Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donor...Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus(HBV) core antibody(HBc Ab) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues(NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBc Ab-positive liver grafts.展开更多
Nucleoside analogues are first line chemotherapy in various severe diseases:AIDS(acquired immunodeficiency disease syndrome),cytomegalovirus infections,cancer,etc.However,many nucleoside analogues exhibit poor oral bi...Nucleoside analogues are first line chemotherapy in various severe diseases:AIDS(acquired immunodeficiency disease syndrome),cytomegalovirus infections,cancer,etc.However,many nucleoside analogues exhibit poor oral bioavailability because of their high polarity and low intestinal permeability.In order to get around this drawback,prodrugs have been utilized to improve lipophilicity by chemical modification of the parent drug.Alternatively,prodrugs targeting transporters present in the intestine have been applied to promote the transport of the nucleoside analogues.Valacyclovir and valganciclovir are two classic valine ester prodrugs transported by oligopeptide transporter 1.The ideal prodrug achieves delivery of a parent drug by attaching a non-toxic moiety that is stable during transport,but is readily degraded to the parent drug once at the target.This article presents advances of prodrug approaches for enhancing oral absorption of nucleoside analogues.展开更多
AIM： To explore the effects of the nucleoside analogues β-L-D4A and β-LPA on hepatitis B virus （HBV） promoters. METHODS： Four HBV promoters were amplified by polymerase chain reaction （PCR） and subcloned into ...AIM： To explore the effects of the nucleoside analogues β-L-D4A and β-LPA on hepatitis B virus （HBV） promoters. METHODS： Four HBV promoters were amplified by polymerase chain reaction （PCR） and subcloned into the expression vector pEGFP-1. The four recombinants controlled by HBV promoters were confirmed by restriction analysis and sequencing. Human hepatoma HepG2 cells transfected with the recombinant plasmids were treated with various concentrations of β-L-D4A and β-LPA. Then, enhanced green fluorescent protein （EGFP）-positive cells were detected by fluorescence microscopy and using a fluorescence activated cell sorter RESULTS： Four HBV promoters were separately obtained and successfully cloned into pEGFP-1, Expression of EGFP under the control of the surface promoter （Sp） and the X promoter （Xp） was inhibited by β-L-D4A in a dosedependent manner, while expression of EGFP under the control of the core promoter （Cp） and Xp was inhibited by β-LPA in a dose-dependent manner. CONCLUSION： The two novel nucleoside analogues investigated here can inhibit the activities of HBV promoters in a dose-dependent manner. These findings may explain the mechanisms of action by which these two novel compounds inhibit HBV DNA replication.展开更多
Objective There are many clinical reports on traditional Chinese medicine(TCM)combined with nucleoside(acid)analogues(NAs)for the treatment of chronic hepatitis B(CHB),but its efficacy and safety are not completely cl...Objective There are many clinical reports on traditional Chinese medicine(TCM)combined with nucleoside(acid)analogues(NAs)for the treatment of chronic hepatitis B(CHB),but its efficacy and safety are not completely clear.This meta-analysis aims to evaluate the clinical efficacy and safety thus providing evidence for clinical applications.Methods We searched Chinese databases the China National Knowledge Infrastructure(CNKI),Wanfang Data,and China Science and Technology Journal Database(VIP),as well as English databases Pub Med and Cochrane Library,from time of establishment to April 14,2021.Literature quality was evaluated according to the bias risk assessment criteria of Cochrane Collaboration network.Rev Man 5.3 and Stata 12.0 software were used to perform this research.Results A total of 23 articles,3282 patients,and 25 TCM prescriptions were included in this study.NAs plus TCM remarkably improved the clinical total effective rate[Odds ratio(OR)=3.92,P<0.00001],TCM syndrome score(Mean difference=-3.73,P<0.00001),hepatitis B virus(HBV)DNA negative conversion rate(OR=1.49,P=0.0001),hepatitis Be antigen(HBe Ag)negative conversion rate(OR=2.03,P<0.00001),alanine aminotransferase levels[Std mean difference(SMD)=-0.95,P<0.00001],and aspartate aminotransferase levels(SMD=-0.70,P=0.0004).Adverse reaction rates did not increase in the combined treatment group(OR=0.97,P=0.84).A comprehensive analysis of the 25 TCM prescriptions suggested that the combination of spleen-strengthening prescriptions with NAs showed better effects than other prescriptions.Conclusion TCM in combination with NAs,demonstrated better clinical efficacy against CHB than NAs alone.In addition,the combination of spleen-strengthening prescriptions and NAs was identified as the best therapeutic strategy.However,more randomized controlled trials of high quality are needed to provide more reliable clinical basis for the application of TCM.展开更多
Objective: To study the effect of different nucleoside analogues on liver fibrosis and peripheral blood dendritic cell function of patients with chronic hepatitis B. Methods: Patients with chronic hepatitis B who rece...Objective: To study the effect of different nucleoside analogues on liver fibrosis and peripheral blood dendritic cell function of patients with chronic hepatitis B. Methods: Patients with chronic hepatitis B who received antiviral therapy in Infectious Diseases Hospital of Shanghai Huangpu District between April 2014 and October 2016 were selected as the research subjects and divided into 3 groups, group A received entecavir therapy, group B received adefovir dipivoxil therapy and group C received lamivudine therapy. 24 weeks and 48 weeks after treatment, the levels of liver fibrosis indexes in serum as well the levels of DC and the expression of surface markers in peripheral blood of the three groups were measured respectively. Results: After treatment, serum hyaluronic acid (HA), procollagen III (PC-III), laminin (LN) and collagen type IV (C-IV) levels of all groups were significantly lower than those before treatment, and the number of myeloid DC (mDC) and plasmacytoid DC (pDC) in peripheral blood as well as the expression levels of DC surface molecules CD80, CD86, CD1αand HLA-DR in peripheral blood were significantly higher than those before treatment. After treatment, the serum levels of HA, PC-III, LN and C-IV in group A were significantly lower than those in group B and C, and the number of mDC and pDC in peripheral blood as well as the expression of DC surface molecules CD80, CD86, CD1α and HLA-DR in peripheral blood were significantly higher than those in group B and C. Conclusion: Antiviral therapy by nucleoside analogues can effectively inhibit liver fibrosis and improve peripheral blood DC function in patients with chronic hepatitis B, and Entecavir function is better than that of adefovir dipivoxil and lamivudine.展开更多
BACKGROUND The effect of nonalcoholic fatty liver disease(NAFLD)on the efficacy of nucleoside analogues(NAs)in antiviral therapy for patients with chronic hepatitis B(CHB)remains controversial.AIM To investigate the i...BACKGROUND The effect of nonalcoholic fatty liver disease(NAFLD)on the efficacy of nucleoside analogues(NAs)in antiviral therapy for patients with chronic hepatitis B(CHB)remains controversial.AIM To investigate the influence of NAFLD on virological response in CHB patients undergoing NAs treatment.METHODS Logistic regression analysis was conducted on a cohort of 465 CHB patients from two hospitals to determine whether NAFLD was a risk factor for adverse reactions to NAs.CHB patients were followed up for more than 28 months after initial antiviral treatment,and further validation was performed using different viral load populations.RESULTS NAFLD was identified as an independent risk factor for partial virological response following antiviral therapy with NAs(odds ratio=1.777,P=0.017).In our subsequent analysis focusing on CHB patients with high viral load,the NAFLD group exhibited significantly longer virus shedding time and lower proportion of the complete virological response compared with the non-NAFLD group(16.8±6.1 vs 13.0±6.8,P<0.05).During the 24-month period of antiviral treatment with NAs,hepatitis B virus(HBV)DNA levels decreased slowly in the NAFLD group,and the negative conversion rate of HBV was notably lower than that observed in non-NAFLD group(P=0.001).Similar results were obtained when analyzing patients with low baseline HBV viral load within the NAFLD group.CONCLUSION Coexistence of NAFLD may diminish virological response among CHB patients receiving antiviral treatment with NAs.展开更多
AIM: To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues (NAs) themselves in patients with chronic hepatitis B (CHB) receiving NA therapy.
For investigating the biological function of ADPR, four novel analogues （compounds 2-5） in which the pyrophosphate linkage was replaced by the aspartic acid dipeptide were synthesized. 5＇-Amino adenosine or its ana...For investigating the biological function of ADPR, four novel analogues （compounds 2-5） in which the pyrophosphate linkage was replaced by the aspartic acid dipeptide were synthesized. 5＇-Amino adenosine or its analogues was used as the starting material, liquid phase peptide synthesis strategy was used to construct these ADPR analogues. The structures were characterized by 1H NMR and HRMS spectra. This study provides a versatile synthesis of peptide modified ADPR analogues and helps to understand the structure-activity relationship of ADPR.展开更多
Hepatitis B virus(HBV)reactivation(HBVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy administration.The asse...Hepatitis B virus(HBV)reactivation(HBVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy administration.The assessment of HBVr traditionally considers factors such as HBV profile,including hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen,along with type of medication(chemotherapy;immunomodulants).Nevertheless,consideration of possible patient’s underlying tumor and the specific malignancy type(solid or hematologic)plays a crucial role and needs to be assessed for decision-making process.展开更多
An efficient protocol for the synthesis of N^6-（2-Hydroxyethyl）adenosine and its analogues through nucleophilic substitution was developed. All the reactions were completed in 10 rain under microwave irradiation. Us...An efficient protocol for the synthesis of N^6-（2-Hydroxyethyl）adenosine and its analogues through nucleophilic substitution was developed. All the reactions were completed in 10 rain under microwave irradiation. Using water as solvent makes our method eco-friendly and easy to handle with.展开更多
This editorial commented on an article in the World Journal of Gastroenterology titled“Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors:Case Report and Literature An...This editorial commented on an article in the World Journal of Gastroenterology titled“Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors:Case Report and Literature Analysis”by Colapietro et al.In this editorial,we focused on providing a more comprehensive exploration of hepatitis B virus reactivation(HBVr)associated with the usage of tyrosine kinase inhibitors(TKIs).It includes insights into the mechanisms underlying HBV reactivation,the temporal relationship between TKIs and HBV reactivation,and preventive measures.The aim is to understand the need for nucleos(t)ide analogs(NAT)and serial blood tests for early recognition of reactivation and acute liver injury,along with management strategies.TKIs are considered to be an intermediate(1%-10%)of HBVr.Current guidelines stipulate that patients receiving therapy with high or moderate risks of reactivation or recent cancer diagnosis must have at least tested hepatitis B surface antigen,anti-hepatitis B core antigen(HBc),and anti-hepatitis B surface antibody.Anti-HBc screening in highly endemic areas means people with negative tests should be vaccinated against HBV.Nucleoside or nucleotide analogs(NAs)like entecavir(ETV),tenofovir disoproxil fumarate(TDF),and tenofovir alafenamide(TAF)form the basis of HBV reactivation prophylaxis and treatment during immunosuppression.Conversely,lamivudine,telbivudine,and adefovir are generally discouraged due to their reduced antiviral efficacy and higher risk of fostering drug-resistant viral strains.However,these less effective NAs may still be utilized in cases where ETV,TDF,and TAF are not feasible treatment options.展开更多
Cytosine-substituted mildiomycin analogue （MIL-C） was produced effectively by supplementing cytosine into the culture of Streptoverticillium rimofaciens. In order to improve the yield of MIL-C, statistically-based e...Cytosine-substituted mildiomycin analogue （MIL-C） was produced effectively by supplementing cytosine into the culture of Streptoverticillium rimofaciens. In order to improve the yield of MIL-C, statistically-based experimental designs were applied to optimize the fermentation medium for S. rimofaciens ZJU 5119. Fifteen culture conditions were examined for their significances on MIL-C production using Plackett-Burman design. The Plackett-Burrnan design and one-variable-at-a-time design indicated that glucose and rice meal as the complex carbon sources, and peanut cake meal and NH4NO3 as the complex nitrogen sources were beneficial for MIL-C production in S. rimofaciens ZJU 5119. The results of further central composition design （CCD） showed that the optimal concentration of glucose, rice meal and peanut cake meal were 18.7 g/L, 64.8 g/L and 65.1 g/L, respectively. By using this optimal fermentation medium, the MIL-C concentration was increased up to 1336.5 mg/L, an approximate 3.8-fold improvement over the previous concentration （350.0 mg/L） with un-optimized medium. This work will be very helpful to the large-scale production of MIL-C in the future.展开更多
BACKGROUND The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity,such as estimated glomerular filtration rate(eGFR)and phosphatemia,are late markers of proximal tubulopathy.Multiple ear...BACKGROUND The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity,such as estimated glomerular filtration rate(eGFR)and phosphatemia,are late markers of proximal tubulopathy.Multiple early markers are available,but no consensus exists on their use.AIM To determine the 24 mo prevalence of subclinical proximal tubulopathy(SPT),as defined with early biomarkers,in treated vs untreated hepatitis B virus(HBV)-monoinfected patients.METHODS A prospective,non-randomized,multicenter study of HBV-monoinfected patients with a low number of renal comorbidities was conducted.The patients were separated into three groups:Naïve,starting entecavir(ETV)treatment,or starting tenofovir disoproxil(TDF)treatment.Data on the early markers of SPT,the eGFR and phosphatemia,were collected quarterly.SPT was defined as a maximal tubular reabsorption of phosphate/eGFR below 0.8 mmoL/L and/or uric acid fractional excretion above 10%.The prevalence and cumulative incidence of SPT at month 24(M24)were calculated.Quantitative data were analyzed using analyses of variance or Kruskal-Wallis tests,whereas chi-squared or Fisher’s exact tests were used to analyze qualitative data.Multivariate analyses were used to adjust for any potential confounding factors.RESULTS Of the 196 patients analyzed,138(84 naïve,28 starting ETV,and 26 starting TDF)had no SPT at inclusion.At M24,the prevalence of SPT was not statistically different between naïve and either treated group(21.1%vs 30.7%,P<0.42 and 50.0%vs 30.7%,P=0.32 for ETV and TDF,respectively);no patient had an eGFR lower than 50 mL/min/1.73 m²or phosphatemia less than 0.48 mmoL/L.In the multivariate analysis,no explanatory variables were identified after adjustment.The cumulative incidence of SPT over 24 mo(25.5%,13.3%,and 52.9%in the naïve,ETV,and TDF groups,respectively)tended to be higher in the TDF group vs the naïve group(hazard ratio:2.283,P=0.05).SPT-free survival at M24 was 57.6%,68.8%,and 23.5%for the naïve,ETV,and TDF groups,respectively.The median survival time without SPT,evaluated only in the TDF group,was 5.9 mo.CONCLUSION The prevalence and incidence of SPT was higher in TDF-treated patients compared to naïve patients.SPT in the naïve population suggests that HBV can induce renal tubular toxicity.展开更多
In a recent study published in Nature,David C.Schultz et al.demonstrated a new high-efficient therapy to fight against SARSCoV-2,that is,combining pyrimidine biosynthetic inhibitors with antiviral nucleoside analogues...In a recent study published in Nature,David C.Schultz et al.demonstrated a new high-efficient therapy to fight against SARSCoV-2,that is,combining pyrimidine biosynthetic inhibitors with antiviral nucleoside analogues.1 By February 10,2022,SARS-CoV-2 has infected more than 400 million people,including more than 5.79 million deaths.Patients infected with SARS-CoV-2 usually develop mild to severe symptoms,and several patients lead to severe clinical outcomes.Although some vaccines or drugs have entered clinical practice,there is still a lack of effective antiviral therapy against the constantly changing virus.展开更多
基金Supported by National High Technology Research and Development Program(863 Program)of China,Grant No.2012AA021001
文摘Hepatitis B is a common yet serious infectious disease of the liver, affecting millions of people worldwide. Liver transplantation is the only possible treatment for those who advance to end-stage liver disease. Donors positive for hepatitis B virus(HBV) core antibody(HBc Ab) have previously been considered unsuitable for transplants. However, those who test negative for the more serious hepatitis B surface antigen can now be used as liver donors, thereby reducing organ shortages. Remarkable improvements have been made in the treatment against HBV, most notably with the development of nucleoside analogues(NAs), which markedly lessen cirrhosis and reduce post-transplantation HBV recurrence. However, HBV recurrence still occurs in many patients following liver transplantation due to the development of drug resistance and poor compliance with therapy. Optimized prophylactic treatment with appropriate NA usage is crucial prior to liver transplantation, and undetectable HBV DNA at the time of transplantation should be achieved. NA-based and hepatitis B immune globulin-based treatment regimens can differ between patients depending on the patients' condition, virus status, and presence of drug resistance. This review focuses on the current progress in applying NAs during the perioperative period of liver transplantation and the prophylactic strategies using NAs to prevent de novo HBV infection in recipients of HBc Ab-positive liver grafts.
基金the Project for Sci-ence and Technology Plan of Liaoning Province(No.2011225020).
文摘Nucleoside analogues are first line chemotherapy in various severe diseases:AIDS(acquired immunodeficiency disease syndrome),cytomegalovirus infections,cancer,etc.However,many nucleoside analogues exhibit poor oral bioavailability because of their high polarity and low intestinal permeability.In order to get around this drawback,prodrugs have been utilized to improve lipophilicity by chemical modification of the parent drug.Alternatively,prodrugs targeting transporters present in the intestine have been applied to promote the transport of the nucleoside analogues.Valacyclovir and valganciclovir are two classic valine ester prodrugs transported by oligopeptide transporter 1.The ideal prodrug achieves delivery of a parent drug by attaching a non-toxic moiety that is stable during transport,but is readily degraded to the parent drug once at the target.This article presents advances of prodrug approaches for enhancing oral absorption of nucleoside analogues.
基金Supported by The National Natural Science Foundation of China, No. 30330680
文摘AIM： To explore the effects of the nucleoside analogues β-L-D4A and β-LPA on hepatitis B virus （HBV） promoters. METHODS： Four HBV promoters were amplified by polymerase chain reaction （PCR） and subcloned into the expression vector pEGFP-1. The four recombinants controlled by HBV promoters were confirmed by restriction analysis and sequencing. Human hepatoma HepG2 cells transfected with the recombinant plasmids were treated with various concentrations of β-L-D4A and β-LPA. Then, enhanced green fluorescent protein （EGFP）-positive cells were detected by fluorescence microscopy and using a fluorescence activated cell sorter RESULTS： Four HBV promoters were separately obtained and successfully cloned into pEGFP-1, Expression of EGFP under the control of the surface promoter （Sp） and the X promoter （Xp） was inhibited by β-L-D4A in a dosedependent manner, while expression of EGFP under the control of the core promoter （Cp） and Xp was inhibited by β-LPA in a dose-dependent manner. CONCLUSION： The two novel nucleoside analogues investigated here can inhibit the activities of HBV promoters in a dose-dependent manner. These findings may explain the mechanisms of action by which these two novel compounds inhibit HBV DNA replication.
基金We thank for the funding support from the Hundred Talents Program of Hunan Province(No.9999004007)the Startup grant of Hunan University of Chinese Medicine(No.999900201107).
文摘Objective There are many clinical reports on traditional Chinese medicine(TCM)combined with nucleoside(acid)analogues(NAs)for the treatment of chronic hepatitis B(CHB),but its efficacy and safety are not completely clear.This meta-analysis aims to evaluate the clinical efficacy and safety thus providing evidence for clinical applications.Methods We searched Chinese databases the China National Knowledge Infrastructure(CNKI),Wanfang Data,and China Science and Technology Journal Database(VIP),as well as English databases Pub Med and Cochrane Library,from time of establishment to April 14,2021.Literature quality was evaluated according to the bias risk assessment criteria of Cochrane Collaboration network.Rev Man 5.3 and Stata 12.0 software were used to perform this research.Results A total of 23 articles,3282 patients,and 25 TCM prescriptions were included in this study.NAs plus TCM remarkably improved the clinical total effective rate[Odds ratio(OR)=3.92,P<0.00001],TCM syndrome score(Mean difference=-3.73,P<0.00001),hepatitis B virus(HBV)DNA negative conversion rate(OR=1.49,P=0.0001),hepatitis Be antigen(HBe Ag)negative conversion rate(OR=2.03,P<0.00001),alanine aminotransferase levels[Std mean difference(SMD)=-0.95,P<0.00001],and aspartate aminotransferase levels(SMD=-0.70,P=0.0004).Adverse reaction rates did not increase in the combined treatment group(OR=0.97,P=0.84).A comprehensive analysis of the 25 TCM prescriptions suggested that the combination of spleen-strengthening prescriptions with NAs showed better effects than other prescriptions.Conclusion TCM in combination with NAs,demonstrated better clinical efficacy against CHB than NAs alone.In addition,the combination of spleen-strengthening prescriptions and NAs was identified as the best therapeutic strategy.However,more randomized controlled trials of high quality are needed to provide more reliable clinical basis for the application of TCM.
文摘Objective: To study the effect of different nucleoside analogues on liver fibrosis and peripheral blood dendritic cell function of patients with chronic hepatitis B. Methods: Patients with chronic hepatitis B who received antiviral therapy in Infectious Diseases Hospital of Shanghai Huangpu District between April 2014 and October 2016 were selected as the research subjects and divided into 3 groups, group A received entecavir therapy, group B received adefovir dipivoxil therapy and group C received lamivudine therapy. 24 weeks and 48 weeks after treatment, the levels of liver fibrosis indexes in serum as well the levels of DC and the expression of surface markers in peripheral blood of the three groups were measured respectively. Results: After treatment, serum hyaluronic acid (HA), procollagen III (PC-III), laminin (LN) and collagen type IV (C-IV) levels of all groups were significantly lower than those before treatment, and the number of myeloid DC (mDC) and plasmacytoid DC (pDC) in peripheral blood as well as the expression levels of DC surface molecules CD80, CD86, CD1αand HLA-DR in peripheral blood were significantly higher than those before treatment. After treatment, the serum levels of HA, PC-III, LN and C-IV in group A were significantly lower than those in group B and C, and the number of mDC and pDC in peripheral blood as well as the expression of DC surface molecules CD80, CD86, CD1α and HLA-DR in peripheral blood were significantly higher than those in group B and C. Conclusion: Antiviral therapy by nucleoside analogues can effectively inhibit liver fibrosis and improve peripheral blood DC function in patients with chronic hepatitis B, and Entecavir function is better than that of adefovir dipivoxil and lamivudine.
基金Supported by National Science and Technology Major Project of China,No.92169121National Key R and D Projects,No.2022YFC2305100Wuhan Science and Technology Bureau Knowledge Innovation Special Foundation of Hubei Province,No.2022020801010588.
文摘BACKGROUND The effect of nonalcoholic fatty liver disease(NAFLD)on the efficacy of nucleoside analogues(NAs)in antiviral therapy for patients with chronic hepatitis B(CHB)remains controversial.AIM To investigate the influence of NAFLD on virological response in CHB patients undergoing NAs treatment.METHODS Logistic regression analysis was conducted on a cohort of 465 CHB patients from two hospitals to determine whether NAFLD was a risk factor for adverse reactions to NAs.CHB patients were followed up for more than 28 months after initial antiviral treatment,and further validation was performed using different viral load populations.RESULTS NAFLD was identified as an independent risk factor for partial virological response following antiviral therapy with NAs(odds ratio=1.777,P=0.017).In our subsequent analysis focusing on CHB patients with high viral load,the NAFLD group exhibited significantly longer virus shedding time and lower proportion of the complete virological response compared with the non-NAFLD group(16.8±6.1 vs 13.0±6.8,P<0.05).During the 24-month period of antiviral treatment with NAs,hepatitis B virus(HBV)DNA levels decreased slowly in the NAFLD group,and the negative conversion rate of HBV was notably lower than that observed in non-NAFLD group(P=0.001).Similar results were obtained when analyzing patients with low baseline HBV viral load within the NAFLD group.CONCLUSION Coexistence of NAFLD may diminish virological response among CHB patients receiving antiviral treatment with NAs.
基金Supported by The Shanghai Natural Science Fund,No.09ZR1400500the National Natural Science Foundation of China,No.30972600+1 种基金the GuangHui Fund of Hepatitis Prevention Fund Committee China,No.GHZ20100204the Shanghai Health Bureau Fund,No.2012092
文摘AIM: To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues (NAs) themselves in patients with chronic hepatitis B (CHB) receiving NA therapy.
基金National Natural Science Foundation of China(Grant No.20472007)the Research Found for the DocroralProgram of Higher Education
文摘For investigating the biological function of ADPR, four novel analogues （compounds 2-5） in which the pyrophosphate linkage was replaced by the aspartic acid dipeptide were synthesized. 5＇-Amino adenosine or its analogues was used as the starting material, liquid phase peptide synthesis strategy was used to construct these ADPR analogues. The structures were characterized by 1H NMR and HRMS spectra. This study provides a versatile synthesis of peptide modified ADPR analogues and helps to understand the structure-activity relationship of ADPR.
文摘Hepatitis B virus(HBV)reactivation(HBVr)represents a severe and potentially life-threatening condition,and preventive measures are available through blood test screening or prophylactic therapy administration.The assessment of HBVr traditionally considers factors such as HBV profile,including hepatitis B surface antigen(HBsAg)and antibody to hepatitis B core antigen,along with type of medication(chemotherapy;immunomodulants).Nevertheless,consideration of possible patient’s underlying tumor and the specific malignancy type(solid or hematologic)plays a crucial role and needs to be assessed for decision-making process.
基金the National Natural Science Foundation of China(No.20372018)
文摘An efficient protocol for the synthesis of N^6-（2-Hydroxyethyl）adenosine and its analogues through nucleophilic substitution was developed. All the reactions were completed in 10 rain under microwave irradiation. Using water as solvent makes our method eco-friendly and easy to handle with.
文摘This editorial commented on an article in the World Journal of Gastroenterology titled“Risks of Reactivation of Hepatitis B Virus in Oncological Patients Using Tyrosine Kinase-Inhibitors:Case Report and Literature Analysis”by Colapietro et al.In this editorial,we focused on providing a more comprehensive exploration of hepatitis B virus reactivation(HBVr)associated with the usage of tyrosine kinase inhibitors(TKIs).It includes insights into the mechanisms underlying HBV reactivation,the temporal relationship between TKIs and HBV reactivation,and preventive measures.The aim is to understand the need for nucleos(t)ide analogs(NAT)and serial blood tests for early recognition of reactivation and acute liver injury,along with management strategies.TKIs are considered to be an intermediate(1%-10%)of HBVr.Current guidelines stipulate that patients receiving therapy with high or moderate risks of reactivation or recent cancer diagnosis must have at least tested hepatitis B surface antigen,anti-hepatitis B core antigen(HBc),and anti-hepatitis B surface antibody.Anti-HBc screening in highly endemic areas means people with negative tests should be vaccinated against HBV.Nucleoside or nucleotide analogs(NAs)like entecavir(ETV),tenofovir disoproxil fumarate(TDF),and tenofovir alafenamide(TAF)form the basis of HBV reactivation prophylaxis and treatment during immunosuppression.Conversely,lamivudine,telbivudine,and adefovir are generally discouraged due to their reduced antiviral efficacy and higher risk of fostering drug-resistant viral strains.However,these less effective NAs may still be utilized in cases where ETV,TDF,and TAF are not feasible treatment options.
基金Project supported by the Ministry of Science and Technology, China (No. 2004BA308A22-14)the Department of Science and Tech- nology of Zhejiang Province, China (No. 011102543)
文摘Cytosine-substituted mildiomycin analogue （MIL-C） was produced effectively by supplementing cytosine into the culture of Streptoverticillium rimofaciens. In order to improve the yield of MIL-C, statistically-based experimental designs were applied to optimize the fermentation medium for S. rimofaciens ZJU 5119. Fifteen culture conditions were examined for their significances on MIL-C production using Plackett-Burman design. The Plackett-Burrnan design and one-variable-at-a-time design indicated that glucose and rice meal as the complex carbon sources, and peanut cake meal and NH4NO3 as the complex nitrogen sources were beneficial for MIL-C production in S. rimofaciens ZJU 5119. The results of further central composition design （CCD） showed that the optimal concentration of glucose, rice meal and peanut cake meal were 18.7 g/L, 64.8 g/L and 65.1 g/L, respectively. By using this optimal fermentation medium, the MIL-C concentration was increased up to 1336.5 mg/L, an approximate 3.8-fold improvement over the previous concentration （350.0 mg/L） with un-optimized medium. This work will be very helpful to the large-scale production of MIL-C in the future.
文摘BACKGROUND The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity,such as estimated glomerular filtration rate(eGFR)and phosphatemia,are late markers of proximal tubulopathy.Multiple early markers are available,but no consensus exists on their use.AIM To determine the 24 mo prevalence of subclinical proximal tubulopathy(SPT),as defined with early biomarkers,in treated vs untreated hepatitis B virus(HBV)-monoinfected patients.METHODS A prospective,non-randomized,multicenter study of HBV-monoinfected patients with a low number of renal comorbidities was conducted.The patients were separated into three groups:Naïve,starting entecavir(ETV)treatment,or starting tenofovir disoproxil(TDF)treatment.Data on the early markers of SPT,the eGFR and phosphatemia,were collected quarterly.SPT was defined as a maximal tubular reabsorption of phosphate/eGFR below 0.8 mmoL/L and/or uric acid fractional excretion above 10%.The prevalence and cumulative incidence of SPT at month 24(M24)were calculated.Quantitative data were analyzed using analyses of variance or Kruskal-Wallis tests,whereas chi-squared or Fisher’s exact tests were used to analyze qualitative data.Multivariate analyses were used to adjust for any potential confounding factors.RESULTS Of the 196 patients analyzed,138(84 naïve,28 starting ETV,and 26 starting TDF)had no SPT at inclusion.At M24,the prevalence of SPT was not statistically different between naïve and either treated group(21.1%vs 30.7%,P<0.42 and 50.0%vs 30.7%,P=0.32 for ETV and TDF,respectively);no patient had an eGFR lower than 50 mL/min/1.73 m²or phosphatemia less than 0.48 mmoL/L.In the multivariate analysis,no explanatory variables were identified after adjustment.The cumulative incidence of SPT over 24 mo(25.5%,13.3%,and 52.9%in the naïve,ETV,and TDF groups,respectively)tended to be higher in the TDF group vs the naïve group(hazard ratio:2.283,P=0.05).SPT-free survival at M24 was 57.6%,68.8%,and 23.5%for the naïve,ETV,and TDF groups,respectively.The median survival time without SPT,evaluated only in the TDF group,was 5.9 mo.CONCLUSION The prevalence and incidence of SPT was higher in TDF-treated patients compared to naïve patients.SPT in the naïve population suggests that HBV can induce renal tubular toxicity.
文摘In a recent study published in Nature,David C.Schultz et al.demonstrated a new high-efficient therapy to fight against SARSCoV-2,that is,combining pyrimidine biosynthetic inhibitors with antiviral nucleoside analogues.1 By February 10,2022,SARS-CoV-2 has infected more than 400 million people,including more than 5.79 million deaths.Patients infected with SARS-CoV-2 usually develop mild to severe symptoms,and several patients lead to severe clinical outcomes.Although some vaccines or drugs have entered clinical practice,there is still a lack of effective antiviral therapy against the constantly changing virus.
