Identification of a suitable nonhuman primate(NHP)model of COVID-19 remains challenging.Here,we characterized severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in three NHP species:Old World monkeys...Identification of a suitable nonhuman primate(NHP)model of COVID-19 remains challenging.Here,we characterized severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in three NHP species:Old World monkeys Macaca mulatta(M.mulatta)and Macaca fascicularis(M.fascicularis)and New World monkey Callithrix jacchus(C.jacchus).Infected M.mulatta and M.fascicularis showed abnormal chest radiographs,an increased body temperature and a decreased body weight.Viral genomes were detected in swab and blood samples from all animals.Viral load was detected in the pulmonary tissues of M.mulatta and M.fascicularis but not C.jacchus.Furthermore,among the three animal species,M.mulatta showed the strongest response to SARS-CoV-2,including increased inflammatory cytokine expression and pathological changes in the pulmonary tissues.Collectively,these data revealed the different susceptibilities of Old World and New World monkeys to SARS-CoV-2 and identified M.mulatta as the most suitable for modeling COVID-19.展开更多
Objective:To explore the value of using the venous-arterial carbon dioxide partial pressure difference and the arterial-venous oxygen content difference ratio(ΔP_(CO2)/Ca-v_(O2))as targets to guide early tissue hypop...Objective:To explore the value of using the venous-arterial carbon dioxide partial pressure difference and the arterial-venous oxygen content difference ratio(ΔP_(CO2)/Ca-v_(O2))as targets to guide early tissue hypoperfusion in sepsis in plateau areas.Methods:90 sepsis patients admitted to the Third People’s Hospital of Xining and Golmud People’s Hospital from June 2017 to December 2022 were selected as the research subjects,and they were divided into the Scv_(O2)(central venous oxygen saturation)group and theΔP_(CO2)/Ca-v_(O2)group,with 45 cases in each group.The two groups were treated with early shock resuscitation according to different protocols.The hemodynamic characteristics of the two groups of patients before and after resuscitation were observed,and the volume responsiveness was evaluated.The ROC(receiver operating characteristic)curve was used to analyze the significance ofΔP_(CO2)/Ca-v_(O2),Scv_(O2),lactate,lactate clearance,and urine output in evaluating patient prognosis and the correlation betweenΔP_(CO2)/Ca-v_(O2)and the above indicators was explored.Results:Compared with before resuscitation,after fluid resuscitation,the heart rate(HR),mean arterial pressure(MAP),central venous pressure(CVP),cardiac index(CI),lactate,lactate clearance rate,and urine output of the two groups of patients were significantly improved(P<0.05);in terms of therapeutic effect,the 28-day mortality rate,6-hour fluid balance,and lactic acid clearance of theΔP_(CO2)/Ca-v_(O2)group were better than the Scv_(O2)group.The ROC characteristic curve showed that theΔP_(CO2)/Ca-v_(O2)value can effectively predict the prognosis of patients(AUC=0.907,sensitivity was 97%,specificity was 72.4%,and critical value was 1.84).ΔP_(CO2)/Ca-v_(O2)significantly correlated with Scv_(O2),lactic acid,and lactic acid clearance rate.Conclusion:TheΔP_(CO2)/Ca-v_(O2)value can be used to guide fluid resuscitation in early hypoperfusion in sepsis in plateau areas,improve patients’hemodynamics,reduce lactate indicators,and increase urine ou展开更多
This study aimed to compare the sensitivity of two-phase separation and the filtration method using a mixed cellulose ester(MCE)membrane to detect enteroviruses in sewage samples.From December 2015 to July 2016,four d...This study aimed to compare the sensitivity of two-phase separation and the filtration method using a mixed cellulose ester(MCE)membrane to detect enteroviruses in sewage samples.From December 2015 to July 2016,four domestic sewage samples(1 L/sample)were collected monthly from the Guangzhou Liede Sewage Treatment Plant,and each sewage sample was divided into two aliquots(500 mL).The sewage sample was concentrated using the two-phase separation and the filtration method using an MCE membrane,and the treated solutions were inoculated into cells for enterovirus isolation.Polymerase chain reaction amplification,VP1 sequencing,and enterovirus molecular typing were performed on the positive isolates.The detection rates of poliovirus(PV)and non-polio enterovirus(NPEV)obtained using the filtration method using an MCE membrane were higher than those using the two-phase separation method.McNemar's test showed that the detection rates of PV,NPEV,type 1 Sabin-like(SL1),type 2 Sabin-like(SL2),and type 3 Sabin-like(SL3)strain were not statistically significant(P>0.05).In Guangdong Province,China,the detection rates for PV and NPEV were 53.13%and 62.50%(20/32),respectively.Twenty-seven PVs were isolated,three highly variable strains of the type 1 vaccine,with seven nucleotide substitutions in the VP1 region,compared with the type 1 Sabin strains.Eighty-seven strains of NPEV were isolated and nine serotypes were identified,among which coxsackievirus B3(CVB3),echovirus 6(E6),and echovirus 11(E11)were the dominant strains.The filtration method using an MCE membrane is more sensitive than two-phase separation and can be used as a robust,sensitive,and cost-effective method to isolate enteroviruses from sewage.展开更多
The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a global pandemic of novel coronavirus disease(COVID-19).The neutralizing monoclonal antibodies(mAbs)targeting the receptor-binding domain(RBD)...The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a global pandemic of novel coronavirus disease(COVID-19).The neutralizing monoclonal antibodies(mAbs)targeting the receptor-binding domain(RBD)of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19.However,SARS-CoV-2 variants of concern(VOCs)profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use.Herein,we demonstrated mAb 35B5 efficiently neutralizes both wild-type(WT)SARS-CoV-2 and VOCs.展开更多
基金supported by the National Research and Development Project of China(2020YFC0841100,2020YFC0846400,and 2020YFA0707600)CAMS Innovation Fund for Medical Sciences(2016-I2M-2-006 and 2020-I2M-CoV19-012)+1 种基金the Talents Project of Yunnan Province(2017HB068)the Special Funds for High-level Health and Family Planning Technical Personnel training of Yunnan Province(D-201653).
文摘Identification of a suitable nonhuman primate(NHP)model of COVID-19 remains challenging.Here,we characterized severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection in three NHP species:Old World monkeys Macaca mulatta(M.mulatta)and Macaca fascicularis(M.fascicularis)and New World monkey Callithrix jacchus(C.jacchus).Infected M.mulatta and M.fascicularis showed abnormal chest radiographs,an increased body temperature and a decreased body weight.Viral genomes were detected in swab and blood samples from all animals.Viral load was detected in the pulmonary tissues of M.mulatta and M.fascicularis but not C.jacchus.Furthermore,among the three animal species,M.mulatta showed the strongest response to SARS-CoV-2,including increased inflammatory cytokine expression and pathological changes in the pulmonary tissues.Collectively,these data revealed the different susceptibilities of Old World and New World monkeys to SARS-CoV-2 and identified M.mulatta as the most suitable for modeling COVID-19.
基金2017 Xining Citizens’Biotechnology Plan Project(Project number:2017-K-15)。
文摘Objective:To explore the value of using the venous-arterial carbon dioxide partial pressure difference and the arterial-venous oxygen content difference ratio(ΔP_(CO2)/Ca-v_(O2))as targets to guide early tissue hypoperfusion in sepsis in plateau areas.Methods:90 sepsis patients admitted to the Third People’s Hospital of Xining and Golmud People’s Hospital from June 2017 to December 2022 were selected as the research subjects,and they were divided into the Scv_(O2)(central venous oxygen saturation)group and theΔP_(CO2)/Ca-v_(O2)group,with 45 cases in each group.The two groups were treated with early shock resuscitation according to different protocols.The hemodynamic characteristics of the two groups of patients before and after resuscitation were observed,and the volume responsiveness was evaluated.The ROC(receiver operating characteristic)curve was used to analyze the significance ofΔP_(CO2)/Ca-v_(O2),Scv_(O2),lactate,lactate clearance,and urine output in evaluating patient prognosis and the correlation betweenΔP_(CO2)/Ca-v_(O2)and the above indicators was explored.Results:Compared with before resuscitation,after fluid resuscitation,the heart rate(HR),mean arterial pressure(MAP),central venous pressure(CVP),cardiac index(CI),lactate,lactate clearance rate,and urine output of the two groups of patients were significantly improved(P<0.05);in terms of therapeutic effect,the 28-day mortality rate,6-hour fluid balance,and lactic acid clearance of theΔP_(CO2)/Ca-v_(O2)group were better than the Scv_(O2)group.The ROC characteristic curve showed that theΔP_(CO2)/Ca-v_(O2)value can effectively predict the prognosis of patients(AUC=0.907,sensitivity was 97%,specificity was 72.4%,and critical value was 1.84).ΔP_(CO2)/Ca-v_(O2)significantly correlated with Scv_(O2),lactic acid,and lactic acid clearance rate.Conclusion:TheΔP_(CO2)/Ca-v_(O2)value can be used to guide fluid resuscitation in early hypoperfusion in sepsis in plateau areas,improve patients’hemodynamics,reduce lactate indicators,and increase urine ou
基金supported by the National Key Research and Development Program of China(Project No.2021YFC2302003)the Natural Science Foundation of Beijing(Project No.L192014).
文摘This study aimed to compare the sensitivity of two-phase separation and the filtration method using a mixed cellulose ester(MCE)membrane to detect enteroviruses in sewage samples.From December 2015 to July 2016,four domestic sewage samples(1 L/sample)were collected monthly from the Guangzhou Liede Sewage Treatment Plant,and each sewage sample was divided into two aliquots(500 mL).The sewage sample was concentrated using the two-phase separation and the filtration method using an MCE membrane,and the treated solutions were inoculated into cells for enterovirus isolation.Polymerase chain reaction amplification,VP1 sequencing,and enterovirus molecular typing were performed on the positive isolates.The detection rates of poliovirus(PV)and non-polio enterovirus(NPEV)obtained using the filtration method using an MCE membrane were higher than those using the two-phase separation method.McNemar's test showed that the detection rates of PV,NPEV,type 1 Sabin-like(SL1),type 2 Sabin-like(SL2),and type 3 Sabin-like(SL3)strain were not statistically significant(P>0.05).In Guangdong Province,China,the detection rates for PV and NPEV were 53.13%and 62.50%(20/32),respectively.Twenty-seven PVs were isolated,three highly variable strains of the type 1 vaccine,with seven nucleotide substitutions in the VP1 region,compared with the type 1 Sabin strains.Eighty-seven strains of NPEV were isolated and nine serotypes were identified,among which coxsackievirus B3(CVB3),echovirus 6(E6),and echovirus 11(E11)were the dominant strains.The filtration method using an MCE membrane is more sensitive than two-phase separation and can be used as a robust,sensitive,and cost-effective method to isolate enteroviruses from sewage.
基金We thank Guangdong Center for Human Pathogen Culture Collection(GDPCC)for providing SARS-CoV-2 isolates.We thank Dr.Junyu Xiao(Peking University)for providing the plasmids encoding the ectodomains of the SARS-CoV-2 S-2P and S-6P mutants.This work was supported by grants from the National Natural Science Fund for Distinguished Young Scholars(No.31825011 to L.Y.)the National Science and Technology Major Project(No.2017ZX10202102-006-002 to L.Y.)+2 种基金Guangdong Innovative and Entrepreneurial Research Team Program(2016ZT06S638 to K.D.)High-level Biosafety Laboratory Construction and Operation Program of the Science and Technology Projects of Guangdong Province of China to K.D.,the National Natural Science Fund(81925024 to Y.Z.)the National Key Research and Development Program of China(2017YFA0503900 to Y.Z.),and the Fundamental Research Funds for the Central Universities to Y.Z.
文摘The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused a global pandemic of novel coronavirus disease(COVID-19).The neutralizing monoclonal antibodies(mAbs)targeting the receptor-binding domain(RBD)of SARS-CoV-2 are among the most promising strategies to prevent and treat COVID-19.However,SARS-CoV-2 variants of concern(VOCs)profoundly reduced the efficacies of most of mAbs and vaccines approved for clinical use.Herein,we demonstrated mAb 35B5 efficiently neutralizes both wild-type(WT)SARS-CoV-2 and VOCs.
