Background and Aims:Few previous studies have reported on a combination response(hepatitis B virus(HBV)DNA undetected,alanine aminotransferase normalization and hepatitis B e antigen(HBeAg)seroconversion)following nuc...Background and Aims:Few previous studies have reported on a combination response(hepatitis B virus(HBV)DNA undetected,alanine aminotransferase normalization and hepatitis B e antigen(HBeAg)seroconversion)following nucleos(t)ide analogue(NAs)long-term therapy in patients with chronic hepatitis B(CHB).This study aimed to investigate the combination response on long-term NAs therapy in patients with HBeAg-positive CHB and to determine whether prolonged therapy is beneficial for combination response,particularly in optimal patients(baseline alanine aminotransferase level≥5 upper limit of normal and HBV DNA level<10^(9) copies/mL).Methods:In total,280 HBeAg-positive CHB patients were enrolled in this study.Among them,190 were treated with entecavir and 90 were treated with telbivudine.Results:The cumulative rates of combination response in the total number of patients were 8.6%at 1 year,13.2%at 2 years,19.1%at 3 years,24.2%at 4 years and 26.0%at 5 years.In optimal patients,the cumulative rate of combination response was significantly higher than that in the non-optimal patients at 3 years(p=0.043);the trend of the cumulative rate was not strong at the later time.Interestingly,in optimal patients,combination response mainly occurred in the first 3 years.Multivariate analysis identified HBeAg/anti-HBe seroconversion at 1 year as the only factor for combination response in optimal patients(hazard ratio:16.321;p=0.000).During the 3 years,the proportion with aspartate aminotransaminase to platelet ratio index≤0.5 increased from 15.6%at baseline to 71.3%at year 3.Conclusions:Upgrading the rate of combination response is limited by prolonging the treatment duration of NAs from 3 years to 5 years in HBeAg-positive CHB patients;a new switch treatment strategy modification should be considered,particularly in optimal patients.展开更多
Enhancement of Fe3O4/Au nanoparticles （Fe3O4/Au NPs） catalyst was observed in the oxidative degradation of methyl orange by employing H2O2 as oxidant. To evaluate the catalytic activity of Fe3O4/Au nanoparticles, di...Enhancement of Fe3O4/Au nanoparticles （Fe3O4/Au NPs） catalyst was observed in the oxidative degradation of methyl orange by employing H2O2 as oxidant. To evaluate the catalytic activity of Fe3O4/Au nanoparticles, different degradation conditions were investigated such as the amounts of catalyst, H2O2 concentration and pH value. Based on our data, methyl orange was degraded completely in a short time. The enhanced catalytic activity and increased oxidation rate constant may be ascribed to synergistic catalyst-activated decomposition of H2O2 to ,OH radical, which was one of the strong oxidizing species. Besides, Fe3O4/Au nanoparticles have exhibited satisfying recycle performance for potential industrial application.展开更多
Inactivated COVID-19 vaccines have been widely used to vaccinate the Chinese population.However,limited literature exists to explore the effect of obesity on the humoral and cellular immune response to these vaccines....Inactivated COVID-19 vaccines have been widely used to vaccinate the Chinese population.However,limited literature exists to explore the effect of obesity on the humoral and cellular immune response to these vaccines.In this study,132 high BMI(Body mass index)(obesity and overweight,BMI≥24 kg/m^(2))and 82 normal BMI(BMI<24 kg/m^(2))participants were enrolled.Adverse events(AEs),Spike receptor-binding domain IgG antibody(anti-RBD-IgG),neutralizing antibodies(NAbs),and specific B-cell and T-cell responses were evaluated 21–105 days after full-course inactivated COVID-19 vaccination.The overall incidence of AEs was similar in individuals with and without obesity/overweight.No serious vaccine-related AEs occurred.Individuals with obesity/overweight had a reduced seropositivity rate of NAbs compared to those with normal BMI.Anti-RBD-IgG and NAbs titers in the high BMI group were significantly lower than those in the normal BMI group.The frequencies of RBD-specific memory B cells(MBCs)and the numbers of spike-specific TNF-α+spot-forming cells(SFCs)in individuals with obesity/overweight were reduced compared with those noted in individuals without obesity/overweight.A similar trend of weakened humoral responses was also observed in individuals with central obesity.Our study results suggested that inactivated COVID-19 vaccines were safe and well tolerated but induced poor humoral and cellular immune responses in Chinese individuals with obesity/overweight.展开更多
Dear Editor Coronavirus disease 19(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),remains a pandemic.Cancer patients have a higher risk of poor outcomes for SARS-CoV-2 infection than t...Dear Editor Coronavirus disease 19(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),remains a pandemic.Cancer patients have a higher risk of poor outcomes for SARS-CoV-2 infection than the general population[1].Vaccines were shown to effectively prevent SARS-CoV-2 infection,severe disease progression,and mortality.Inactivated SARS-CoV-2 vaccines(BBIBPCorV and CoronaVac)have been approved and widely used in China,with the former shown to be more effective than the latter[2].Hence,there is an urgent need to investigate the safety and humoral immune responses of inactivated vaccines in cancer patients.展开更多
Background and Aims:SARS-CoV-2 vaccines-associated autoimmune liver diseases have been reported in several case reports.However,the safety and immunogenicity after primary and booster inactivated SARS-CoV-2 vaccinatio...Background and Aims:SARS-CoV-2 vaccines-associated autoimmune liver diseases have been reported in several case reports.However,the safety and immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in patients with autoimmune liver diseases(AILD)is still unknown.Methods:Eighty-four patients with AILD were prospectively followed up after the second dose(primary)of inactivated SARS-CoV-2 vaccine.Some of them received the third dose(booster)of inactivated vaccine.Adverse events(AEs),autoimmune activation,and liver inflammation exacerbation after primary and booster vaccination were recorded.Meanwhile,dynamics of antireceptor-binding-domain IgG(anti-RBD-IgG),neutralizing antibodies(NAbs)and RBD-specific B cells responses were evaluated.Results:The overall AEs in AILD patients after primary and booster vaccination were 26.2%and 13.3%,respectively.The decrease of C3 level and increase of immunoglobulin light chain K andλlevels were observed in AILD patients after primary vaccination,however,liver inflammation was not exacerbated,even after booster vaccination.Both the seroprevalence and titers of anti-RBD-IgG and NAbs were decreased over time in AILD patients after primary vaccination.Notably,the antibody titers were significantly elevated after booster vaccination(10-fold in anti-RBD-IgG and 7.4-fold in NAbs,respectively),which was as high as in healthy controls.Unfortunately,the inferior antibody response was not enhanced after booster vaccination in patients with immunosuppressants.Changes of atypical memory B cells were inversely related to antibody levels,which indicate that the impaired immune memory was partially restored partly by the booster vaccination.Conclusions:The well tolerability and enhanced humoral immune response of inactivated vaccine supports an additional booster vaccination in AILD patients without immunosuppressants.展开更多
Background and Aims:Our aim was to determine the immune efficacy of a severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)booster vaccination in cirrhotic patients who had received the primary series.Methods:We...Background and Aims:Our aim was to determine the immune efficacy of a severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)booster vaccination in cirrhotic patients who had received the primary series.Methods:We performed a longitudinal assessment in 48 patients with cirrhosis,57 patients with chronic hepatitis B(CHB)and 68 healthy controls(HCs)to continuously track the dynamics of SARS-CoV-2 specific antibodies and memory B cells after receiving the primary series and booster dose at different times.A pseudovirus neutralization assay was used to determine neutralization against Omicron subvariants BA.2.12.1,BA.4 and BA.5 from serum samples collected from three cohorts.Results:Serum anti-receptor-binding domain(RBD)immunoglobulin(Ig)G and neutralizing antibody(NAb)levels in cirrhotic patients were elevated within 15–45 days after completing the primary series before rapidly declining and reaching a valley at around 165–195 days.After receiving the booster dose,both antibody levels were significantly increased to levels comparable to patients with CHB and HCs.Subgroup analysis showed that booster vaccination induced weaker antibody responses in patients with decompensated cirrhosis than in those with compensated cirrhosis.The SARS-CoV-2 memory B-cell response in cirrhotic patients was durable during follow-up regardless of the hepatic fibrocirrhosis grade.However,compared with the primary series,the booster dose did not result in an evident improvement of neutralization activity against the Omicron subvariants BA.2.12.1 and BA.4,and was followed by a significant decrease in the titer against BA.5.Conclusions:A booster dose elicited a robust and durable humoral response to the wild-type strain in cirrhotic patients but not the Omicron subvariants.Repeated vaccination of inactivated SARS-CoV-2 vaccine may not benefit cirrhotic patients in neutralization against newly circulating strains.展开更多
Tenofovir disoproxil fumarate(TDF),is a product of tenofovir and has been recommended for long-term use by guidelines1 because of its favorable efficacy in the treatment of human immunodeficiency virus(HIV)and hepatit...Tenofovir disoproxil fumarate(TDF),is a product of tenofovir and has been recommended for long-term use by guidelines1 because of its favorable efficacy in the treatment of human immunodeficiency virus(HIV)and hepatitis B virus(HBV)infection.Hence,a better understanding of the safety profiles of long-term TDF use is extremely important.Lactic acidosis,as a rare but fatal adverse event of TDF,were reported both in HIV-infected patients,2-4 and in CHB patients.5-7 Hyperlactatemia occurred in 15.6%HIV-infected patients using TDF in a Cameroon cohort study8 and was 3%in another South Africa cohort study.9 Therefore,TDF increases the risk of abnormal serum lactate,but the mechanism is unclear.展开更多
基金The authors thank the patients,investigators and study centers for their participationThis study was supported in part by grants from the National Natural Science Foundation of China(Nos.30930082,81171561,30972584)the National Science and Technology Major Project of China(Nos.2008ZX10002-006,2012ZX10002007001,2017ZX10202203-007,2017ZX10202203-008)
文摘Background and Aims:Few previous studies have reported on a combination response(hepatitis B virus(HBV)DNA undetected,alanine aminotransferase normalization and hepatitis B e antigen(HBeAg)seroconversion)following nucleos(t)ide analogue(NAs)long-term therapy in patients with chronic hepatitis B(CHB).This study aimed to investigate the combination response on long-term NAs therapy in patients with HBeAg-positive CHB and to determine whether prolonged therapy is beneficial for combination response,particularly in optimal patients(baseline alanine aminotransferase level≥5 upper limit of normal and HBV DNA level<10^(9) copies/mL).Methods:In total,280 HBeAg-positive CHB patients were enrolled in this study.Among them,190 were treated with entecavir and 90 were treated with telbivudine.Results:The cumulative rates of combination response in the total number of patients were 8.6%at 1 year,13.2%at 2 years,19.1%at 3 years,24.2%at 4 years and 26.0%at 5 years.In optimal patients,the cumulative rate of combination response was significantly higher than that in the non-optimal patients at 3 years(p=0.043);the trend of the cumulative rate was not strong at the later time.Interestingly,in optimal patients,combination response mainly occurred in the first 3 years.Multivariate analysis identified HBeAg/anti-HBe seroconversion at 1 year as the only factor for combination response in optimal patients(hazard ratio:16.321;p=0.000).During the 3 years,the proportion with aspartate aminotransaminase to platelet ratio index≤0.5 increased from 15.6%at baseline to 71.3%at year 3.Conclusions:Upgrading the rate of combination response is limited by prolonging the treatment duration of NAs from 3 years to 5 years in HBeAg-positive CHB patients;a new switch treatment strategy modification should be considered,particularly in optimal patients.
基金This work was supported by the National Natural Science Foundation of China （No. 21303136）.
文摘Enhancement of Fe3O4/Au nanoparticles （Fe3O4/Au NPs） catalyst was observed in the oxidative degradation of methyl orange by employing H2O2 as oxidant. To evaluate the catalytic activity of Fe3O4/Au nanoparticles, different degradation conditions were investigated such as the amounts of catalyst, H2O2 concentration and pH value. Based on our data, methyl orange was degraded completely in a short time. The enhanced catalytic activity and increased oxidation rate constant may be ascribed to synergistic catalyst-activated decomposition of H2O2 to ,OH radical, which was one of the strong oxidizing species. Besides, Fe3O4/Au nanoparticles have exhibited satisfying recycle performance for potential industrial application.
基金supported by the National Science and Technology Major Project of China(No.2017ZX10202203-007,No.2017ZX10202203-008,and No.2018ZX10302206-003)a pilot project of clinical cooperation between traditional Chinese and western medicine for significant and complicated diseases of National Administration of Traditional Chinese Medicine:hepatic fibrosis.We also acknowledge the support of the National Natural Science Foundation of China(No.81772198)+1 种基金the Natural Science Foundation of Chongqing,China(No.cstc2020jcyj-msxmX0389)General Project of Chongqing Natural Science Foundation(No.cstc2020jcyj-msxmX0015).
文摘Inactivated COVID-19 vaccines have been widely used to vaccinate the Chinese population.However,limited literature exists to explore the effect of obesity on the humoral and cellular immune response to these vaccines.In this study,132 high BMI(Body mass index)(obesity and overweight,BMI≥24 kg/m^(2))and 82 normal BMI(BMI<24 kg/m^(2))participants were enrolled.Adverse events(AEs),Spike receptor-binding domain IgG antibody(anti-RBD-IgG),neutralizing antibodies(NAbs),and specific B-cell and T-cell responses were evaluated 21–105 days after full-course inactivated COVID-19 vaccination.The overall incidence of AEs was similar in individuals with and without obesity/overweight.No serious vaccine-related AEs occurred.Individuals with obesity/overweight had a reduced seropositivity rate of NAbs compared to those with normal BMI.Anti-RBD-IgG and NAbs titers in the high BMI group were significantly lower than those in the normal BMI group.The frequencies of RBD-specific memory B cells(MBCs)and the numbers of spike-specific TNF-α+spot-forming cells(SFCs)in individuals with obesity/overweight were reduced compared with those noted in individuals without obesity/overweight.A similar trend of weakened humoral responses was also observed in individuals with central obesity.Our study results suggested that inactivated COVID-19 vaccines were safe and well tolerated but induced poor humoral and cellular immune responses in Chinese individuals with obesity/overweight.
基金the Ethics Committee of the Second Affiliated Hospital of Chongqing Medical University and conformed with the ethical guidelines of the Declaration of Helsinki(Ratification No.133/2022)Written informed consentwas obtained fromall the participants.This study has been registered at ClinicalTrials.gov(NCT05043246).
文摘Dear Editor Coronavirus disease 19(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),remains a pandemic.Cancer patients have a higher risk of poor outcomes for SARS-CoV-2 infection than the general population[1].Vaccines were shown to effectively prevent SARS-CoV-2 infection,severe disease progression,and mortality.Inactivated SARS-CoV-2 vaccines(BBIBPCorV and CoronaVac)have been approved and widely used in China,with the former shown to be more effective than the latter[2].Hence,there is an urgent need to investigate the safety and humoral immune responses of inactivated vaccines in cancer patients.
基金supported by the National Science and Technology Major Project of China(Nos 2017ZX10202203-007,2017ZX10202203-008,2018ZX10302206-003)and a pilot project of clinical cooperation between traditional Chinese and western medicine for significant and complicated diseases of National Administration of Traditional Chinese Medicine:hepatic fibrosis.We also acknowledge the support of the National Natural Science Foundation of China(No 81772198)Natural Science Foundation of Chongqing,China(No.cstc2020jcyjmsxmX0389).
文摘Background and Aims:SARS-CoV-2 vaccines-associated autoimmune liver diseases have been reported in several case reports.However,the safety and immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in patients with autoimmune liver diseases(AILD)is still unknown.Methods:Eighty-four patients with AILD were prospectively followed up after the second dose(primary)of inactivated SARS-CoV-2 vaccine.Some of them received the third dose(booster)of inactivated vaccine.Adverse events(AEs),autoimmune activation,and liver inflammation exacerbation after primary and booster vaccination were recorded.Meanwhile,dynamics of antireceptor-binding-domain IgG(anti-RBD-IgG),neutralizing antibodies(NAbs)and RBD-specific B cells responses were evaluated.Results:The overall AEs in AILD patients after primary and booster vaccination were 26.2%and 13.3%,respectively.The decrease of C3 level and increase of immunoglobulin light chain K andλlevels were observed in AILD patients after primary vaccination,however,liver inflammation was not exacerbated,even after booster vaccination.Both the seroprevalence and titers of anti-RBD-IgG and NAbs were decreased over time in AILD patients after primary vaccination.Notably,the antibody titers were significantly elevated after booster vaccination(10-fold in anti-RBD-IgG and 7.4-fold in NAbs,respectively),which was as high as in healthy controls.Unfortunately,the inferior antibody response was not enhanced after booster vaccination in patients with immunosuppressants.Changes of atypical memory B cells were inversely related to antibody levels,which indicate that the impaired immune memory was partially restored partly by the booster vaccination.Conclusions:The well tolerability and enhanced humoral immune response of inactivated vaccine supports an additional booster vaccination in AILD patients without immunosuppressants.
基金supported by the National Science and Technology Major Project of China(2017ZX10202203-007,2017 ZX10202203-008,2018ZX10302206-003)Remarkable Innovation-Clinical Research Project,The Second Affiliated Hospital of Chongqing Medical University and The First batch of key Disciplines On Public Health in Chongqing+1 种基金support of the National Natural Science Foundation of China(81772198)Natural Science Foundation of Chongqing,China(cstc2020jcyj-msxmX0389).
文摘Background and Aims:Our aim was to determine the immune efficacy of a severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)booster vaccination in cirrhotic patients who had received the primary series.Methods:We performed a longitudinal assessment in 48 patients with cirrhosis,57 patients with chronic hepatitis B(CHB)and 68 healthy controls(HCs)to continuously track the dynamics of SARS-CoV-2 specific antibodies and memory B cells after receiving the primary series and booster dose at different times.A pseudovirus neutralization assay was used to determine neutralization against Omicron subvariants BA.2.12.1,BA.4 and BA.5 from serum samples collected from three cohorts.Results:Serum anti-receptor-binding domain(RBD)immunoglobulin(Ig)G and neutralizing antibody(NAb)levels in cirrhotic patients were elevated within 15–45 days after completing the primary series before rapidly declining and reaching a valley at around 165–195 days.After receiving the booster dose,both antibody levels were significantly increased to levels comparable to patients with CHB and HCs.Subgroup analysis showed that booster vaccination induced weaker antibody responses in patients with decompensated cirrhosis than in those with compensated cirrhosis.The SARS-CoV-2 memory B-cell response in cirrhotic patients was durable during follow-up regardless of the hepatic fibrocirrhosis grade.However,compared with the primary series,the booster dose did not result in an evident improvement of neutralization activity against the Omicron subvariants BA.2.12.1 and BA.4,and was followed by a significant decrease in the titer against BA.5.Conclusions:A booster dose elicited a robust and durable humoral response to the wild-type strain in cirrhotic patients but not the Omicron subvariants.Repeated vaccination of inactivated SARS-CoV-2 vaccine may not benefit cirrhotic patients in neutralization against newly circulating strains.
基金supported in part by grants from the National Science and Technology Major Project of China(2017ZX10202203008,2017ZX10202203007)the National Natural Science Foundation of China(81772171)+1 种基金the Chongqing Talents Project(cstc2021ycjh-bgzxm0150)Remarkable Innovation–Clinical Research Project,the Second Affiliated Hospital of Chongqing Medical University。
文摘Tenofovir disoproxil fumarate(TDF),is a product of tenofovir and has been recommended for long-term use by guidelines1 because of its favorable efficacy in the treatment of human immunodeficiency virus(HIV)and hepatitis B virus(HBV)infection.Hence,a better understanding of the safety profiles of long-term TDF use is extremely important.Lactic acidosis,as a rare but fatal adverse event of TDF,were reported both in HIV-infected patients,2-4 and in CHB patients.5-7 Hyperlactatemia occurred in 15.6%HIV-infected patients using TDF in a Cameroon cohort study8 and was 3%in another South Africa cohort study.9 Therefore,TDF increases the risk of abnormal serum lactate,but the mechanism is unclear.
