The Chinese Clinical Practice Guidelines for the prevention and treatment of mother-to-child transmission of hepatitis B virus,developed by the Chinese Society of Infectious Diseases of the Chinese Medical Association...The Chinese Clinical Practice Guidelines for the prevention and treatment of mother-to-child transmission of hepatitis B virus,developed by the Chinese Society of Infectious Diseases of the Chinese Medical Association in 2019,serves as a valuable reference for standardizing the process of preventing mother-to-child transmission in China.As new evidence emerges,it is crucial that timely and regular updates are made to the clinical practice guidelines so as to optimize guidance for clinical practice and research.To this end,the Infectious Disease Physician Branch of Chinese Medical Doctor Association and the Chinese Society of Infectious Diseases of Chinese Medical Association,in collaboration with multidisciplinary experts,have updated the guidelines based on the latest domestic and international research advancements and clinical practice,in order to provide guidance and reference for clinicians and maternal and child healthcare workers.展开更多
The Wnt/b-catenin signaling pathway is renowned for its contribution to the immunosuppressive microenvironment in non-small cell lung cancer(NSCLC).Consequently,inhibiting this pathway has emerged as a promising strat...The Wnt/b-catenin signaling pathway is renowned for its contribution to the immunosuppressive microenvironment in non-small cell lung cancer(NSCLC).Consequently,inhibiting this pathway has emerged as a promising strategy to enhance immune activation and reinstate T cell responses in cancer treatment.In this study,we initially investigate the metabolic characteristics of Wnt-hyperactivated NSCLC using mass spectroscopic detection in a mouse in-situ model and unveil its significant feature of acid accumulation at tumor sites.Building upon this discovery,we design an acid-sensitive peptidecarnosic acid(CA)supramolecular droplet(Pep1@CA),which leverages the acidic microenvironment characteristic of NSCLC for controlled release.By doing so,we aim to enhance targeting efficiency while minimizing off-target effects.As anticipated,Pep1@CA demonstrates potent tumor-specific inhibition of the Wnt signaling pathway and effectively reactivates T cell immunity in Wnt-hyperactivated NSCLC.Importantly,comprehensive in vivo evaluations reveal significant antitumor efficacy alongside excellent biosafety profiles.Collectively,this study provides a therapeutic strategy with promising clinical translational potential for targeting the Wnt signaling pathway and offers theoretical support for its application in immunotherapy.This innovative approach underscores that targeting pathways beyond traditional immunotherapy can also activate tumor immunity,thereby expanding the potential of cancer immunotherapy.展开更多
Immunocompromised status and interrupted routine care may render patients with cirrhosis vulnerable to the coronavi-rus disease 2019(COVID-19)pandemic.A nationwide data-set that includes more than 99%of the decedents ...Immunocompromised status and interrupted routine care may render patients with cirrhosis vulnerable to the coronavi-rus disease 2019(COVID-19)pandemic.A nationwide data-set that includes more than 99%of the decedents in the U.S.between April 2012 and September 2021 was used.Projected age-standardized mortality during the pandemic were esti-mated according to prepandemic mortality rates,stratified by season.Excess deaths were determined by estimating the difference between observed and projected mortality rates.A temporal trend analysis of observed mortality rates was also performed in 0.83 million decedents with cirrhosis between April 2012 and September 2021 was included.Following an increasing trend of cirrhosis-related mortality before the pandemic,with a semiannual percentage change(SAPC)of 0.54%[95%confidence interval(CI):(0.0-1.0%),p=0.036],a precipitous increase with seasonal variation occurred dur-ing the pandemic(SAPC 5.35,95%CI:1.9-8.9,p=0.005).Significantly increased mortality rates were observed in those with alcohol-associated liver disease(ALD),with a SAPC of 8.44(95%CI:4.3-12.8,p=0.001)during the pandemic.All-cause mortality of nonalcoholic fatty liver disease rose stead-ily across the entire study period with a SAPC of 6.79(95%CI:6.3-7.3,p<0.001).The decreasing trend of HCV-related mortality was reversed during the pandemic,while there was no significant change in HBV-related deaths.While there was significant increase in COVID-19-related deaths,more than 55%of the excess deaths were the indirect impact of the pandemic.We observed an alarming increase in cirrhosis-related deaths during the pandemic especially for ALD,with evidence in both direct and indirect impact.Our findings have implications on formulating policies for patients with cirrhosis.展开更多
Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HC...Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal.This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs,focusing on GT3 and GT6.Methods:We analyzed the sustained virological response(SVR12)of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific,North America,and Europe between 07/01/2014–07/01/2021.Results:The mean age was 62±13 years,with 49.6%male.The demographic breakdown was 91.1%Asian(52.9%Japanese,25.7%Chinese/Taiwan residents,5.4%Korean,3.3%Malaysian,and 2.9%Vietnamese),6.4%White,1.3%Hispanic/Latino,and 1%Black/African-American.Additionally,34.8%had cirrhosis,8.6%had hepatocellular carcinoma(HCC),and 24.9%were treatment-experienced(20.7%with interferon,4.3%with direct-acting antivirals).The largest group was GT1(10,246[64.6%]),followed by GT2(3,686[23.2%]),GT3(1,151[7.2%]),GT6(457[2.8%]),GT4(47[0.3%]),GT5(1[0.006%]),and untyped GTs(261[1.6%]).The overall SVR12 was 96.9%,with rates over 95%for GT1/2/3/6 but 91.5%for GT4.SVR12 for GT3 was 95.1%overall,98.2%for GT3a,and 94.0%for GT3b.SVR12 was 98.3%overall for GT6,lower for patients with cirrhosis and treatment-experienced(TE)(93.8%)but≥97.5%for tretment-naive patients regardless of cirrhosis status.On multivariable analysis,advanced age,prior treatment failure,cirrhosis,active HCC,and GT3/4 were independent predictors of lower SVR12,while being Asian was a significant predictor of achieving SVR12.Conclusions:In this diverse multinational realworld cohort of patients with various GTs,the overall cure rate was 96.9%,despite large numbers of patients with cirrhosis,HCC,TE,and GT3/6.SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent(>91%).展开更多
The Chinese Clinical Practice Guidelines for the Prevention and Treatment of Mother-to-child Transmission of Hepatitis B Virus,developed by the Chinese Society of Infectious Diseases of the Chinese Medical Association...The Chinese Clinical Practice Guidelines for the Prevention and Treatment of Mother-to-child Transmission of Hepatitis B Virus,developed by the Chinese Society of Infectious Diseases of the Chinese Medical Association in 2019,serves as a valuable reference for standardizing the prevention of mother-to-child transmission in China.As new evidence continues to emerge,it is essential to update these guidelines regularly to optimize clinical practice and research.To this end,the Infectious Disease Physician Branch of the Chinese Medical Doctor Association and the Chinese Society of Infectious Diseases of the Chinese Medical Association,in collaboration with multidisciplinary experts,have updated the guidelines based on the latest domestic and international research advancements and clinical practices,providing upto-date guidance for clinicians and maternal and child healthcare workers.展开更多
The Chinese Clinical Practice Guidelines for the prevention and treatment ofmother-to-child transmission of hepatitis B virus,developed by the Chinese Society of Infectious Diseases of the Chinese Medical Association ...The Chinese Clinical Practice Guidelines for the prevention and treatment ofmother-to-child transmission of hepatitis B virus,developed by the Chinese Society of Infectious Diseases of the Chinese Medical Association in 2019,serves as a valuable reference for standardizing the process of preventing mother-to-child transmission in China.As new evidence emerges,it is crucial that timely and regular updates are made to the clinical practice guidelines so as to optimize guidance for clinical practice and research.To this end,the Infectious Disease Physician Branch of Chinese Medical Doctor Association and the Chinese Society of Infectious Diseases of Chinese Medical Association,in collaboration with multidisciplinary experts,have updated the guidelines based on the latest domestic and international research advancements and clinical practice,in order to provide guidance and reference for clinicians andmaternal and child healthcare workers.展开更多
There is evidence that allergic diseases are associated with carcinogenesis.According to translational and epidemiological data,it appears that different cancer types yield different associations.We investigated the r...There is evidence that allergic diseases are associated with carcinogenesis.According to translational and epidemiological data,it appears that different cancer types yield different associations.We investigated the relationship between allergic dis-eases and 28 cancers by Mendelian randomization.Quantitative trait locus analysis was utilized to determine genes expressed in kidney tissue that were affected by allergy-related loci.We further explored the underlying molecular mechanism between allergic diseases and renal cell carcinoma(RCC)with bioinformatics.Of the 28 cancers,evidence suggested that allergies specifically suppressed kidney cancer.Seventy single nucleotide polymorphisms associated with allergic diseases affected the expression of 134 genes in kidney tissue.These 134 genes were enriched in immune-related pathways represented by the major histocompatibility complex class II antigen presentation pathway.Among them,seven core genes were significantly positively correlated with T helper 2 cells.Allergic diseases specifically suppressed RCC through multiple immune path-ways.Among them,the major histocompatibility complex class II antigen presentation pathway and T helper 2 cells were the most critical.Our study sheds light on the underlying mechanisms of allergic diseases and RCC and provides therapeutic targets for RCC.展开更多
基金supported by Key Research and Development Projects of Shaanxi Province(2018ZDXM-SF-037,2024SF-LCZX-14).
文摘The Chinese Clinical Practice Guidelines for the prevention and treatment of mother-to-child transmission of hepatitis B virus,developed by the Chinese Society of Infectious Diseases of the Chinese Medical Association in 2019,serves as a valuable reference for standardizing the process of preventing mother-to-child transmission in China.As new evidence emerges,it is crucial that timely and regular updates are made to the clinical practice guidelines so as to optimize guidance for clinical practice and research.To this end,the Infectious Disease Physician Branch of Chinese Medical Doctor Association and the Chinese Society of Infectious Diseases of Chinese Medical Association,in collaboration with multidisciplinary experts,have updated the guidelines based on the latest domestic and international research advancements and clinical practice,in order to provide guidance and reference for clinicians and maternal and child healthcare workers.
基金supported by the National Natural Science Foundation of China(Grant No.:82141126)the Key Research and Development Program of Shaanxi Province(Program No.:2020GXLH-Y-020)+4 种基金the Innovation Capability Support Program of Shaanxi(Program No.:2021TD-44)the Key Research and Development Program of Shaanxi(Program No.:2023-GHZD-18)the Natural Science Basic Research Program of Shaanxi(Program No.:2023-JC-QN-0828)the Elite talent program of Shaanxi Provincial People's Hospital(Grant No.:2022JY-43)the Beijing Xisike Clinical Oncology Research Foundation(Grant No.:Y-HH202101-0234).
文摘The Wnt/b-catenin signaling pathway is renowned for its contribution to the immunosuppressive microenvironment in non-small cell lung cancer(NSCLC).Consequently,inhibiting this pathway has emerged as a promising strategy to enhance immune activation and reinstate T cell responses in cancer treatment.In this study,we initially investigate the metabolic characteristics of Wnt-hyperactivated NSCLC using mass spectroscopic detection in a mouse in-situ model and unveil its significant feature of acid accumulation at tumor sites.Building upon this discovery,we design an acid-sensitive peptidecarnosic acid(CA)supramolecular droplet(Pep1@CA),which leverages the acidic microenvironment characteristic of NSCLC for controlled release.By doing so,we aim to enhance targeting efficiency while minimizing off-target effects.As anticipated,Pep1@CA demonstrates potent tumor-specific inhibition of the Wnt signaling pathway and effectively reactivates T cell immunity in Wnt-hyperactivated NSCLC.Importantly,comprehensive in vivo evaluations reveal significant antitumor efficacy alongside excellent biosafety profiles.Collectively,this study provides a therapeutic strategy with promising clinical translational potential for targeting the Wnt signaling pathway and offers theoretical support for its application in immunotherapy.This innovative approach underscores that targeting pathways beyond traditional immunotherapy can also activate tumor immunity,thereby expanding the potential of cancer immunotherapy.
文摘Immunocompromised status and interrupted routine care may render patients with cirrhosis vulnerable to the coronavi-rus disease 2019(COVID-19)pandemic.A nationwide data-set that includes more than 99%of the decedents in the U.S.between April 2012 and September 2021 was used.Projected age-standardized mortality during the pandemic were esti-mated according to prepandemic mortality rates,stratified by season.Excess deaths were determined by estimating the difference between observed and projected mortality rates.A temporal trend analysis of observed mortality rates was also performed in 0.83 million decedents with cirrhosis between April 2012 and September 2021 was included.Following an increasing trend of cirrhosis-related mortality before the pandemic,with a semiannual percentage change(SAPC)of 0.54%[95%confidence interval(CI):(0.0-1.0%),p=0.036],a precipitous increase with seasonal variation occurred dur-ing the pandemic(SAPC 5.35,95%CI:1.9-8.9,p=0.005).Significantly increased mortality rates were observed in those with alcohol-associated liver disease(ALD),with a SAPC of 8.44(95%CI:4.3-12.8,p=0.001)during the pandemic.All-cause mortality of nonalcoholic fatty liver disease rose stead-ily across the entire study period with a SAPC of 6.79(95%CI:6.3-7.3,p<0.001).The decreasing trend of HCV-related mortality was reversed during the pandemic,while there was no significant change in HBV-related deaths.While there was significant increase in COVID-19-related deaths,more than 55%of the excess deaths were the indirect impact of the pandemic.We observed an alarming increase in cirrhosis-related deaths during the pandemic especially for ALD,with evidence in both direct and indirect impact.Our findings have implications on formulating policies for patients with cirrhosis.
基金partially supported by an investigator-initiated research grant(IN-US-334-4309)from Gilead Sciences to Stanford University.
文摘Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal.This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs,focusing on GT3 and GT6.Methods:We analyzed the sustained virological response(SVR12)of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific,North America,and Europe between 07/01/2014–07/01/2021.Results:The mean age was 62±13 years,with 49.6%male.The demographic breakdown was 91.1%Asian(52.9%Japanese,25.7%Chinese/Taiwan residents,5.4%Korean,3.3%Malaysian,and 2.9%Vietnamese),6.4%White,1.3%Hispanic/Latino,and 1%Black/African-American.Additionally,34.8%had cirrhosis,8.6%had hepatocellular carcinoma(HCC),and 24.9%were treatment-experienced(20.7%with interferon,4.3%with direct-acting antivirals).The largest group was GT1(10,246[64.6%]),followed by GT2(3,686[23.2%]),GT3(1,151[7.2%]),GT6(457[2.8%]),GT4(47[0.3%]),GT5(1[0.006%]),and untyped GTs(261[1.6%]).The overall SVR12 was 96.9%,with rates over 95%for GT1/2/3/6 but 91.5%for GT4.SVR12 for GT3 was 95.1%overall,98.2%for GT3a,and 94.0%for GT3b.SVR12 was 98.3%overall for GT6,lower for patients with cirrhosis and treatment-experienced(TE)(93.8%)but≥97.5%for tretment-naive patients regardless of cirrhosis status.On multivariable analysis,advanced age,prior treatment failure,cirrhosis,active HCC,and GT3/4 were independent predictors of lower SVR12,while being Asian was a significant predictor of achieving SVR12.Conclusions:In this diverse multinational realworld cohort of patients with various GTs,the overall cure rate was 96.9%,despite large numbers of patients with cirrhosis,HCC,TE,and GT3/6.SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent(>91%).
文摘The Chinese Clinical Practice Guidelines for the Prevention and Treatment of Mother-to-child Transmission of Hepatitis B Virus,developed by the Chinese Society of Infectious Diseases of the Chinese Medical Association in 2019,serves as a valuable reference for standardizing the prevention of mother-to-child transmission in China.As new evidence continues to emerge,it is essential to update these guidelines regularly to optimize clinical practice and research.To this end,the Infectious Disease Physician Branch of the Chinese Medical Doctor Association and the Chinese Society of Infectious Diseases of the Chinese Medical Association,in collaboration with multidisciplinary experts,have updated the guidelines based on the latest domestic and international research advancements and clinical practices,providing upto-date guidance for clinicians and maternal and child healthcare workers.
基金supported by the Key Research and Development Projects of Shaanxi Province(2018ZDXM-SF-037,2024SF-LCZX-14).
文摘The Chinese Clinical Practice Guidelines for the prevention and treatment ofmother-to-child transmission of hepatitis B virus,developed by the Chinese Society of Infectious Diseases of the Chinese Medical Association in 2019,serves as a valuable reference for standardizing the process of preventing mother-to-child transmission in China.As new evidence emerges,it is crucial that timely and regular updates are made to the clinical practice guidelines so as to optimize guidance for clinical practice and research.To this end,the Infectious Disease Physician Branch of Chinese Medical Doctor Association and the Chinese Society of Infectious Diseases of Chinese Medical Association,in collaboration with multidisciplinary experts,have updated the guidelines based on the latest domestic and international research advancements and clinical practice,in order to provide guidance and reference for clinicians andmaternal and child healthcare workers.
文摘There is evidence that allergic diseases are associated with carcinogenesis.According to translational and epidemiological data,it appears that different cancer types yield different associations.We investigated the relationship between allergic dis-eases and 28 cancers by Mendelian randomization.Quantitative trait locus analysis was utilized to determine genes expressed in kidney tissue that were affected by allergy-related loci.We further explored the underlying molecular mechanism between allergic diseases and renal cell carcinoma(RCC)with bioinformatics.Of the 28 cancers,evidence suggested that allergies specifically suppressed kidney cancer.Seventy single nucleotide polymorphisms associated with allergic diseases affected the expression of 134 genes in kidney tissue.These 134 genes were enriched in immune-related pathways represented by the major histocompatibility complex class II antigen presentation pathway.Among them,seven core genes were significantly positively correlated with T helper 2 cells.Allergic diseases specifically suppressed RCC through multiple immune path-ways.Among them,the major histocompatibility complex class II antigen presentation pathway and T helper 2 cells were the most critical.Our study sheds light on the underlying mechanisms of allergic diseases and RCC and provides therapeutic targets for RCC.
