BACKGROUND Enhancing awareness and use of pre-exposure prophylaxis(PrEP)and postexposure prophylaxis(PEP)is vital to curb human immunodeficiency virus(HIV)spread.High-risk behaviors prevalent among sexually transmitte...BACKGROUND Enhancing awareness and use of pre-exposure prophylaxis(PrEP)and postexposure prophylaxis(PEP)is vital to curb human immunodeficiency virus(HIV)spread.High-risk behaviors prevalent among sexually transmitted infection clinic outpatients underscore the need for increased PrEP/PEP education in this group.AIM To investigate the effects of both onsite and online health education on the knowledge of,and willingness to use,PrEP and PEP among individuals receiving PEP services.METHODS Participants were drawn from a cohort study on PEP service intervention at an STD/AIDS outpatient clinic in designated HIV/AIDS hospitals in Beijing,conducted from January 1 to June 30,2022.Health education was provided both onsite and online during follow-up.Surveys assessing knowledge of,and willingness to use,PrEP/PEP were administered at baseline and again at 24 wk post-intervention.RESULTS A total of 112 participants were enrolled in the study;105 completed the follow-up at week 24.The percentage of participants with adequate knowledge of,and willingness to use,PrEP significantly increased from 65.2%and 69.6%at baseline to 83.8%and 82.9%at the end of the intervention(both P<0.05).Similarly,those with adequate knowledge of,and willingness to use,PEP increased from 74.1%and 77.7%at baseline to 92.4%and 89.5%at week 24(P<0.05).Being between 31 years and 40 years of age,having a postgraduate degree or higher,and reporting a monthly expenditure of RMB 5000 or more were found to be significantly associated with knowledge of PrEP and PEP(both P<0.05).CONCLUSION The findings show that both onsite and online health education significantly improved the knowledge of,and increased willingness to use,PrEP and PEP in individuals utilizing PEP services.展开更多
A comprehensive experimental program has been performed to characterize the hydration and engineering property evolution of a class G oil well cement under various curing temperatures from 30 to 90℃.The progress of h...A comprehensive experimental program has been performed to characterize the hydration and engineering property evolution of a class G oil well cement under various curing temperatures from 30 to 90℃.The progress of hydration was monitored by isothermal calorimetry(atmospheric pressure);the viscosity evolution was measured using a high temperature and high pressure consistometer(up to 200 MPa);the ultrasonic property development was evaluated by an ultrasonic cement analyzer(up to 100 MPa).Test results indicate that the influences of curing temperature and pressure on the hydration,viscosity and ultrasonic property development can be modeled by a scale factor method that is similar to the maturity method used in the concrete industry.However,the key parameters of the scale factor model,namely the apparent activation energy and the apparent activation volume of cement showed obvious variations with test method and curing condition.The test results indicate that the curing temperature has a stronger effect on cement hydration rate than viscosity and ultrasonic property development rate,while the curing pressure has a much stronger influence on cement slurry properties before setting(viscosity)than after setting(ultrasonic property).展开更多
BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of h...BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of hepatitis B core-related antigen(HBcrAg)for hepatic histologic changes in patients with chronic hepatitis B(CHB)treated with entecavir.METHODS This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression,respectively,in 403 CHB patients,including 374 with entecavir for 72 weeks(291 underwent paired liver biopsy)and 29 as controls.RESULTS Level of HBcrAg correlated negatively with liver fibrosis staging(γ=-0.357,P<0.001)in hepatitis B e antigen(HBeAg)-positive patients,and positively with liver fibrosis staging in HBeAg-negative patients.Higher HBcrAg concentration was associated with younger age,HBeAg positive status,high HBV DNA loads,high level of hepatitis B surface antigen(HBsAg)and higher necroinflammation,but not with HBV genotype.Serum concentration of HBcrAg,basal core promoter/precore(BCP/PC)mutant,quantitation of HBsAg(qHBsAg)and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression.HBV DNA was undetectable in 88.37%of patients treated with entecavir at week 72,while their level of HBcrAg was still detectable.A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement.HBcrAg concentration>6.33 log IU/mL at baseline and logarithmic reduction>1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement,respectively.CONCLUSION HBcrAg level is associated with liver fibrosis progression.HBcrAg is an excellent monitor of hepatic histological changes,especially in CHB patients treated with nucleoside analogs.展开更多
High Mountain Asia(HMA)shows a remarkable warming tendency and divergent trend of regional precipitation with enhanced meteorological extremes.The rapid thawing of the HMA cryosphere may alter the magnitude and freque...High Mountain Asia(HMA)shows a remarkable warming tendency and divergent trend of regional precipitation with enhanced meteorological extremes.The rapid thawing of the HMA cryosphere may alter the magnitude and frequency of nature hazards.We reviewed the influence of climate change on various types of nature hazards in HMA region,including their phenomena,mechanisms and impacts.It reveals that:1)the occurrences of extreme rainfall,heavy snowfall,and drifting snow hazards are escalating;accelerated ice and snow melting have advanced the onset and increased the magnitude of snowmelt floods;2)due to elevating trigger factors,such as glacier debuttressing and the rapid shift of thermal and hydrological regime of bedrock/snow/ice interface or subsurface,the mass flow hazards including bedrock landslide,snow avalanche,ice-rock avalanches or glacier detachment,and debris flow will become more severe;3)increased active-layer detachment and retrogressive thaw slumps slope failures,thaw settlement and thermokarst lake will damage many important engineering structures and infrastructure in permafrost region;4)multi-hazards cascading hazard in HMA,such as the glacial lake outburst flood(GLOF)and avalanche-induced mass flow may greatly enlarge the destructive power of the primary hazard by amplifying its volume,mobility,and impact force;and 5)enhanced slope instability and sediment supply in the highland areas could impose remote catastrophic impacts upon lowland regions,and threat hydropower security and future water shortage.In future,ongoing thawing of HMA will profoundly weaken the multiple-phase material of bedrock,ice,water,and soil,and enhance activities of nature hazards.Compounding and cascading hazards of high magnitude will prevail in HMA.As the glacier runoff overpasses the peak water,low flow or droughts in lowland areas downstream of glacierized mountain regions will became more frequent and severe.Addressing escalating hazards in the HMA region requires tackling scientific challenges,including understanding multiscale evolution and formation mechanism of HMA hazard-prone systems,coupling thermo‒hydro‒mechanical processes in multi-phase flows,predicting catastrophes arising from extreme weather and climate events,and comprehending how highland hazards propagate to lowlands due to climate change.展开更多
Background:Albuvirtide is a once-weekly injectable human immunodeficiency virus(HIV)-1 fusion inhibitor.We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-riton...Background:Albuvirtide is a once-weekly injectable human immunodeficiency virus(HIV)-1 fusion inhibitor.We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.Methods:We carried out a 48-week,randomized,controlled,open-label non-inferiority trial at 12 sites in China.Adults on the World Health Organization(WHO)-recommended first-line treatment for>6 months with a plasma viral load>1000 copies/mL were enrolled and randomly assigned(1:1)to receive albuvirtide(once weekly)plus ritonavir-boosted lopinavir(ABT group)or the WHO-recommended second-line treatment(NRTI group).The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks.Non-inferiority was prespecified with a margin of 12%.Results:At the time of analysis,week 24 data were available for 83 and 92 patients,and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups,respectively.At 48 weeks,80.4%of patients in the ABT group and 66.0%of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL,meeting the criteria for non-inferiority.For the per-protocol population,the superiority of albuvirtide over NRTI was demonstrated.The frequency of grade 3 to 4 adverse events was similar in the two groups;the most common adverse events were diarrhea,upper respiratory tract infections,and grade 3 to 4 increases in triglyceride concentration.Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.Conclusions:The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug.This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.Trial registration:ClinicalTrials.gov Identifier:NCT02369965;https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No.ChiCTR-TRC-14004276;http://www.chictr.org.cn/enindex.aspx.展开更多
Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the...Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R).This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation ofNLRP3 inflammasome.Methods:A mouse model of ORG was established by high-fat diet feeding.The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079).The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3,ASC,and caspase-1,as well as the podocyte-associated molecules including nephrin,podocin,and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Westem blot analysis,respectively.Results:The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo,which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules.Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression ofpodocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro,and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079.Conclusions:P2X7R could trigger the activation ofNLRP3 inflammasome,and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.展开更多
Objective:This study summarizes and compares clinical and laboratory characteristics of 34 patients admitted to the intensive care unit(ICU)for complications from coronavirus disease 2019(COVID-19)at the First Affilia...Objective:This study summarizes and compares clinical and laboratory characteristics of 34 patients admitted to the intensive care unit(ICU)for complications from coronavirus disease 2019(COVID-19)at the First Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou,China from Jan.22 to Mar.5,2020.Methods:A total of 34 patients were divided into two groups,including those who required noninvasive ventilation(NIV)and invasive mechanical ventilation(IMV)with additional extracorporeal membrane oxygenation(ECMO)in 11 patients.Clinical features of COVID-19 patients were described and the parameters of clinical characteristics between the two groups were compared.Results:The rates of the acute cardiac and kidney complications were higher in IMV cases than those in NIV cases.Most patients had lymphocytopenia on admission,with lymphocyte levels dropping progressively on the following days,and the more severe lymphopenia developed in the IMV group.In both groups,T lymphocyte counts were below typical lower limit norms compared to B lymphocytes.On admission,both groups had higher than expected amounts of plasma interleukin-6(IL-6),which over time declined more in NIV patients.The prothrombin time was increased and the levels of platelet,hemoglobin,blood urea nitrogen(BUN),D-dimer,lactate dehydrogenase(LDH),and IL-6 were higher in IMV cases compared with NIV cases during hospitalization.Conclusions:Data showed that the rates of complications,dynamics of lymphocytopenia,and changes in levels of platelet,hemoglobin,BUN,D-dimer,LDH and IL-6,and prothrombin time in these ICU patients were significantly different between IMV and NIV cases.展开更多
Previous studies have indicated that two monoclonal antibodies(mAbs;A1-10 and H1-84)of the hemagglutinin(HA)antigen on the H1N1 influenza virus cross-react with human brain tissue.It has been proposed that there are h...Previous studies have indicated that two monoclonal antibodies(mAbs;A1-10 and H1-84)of the hemagglutinin(HA)antigen on the H1N1 influenza virus cross-react with human brain tissue.It has been proposed that there are heterophilic epitopes between the HA protein and human brain tissue(Guo et al.in Immunobiology 220:941-946,2015).However,characterisation of the two mAbs recognising the heterophilic epitope on HA has not yet been performed.In the present study,the common antigens of influenza virus HA were confirmed using indirect enzyme-linked immunosorbent assays and analysed with DNAMAN software.The epitopes were localized to nine peptides in the influenza virus HA sequence and the distribution of the peptides in the three-dimensional structure of HA was determined using PyMOL software.Key amino acids and variable sequences of the antibodies were identified using abYsis software.The results demonstrated that there were a number of common antigens among the five influenza viruses studied that were recognised by the mAbs.One of the peptides,P2(LVLWGIHHP191-199),bound both of the mAbs and was located in the head region of HA.The key amino acids of this epitope and the variable regions in the heavy and light chain sequences of the mAbs that recognised the epitope are described.A heterophilic epitope on H1N1 influenza virus HA was also introduced.The existence of this epitope provides a novel perspective for the occurrence of nervous system diseases that could be caused by influenza virus infection,which might aid in influenza prevention and control.展开更多
Objective:To investigate the effects of exogenousα-linolenic acid(ALA)on in vitro maturation(IVM)and developmental competence of human oocytes.Methods:Experiment 1 examined the effects of ALA at different concentrati...Objective:To investigate the effects of exogenousα-linolenic acid(ALA)on in vitro maturation(IVM)and developmental competence of human oocytes.Methods:Experiment 1 examined the effects of ALA at different concentrations(0[control],10,50,100,and 200μmol/L)in the IVM medium on oocyte maturation.Treatment with 50μmol/L ALA significantly accelerated oocyte maturation(P<0.05)and resulted in significantly higher mitochondrial DNA(mtDNA)copy number compared to the control.Hence,50μmol/L ALA was selected for combination with follicular fluid(FF)to investigate oocyte developmental potential.mtDNA of the matured oocyte was analyzed by real-time polymerase chain reaction.Experiment 2 investigated the effects of FF with optimal ALA concentration(Group A:ALA+FF+IVM medium)or without ALA(Group B:FF+IVM medium)on oocyte maturation,fertilization,2 pronuclear cleavage,and embryo and blastocyst development.Malondialdehyde(MDA)content and superoxide dismutase(SOD)activity were measured for maturation medium from Group A,Group B,and Group C(control group,IVM medium only).Results:Treatment with 50μmol/L ALA obviously accelerated oocyte maturation(P<0.05)and resulted in significantly higher mtDNA copy number(P<0.05)in the matured oocytes compared to the control(0μmol/L ALA).Supplementation of 50μmol/L ALA and FF(Group A)obviously increased the total maturation rate than FF-treated group(Group B)which has higher(P<0.05)total maturation rate than that of Group C.However,no significant differences were observed in fertilization,embryo availability,and blastocyst production among Group A,B,and C.Treatment with 50μmol/L ALA decreased the level of MDA(P<0.05),but had no effect on the activity of SOD in the IVM medium.Conclusions:Our results suggested that the treatment with 50μmol/L ALA during IVM improves maturation in human oocytes.It is also likely to improve embryo availability and blastocyst formation.This might be associated with the alteration of mtDNA replication(increased mtDNA copy number)and the reduction of oxidative stress(reduced MDA level).展开更多
Introduction The Jiangmen Underground Neutrino Observatory has critical requirements on quality of the liquid scintillator,one of which is long attenuation length.Purpose A system with a height of 3 m is used to preci...Introduction The Jiangmen Underground Neutrino Observatory has critical requirements on quality of the liquid scintillator,one of which is long attenuation length.Purpose A system with a height of 3 m is used to precisely measure the attenuation length of the liquid scintillators.Methods The light generated by a LED is transmitted through an optical fiber.After being focused,filtered and collimated,the light enters the test tube with the liquid scintillator and is detected by the PMT.The stepping motor is controlled by the Labview program to adjust the level of the liquid scintillator,and the emitted light intensity of different liquid levels can be obtained to fit the attenuation length.In addition,the systematic errors have been studied,which includes the measurement error of the emitted light intensity and the error caused by the movement of light spot,and the latter is responded to the non-uniformity of the PMT photocathode.Meanwhile,analytical methods were improved.Results The system can measure the attenuation length stably and a small error was obtained,including statistical error and systematic error(0.69-23.70 m).展开更多
基金This study received ethical approval from the ethics committee of Beijing Youan Hospital,Capital Medical University[No.(2021)078]the research was implemented in strict conformity with the guidelines outlined in the Declaration of Helsinki.
文摘BACKGROUND Enhancing awareness and use of pre-exposure prophylaxis(PrEP)and postexposure prophylaxis(PEP)is vital to curb human immunodeficiency virus(HIV)spread.High-risk behaviors prevalent among sexually transmitted infection clinic outpatients underscore the need for increased PrEP/PEP education in this group.AIM To investigate the effects of both onsite and online health education on the knowledge of,and willingness to use,PrEP and PEP among individuals receiving PEP services.METHODS Participants were drawn from a cohort study on PEP service intervention at an STD/AIDS outpatient clinic in designated HIV/AIDS hospitals in Beijing,conducted from January 1 to June 30,2022.Health education was provided both onsite and online during follow-up.Surveys assessing knowledge of,and willingness to use,PrEP/PEP were administered at baseline and again at 24 wk post-intervention.RESULTS A total of 112 participants were enrolled in the study;105 completed the follow-up at week 24.The percentage of participants with adequate knowledge of,and willingness to use,PrEP significantly increased from 65.2%and 69.6%at baseline to 83.8%and 82.9%at the end of the intervention(both P<0.05).Similarly,those with adequate knowledge of,and willingness to use,PEP increased from 74.1%and 77.7%at baseline to 92.4%and 89.5%at week 24(P<0.05).Being between 31 years and 40 years of age,having a postgraduate degree or higher,and reporting a monthly expenditure of RMB 5000 or more were found to be significantly associated with knowledge of PrEP and PEP(both P<0.05).CONCLUSION The findings show that both onsite and online health education significantly improved the knowledge of,and increased willingness to use,PrEP and PEP in individuals utilizing PEP services.
基金Financial support comes from China National Natural Science Foundation(No.51974352)as well as from China University of Petroleum(East China)(No.2018000025 and No.2019000011).
文摘A comprehensive experimental program has been performed to characterize the hydration and engineering property evolution of a class G oil well cement under various curing temperatures from 30 to 90℃.The progress of hydration was monitored by isothermal calorimetry(atmospheric pressure);the viscosity evolution was measured using a high temperature and high pressure consistometer(up to 200 MPa);the ultrasonic property development was evaluated by an ultrasonic cement analyzer(up to 100 MPa).Test results indicate that the influences of curing temperature and pressure on the hydration,viscosity and ultrasonic property development can be modeled by a scale factor method that is similar to the maturity method used in the concrete industry.However,the key parameters of the scale factor model,namely the apparent activation energy and the apparent activation volume of cement showed obvious variations with test method and curing condition.The test results indicate that the curing temperature has a stronger effect on cement hydration rate than viscosity and ultrasonic property development rate,while the curing pressure has a much stronger influence on cement slurry properties before setting(viscosity)than after setting(ultrasonic property).
基金Supported by Chinese Ministry of Science and Technology Grants the Major Science and Technology Special Project Fund Scheme,No.2013ZX10005002Beijing the Special Clinical Application Research and Translational Grants,No.Z151100004015221
文摘BACKGROUND Non-invasive evaluation for liver fibrosis is clinically important,especially in patients with undetectable hepatitis B virus(HBV)DNA treated with nucleoside analogs.AIM To clarify the monitoring power of hepatitis B core-related antigen(HBcrAg)for hepatic histologic changes in patients with chronic hepatitis B(CHB)treated with entecavir.METHODS This prospective multicenter study used multiple ordinal and multivariate logistics regression analysis to assess variables associated with Ishak fibrosis score and regression for fibrosis regression,respectively,in 403 CHB patients,including 374 with entecavir for 72 weeks(291 underwent paired liver biopsy)and 29 as controls.RESULTS Level of HBcrAg correlated negatively with liver fibrosis staging(γ=-0.357,P<0.001)in hepatitis B e antigen(HBeAg)-positive patients,and positively with liver fibrosis staging in HBeAg-negative patients.Higher HBcrAg concentration was associated with younger age,HBeAg positive status,high HBV DNA loads,high level of hepatitis B surface antigen(HBsAg)and higher necroinflammation,but not with HBV genotype.Serum concentration of HBcrAg,basal core promoter/precore(BCP/PC)mutant,quantitation of HBsAg(qHBsAg)and platelet counts were independently associated with Ishak fibrosis score on multiple ordinal regression.HBV DNA was undetectable in 88.37%of patients treated with entecavir at week 72,while their level of HBcrAg was still detectable.A greater reduction in post-treatment HBcrAg concentration was associated with the regression of hepatic fibrosis and histological improvement.HBcrAg concentration>6.33 log IU/mL at baseline and logarithmic reduction>1.03 log IU/mL at week 72 were associated with a higher chance of regression of liver fibrosis and histological improvement,respectively.CONCLUSION HBcrAg level is associated with liver fibrosis progression.HBcrAg is an excellent monitor of hepatic histological changes,especially in CHB patients treated with nucleoside analogs.
基金the National Natural Science Foundation of China(41941017,42101083)the Second Tibetan Plateau Scientific Expedition and Research Program(STEP)(2019QZKK0906)Science and Technology Research Program of Institute of Mountain Hazards and Environment,Chinese Academy of Sciences(IMHE-ZDRW-02).
文摘High Mountain Asia(HMA)shows a remarkable warming tendency and divergent trend of regional precipitation with enhanced meteorological extremes.The rapid thawing of the HMA cryosphere may alter the magnitude and frequency of nature hazards.We reviewed the influence of climate change on various types of nature hazards in HMA region,including their phenomena,mechanisms and impacts.It reveals that:1)the occurrences of extreme rainfall,heavy snowfall,and drifting snow hazards are escalating;accelerated ice and snow melting have advanced the onset and increased the magnitude of snowmelt floods;2)due to elevating trigger factors,such as glacier debuttressing and the rapid shift of thermal and hydrological regime of bedrock/snow/ice interface or subsurface,the mass flow hazards including bedrock landslide,snow avalanche,ice-rock avalanches or glacier detachment,and debris flow will become more severe;3)increased active-layer detachment and retrogressive thaw slumps slope failures,thaw settlement and thermokarst lake will damage many important engineering structures and infrastructure in permafrost region;4)multi-hazards cascading hazard in HMA,such as the glacial lake outburst flood(GLOF)and avalanche-induced mass flow may greatly enlarge the destructive power of the primary hazard by amplifying its volume,mobility,and impact force;and 5)enhanced slope instability and sediment supply in the highland areas could impose remote catastrophic impacts upon lowland regions,and threat hydropower security and future water shortage.In future,ongoing thawing of HMA will profoundly weaken the multiple-phase material of bedrock,ice,water,and soil,and enhance activities of nature hazards.Compounding and cascading hazards of high magnitude will prevail in HMA.As the glacier runoff overpasses the peak water,low flow or droughts in lowland areas downstream of glacierized mountain regions will became more frequent and severe.Addressing escalating hazards in the HMA region requires tackling scientific challenges,including understanding multiscale evolution and formation mechanism of HMA hazard-prone systems,coupling thermo‒hydro‒mechanical processes in multi-phase flows,predicting catastrophes arising from extreme weather and climate events,and comprehending how highland hazards propagate to lowlands due to climate change.
基金Frontier Biotechnologies Inc.,Ministry of Science and Technology of China(Nos.2013ZX09101001 and 2017ZX09201007)the Beijing Municipal of Science and Technology Major Project(Nos.D141100000314005,D141100000314002,and D161100000416003)+1 种基金the National Natural Science Foundation of China(Nos.81772165,81974303,and 81571973)Beijing Key Laboratory for HIV/AIDS Research(No.BZ0089)。
文摘Background:Albuvirtide is a once-weekly injectable human immunodeficiency virus(HIV)-1 fusion inhibitor.We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.Methods:We carried out a 48-week,randomized,controlled,open-label non-inferiority trial at 12 sites in China.Adults on the World Health Organization(WHO)-recommended first-line treatment for>6 months with a plasma viral load>1000 copies/mL were enrolled and randomly assigned(1:1)to receive albuvirtide(once weekly)plus ritonavir-boosted lopinavir(ABT group)or the WHO-recommended second-line treatment(NRTI group).The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks.Non-inferiority was prespecified with a margin of 12%.Results:At the time of analysis,week 24 data were available for 83 and 92 patients,and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups,respectively.At 48 weeks,80.4%of patients in the ABT group and 66.0%of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL,meeting the criteria for non-inferiority.For the per-protocol population,the superiority of albuvirtide over NRTI was demonstrated.The frequency of grade 3 to 4 adverse events was similar in the two groups;the most common adverse events were diarrhea,upper respiratory tract infections,and grade 3 to 4 increases in triglyceride concentration.Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.Conclusions:The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug.This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.Trial registration:ClinicalTrials.gov Identifier:NCT02369965;https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No.ChiCTR-TRC-14004276;http://www.chictr.org.cn/enindex.aspx.
基金grants from the National Natural Science Foundation of China (No.81573745and No.8160140274)Beijing Municipal Natural Science Foundation (No.7172066) Beijing Development Foundation of Traditional Chinese Medicine (QN2016-23).
文摘Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R).This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation ofNLRP3 inflammasome.Methods:A mouse model of ORG was established by high-fat diet feeding.The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079).The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3,ASC,and caspase-1,as well as the podocyte-associated molecules including nephrin,podocin,and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Westem blot analysis,respectively.Results:The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo,which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules.Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression ofpodocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro,and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079.Conclusions:P2X7R could trigger the activation ofNLRP3 inflammasome,and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.
基金the Project for Emergency of Key R&D Plan from Zhejiang Science and Technology Agency(No.2020C03123),China。
文摘Objective:This study summarizes and compares clinical and laboratory characteristics of 34 patients admitted to the intensive care unit(ICU)for complications from coronavirus disease 2019(COVID-19)at the First Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou,China from Jan.22 to Mar.5,2020.Methods:A total of 34 patients were divided into two groups,including those who required noninvasive ventilation(NIV)and invasive mechanical ventilation(IMV)with additional extracorporeal membrane oxygenation(ECMO)in 11 patients.Clinical features of COVID-19 patients were described and the parameters of clinical characteristics between the two groups were compared.Results:The rates of the acute cardiac and kidney complications were higher in IMV cases than those in NIV cases.Most patients had lymphocytopenia on admission,with lymphocyte levels dropping progressively on the following days,and the more severe lymphopenia developed in the IMV group.In both groups,T lymphocyte counts were below typical lower limit norms compared to B lymphocytes.On admission,both groups had higher than expected amounts of plasma interleukin-6(IL-6),which over time declined more in NIV patients.The prothrombin time was increased and the levels of platelet,hemoglobin,blood urea nitrogen(BUN),D-dimer,lactate dehydrogenase(LDH),and IL-6 were higher in IMV cases compared with NIV cases during hospitalization.Conclusions:Data showed that the rates of complications,dynamics of lymphocytopenia,and changes in levels of platelet,hemoglobin,BUN,D-dimer,LDH and IL-6,and prothrombin time in these ICU patients were significantly different between IMV and NIV cases.
基金supported by The National Key Research and Development Program of China (Grant No. 2016YFD0500700)The Natural Science Basic Research Program of Shaanxi Province (Grant No. 2016JM8065)Shaanxi Provincial People’s Hospital Incubation Fund Program (Grant No. 2015YX-4)
文摘Previous studies have indicated that two monoclonal antibodies(mAbs;A1-10 and H1-84)of the hemagglutinin(HA)antigen on the H1N1 influenza virus cross-react with human brain tissue.It has been proposed that there are heterophilic epitopes between the HA protein and human brain tissue(Guo et al.in Immunobiology 220:941-946,2015).However,characterisation of the two mAbs recognising the heterophilic epitope on HA has not yet been performed.In the present study,the common antigens of influenza virus HA were confirmed using indirect enzyme-linked immunosorbent assays and analysed with DNAMAN software.The epitopes were localized to nine peptides in the influenza virus HA sequence and the distribution of the peptides in the three-dimensional structure of HA was determined using PyMOL software.Key amino acids and variable sequences of the antibodies were identified using abYsis software.The results demonstrated that there were a number of common antigens among the five influenza viruses studied that were recognised by the mAbs.One of the peptides,P2(LVLWGIHHP191-199),bound both of the mAbs and was located in the head region of HA.The key amino acids of this epitope and the variable regions in the heavy and light chain sequences of the mAbs that recognised the epitope are described.A heterophilic epitope on H1N1 influenza virus HA was also introduced.The existence of this epitope provides a novel perspective for the occurrence of nervous system diseases that could be caused by influenza virus infection,which might aid in influenza prevention and control.
基金This work has been supported by the Henan Province Medical Science and Technique Project(grant no.201403109).
文摘Objective:To investigate the effects of exogenousα-linolenic acid(ALA)on in vitro maturation(IVM)and developmental competence of human oocytes.Methods:Experiment 1 examined the effects of ALA at different concentrations(0[control],10,50,100,and 200μmol/L)in the IVM medium on oocyte maturation.Treatment with 50μmol/L ALA significantly accelerated oocyte maturation(P<0.05)and resulted in significantly higher mitochondrial DNA(mtDNA)copy number compared to the control.Hence,50μmol/L ALA was selected for combination with follicular fluid(FF)to investigate oocyte developmental potential.mtDNA of the matured oocyte was analyzed by real-time polymerase chain reaction.Experiment 2 investigated the effects of FF with optimal ALA concentration(Group A:ALA+FF+IVM medium)or without ALA(Group B:FF+IVM medium)on oocyte maturation,fertilization,2 pronuclear cleavage,and embryo and blastocyst development.Malondialdehyde(MDA)content and superoxide dismutase(SOD)activity were measured for maturation medium from Group A,Group B,and Group C(control group,IVM medium only).Results:Treatment with 50μmol/L ALA obviously accelerated oocyte maturation(P<0.05)and resulted in significantly higher mtDNA copy number(P<0.05)in the matured oocytes compared to the control(0μmol/L ALA).Supplementation of 50μmol/L ALA and FF(Group A)obviously increased the total maturation rate than FF-treated group(Group B)which has higher(P<0.05)total maturation rate than that of Group C.However,no significant differences were observed in fertilization,embryo availability,and blastocyst production among Group A,B,and C.Treatment with 50μmol/L ALA decreased the level of MDA(P<0.05),but had no effect on the activity of SOD in the IVM medium.Conclusions:Our results suggested that the treatment with 50μmol/L ALA during IVM improves maturation in human oocytes.It is also likely to improve embryo availability and blastocyst formation.This might be associated with the alteration of mtDNA replication(increased mtDNA copy number)and the reduction of oxidative stress(reduced MDA level).
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA10010500)National Natural Science Foundation of China(11390384).
文摘Introduction The Jiangmen Underground Neutrino Observatory has critical requirements on quality of the liquid scintillator,one of which is long attenuation length.Purpose A system with a height of 3 m is used to precisely measure the attenuation length of the liquid scintillators.Methods The light generated by a LED is transmitted through an optical fiber.After being focused,filtered and collimated,the light enters the test tube with the liquid scintillator and is detected by the PMT.The stepping motor is controlled by the Labview program to adjust the level of the liquid scintillator,and the emitted light intensity of different liquid levels can be obtained to fit the attenuation length.In addition,the systematic errors have been studied,which includes the measurement error of the emitted light intensity and the error caused by the movement of light spot,and the latter is responded to the non-uniformity of the PMT photocathode.Meanwhile,analytical methods were improved.Results The system can measure the attenuation length stably and a small error was obtained,including statistical error and systematic error(0.69-23.70 m).