Objective To investigate the prevalence and levels of anti-HEV IgG in the population of Jiangsu Province.Methods Total of 2 656 samples from Qindong and 11 463 samples from Anfeng were colleted.The antiHEV antibody wa...Objective To investigate the prevalence and levels of anti-HEV IgG in the population of Jiangsu Province.Methods Total of 2 656 samples from Qindong and 11 463 samples from Anfeng were colleted.The antiHEV antibody was qualitatively and quantitatively detected using ELISA kits and the references had been established.Results The positive rates of anti-HEV IgG in male and female were 55.6%and 40.1%,respectively.The positive rate of anti-HEV IgM in male and female were both 3.4%.In opposite to anti-HEV IgG,the positive rate of anti-HEV IgM in Anfeng was significant higher than that in Qindong.The mean anti-HEV IgG titers for6 age groups were 0.94,0.92,1.07,1.46,1.27,1.19 and 0.68,1.31,1.08,1.14,1.31,1.68 IU/ml,in Qindong and Anfeng region,respectively.The positive rate of anti-HEV IgG tended to increase with age and the titer of antiHEV IgG was associated with age(R>0.90).Conclusions The results in this study showed that HEV was widely prevalent in both Qindong and Anfeng of Jiansu Province and the prevalence and the anti-HEV IgG titer were associated with gender and age.展开更多
本文是基于考古发掘获取的人骨遗存在内的89组古代及现代的人群样本而做的颅骨形态测量研究,侧重说明解剖学意义上的现代人(anatomically modern humans)在欧亚大陆东部演化分布的“二层”模式。距今6.5万~5万年以前,“第一层”现代人...本文是基于考古发掘获取的人骨遗存在内的89组古代及现代的人群样本而做的颅骨形态测量研究,侧重说明解剖学意义上的现代人(anatomically modern humans)在欧亚大陆东部演化分布的“二层”模式。距今6.5万~5万年以前,“第一层”现代人经东南亚大陆向东、向南扩散,他们与现今安达曼人、澳大利亚人、巴布亚人的祖先以及日本绳纹时代人群最为接近。距今约九千年前,拥有东北亚血统的“第二层”现代人出现在中国中部地区,并于距今四千年前后向南扩张至东南亚地区,这些人群在颅骨形态上与西伯利亚人具有密切的亲缘关系。上述两大人群最初交流有限,在农业能够支撑增加人口密度的情境下,“第二层”现代人增长速度较快,人口数量较多。这两层人群显著的二重结构特征,表明了现代人在欧亚大陆南、北不同迁移路线间的历时性差异。展开更多
Background:The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)call for urgent development of effective and safe vaccines.We report the i...Background:The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)call for urgent development of effective and safe vaccines.We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine,KCONVAC,in healthy adults.Methods:Phase 1 and phase 2 randomized,double-blind,and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years.The participants in the phase 1 trial were randomized to receive two doses,one each on Days 0 and 14,of either KCONVAC(5 or 10 mg/dose)or placebo.The participants in the phase 2 trial were randomized to receive either KCONVAC(at 5 or 10 mg/dose)or placebo on Days 0 and 14(0/14 regimen)or Days 0 and 28(0/28 regimen).In the phase 1 trial,the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose.In the phase 2 trial,the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.Results:Inthe phase1 trial,60 participantswere enrolled andreceived at least one dose of 5-mgvaccine(n=24),10-mgvaccine(n=24),or placebo(n=12).In the phase 2 trial,500 participantswere enrolled and received at least one dose of 5-mg vaccine(n=100 for 0/14 or 0/28 regimens),10-mg vaccine(n=100 for each regimen),or placebo(n=50 for each regimen).In the phase 1 trial,13(54%),11(46%),and seven(7/12)participants reported at least one adverse event(AE)after receiving 5-,10-mg vaccine,or placebo,respectively.In the phase 2 trial,16(16%),19(19%),and nine(18%)0/14-regimen participants reported at least oneAEafter receiving 5-,10-mg vaccine,or placebo,respectively.Similar AE incidences were observed in the three 0/28-regimen treatment groups.No AEs with an intensity of grade 3+were reported,expect for one vaccine-unrelated seriousAE(foot fracture)reported in the phase 1 trial.KCONVACinduced significant antibody responses;0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.Conclusions:Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults.These results support testing 5-mg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.Trial Registration:http://www.chictr.org.cn/index.aspx(No.ChiCTR2000038804,http://www.chictr.org.cn/showproj.aspx?proj=62350;No.ChiCTR2000039462,http://www.chictr.org.cn/showproj.aspx?proj=63353).展开更多
To discover new drugs to combat COVID-19,an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed.Here,for the first time,we report the crucial role of cathepsin L(CTSL)in patients with COVID...To discover new drugs to combat COVID-19,an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed.Here,for the first time,we report the crucial role of cathepsin L(CTSL)in patients with COVID-19.The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity.Correspondingly,SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo,while CTSL overexpression,in turn,enhanced pseudovirus infection in human cells.CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry,as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo.Furthermore,amantadine,a licensed anti-influenza drug,significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo.Therefore,CTSL is a promising target for new anti-COVID-19 drug development.展开更多
文摘Objective To investigate the prevalence and levels of anti-HEV IgG in the population of Jiangsu Province.Methods Total of 2 656 samples from Qindong and 11 463 samples from Anfeng were colleted.The antiHEV antibody was qualitatively and quantitatively detected using ELISA kits and the references had been established.Results The positive rates of anti-HEV IgG in male and female were 55.6%and 40.1%,respectively.The positive rate of anti-HEV IgM in male and female were both 3.4%.In opposite to anti-HEV IgG,the positive rate of anti-HEV IgM in Anfeng was significant higher than that in Qindong.The mean anti-HEV IgG titers for6 age groups were 0.94,0.92,1.07,1.46,1.27,1.19 and 0.68,1.31,1.08,1.14,1.31,1.68 IU/ml,in Qindong and Anfeng region,respectively.The positive rate of anti-HEV IgG tended to increase with age and the titer of antiHEV IgG was associated with age(R>0.90).Conclusions The results in this study showed that HEV was widely prevalent in both Qindong and Anfeng of Jiansu Province and the prevalence and the anti-HEV IgG titer were associated with gender and age.
基金supported by the National Natural Science Foundation of China(81991491,82273640,and 82072323)CAMS Innovation Fund for Medical Sciences of China(2019RU022)+1 种基金Fundamental Research Funds for the Central Universities(20720220006 and 20720200105)Xiamen Innovax(provided qualified test and control vaccine)。
文摘本文是基于考古发掘获取的人骨遗存在内的89组古代及现代的人群样本而做的颅骨形态测量研究,侧重说明解剖学意义上的现代人(anatomically modern humans)在欧亚大陆东部演化分布的“二层”模式。距今6.5万~5万年以前,“第一层”现代人经东南亚大陆向东、向南扩散,他们与现今安达曼人、澳大利亚人、巴布亚人的祖先以及日本绳纹时代人群最为接近。距今约九千年前,拥有东北亚血统的“第二层”现代人出现在中国中部地区,并于距今四千年前后向南扩张至东南亚地区,这些人群在颅骨形态上与西伯利亚人具有密切的亲缘关系。上述两大人群最初交流有限,在农业能够支撑增加人口密度的情境下,“第二层”现代人增长速度较快,人口数量较多。这两层人群显著的二重结构特征,表明了现代人在欧亚大陆南、北不同迁移路线间的历时性差异。
基金by grants from the Guangdong Emergency Program for Prevention and Control of COVID-19(No.2020A1111340002)the Shenzhen Key Research Project for Prevention and Control of COVID-19.
文摘Background:The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)call for urgent development of effective and safe vaccines.We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine,KCONVAC,in healthy adults.Methods:Phase 1 and phase 2 randomized,double-blind,and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years.The participants in the phase 1 trial were randomized to receive two doses,one each on Days 0 and 14,of either KCONVAC(5 or 10 mg/dose)or placebo.The participants in the phase 2 trial were randomized to receive either KCONVAC(at 5 or 10 mg/dose)or placebo on Days 0 and 14(0/14 regimen)or Days 0 and 28(0/28 regimen).In the phase 1 trial,the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose.In the phase 2 trial,the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.Results:Inthe phase1 trial,60 participantswere enrolled andreceived at least one dose of 5-mgvaccine(n=24),10-mgvaccine(n=24),or placebo(n=12).In the phase 2 trial,500 participantswere enrolled and received at least one dose of 5-mg vaccine(n=100 for 0/14 or 0/28 regimens),10-mg vaccine(n=100 for each regimen),or placebo(n=50 for each regimen).In the phase 1 trial,13(54%),11(46%),and seven(7/12)participants reported at least one adverse event(AE)after receiving 5-,10-mg vaccine,or placebo,respectively.In the phase 2 trial,16(16%),19(19%),and nine(18%)0/14-regimen participants reported at least oneAEafter receiving 5-,10-mg vaccine,or placebo,respectively.Similar AE incidences were observed in the three 0/28-regimen treatment groups.No AEs with an intensity of grade 3+were reported,expect for one vaccine-unrelated seriousAE(foot fracture)reported in the phase 1 trial.KCONVACinduced significant antibody responses;0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.Conclusions:Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults.These results support testing 5-mg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.Trial Registration:http://www.chictr.org.cn/index.aspx(No.ChiCTR2000038804,http://www.chictr.org.cn/showproj.aspx?proj=62350;No.ChiCTR2000039462,http://www.chictr.org.cn/showproj.aspx?proj=63353).
基金This work was supported by grants from the National Key R&D Program of China(2017YFC0909600)National Natural Science Foundation of China(81930019,8151101058,81471014)+1 种基金Scientific Project of Beijing Municipal Science&Technology Commission(D171100002817005)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(ZYLX201823)。
文摘To discover new drugs to combat COVID-19,an understanding of the molecular basis of SARS-CoV-2 infection is urgently needed.Here,for the first time,we report the crucial role of cathepsin L(CTSL)in patients with COVID-19.The circulating level of CTSL was elevated after SARS-CoV-2 infection and was positively correlated with disease course and severity.Correspondingly,SARS-CoV-2 pseudovirus infection increased CTSL expression in human cells in vitro and human ACE2 transgenic mice in vivo,while CTSL overexpression,in turn,enhanced pseudovirus infection in human cells.CTSL functionally cleaved the SARS-CoV-2 spike protein and enhanced virus entry,as evidenced by CTSL overexpression and knockdown in vitro and application of CTSL inhibitor drugs in vivo.Furthermore,amantadine,a licensed anti-influenza drug,significantly inhibited CTSL activity after SARS-CoV-2 pseudovirus infection and prevented infection both in vitro and in vivo.Therefore,CTSL is a promising target for new anti-COVID-19 drug development.