Chronic hepatitis B(CHB)remains a significant global health challenge,affecting more than 250 million individuals worldwide.A functional cure,defined as the loss of hepatitis B surface antigen(HBsAg)and suppression of...Chronic hepatitis B(CHB)remains a significant global health challenge,affecting more than 250 million individuals worldwide.A functional cure,defined as the loss of hepatitis B surface antigen(HBsAg)and suppression of hepatitis B virus(HBV)DNA to undetectable levels,represents the optimal therapeutic endpoint for managing CHB.However,the complex pathogenesis of CHB,which includes HBV DNA integration,persistence of covalently closed circular DNA,and impaired immune responses,presents substantial barriers to HBsAg clearance.Current therapies offer limited success in achieving a functional cure,with HBsAg seroclearance occurring in only 3%-5%of patients after 10 years of nucleos(t)ide analogs(NAs)therapy and 8%-14%within 3-5 years of pegylated interferon treatment.To overcome these limitations,novel direct-acting antivirals targeting different stages of the HBV life cycle are being investigated.Additionally,immunomodulatory approaches,including therapeutic vaccines and immune checkpoint inhibitors,are being explored to enhance HBV-specific immune responses.The concept of NAs cessation in carefully selected non-cirrhotic patients may accelerate HBsAg loss,although the risks of hepatic flare and hepatocellular carcinoma necessitate rigorous monitoring.This review provides a comprehensive overview of the current understanding of HBsAg seroclearance in CHB,discussing its clinical significance,therapeutic challenges,and evolving treatment landscape in the pursuit of a functional cure.展开更多
Sodium chloride is one of the most widely used additives in meat curing.However,cured meat products contribute to a portion of the total sodium dietary intake.Consumers and researchers'concern about excessive sodi...Sodium chloride is one of the most widely used additives in meat curing.However,cured meat products contribute to a portion of the total sodium dietary intake.Consumers and researchers'concern about excessive sodium intake has prompted the food industry to consider ways to reduce salt content of cured meat products.The aim of this review is to provide a broad but comprehensive understanding of salt reduction strategies for cured meat products.The implications and limitations of each approach were discussed.Green technologies treatments,such as ultrasonic technology,high-pressure processing,seem to be potential to ensure microbiological safety in low-sodium cured meat products.However,these novel technologies can cause protein and fat oxidization in meat products.A combination of multiple treatments could give the desired effect.In addition,different parameter conditions need to be set according to the specific meat to achieve better salt reduction effect.展开更多
BACKGROUND Occult hepatitis B virus infection(OBI)is defined by the detection of replication-competent hepatitis B virus(HBV)DNA in the liver and/or blood despite the ab-sence of detectable hepatitis B surface antigen...BACKGROUND Occult hepatitis B virus infection(OBI)is defined by the detection of replication-competent hepatitis B virus(HBV)DNA in the liver and/or blood despite the ab-sence of detectable hepatitis B surface antigen(HBsAg)using conventional ser-ological assays.Although OBI has been well-documented in individuals with resolved HBV infection or those receiving immunosuppressive therapy,reports of its occurrence during sequential antiviral treatment remain scarce.This report describes a case of chronic hepatitis B(CHB)transitioning through OBI during sequential combination therapy before ultimately achieving a functional cure.This case provides new insights into the emergence of OBI as a transitional phase during CHB treatment and emphasizes the importance of monitoring its clinical significance.CASE SUMMARY A 33-year-old Chinese male was diagnosed with HBV infection in 2001.The patient first presented in 2012 with abnormal liver function tests and received initial treatment with conventional interferon therapy,which failed to achieve a virological response.Antiviral therapy was subsequently switched to entecavir monotherapy.By August 2019,the patient exhibited an HBsAg level of 29.93 IU/mL with undetectable HBV DNA(<25 IU/mL).At this point,combination therapy with entecavir and pegylated interferonα(PEG-IFNα)was initiated.Remarkably,while HBsAg declined to 0.42 IU/mL by April 2020,a paradoxical HBV DNA rebound to 173 IU/mL was observed.The regimen was consequently modified to tenofovir alafenamide and PEG-IFNα.By October 2020,the patient achieved HBsAg seroconversion(HBsAg 0.01 IU/mL,hepatitis B surface antibody 52.18 mIU/mL)for the first time,while maintaining low-level viremia(37 IU/mL),consistent with transition to OBI.The patient was then switched to PEG-IFNαmonotherapy.In November 2021,he discontinued PEG-IFNαtherapy,and one month later,both HBV DNA(<10 IU/mL)and HBsAg(<0.05 IU/mL)were negative.This response has been sustained through follow-up.CONCLUSION This case study illustrates the efficacy of sequential combination therapy in achieving functional cure in CHB patients,including those with a prolonged infection history.It highlights OBI as a transitional yet underrecognized phase during sequential antiviral therapy.While the patient ultimately achieved functional cure,the transient persistence of HBV DNA despite HBsAg clearance suggests the need for continued monitoring.This case provides new insights into OBI development during treatment and underscores the importance of further research into its long-term implications.展开更多
Hepatitis B virus(HBV)infection is a global health concern.The current sequen-tial endpoints for the treatment of HBV infection include viral suppression,hepatitis B e antigen(HBeAg)seroconversion,functional cure,and ...Hepatitis B virus(HBV)infection is a global health concern.The current sequen-tial endpoints for the treatment of HBV infection include viral suppression,hepatitis B e antigen(HBeAg)seroconversion,functional cure,and covalently closed circular DNA(cccDNA)clearance.Serum hepatitis B core-related antigen(HBcrAg)is an emerging HBV marker comprising three components:HBeAg,hepatitis B core antigen,and p22cr.It responds well to the transcriptional activity of cccDNA in the patient's liver and is a promising alternative marker for serolo-gical testing.There is a strong correlation,and a decrease in its level corresponds to sustained viral suppression.In patients with chronic hepatitis B(CHB),serum HBcrAg levels are good predictors of HBeAg seroconversion(both spontaneous and after antiviral therapy),particularly in HBeAg-positive patients.Both low baseline HBcrAg levels and decreasing levels early in antiviral therapy favored HBsAg seroconversion,which may serve as a good surrogate option for treatment endpoints.In this review,we summarize the role of serum HBcrAg in the treat-ment of CHB.Therefore,long-term continuous monitoring of serum HBcrAg levels contributes to the clinical management of patients with CHB and optimizes the choice of treatment regimen,making it a promising marker for monitoring HBV cure.展开更多
为了提高传统CURE(clustering using representatives)聚类算法的质量,引入信息熵对其进行改进。该算法使用K-means算法对样本数据集进行预聚类;采用基于信息熵的相似性度量,利用簇中元素提供的信息度量不同簇之间的相互关系,并描述数...为了提高传统CURE(clustering using representatives)聚类算法的质量,引入信息熵对其进行改进。该算法使用K-means算法对样本数据集进行预聚类;采用基于信息熵的相似性度量,利用簇中元素提供的信息度量不同簇之间的相互关系,并描述数据的分布;在高、低层聚类阶段,采取不同的选取策略,分别选取相应的代表点。在UCI和人造数据集上的实验结果表明,提出的算法在一定程度上提高了聚类的准确率,且在大型数据集上比传统CURE算法有着更高的聚类效率。展开更多
[目的]评价经跗骨窦Hy Pro Cure螺钉的距下关节制动术治疗儿童柔韧性平足症的短期临床疗效。[方法]采用经跗骨窦Hy Pro Cure螺钉的距下关节制动术治疗儿童柔韧性平足症16例(19足)。对照比较术前、术后正位X线片上的距舟覆盖角,侧位X线...[目的]评价经跗骨窦Hy Pro Cure螺钉的距下关节制动术治疗儿童柔韧性平足症的短期临床疗效。[方法]采用经跗骨窦Hy Pro Cure螺钉的距下关节制动术治疗儿童柔韧性平足症16例(19足)。对照比较术前、术后正位X线片上的距舟覆盖角,侧位X线片上的距骨第1跖骨角、跟骨倾斜角变化;并采用美国足踝外科协会(American Orthopedic Foot and Ankle Society,AOFAS)踝与后足功能评分和视觉模拟评分(visual analogue score,VAS)进行疗效评定。[结果]16例(19足)患儿均获随访,平均随访时间6.70个月(3.50~12月)。正位X线片上的距舟覆盖角;侧位X线片上的距骨第1跖骨角(Meary角)、跟骨倾斜角(Pitch角)均较术前改善(P<0.05)。末次随访时AOFAS评分及VAS评分与术前比较,差异均有统计学意义(P<0.05)。[结论]经跗骨窦Hy Pro Cure螺钉的距下关节制动术是治疗儿童柔韧性平足的有效方法,具有简单、创伤小、术后并发症少等优点,但还需长期随访观察远期疗效。展开更多
[Objective] We aimed to improve the quality of flue-cured tobacco with K326 upper leaves and explore the optimal tobacco baking process in Chongqing tobacco-producing region. [Method] Four different baking processes ...[Objective] We aimed to improve the quality of flue-cured tobacco with K326 upper leaves and explore the optimal tobacco baking process in Chongqing tobacco-producing region. [Method] Four different baking processes （endogenetic force moisture-removing flue-curing technique, exogenetic force moisture-removing flue-curing technique, three-stage flue-curing process, three-stage and six-step flue- curing process） were adopted in this research to investigate the effects of different baking processes on carotenoid content of same-maturity degree upper leaves of the flue-cured tobacco K326. [Result] The results showed at the yellowing and color fixing stages, the carotenoids were most fully decomposed in endogenetic force moisture-removing flue-curing technique. The decomposed carotenoid content was lowest in exogenetic force moisture-removing flue-curing technique, for which the carotenoid content was highest （50.53 mg/g）. [Conclusion] At the yellowing and color fixing stages, exogenetic force moisture-removing flue-curing technique was most conducive to the carotenoid accumulation in tobacco baking process.展开更多
CURE(the Clopidogres in Unstable angina to prevent Recurrent Events)试验的主要目的是观察氯吡格雷合用阿司匹林的长、短期疗效,确定是否优于单独使用阿司匹林.该试验采用多中心(28个国家,482家医院)随机双盲方法,1998年12月开始...CURE(the Clopidogres in Unstable angina to prevent Recurrent Events)试验的主要目的是观察氯吡格雷合用阿司匹林的长、短期疗效,确定是否优于单独使用阿司匹林.该试验采用多中心(28个国家,482家医院)随机双盲方法,1998年12月开始入组病人,共收集了12562例ST段抬高＜1 mm,缺血发作24小时以内的急性冠脉综合征病人,其中32.0%的患者即往有心肌梗死病史,22.5%有糖尿病史,58.0%有高血压史,11.0%有即往冠状动脉移植术史.展开更多
文摘Chronic hepatitis B(CHB)remains a significant global health challenge,affecting more than 250 million individuals worldwide.A functional cure,defined as the loss of hepatitis B surface antigen(HBsAg)and suppression of hepatitis B virus(HBV)DNA to undetectable levels,represents the optimal therapeutic endpoint for managing CHB.However,the complex pathogenesis of CHB,which includes HBV DNA integration,persistence of covalently closed circular DNA,and impaired immune responses,presents substantial barriers to HBsAg clearance.Current therapies offer limited success in achieving a functional cure,with HBsAg seroclearance occurring in only 3%-5%of patients after 10 years of nucleos(t)ide analogs(NAs)therapy and 8%-14%within 3-5 years of pegylated interferon treatment.To overcome these limitations,novel direct-acting antivirals targeting different stages of the HBV life cycle are being investigated.Additionally,immunomodulatory approaches,including therapeutic vaccines and immune checkpoint inhibitors,are being explored to enhance HBV-specific immune responses.The concept of NAs cessation in carefully selected non-cirrhotic patients may accelerate HBsAg loss,although the risks of hepatic flare and hepatocellular carcinoma necessitate rigorous monitoring.This review provides a comprehensive overview of the current understanding of HBsAg seroclearance in CHB,discussing its clinical significance,therapeutic challenges,and evolving treatment landscape in the pursuit of a functional cure.
基金financially supported by Youth Talent Support Programme of Guangdong Provincial Association for Science and Technology(SKXRC202317)the Open Project of Beijing Laboratory of Food Quality and Safety/Key Laboratory of Alcoholic Beverages Quality and Safety of China Light Industry(FQS-202201)+3 种基金Characteristic Innovation Project of Guangdong Universities(2022KTSCX058)Special Projects in Key Field of Guangdong Universities(2022ZDZX4015,2022ZDZX4016)Guangdong Maoming Binhai New Area Marine Fishery Industrial Park Project(0835-220FA8102621)Guangdong Provincial Key Laboratory of Lingnan Specialty Food Science and Technology(2021B1212040013)。
文摘Sodium chloride is one of the most widely used additives in meat curing.However,cured meat products contribute to a portion of the total sodium dietary intake.Consumers and researchers'concern about excessive sodium intake has prompted the food industry to consider ways to reduce salt content of cured meat products.The aim of this review is to provide a broad but comprehensive understanding of salt reduction strategies for cured meat products.The implications and limitations of each approach were discussed.Green technologies treatments,such as ultrasonic technology,high-pressure processing,seem to be potential to ensure microbiological safety in low-sodium cured meat products.However,these novel technologies can cause protein and fat oxidization in meat products.A combination of multiple treatments could give the desired effect.In addition,different parameter conditions need to be set according to the specific meat to achieve better salt reduction effect.
文摘BACKGROUND Occult hepatitis B virus infection(OBI)is defined by the detection of replication-competent hepatitis B virus(HBV)DNA in the liver and/or blood despite the ab-sence of detectable hepatitis B surface antigen(HBsAg)using conventional ser-ological assays.Although OBI has been well-documented in individuals with resolved HBV infection or those receiving immunosuppressive therapy,reports of its occurrence during sequential antiviral treatment remain scarce.This report describes a case of chronic hepatitis B(CHB)transitioning through OBI during sequential combination therapy before ultimately achieving a functional cure.This case provides new insights into the emergence of OBI as a transitional phase during CHB treatment and emphasizes the importance of monitoring its clinical significance.CASE SUMMARY A 33-year-old Chinese male was diagnosed with HBV infection in 2001.The patient first presented in 2012 with abnormal liver function tests and received initial treatment with conventional interferon therapy,which failed to achieve a virological response.Antiviral therapy was subsequently switched to entecavir monotherapy.By August 2019,the patient exhibited an HBsAg level of 29.93 IU/mL with undetectable HBV DNA(<25 IU/mL).At this point,combination therapy with entecavir and pegylated interferonα(PEG-IFNα)was initiated.Remarkably,while HBsAg declined to 0.42 IU/mL by April 2020,a paradoxical HBV DNA rebound to 173 IU/mL was observed.The regimen was consequently modified to tenofovir alafenamide and PEG-IFNα.By October 2020,the patient achieved HBsAg seroconversion(HBsAg 0.01 IU/mL,hepatitis B surface antibody 52.18 mIU/mL)for the first time,while maintaining low-level viremia(37 IU/mL),consistent with transition to OBI.The patient was then switched to PEG-IFNαmonotherapy.In November 2021,he discontinued PEG-IFNαtherapy,and one month later,both HBV DNA(<10 IU/mL)and HBsAg(<0.05 IU/mL)were negative.This response has been sustained through follow-up.CONCLUSION This case study illustrates the efficacy of sequential combination therapy in achieving functional cure in CHB patients,including those with a prolonged infection history.It highlights OBI as a transitional yet underrecognized phase during sequential antiviral therapy.While the patient ultimately achieved functional cure,the transient persistence of HBV DNA despite HBsAg clearance suggests the need for continued monitoring.This case provides new insights into OBI development during treatment and underscores the importance of further research into its long-term implications.
基金Supported by The Chongqing Talents Project,No.cstc2021ycjh-bgzxm0150The First Batch of Key Disciplines on Public Health in Chongqing,The Health Commission of Chongqing,No.2022(72)+1 种基金The Remarkable Innovation-Clinical Research Project,The Second Affiliated Hospital of Chongqing Medical UniversityThe Scientific and Technological Research Program of Chongqing Municipal Education Commission,the Second Affiliated Hospital of Chongqing Medical University,No.KJZD-K202300404.
文摘Hepatitis B virus(HBV)infection is a global health concern.The current sequen-tial endpoints for the treatment of HBV infection include viral suppression,hepatitis B e antigen(HBeAg)seroconversion,functional cure,and covalently closed circular DNA(cccDNA)clearance.Serum hepatitis B core-related antigen(HBcrAg)is an emerging HBV marker comprising three components:HBeAg,hepatitis B core antigen,and p22cr.It responds well to the transcriptional activity of cccDNA in the patient's liver and is a promising alternative marker for serolo-gical testing.There is a strong correlation,and a decrease in its level corresponds to sustained viral suppression.In patients with chronic hepatitis B(CHB),serum HBcrAg levels are good predictors of HBeAg seroconversion(both spontaneous and after antiviral therapy),particularly in HBeAg-positive patients.Both low baseline HBcrAg levels and decreasing levels early in antiviral therapy favored HBsAg seroconversion,which may serve as a good surrogate option for treatment endpoints.In this review,we summarize the role of serum HBcrAg in the treat-ment of CHB.Therefore,long-term continuous monitoring of serum HBcrAg levels contributes to the clinical management of patients with CHB and optimizes the choice of treatment regimen,making it a promising marker for monitoring HBV cure.
文摘为了提高传统CURE(clustering using representatives)聚类算法的质量,引入信息熵对其进行改进。该算法使用K-means算法对样本数据集进行预聚类;采用基于信息熵的相似性度量,利用簇中元素提供的信息度量不同簇之间的相互关系,并描述数据的分布;在高、低层聚类阶段,采取不同的选取策略,分别选取相应的代表点。在UCI和人造数据集上的实验结果表明,提出的算法在一定程度上提高了聚类的准确率,且在大型数据集上比传统CURE算法有着更高的聚类效率。
文摘[目的]评价经跗骨窦Hy Pro Cure螺钉的距下关节制动术治疗儿童柔韧性平足症的短期临床疗效。[方法]采用经跗骨窦Hy Pro Cure螺钉的距下关节制动术治疗儿童柔韧性平足症16例(19足)。对照比较术前、术后正位X线片上的距舟覆盖角,侧位X线片上的距骨第1跖骨角、跟骨倾斜角变化;并采用美国足踝外科协会(American Orthopedic Foot and Ankle Society,AOFAS)踝与后足功能评分和视觉模拟评分(visual analogue score,VAS)进行疗效评定。[结果]16例(19足)患儿均获随访,平均随访时间6.70个月(3.50~12月)。正位X线片上的距舟覆盖角;侧位X线片上的距骨第1跖骨角(Meary角)、跟骨倾斜角(Pitch角)均较术前改善(P<0.05)。末次随访时AOFAS评分及VAS评分与术前比较,差异均有统计学意义(P<0.05)。[结论]经跗骨窦Hy Pro Cure螺钉的距下关节制动术是治疗儿童柔韧性平足的有效方法,具有简单、创伤小、术后并发症少等优点,但还需长期随访观察远期疗效。
基金Supported by General Program of Science and Technology Research of China National Tobacco Corporation([2012]No.122)Science and Technology Research Program of Chongqing Branch of China National Tobacco Corporation(NY20110601070010)Technology Project of Chinese Tobacco Corporation~~
文摘[Objective] We aimed to improve the quality of flue-cured tobacco with K326 upper leaves and explore the optimal tobacco baking process in Chongqing tobacco-producing region. [Method] Four different baking processes （endogenetic force moisture-removing flue-curing technique, exogenetic force moisture-removing flue-curing technique, three-stage flue-curing process, three-stage and six-step flue- curing process） were adopted in this research to investigate the effects of different baking processes on carotenoid content of same-maturity degree upper leaves of the flue-cured tobacco K326. [Result] The results showed at the yellowing and color fixing stages, the carotenoids were most fully decomposed in endogenetic force moisture-removing flue-curing technique. The decomposed carotenoid content was lowest in exogenetic force moisture-removing flue-curing technique, for which the carotenoid content was highest （50.53 mg/g）. [Conclusion] At the yellowing and color fixing stages, exogenetic force moisture-removing flue-curing technique was most conducive to the carotenoid accumulation in tobacco baking process.
文摘CURE(the Clopidogres in Unstable angina to prevent Recurrent Events)试验的主要目的是观察氯吡格雷合用阿司匹林的长、短期疗效,确定是否优于单独使用阿司匹林.该试验采用多中心(28个国家,482家医院)随机双盲方法,1998年12月开始入组病人,共收集了12562例ST段抬高＜1 mm,缺血发作24小时以内的急性冠脉综合征病人,其中32.0%的患者即往有心肌梗死病史,22.5%有糖尿病史,58.0%有高血压史,11.0%有即往冠状动脉移植术史.
