可显著提高作物水分利用效率,但针对滴灌条件下冬小麦节水灌溉制度的优化研究相对较少,利用作物模型优化节水灌溉制度可以弥补田间试验的不足,对于作物精确灌溉具有重要的指导意义。本研究利用胶东冬小麦滴灌节水试验数据(2016—2019年)评价了根区水质模型(RZWQM-CERES)的适应性,并模拟评价了不同节水滴灌制度对冬小麦产量和水分利用效率的影响,以筛选最佳节水滴灌制度。结果表明RZWQM-CERES可以较好地模拟土壤水分、冬小麦生长和产量对不同滴灌处理和季节的响应,其中模拟0~90 cm土壤贮水量的均方根误差(RMSE)为22.7~32.3 mm、相对均方根误差(NRMSE)为11.9%~16.3%、决定系数(R2)为0.52~0.69,模拟收获期生物量的RMSE为1184~1904 kg hm-2、NRMSE为9.9%~16.8%、R2为0.67,模拟产量的RMSE为361~491 kg hm^(–2)、NRMSE为5.7%~7.8%、R2为0.75。长期模拟结果表明该地区冬小麦需水关键期为孕穗期(丰水年和平水年)或拔节期(枯水年)。针对不同降水年型冬小麦产量和水分利用效率对灌溉量的响应差异,筛选滴灌条件下冬小麦最佳灌溉制度为:丰水年在拔节期和开花期各灌水45mm;平水年(或枯水年)在拔节期、孕穗期及开花期各灌水35mm(或45 mm)。本研究结果扩展了RZWQM-CERES优化冬小麦滴灌制度的应用潜力,为实施冬小麦精确灌溉提供了重要的技术支持。展开更多
基金This work was supported by the CAMS Innovation Fund for Medical Sciences(No.2020-I2M-1-003,2020-I2M-2-010,2020HY320001,China)The Drug Innovation Major Project(No.2018ZX09711001-003-002,China)+2 种基金National Natural Science Foundation(No.81621064,China)National key R&D project(No.2019YFC170890,China)CAMS Innovation Fund for Medical Sciences(No.2021-1-I2M-009,2021-1-I2M-030).
文摘Azvudine(FNC)is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase(RdRp).Recently,we discovered FNC an agent against SARS-CoV-2,and have taken it into Phase III trial for COVID-19 patients.FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC_(50) between 1.2 and 4.3 μM,depending on viruses or cells,and selective index(SI)in 15-83 range.Oral administration of FNC in rats revealed a substantial thymus-homing feature,with FNC triphosphate(the active form)concentrated in the thymus and peripheral blood mononuclear cells(PBMC).Treating SARS-CoV-2 infected rhesus macaques with FNC(0.07 mg/kg, qd,orally)reduced viral load,recuperated the thymus,improved lymphocyte profiles,alleviated in flammation and orga n damage,and lessened grou nd・glass opacities in chest X-ray.Sin gle-cell seque ncing suggested the promotion of thymus function by FNC.A randomized,single-arm clinical trial of FNC on compassionate use(n=31)showed that oral FNC(5 mg,qd)cured all COVID-19 patients,with 100%viral ribonucleic acid negative conversion in 3.29±2.22 days(range:1-9 days)and 100%hospital discharge rate in 9.00±4.93 days(range:2-25 days).The side-effect of FNC is minor and transient dizziness and nausea in 16.12%(5/31)patients.Thus,FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus,followed by promoted immunity.
基金supported by the National Natural Science Foundation of China(No.81573705)the Natural Science Foundation of Jiangsu Province(No.BK20171392)the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘Si-Miao-Wan(SMW), a tradiational Chinese medicinal formula consisting of Atractylodis Rhizoma, Phellodendri Chinensis Cortex, Coicis Semen, and Achyranthis Bidentatae Radix, has been used for the treatment of gout and gouty arthritis for many years. In the present study, a liquid chromatography quadrupole-time-of-flight mass spectrometry(LC-Q-TOF/MS) method was established to identify the multiple constituents of SMW and its metabolites in rat biological samples after oral administration. A total of 48 compounds in SMW, including 21 alkaloids, 12 organic acids, 2 terpenes, 3 lactones, 2 phytosterols, and 8 other compounds, were tentatively characterized with the diagnostic-ion filtering strategy. Based on the diagnostic ions applied to identify compounds in SMW, 28 prototype compounds and 10 metabolic compounds were detected in the biological samples. This was the first comprehensive drug metabolism investigation of SMW in rats. The developed method could be a useful means for identifying the multi-components in SMW and the metabolic components. The results may help explore the possible metabolic processes and mechanism of action for SMW in vivo.
基金Supported by the National Natural Science Foundation of China(No.81173176)
文摘Objective：To exam the effect and safety of conventional acupuncture（CA） on cardiac arrhythmia.Methods：Nine medical databases were searched until February 2016 for randomized controlled trials.Heterogeneity was measured by Cochran Q test.Meta-analysis was conducted if I2 was less than 85% and the characteristics of included trials were similar.Results：Nine qualified studies involving 638 patients were included.Only 1 study had definitely low risk of bias,while 7 trials were rated as unclear and 1 as high.Meta-analysis of CA alone did not have a significant benefit on response rate compared to amiodarone in patients with atrial fibrillation（Af） and atrial flutter（AF） [relative risk（RR）：1.09;95% confidence interval（CI）：0.79–1.49;P=0.61;I2=61%,P=0.11].However,1 study with higher methodological quality detected a lower recurrence rate of Af in CA alone as compared with sham acupuncture plus no treatment,and benefits on ventricular rate and time of conversion to normal sinus rhythm were found in CA alone group by 1 study,as well as the response rate in CA plus deslanoside group by another study.Meta-analysis of CA plus anti-arrhythmia drug（AAD） was associated with a significant benefit on the response rate when compared with AAD alone in ventricular premature beat（VPB） patients（RR,1.19,95% CI：1.05–1.34;P=0.005;I2=13%,P=0.32）,and an improvement in quality-of-life score（QOLS） of VPB also showed in 1 individual study.Besides,a lower heart rate was detected in the CA alone group by 1 individual study when compared with no treatment in sinus tachycardia patients（MD –21.84 [–27.21,–16.47]） and lower adverse events of CA alone were reported than amiodarone.Conclusions：CA may be a useful and safe alternative or additive approach to AADs for cardiac arrhythmia,especially in VPB and Af patients,which mainly based on a pooled estimate and result from 1 study with higher methodological quality.However,we could not reach a robust conclusion due to low quality of overal
基金Supported by the Applied Technology Research and Development and Demonstration Projects of Beijing Province(No.Z191100006619071)。
文摘Acute coronary syndrome(ACS)is one of the leading causes of death in cardiovascular disease.Percutaneous coronary intervention(PCI)is an important method for the treatment of coronary heart disease(CHD),and it has greatly reduced the mortality of ACS patients since its application.However,a series of new problems may occur after PCI,such as in-stent restenosis,no-reflow phenomenon,in-stent neoatherosclerosis,late stent thrombosis,myocardial ischemia-reperfusion injury,and malignant ventricular arrhythmias,which result in the occurrence of major adverse cardiac events(MACE)that seriously reduce the postoperative benefit for patients.The inflammatory response is a key mechanism of MACE after PCI.Therefore,examining effective anti-inflammatory therapies after PCI in patients with ACS is a current research focus to reduce the incidence of MACE.The pharmacological mechanism and clinical efficacy of routine Western medicine treatment for the anti-inflammatory treatment of CHD have been verified.Many Chinese medicine(CM)preparations have been widely used in the treatment of CHD.Basic and clinical studies showed that effectiveness of the combination of CM and Western medicine treatments in reducing incidence of MACE after PCI was better than Western medicine treatment alone.The current paper reviewed the potential mechanism of the inflammatory response and occurrence of MACE after PCI in patients with ACS and the research progress of combined Chinese and Western medicine treatments in reducing incidence of MACE.The results provide a theoretical basis for further research and clinical treatment.
文摘滴灌技术结合节水灌溉制度可显著提高作物水分利用效率,但针对滴灌条件下冬小麦节水灌溉制度的优化研究相对较少,利用作物模型优化节水灌溉制度可以弥补田间试验的不足,对于作物精确灌溉具有重要的指导意义。本研究利用胶东冬小麦滴灌节水试验数据(2016—2019年)评价了根区水质模型(RZWQM-CERES)的适应性,并模拟评价了不同节水滴灌制度对冬小麦产量和水分利用效率的影响,以筛选最佳节水滴灌制度。结果表明RZWQM-CERES可以较好地模拟土壤水分、冬小麦生长和产量对不同滴灌处理和季节的响应,其中模拟0~90 cm土壤贮水量的均方根误差(RMSE)为22.7~32.3 mm、相对均方根误差(NRMSE)为11.9%~16.3%、决定系数(R2)为0.52~0.69,模拟收获期生物量的RMSE为1184~1904 kg hm-2、NRMSE为9.9%~16.8%、R2为0.67,模拟产量的RMSE为361~491 kg hm^(–2)、NRMSE为5.7%~7.8%、R2为0.75。长期模拟结果表明该地区冬小麦需水关键期为孕穗期(丰水年和平水年)或拔节期(枯水年)。针对不同降水年型冬小麦产量和水分利用效率对灌溉量的响应差异,筛选滴灌条件下冬小麦最佳灌溉制度为:丰水年在拔节期和开花期各灌水45mm;平水年(或枯水年)在拔节期、孕穗期及开花期各灌水35mm(或45 mm)。本研究结果扩展了RZWQM-CERES优化冬小麦滴灌制度的应用潜力,为实施冬小麦精确灌溉提供了重要的技术支持。
