BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accu...BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality.Soluble triggering receptor expressed on myeloid cells-1(sTREM-1)is released from activated innate immune cells and correlated with various inflammatory processes.AIM To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis.METHODS A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort(n=309)and validation cohort(n=133).Demographic and clinical data were collected,and serum sTREM-1 was measured at admission.All enrolled patients were followed-up for at least 1 year.RESULTS In patients with AD and cirrhosis,serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver,coagulation,cerebral and kidney failure.A new prognostic model of AD(P-AD)incorporating sTREM-1,blood urea nitrogen(BUN),total bilirubin(TBil),international normalized ratio(INR)and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease(MELD),MELD-sodium(MELD-Na),chronic liver failure-consortium(CLIF-C)ACLF and CLIF-C AD scores.Additionally,sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up.The ACLF risk score incorporating serum sTREM-1,BUN,INR,TBil and aspartate aminotransferase levels was established and significantly superior to MELD,MELD-Na,CLIF-C ACLF,CLIF-C AD and P-AD in predicting risk of ACLF development.CONCLUSION Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.展开更多
Background:Although concomitant nonalcoholic steatohepatitis(NASH)is common in chronic hepatitis B(CHB),the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear.We aimed...Background:Although concomitant nonalcoholic steatohepatitis(NASH)is common in chronic hepatitis B(CHB),the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear.We aimed to investigate the outcomes of NASH in CHB patients receiving antiviral treatment.Methods:In the post-hoc analysis of a multicenter trial,na?ve CHB patients receiving 72-week entecavir treatment were enrolled.We evaluated the biochemical,viral and histopathological responses of these patients.The histopathological features of NASH were also evaluated,using paired liver biopsies at baseline and week 72.Results:A total of 1000 CHB patients were finally enrolled for analysis,with 18.2%of whom fulfilling the criteria of NASH.A total of 727 patients completed entecavir antiviral treatment and received the second biopsy.Serum HBe Ag loss,HBe Ag seroconversion and HBV-DNA undetectable rates were similar between patients with or without NASH(P>0.05).Among patients with NASH,the hepatic steatosis,ballooning,lobular inflammation scores and fibrosis stages all improved during follow-up(all P<0.001),46%(63/136)achieved NASH resolution.Patients with baseline body mass index(BMI)≥23 kg/m2(Asian criteria)[odds ratio(OR):0.414;95%confidence interval(95%CI):0.190-0.899;P=0.012]and weight gain(OR:0.187;95%CI:0.050-0.693;P=0.026)were less likely to have NASH resolution.Among patients without NASH at baseline,22(3.7%)developed NASH.Baseline BMI≥23 kg/m2(OR:12.506;95%CI:2.813-55.606;P=0.001)and weight gain(OR:5.126;95%CI:1.674-15.694;P=0.005)were predictors of incident NASH.Conclusions:Lower BMI and weight reduction but not virologic factors determine NASH resolution in CHB.The value of weight management in CHB patients during antiviral treatment deserves further evaluation.展开更多
BACKGROUND Nucleos(t)ide analogs(NAs)cessation in chronic hepatitis B(CHB)patients remains a matter of debate in clinical practice.Current guidelines recommend that patients with hepatitis B e antigen(HBeAg)seroconver...BACKGROUND Nucleos(t)ide analogs(NAs)cessation in chronic hepatitis B(CHB)patients remains a matter of debate in clinical practice.Current guidelines recommend that patients with hepatitis B e antigen(HBeAg)seroconversion discontinue NAs after relatively long-term consolidation therapy.However,many patients fail to achieve HBeAg seroconversion after the long-term loss of HBeAg,even if hepatitis B surface antigen(HBsAg)loss occurs.It remains unclear whether NAs can be discontinued in this subset of patients.AIM To investigate the outcomes and factors associated with HBeAg-positive CHB patients with HBeAg loss(without hepatitis B e antibody)after cessation of NAs.METHODS We studied patients who discontinued NAs after achieving HBeAg loss.The Cox proportional hazards model was used to identify predictors for virological relapse after cessation of NAs.The cut-off value of the consolidation period was confirmed using receiver operating characteristic curves;we confirmed the cut-off value of HBsAg according to a previous study.The log-rank test was used to compare cumulative relapse rates among groups.We also studied patients with CHB who achieved HBeAg seroconversion and compared their cumulative relapse rates.Propensity score matching analysis(PSM)was used to balance baseline characteristics between the groups.RESULTS We included 83 patients with HBeAg loss.The mean age of these patients was 32.1±9.5 years,and the majority was male(67.5%).Thirty-eight patients relapsed,and the cumulative relapse rate at months 3,6,12,24,36,60,120,and 180 were 22.9%,36.1%,41.0%,43.5%,45.0%,45.0%,45.0%,and 52.8%,respectively.Twentysix(68.4%)patients relapsed in the first 3 mo after NAs cessation,and 35 patients(92.1%)relapsed in the first year after NAs cessation.Consolidation period(≥24 mo vs<24 mo)(HR 0.506,P=0.043)and HBsAg at cessation(≥100 IU/mL vs<100 IU/mL)(HR 14.869,P=0.008)were significant predictors in multivariate Cox regression.In the PSM cohort,which included 144 patients,there were lower cumulative relapse rates in patients with HBeAg seroconversion(P=0.036).CONCLUSION HBeAg-positive CHB patients with HBeAg loss may be able to discontinue NAs therapy after long-term consolidation,especially in patients with HBsAg at cessation<100 IU/mL.Careful monitoring,especially in the early stages after cessation,may ensure a favorable outcome.展开更多
BACKGROUND Autoimmune liver disease(AILD)has been considered a relatively uncommon disease in China,epidemiological data for AILD in patients with cirrhosis and acute decompensation(AD)is sparse.AIM To investigate the...BACKGROUND Autoimmune liver disease(AILD)has been considered a relatively uncommon disease in China,epidemiological data for AILD in patients with cirrhosis and acute decompensation(AD)is sparse.AIM To investigate the prevalence,outcome and risk factors for AILD in cirrhotic patients complicated with AD in China.METHODS We collected data from patients with cirrhosis and AD from two prospective,multicenter cohorts in hepatitis B virus endemic areas.Patients were regularly followed up at the end of 28-d,90-d and 365-d,or until death or liver transplantation(LT).The primary outcome in this study was 90-d LTfree mortality.Acute-on-chronic liver failure(ACLF)was assessed on admission and during 28-d hospitalization,according to the diagnostic criteria of the European Association for the Study of the Liver(EASL).Risk factors for death were analyzed with logistic regression model.RESULTS In patients with cirrhosis and AD,the overall prevalence of AILD was 9.3%(242/2597).Prevalence of ACLF was significantly lower in AILD cases(14%)than those with all etiology groups with cirrhosis and AD(22.8%)(P<0.001).Among 242 enrolled AILD patients,the prevalence rates of primary biliary cirrhosis(PBC),autoimmune hepatitis(AIH)and PBC-AIH overlap syndrome(PBC/AIH)were 50.8%,28.5%and 12.0%,respectively.In ACLF patients,the proportions of PBC,AIH and PBC/AIH were 41.2%,29.4% and 20.6%.28-d and 90-d mortality were 43.8% and 80.0% in AILD-related ACLF.The etiology of AILD had no significant impact on 28-d,90-d or 365-d LTfree mortality in patients with cirrhosis and AD in both univariate and multivariate analysis.Total bilirubin(TB),hepatic encephalopathy(HE)and blood urea nitrogen(BUN)were independent risk factors for 90-d LT-free mortality in multivariate analysis.The development of ACLF during hospitalization only independently correlated to TB and international normalized ratio.CONCLUSION AILD was not rare in hospitalized patients with cirrhosis and AD in China,among which PBC was the most common etiology.90-d LT-free mortality were independently associated with TB,HE and BUN.展开更多
Aim:The study aimed to investigate the short-term outcomes of hospitalized patients with chronic liver disease(CLDs)and assess the prognostic impact of predisposition and precipitants,which currently remains unclear.M...Aim:The study aimed to investigate the short-term outcomes of hospitalized patients with chronic liver disease(CLDs)and assess the prognostic impact of predisposition and precipitants,which currently remains unclear.Methods:The study included 3970 hospitalized patients with CLDs from two prospective longitudinal multicenter studies(NCT02457637 and NCT03641872)conducted in highly endemic hepatitis B virus(HBV)areas.Competing risk analysis was used to evaluate the effect of predispositions,including the etiology and severity of CLDs and precipitants;on sequential 28,90,and 365-day liver transplantation(LT)-free mortality.Results:Among all enrolled patients,76.8%of adverse outcomes(including death and LT)within one year occurred within 90 days.Compared with alcoholic etiology,the association of HBV etiology with poorer outcomes was remarkably on the 28th day(hazard ratio[HR],1.81;95%confidence interval[CI],1.07-3.06;p=0.026);however,and dimin-ished or became insignificant at 90 days and 365 days.Cirrhosis increased the adjusted risk for 365-day(HR,1.50;CI,1.13-1.99;p=0.004)LT-free mortality when compared with noncirrhosis.In patients with cirrhosis,prior decompensation(PD)independently increased the adjusted risk of 365-day LT-free mortality by 1.25-fold(p=0.021);however,it did not increase the risk for 90-day mortality.Neither the category nor the number of precipitants influenced the adjusted risk of 28 or 90-day LT-free mortality.Conclusions:The 90-day outcome should be considered a significant endpoint for evaluating the short-term prognosis of hospitalized patients with CLD.Predisposing factors,other than etiology,mainly affected the delayed(365-day)outcome.Timely effective therapy for CLD etiology,especially antiviral treatments for HBV,and post-discharge long-term surveillance monitoring in cirrhotic patients undergoing PD are suggested to enhance disease management and reduce mortality.展开更多
Objective: Fatigue has become one of the major threats to human health in the 21 st century. Traditional Chinese medicine(TCM), which proved to be safer and more effective, has become a hot spot in antifatigue researc...Objective: Fatigue has become one of the major threats to human health in the 21 st century. Traditional Chinese medicine(TCM), which proved to be safer and more effective, has become a hot spot in antifatigue research. Human placenta, also called "Ziheche", has drawn great attention in the antifatigue effect since the Tang dynasty. However, the shortage of human placenta restricts wide usage of it. According to the theory of TCM, sheep placenta(SP) also has the effect of nourishing blood, tranquilization, nourishing skin, and prolongation of life. The aim of this study was to examine the antifatigue effects of sheep placenta peptide(SPP), an extract of sheep placenta, in mice and the mechanism was also studied.Methods: Peptide from fresh SP was extracted via enzymolysis. SPP(0.13 g/kg) and soybean peptide(0.65 g/kg) were administrated orally and daily to mice for four weeks. Antifatigue effects of SPP were estimated on weight-loaded swimming test; A non-weight-loaded swimming test was conducted to elucidate underlying the mechanisms of the anti-fatigue effects.Results: Administration of SPP prolonged the weight-loaded swimming time in mice. In addition, SPP significantly decreased the levels of muscle malondialdehyde(MDA) and serum lactic acid(LD), and increased the activities of muscle glutathione peroxidase(GSH), and superoxide dismutase(SOD) and liver glycogen in mice after non-weight-loaded swimming test. Moreover, the electron microscope observation showed that the muscle fiber bundle ranked neatly, the H band, I band, Z line as well as M line were clear and the numbers of mitochondria was normal though some of the mitochondria were swell in SPP treated mice after non-weight-loaded swimming test.Conclusion: SPP possesses potent abilities for antifatigue; Increasing the anti-oxidant activities and energy reserve as well as improving the ultrastructures in gastrocnemius muscle cells, which may be the mechanisms of SPP exerting its antifatigue effects.展开更多
Background:Allogeneic natural killer(NK)cell immunotherapy is recognized as a promising anti-tumor strategy,but whether it plays a role in poor CD4 recovery among human immunodeficiency virus type 1(HIV-1)infected pat...Background:Allogeneic natural killer(NK)cell immunotherapy is recognized as a promising anti-tumor strategy,but whether it plays a role in poor CD4 recovery among human immunodeficiency virus type 1(HIV-1)infected patients is unknown.This study aimed to investigate the safety and effectiveness of allogeneic NK cells immunotherapy on HIV-1 immunological non-responders(INRs)receiving antiretroviral therapy(ART).Methods:From February to April 2018,a prospective,randomized,controlled,open-label clinical trial,which enrolled 20 HIV-1 INRs following specific inclusion criteria,was conducted at Nankai University Second People’s Hospital.Participants were randomly allocated(simple randomization 1:1)to either the combined treatment(NK+ART)group(n=10)or the control(ART)group(n=10).The allogenic highly activated NK cells from killer cell immunoglobulin-like receptor(KIR)/human leukocyte antigen(HLA)-Cw mismatched healthy donor were prepared(108 cells in each injection)and intravenously infused to each recruited patient of NK+ART group in three courses.Key immune parameters(CD4 count,CD8 count,CD4/CD8 ratio),laboratory tests(count of blood cells,biochemistry panel)and symptoms at baseline and at month 1,3,6,9,12,and 24 were measured/collected to analyze the safety and efficacy of the therapy.Comparisons were between the seven time-points of both groups using repeated measurement analysis of variance(ANOVA)test.Generalized estimating equations(GEE)model was performed to evaluate the overall effect of the NK+ART group vs.the ART group.Results:From baseline to 24 months,we noted a mean CD4 count augmentation(139 to 243 cells/μL)in the NK+ART group and(144 to 176 cells/μL)in the ART group(difference,67;95%CI,10 to 124;P=0.024).Our estimations revealed that NK+ART group could improve CD4 level(β=54.59,P=0.006)and CD8 level(β=322.47,P=0.010)on average among the six measurements compared with the ART group.Only two(2/10,20%)participants in the NK+ART group developed a transient mild fever after the first course.Conclusions:This preliminary study informs that HIV-1 INRs,allogenic NK cells immunotherapy is safe and could significantly improve CD4 recovery but not CD4/CD8 ratio.The practical effects,however,need long-term follow-up observations.Further study on the potential underlying mechanism is warranted.Registration info:www.chictr.org.cn/showproj.aspx?proj=34912(No.ChiCTR1900020634).展开更多
基金National Natural Science Foundation of China,No.81970550,No.82070613 and No.82370638Natural Science Foundation of Hunan Province,China,No.2021JJ31067 and No.2021JJ41048+1 种基金Hunan innovative province construction project,No.2023JJ10095Innovative Talented Project of Hunan province,China,No.2022RC1212.
文摘BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and mortality.Soluble triggering receptor expressed on myeloid cells-1(sTREM-1)is released from activated innate immune cells and correlated with various inflammatory processes.AIM To explore the prognostic value of sTREM-1 in patients with AD of cirrhosis.METHODS A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort(n=309)and validation cohort(n=133).Demographic and clinical data were collected,and serum sTREM-1 was measured at admission.All enrolled patients were followed-up for at least 1 year.RESULTS In patients with AD and cirrhosis,serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver,coagulation,cerebral and kidney failure.A new prognostic model of AD(P-AD)incorporating sTREM-1,blood urea nitrogen(BUN),total bilirubin(TBil),international normalized ratio(INR)and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease(MELD),MELD-sodium(MELD-Na),chronic liver failure-consortium(CLIF-C)ACLF and CLIF-C AD scores.Additionally,sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d follow-up.The ACLF risk score incorporating serum sTREM-1,BUN,INR,TBil and aspartate aminotransferase levels was established and significantly superior to MELD,MELD-Na,CLIF-C ACLF,CLIF-C AD and P-AD in predicting risk of ACLF development.CONCLUSION Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.
基金supported by grants from the National Major Special Project for the Prevention and Treatment of Major Infectious Diseases:AIDS and viral hepatitis(2013ZX10005002,2018ZX10725506)the National Key Research and Development Program(2017YFC0908903)。
文摘Background:Although concomitant nonalcoholic steatohepatitis(NASH)is common in chronic hepatitis B(CHB),the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear.We aimed to investigate the outcomes of NASH in CHB patients receiving antiviral treatment.Methods:In the post-hoc analysis of a multicenter trial,na?ve CHB patients receiving 72-week entecavir treatment were enrolled.We evaluated the biochemical,viral and histopathological responses of these patients.The histopathological features of NASH were also evaluated,using paired liver biopsies at baseline and week 72.Results:A total of 1000 CHB patients were finally enrolled for analysis,with 18.2%of whom fulfilling the criteria of NASH.A total of 727 patients completed entecavir antiviral treatment and received the second biopsy.Serum HBe Ag loss,HBe Ag seroconversion and HBV-DNA undetectable rates were similar between patients with or without NASH(P>0.05).Among patients with NASH,the hepatic steatosis,ballooning,lobular inflammation scores and fibrosis stages all improved during follow-up(all P<0.001),46%(63/136)achieved NASH resolution.Patients with baseline body mass index(BMI)≥23 kg/m2(Asian criteria)[odds ratio(OR):0.414;95%confidence interval(95%CI):0.190-0.899;P=0.012]and weight gain(OR:0.187;95%CI:0.050-0.693;P=0.026)were less likely to have NASH resolution.Among patients without NASH at baseline,22(3.7%)developed NASH.Baseline BMI≥23 kg/m2(OR:12.506;95%CI:2.813-55.606;P=0.001)and weight gain(OR:5.126;95%CI:1.674-15.694;P=0.005)were predictors of incident NASH.Conclusions:Lower BMI and weight reduction but not virologic factors determine NASH resolution in CHB.The value of weight management in CHB patients during antiviral treatment deserves further evaluation.
基金The Shandong Province Natural Science Foundation,No.ZR2019PH052the National Key Research and Development Program of China,No.2017YFC0908104.
文摘BACKGROUND Nucleos(t)ide analogs(NAs)cessation in chronic hepatitis B(CHB)patients remains a matter of debate in clinical practice.Current guidelines recommend that patients with hepatitis B e antigen(HBeAg)seroconversion discontinue NAs after relatively long-term consolidation therapy.However,many patients fail to achieve HBeAg seroconversion after the long-term loss of HBeAg,even if hepatitis B surface antigen(HBsAg)loss occurs.It remains unclear whether NAs can be discontinued in this subset of patients.AIM To investigate the outcomes and factors associated with HBeAg-positive CHB patients with HBeAg loss(without hepatitis B e antibody)after cessation of NAs.METHODS We studied patients who discontinued NAs after achieving HBeAg loss.The Cox proportional hazards model was used to identify predictors for virological relapse after cessation of NAs.The cut-off value of the consolidation period was confirmed using receiver operating characteristic curves;we confirmed the cut-off value of HBsAg according to a previous study.The log-rank test was used to compare cumulative relapse rates among groups.We also studied patients with CHB who achieved HBeAg seroconversion and compared their cumulative relapse rates.Propensity score matching analysis(PSM)was used to balance baseline characteristics between the groups.RESULTS We included 83 patients with HBeAg loss.The mean age of these patients was 32.1±9.5 years,and the majority was male(67.5%).Thirty-eight patients relapsed,and the cumulative relapse rate at months 3,6,12,24,36,60,120,and 180 were 22.9%,36.1%,41.0%,43.5%,45.0%,45.0%,45.0%,and 52.8%,respectively.Twentysix(68.4%)patients relapsed in the first 3 mo after NAs cessation,and 35 patients(92.1%)relapsed in the first year after NAs cessation.Consolidation period(≥24 mo vs<24 mo)(HR 0.506,P=0.043)and HBsAg at cessation(≥100 IU/mL vs<100 IU/mL)(HR 14.869,P=0.008)were significant predictors in multivariate Cox regression.In the PSM cohort,which included 144 patients,there were lower cumulative relapse rates in patients with HBeAg seroconversion(P=0.036).CONCLUSION HBeAg-positive CHB patients with HBeAg loss may be able to discontinue NAs therapy after long-term consolidation,especially in patients with HBsAg at cessation<100 IU/mL.Careful monitoring,especially in the early stages after cessation,may ensure a favorable outcome.
基金Supported by Shanghai Hospital Development Commission,No.SHDC2020CR1037Bthe National Key R&D Program of China,No.2017YFC0908100+7 种基金the National Science and Technology Major Project,No.2018ZX10302206,2018ZX10723203 and 2017ZX10202202Shanghai Municipal Education Commission-Guofeng Clinical Medicine Grant,No.20152213the National Natural Science Foundation of China,No.82170629,81930061,81900579,81970550,82070613,82070650,and 81972265Chongqing Natural Science Foundation,No.CSTC2019jcyj-zdxmX0004Beijing Municipal Science&Technology Commission,No.Z191100006619033Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program,No.2017BT01S131the Foundation for Innovative Research Groups of Hubei Provincial Natural Science Foundation,No.2018CFA031Guangdong Basic and Applied Basic Research Foundation,No.2020A1515010052.
文摘BACKGROUND Autoimmune liver disease(AILD)has been considered a relatively uncommon disease in China,epidemiological data for AILD in patients with cirrhosis and acute decompensation(AD)is sparse.AIM To investigate the prevalence,outcome and risk factors for AILD in cirrhotic patients complicated with AD in China.METHODS We collected data from patients with cirrhosis and AD from two prospective,multicenter cohorts in hepatitis B virus endemic areas.Patients were regularly followed up at the end of 28-d,90-d and 365-d,or until death or liver transplantation(LT).The primary outcome in this study was 90-d LTfree mortality.Acute-on-chronic liver failure(ACLF)was assessed on admission and during 28-d hospitalization,according to the diagnostic criteria of the European Association for the Study of the Liver(EASL).Risk factors for death were analyzed with logistic regression model.RESULTS In patients with cirrhosis and AD,the overall prevalence of AILD was 9.3%(242/2597).Prevalence of ACLF was significantly lower in AILD cases(14%)than those with all etiology groups with cirrhosis and AD(22.8%)(P<0.001).Among 242 enrolled AILD patients,the prevalence rates of primary biliary cirrhosis(PBC),autoimmune hepatitis(AIH)and PBC-AIH overlap syndrome(PBC/AIH)were 50.8%,28.5%and 12.0%,respectively.In ACLF patients,the proportions of PBC,AIH and PBC/AIH were 41.2%,29.4% and 20.6%.28-d and 90-d mortality were 43.8% and 80.0% in AILD-related ACLF.The etiology of AILD had no significant impact on 28-d,90-d or 365-d LTfree mortality in patients with cirrhosis and AD in both univariate and multivariate analysis.Total bilirubin(TB),hepatic encephalopathy(HE)and blood urea nitrogen(BUN)were independent risk factors for 90-d LT-free mortality in multivariate analysis.The development of ACLF during hospitalization only independently correlated to TB and international normalized ratio.CONCLUSION AILD was not rare in hospitalized patients with cirrhosis and AD in China,among which PBC was the most common etiology.90-d LT-free mortality were independently associated with TB,HE and BUN.
基金Clinical Research Plan of SHDC,Grant/Award Number:SHDC2020CR1037BShanghai Municipal Key Clinic Specialty,Grant/Award Number:shslczdzk00602+16 种基金National Key R&D Program of China,Grant/Award Number:2017YFC0908100National Science and Technology Major Project,Grant/Award Numbers:2018ZX10302206,2018ZX10723203,2017ZX10202202Shanghai Municipal Education Commission–Guofeng Clinical Medicine Grant Support,Grant/Award Number:20152213National Natural Science Foundation of China,Grant/Award Numbers:82170629,81930061,81900579,81970550,82070613,82070650,81972265,81870425,81774234Shanghai Hospital Development Commission,Grant/Award Number:16CR1024BChongqing Natural Science Foundation,Grant/Award Number:CSTC2019jcyjzdxmX0004Beijing Municipal Science&Technology Commission,Grant/Award Number:Z191100006619033Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program,Grant/Award Number:2017BT01S131Clinical Research Program of Nanfang Hospital,Southern Medical University,Grant/Award Numbers:2018CR037,2020CR026Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education,Grant/Award Number:LC2019ZD006President Foundation of Nanfang Hospital,Southern Medical University,Grant/Award Number:2019Z003Foundation for Innovative Research Groups of Hubei Provincial Natural Science Foundation,Grant/Award Number:2018CFA031Hubei Province's Outstanding Medical Academic Leader Program and Project of Hubei University of Medicine,Grant/Award Numbers:FDFR201902,2020XGFYZR05Fundamental Research Funds for the Central Universities,Grant/Award Number:2021FZZX001-41Guangdong Basic and Applied Basic Research Foundation,Grant/Award Number:2020A1515010052Natural Fund of Guangdong Province,Grant/Award Number:2016A030313237Guangzhou City Science and Technology Project,Grant/Award Number:201607010064。
文摘Aim:The study aimed to investigate the short-term outcomes of hospitalized patients with chronic liver disease(CLDs)and assess the prognostic impact of predisposition and precipitants,which currently remains unclear.Methods:The study included 3970 hospitalized patients with CLDs from two prospective longitudinal multicenter studies(NCT02457637 and NCT03641872)conducted in highly endemic hepatitis B virus(HBV)areas.Competing risk analysis was used to evaluate the effect of predispositions,including the etiology and severity of CLDs and precipitants;on sequential 28,90,and 365-day liver transplantation(LT)-free mortality.Results:Among all enrolled patients,76.8%of adverse outcomes(including death and LT)within one year occurred within 90 days.Compared with alcoholic etiology,the association of HBV etiology with poorer outcomes was remarkably on the 28th day(hazard ratio[HR],1.81;95%confidence interval[CI],1.07-3.06;p=0.026);however,and dimin-ished or became insignificant at 90 days and 365 days.Cirrhosis increased the adjusted risk for 365-day(HR,1.50;CI,1.13-1.99;p=0.004)LT-free mortality when compared with noncirrhosis.In patients with cirrhosis,prior decompensation(PD)independently increased the adjusted risk of 365-day LT-free mortality by 1.25-fold(p=0.021);however,it did not increase the risk for 90-day mortality.Neither the category nor the number of precipitants influenced the adjusted risk of 28 or 90-day LT-free mortality.Conclusions:The 90-day outcome should be considered a significant endpoint for evaluating the short-term prognosis of hospitalized patients with CLD.Predisposing factors,other than etiology,mainly affected the delayed(365-day)outcome.Timely effective therapy for CLD etiology,especially antiviral treatments for HBV,and post-discharge long-term surveillance monitoring in cirrhotic patients undergoing PD are suggested to enhance disease management and reduce mortality.
基金supported by Science and Technology Research Program for Colleges and Universities in Tianjin,China(No.2013082)Program for Changjiang Scholars and Innovative Research Team in University(PCSIRT,IRT_14R41)Tianjin Jiani Biotechnology Development Co.,Ltd.(Tianjin,China)
文摘Objective: Fatigue has become one of the major threats to human health in the 21 st century. Traditional Chinese medicine(TCM), which proved to be safer and more effective, has become a hot spot in antifatigue research. Human placenta, also called "Ziheche", has drawn great attention in the antifatigue effect since the Tang dynasty. However, the shortage of human placenta restricts wide usage of it. According to the theory of TCM, sheep placenta(SP) also has the effect of nourishing blood, tranquilization, nourishing skin, and prolongation of life. The aim of this study was to examine the antifatigue effects of sheep placenta peptide(SPP), an extract of sheep placenta, in mice and the mechanism was also studied.Methods: Peptide from fresh SP was extracted via enzymolysis. SPP(0.13 g/kg) and soybean peptide(0.65 g/kg) were administrated orally and daily to mice for four weeks. Antifatigue effects of SPP were estimated on weight-loaded swimming test; A non-weight-loaded swimming test was conducted to elucidate underlying the mechanisms of the anti-fatigue effects.Results: Administration of SPP prolonged the weight-loaded swimming time in mice. In addition, SPP significantly decreased the levels of muscle malondialdehyde(MDA) and serum lactic acid(LD), and increased the activities of muscle glutathione peroxidase(GSH), and superoxide dismutase(SOD) and liver glycogen in mice after non-weight-loaded swimming test. Moreover, the electron microscope observation showed that the muscle fiber bundle ranked neatly, the H band, I band, Z line as well as M line were clear and the numbers of mitochondria was normal though some of the mitochondria were swell in SPP treated mice after non-weight-loaded swimming test.Conclusion: SPP possesses potent abilities for antifatigue; Increasing the anti-oxidant activities and energy reserve as well as improving the ultrastructures in gastrocnemius muscle cells, which may be the mechanisms of SPP exerting its antifatigue effects.
基金This study was funded by the Key Project of Tianjin Second People’s Hospital(No.YS0001)the National Natural Science Foundation of China(No.82002136)the 13th Five-year National Major Project for HIV/AIDS and Hepatitis B Control and Prevention,and the Chinese Ministry of Science and Technology(Nos.2017ZX10202102005004,2018ZX10302104-002)。
文摘Background:Allogeneic natural killer(NK)cell immunotherapy is recognized as a promising anti-tumor strategy,but whether it plays a role in poor CD4 recovery among human immunodeficiency virus type 1(HIV-1)infected patients is unknown.This study aimed to investigate the safety and effectiveness of allogeneic NK cells immunotherapy on HIV-1 immunological non-responders(INRs)receiving antiretroviral therapy(ART).Methods:From February to April 2018,a prospective,randomized,controlled,open-label clinical trial,which enrolled 20 HIV-1 INRs following specific inclusion criteria,was conducted at Nankai University Second People’s Hospital.Participants were randomly allocated(simple randomization 1:1)to either the combined treatment(NK+ART)group(n=10)or the control(ART)group(n=10).The allogenic highly activated NK cells from killer cell immunoglobulin-like receptor(KIR)/human leukocyte antigen(HLA)-Cw mismatched healthy donor were prepared(108 cells in each injection)and intravenously infused to each recruited patient of NK+ART group in three courses.Key immune parameters(CD4 count,CD8 count,CD4/CD8 ratio),laboratory tests(count of blood cells,biochemistry panel)and symptoms at baseline and at month 1,3,6,9,12,and 24 were measured/collected to analyze the safety and efficacy of the therapy.Comparisons were between the seven time-points of both groups using repeated measurement analysis of variance(ANOVA)test.Generalized estimating equations(GEE)model was performed to evaluate the overall effect of the NK+ART group vs.the ART group.Results:From baseline to 24 months,we noted a mean CD4 count augmentation(139 to 243 cells/μL)in the NK+ART group and(144 to 176 cells/μL)in the ART group(difference,67;95%CI,10 to 124;P=0.024).Our estimations revealed that NK+ART group could improve CD4 level(β=54.59,P=0.006)and CD8 level(β=322.47,P=0.010)on average among the six measurements compared with the ART group.Only two(2/10,20%)participants in the NK+ART group developed a transient mild fever after the first course.Conclusions:This preliminary study informs that HIV-1 INRs,allogenic NK cells immunotherapy is safe and could significantly improve CD4 recovery but not CD4/CD8 ratio.The practical effects,however,need long-term follow-up observations.Further study on the potential underlying mechanism is warranted.Registration info:www.chictr.org.cn/showproj.aspx?proj=34912(No.ChiCTR1900020634).
