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The role of genetic factors in HBV-related HCC:perspectives from local genetic backgrounds and clinical epidemiology

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Hepatoma Research 2020年第11期6卷 1-12页

作者： dar-in tai Jennifer tai Liver Research Center Chang Gung Memorial HospitalLinkou Medical CenterTaoyuan 33305Taiwan Department of Internal Medicine Chang Gung Memorial HospitalLinkou Medical CenterTaoyuan 33305Taiwan

Familial clustering of hepatitis B surface antigen carriers(HBsAg)and hepatocellular carcinoma(HCC)has led to the evaluation of the role of genetics in hepatitis B-related *** reports indicate that the HLA-DP and-DQ loci are associated with persistent hepatitis B virus(HBV)***,for hepatocarcinogenesis,existing studies have low power and conflicting *** single nucleotide polymorphism(SNP)data was collected from the 1000 Genomes Project and correlated with local epidemiological *** Asia has a higher prevalence of HBsAg than Northeastern Asia;this was used in the evaluation of persistent HBV *** higher incidence of HCC in West Africa compared with East Africa was used in the evaluation of *** allele frequencies for SNPs were significantly different between East Asians and ***,SNPs that have been identified in persistent HBV infections in East Asia may not be completely applicable in *** in NTCP,CTF19,and the HLA-DQ and-DP loci showed North-to-South allele frequency changes in East *** findings confirm the role of genetics in persistent HBV *** of the SNPs in the HLA loci show a trend of West-to-East allele frequency changes in Africa,indicating they may participate in *** the non-HLA related SNPs,rs2596542 in MICA shows a strong trend of allele frequency changes and is correlated with HCC incidence in *** in KIF1,IL-1A,and STAT4 also show,albeit with low statistical power,allele frequency trends compatible with HCC *** together,there are strong correlations between background genetics in HLA-DP and-DQ loci with persistent HBV infection and *** correlations were weak-positive in non-HLA loci.

关键词： Genetic polymorphism genome-wide associated studies hepatitis B virus hepatocellular carcinoma

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Hepatocellular carcinoma occurred in a Hepatitis B carrier clinic cohort during a mean follow up of 10 years

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Hepatoma Research 2019年第7期5卷 18-25页

作者： Cheng-Jen Chen Jennifer tai dar-in tai Liver Research Center Chang Gung Memorial HospitalLinkou Medical CenterTaoyuan 33305Taiwan Department of Internal Medicine Chang Gung Memorial HospitalLinkou Medical CenterTaoyuan 33305Taiwan

Aim:Chronic persistent hepatitis B virus carriers are generally asymptomatic until the advanced stage of the ***"Hepatitis B-Carrier Clinics"of Chang Gung Memorial Hospital has been using alpha-fetoprotein(AFP)and liver ultrasound for early detection of hepatocellular carcinoma(HCC)in hepatitis B surface antigen(HBsAg)carriers since ***:We evaluated the results of surveillance between 1980 and 2012 by collecting clinic data,matched cancer registry status,and national mortality database ***:Of 15,235 HBsAg carriers,238 instances of HCC(1.5%or 156.2/100,000 person-years)were detected over a mean follow-up period of 10.0±7.6 *** were more men(89.1%)and patients with liver cirrhosis(70.2%)in the HCC group(P<0.001),and both the initial and maximal alanine aminotransferase(ALT)levels were higher in this group(P<0.001).One hundred and thirty cases of HCC(54.6%)were identified during regular follow-up sessions,55(23.1%)were detected after the regular schedule had lapsed("out-of-schedule"),and 53(22.3%)were lost to follow-up *** mean tumor size was smaller in the regular group than in the out-of-schedule group(2.72 cm vs.4.59 cm,P<0.001),and the survival rate was higher(43.8%vs.30.9%,P<0.001).Conclusion:The incidence of HCC was relatively low in the HBsAg-Carrier Clinics *** for early diagnosis of HCC improved the survival of high-risk HBsAg *** ensure cost-effectiveness,we suggest using different screening strategies according to the individual risk of hepatocarcinogenesis.

关键词： Hepatitis B surface antigen retrospective cohort hepatocellular carcinoma surveillance

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Hepatitis B virus persistent infection-related single nucleotide polymorphisms in HLA regions are associated with viral load in hepatoma families

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World Journal of Gastroenterology 2021年第37期27卷 6262-6276页

作者： Ai-Ru Hsieh Cathy S J Fann Hung-Chun Lin Jennifer tai Sen-Yung Hsieh dar-in tai Department of Statistics Tamkang UniversityNew Taipei City 25137Taiwan Institute of Biomedical Sciences Academia SinicaNankangTaipei 11529Taiwan Division of Hepatology Department of Gastroenterology and HepatologyChang Gung Memorial HospitalLinkou Medical CenterTaoyuan 33305Taiwan

BACKGROUND Genome-wide association studies from Asia indicate that HLA-DP and HLA-DQ loci are important in persistent hepatitis B virus(HBV)*** of the key elements for HBV-related carcinogenesis is persistent viral replication and *** To examine genetic and nongenetic factors with persistent HBV infection and viral load in families with hepatocellular carcinoma(HCC).METHODS The HCC families included 301 hepatitis B surface antigen(HBsAg)carriers and 424 noncarriers born before the nationwide vaccination program was initiated in *** HBV-related single nucleotide polymorphisms(SNPs)—rs477515,rs9272105,rs9276370,rs7756516,and rs9277535—were *** associated with persistent HBV infection and viral load were analyzed by a generalized estimating *** In the first-stage persistent HBV study,all SNPs except rs9272105 were associated with persistent infection.A significantly higher area under the reciprocal operating characteristic curve for nongenetic factors vs genetic factors(P<0.001)suggests that the former play a major role in persistent HBV *** the second-stage viral load study,we added 8 HBsAg carriers born after *** 309 HBsAg carriers were divided into low(n=162)and high viral load(n=147)groups with an HBV DNA cutoff of 105 cps/***,relationship to the index case,rs477515,rs9272105,and rs7756516 were associated with viral *** on the receiver operating characteristic curve analysis,genetic and nongenetic factors affected viral load equally in the HCC family cohort(P=0.3117).CONCLUSION In these east Asian adults,the mechanism of persistent HBV infection-related SNPs was a prolonged viral replication phase.

关键词： Generalized estimating equation Genetic polymorphism Genome-wide association study Hepatitis B surface antigen Hepatitis B virus Replication

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Acoustic radiation force impulse predicts long-term outcomes in a large-scale cohort:High liver cancer,low comorbidity in hepatitis B virus

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World Journal of Gastroenterology 2023年第14期29卷 2188-2201页

作者： Jennifer tai Adam P Harrison Hui-Ming Chen Chiu-Yi Hsu Tse-Hwa Hsu Cheng-Jen Chen Wen-Juei Jeng Ming-Ling Chang Le Lu dar-in tai Department of Gastroenterology and Hepatology Chang Gung Memorial HospitalTaoyuan 33305Taiwan Radiomics Group Q BioSan CarlosCA 94063United States Center for Big Data Analytics and Statistics Chang Gung Memorial HospitalTaoyuan 33305Taiwan DAMO Academy Alibaba GroupNew YorkNY 94085United States

BACKGROUND Acoustic radiation force impulse(ARFI)is used to measure liver fibrosis and predict *** performance of elastography in assessment of fibrosis is poorer in hepatitis B virus(HBV)than in other etiologies of chronic liver *** To evaluate the performance of ARFI in long-term outcome prediction among different etiologies of chronic liver *** Consecutive patients who received an ARFI study between 2011 and 2018 were *** excluding dual infection,alcoholism,autoimmune hepatitis,and others with incomplete data,this retrospective cohort were divided into hepatitis B(HBV,n=1064),hepatitis C(HCV,n=507),and non-HBV,non-HCV(NBNC,n=391)*** indexed cases were linked to cancer registration(1987-2020)and national mortality *** differences in morbidity and mortality among the groups were *** At the enrollment,the HBV group showed more males(77.5%),a higher prevalence of prediagnosed hepatocellular carcinoma(HCC),and a lower prevalence of comorbidities than the other groups(P<0.001).The HCV group was older and had a lower platelet count and higher ARFI score than the other groups(P<0.001).The NBNC group showed a higher body mass index and platelet count,a higher prevalence of pre-diagnosed non-HCC cancers(P<0.001),especially breast cancer,and a lower prevalence of *** gender,ARFI score,and HBV were independent predictors of *** 5-year risk of HCC was 5.9%and 9.8%for those ARFI-graded with severe fibrosis and *** alone had an area under the receiver operating characteristic curve(AUROC)of 0.742 for prediction of HCC in 5 *** increased to 0.828 after adding etiology,gender,age,and platelet *** difference was found in mortality rate among the *** The HBV group showed a higher prevalence of HCC but lower comorbidity that made mortality similar among the *** patients with ARFI-graded severe fibrosis or cirrhosis should receive regular surveillance.

关键词： Non-alcoholic fatty liver disease Hepatitis B Hepatocellular carcinoma Acoustic radiation force impulse Mortality Comorbidity

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Effects of sex and generation on hepatitis B viral load in families with hepatocellular carcinoma

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World Journal of Gastroenterology 2017年第5期23卷 876-884页

作者： Ai-Ru Hsieh Cathy SJ Fann Chau-Ting Yeh Hung-Chun Lin Shy-Yi Wan Yi-Cheng Chen Chia-Lin Hsu Jennifer tai Shi-Ming Lin dar-in tai Graduate Institute of Biostatistics China Medical University Institute of Biomedical Sciences Academia Sinica Division of Hepatology Department of Gastroenterology and Hepatology Chang Gung Memorial Hospital Kaohsiung Medical University College of Medicine

AIM To explore factors associated with persistent hepatitis B virus (HBV) infection in a cohort of hepatocellular carcinoma (HCC)-affected families and then investigate factors that correlate with individual viral load among hepatitis B surface antigen (HBsAg)-positive relatives. METHODS questionnaire. Demographics, relationship to index case, HBsAg status of mothers and index cases were evaluated for association with the HBV persistent infection or viral load by generalized estimating equation analysis. RESULTS Among 729 relatives enrolled, parent generation (P = 0.0076), index generation (P = 0.0044), mothers positive for HBsAg (P = 0.0007), and HBsAg-positive index cases (P = 5.98 x 10(-8)) were associated with persistent HBV infection. Factors associated with HBV viral load were evaluated among 303 HBsAg-positive relatives. Parent generation (P = 0.0359) and sex (P = 0.0007) were independent factors associated with HBV viral load. The intra-family HBV viral load was evaluated in families clustered with HBsAg-positive siblings. An intra-family trend of similar HBV viral load was found for 27 of 46 (58.7%) families. Male offspring of HBsAg-positive mothers (P = 0.024) and older siblings were associated with high viral load. CONCLUSION Sex and generation play important roles on HBV viral load. Maternal birth age and nutritional changes could be the reasons of viral load difference between generations.

关键词： Familial generation Sex Hepatitis B virus Perinatal infection Viral replication

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Topological and evolutional relationships between HCV core protein and hepatic lipid vesicles: Studies in vitro and in conditionally transgenic mice

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World Journal of Gastroenterology 2007年第25期13卷 3472-3477页

作者： Ming-Ling Chang Jeng-Chang Chen Chau-Ting Yeh I-Shyan Sheen dar-in tai Ming-Yu Chang Cheng-Tang Chiu Deng-Yn Lin D Montgomery Bissell Liver Research Center and Department of Hepatogastroenterology Chang Gung MemorialHospital Chang Gung University College of Medicine TaoyuanTaiwan China Department of Surgery Chang Gung Children's Hospital Taoyuan Taiwan China Liver Center and Department of Medicine University of California San FranciscoUnited States

AIM: To investigate a specific association between hepatic steatosis and hepatitis C virus (HCV) core. METHODS: HeLa cells and primary mouse hepatocytes were transfected with HCV core plasmid, and conditional transgenics in which hepatic over-expression of HCV core is regulated by the tetracycline-off system, were developed. The expression of the HCV core was assessed over one to six months after withdrawal of doxycycline (dox) by immunohistochemistry (IHC) and Western blotting and by sequential liver biopsy. Hepatic steatosis was evaluated using oil red stain. 8-hydroxydeoxyguanosine (8-OHdG) stains and caspase levels were conducted to clarify hepatic oxidative stress and apoptosis rate. Serum aminotransferase was checked. RESULTS: The transfected hepatocytes had globular cores under the lipid vesicles. In transgenic mice on control diet, core expression was robust, localized to the cytoplasmic vesicle membrane and strongly associatedwith microvesicular steatosis, which was gradually replaced by macrovesicular steatosis. However, both steatosis and core positive hepatocytes diminished with time. Increases in aminotransferase, caspase and 8-OHdG were associated with peak core expression. CONCLUSION: The core protein was readily detected and morphologically associated with steatosis in individual hepatocytes both in vitro and in vivo. In vivo, oxidative stress caused by the core potentially reduced the number of core positive hepatocytes and in parallel the level of steatosis. To our knowledge, this is the f irst animal model that directly shows topological relationship between HCV core and hepatic lipid vesicles.

关键词： Hepatic steatosis Conditional transgenicmice HCV core Oxidative stress

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Accurate and generalizable quantitative scoring of liver steatosis from ultrasound images via scalable deep learning

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World Journal of Gastroenterology 2022年第22期28卷 2494-2508页

作者： Bowen Li dar-in tai Ke Yan Yi-Cheng Chen Cheng-Jen Chen Shiu-Feng Huang Tse-Hwa Hsu Wan-Ting Yu Jing Xiao Lu Le Adam P Harrison Research and Development PAII Inc.BethesdaMD 20817United States Department of Gastroenterology and Hepatology Chang Gung Memorial HospitalLinkou Medical CenterTaoyuan 33305Taiwan Division of Molecular and Genomic Medicine National Health Research InstituteTaoyuan 33305Taiwan Research and Development Ping An Insurance GroupShenzhen 518001GuangdongChina

BACKGROUND Hepatic steatosis is a major cause of chronic liver ***-dimensional(2D)ultrasound is the most widely used non-invasive tool for screening and monitoring,but associated diagnoses are highly *** To develop a scalable deep learning(DL)algorithm for quantitative scoring of liver steatosis from 2D ultrasound *** Using multi-view ultrasound data from 3310 patients,19513 studies,and 228075 images from a retrospective cohort of patients received elastography,we trained a DL algorithm to diagnose steatosis stages(healthy,mild,moderate,or severe)from clinical ultrasound *** was validated on two multiscanner unblinded and blinded(initially to DL developer)histology-proven cohorts(147 and 112 patients)with histopathology fatty cell percentage diagnoses and a subset with FibroScan *** also quantified reliability across scanners and *** were evaluated using Bland-Altman and receiver operating characteristic(ROC)*** The DL algorithm demonstrated repeatable measurements with a moderate number of images(three for each viewpoint)and high agreement across three premium ultrasound *** diagnostic performance was observed across all viewpoints:Areas under the curve of the ROC to classify mild,moderate,and severe steatosis grades were 0.85,0.91,and 0.93,*** DL algorithm outperformed or performed at least comparably to FibroScan control attenuation parameter(CAP)with statistically significant improvements for all levels on the unblinded histology-proven cohort and for“=severe”steatosis on the blinded histology-proven *** The DL algorithm provides a reliable quantitative steatosis assessment across view and scanners on two multi-scanner *** performance was high with comparable or better performance than the CAP.

关键词： Ultrasound Liver steatosis Deep learning Screening Computer-aided diagnosis

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保幼激素类似物对黄胸散白蚁兵蚁分化的诱导

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昆虫学报 1974年第2期17卷 161-165页

作者：朱湘雄戴季达陈志辅金美文上海昆虫研究所

本文报道保幼激素类似物诱导黄胸散白蚁兵蚁分化的作用。试验证明:用保幼激素类似物处理的滤纸喂食工蚁组成的实验群体,可以引起工蚁向前兵蚁方向分化,发生这种分化的工蚁数量最高达45％。三种保幼激素类似物具有明显的作用,它们是:3,7,... 详细信息

本文报道保幼激素类似物诱导黄胸散白蚁兵蚁分化的作用。试验证明:用保幼激素类似物处理的滤纸喂食工蚁组成的实验群体,可以引起工蚁向前兵蚁方向分化,发生这种分化的工蚁数量最高达45％。三种保幼激素类似物具有明显的作用,它们是:3,7,11-三甲基十二碳-2,4-二烯酸乙酯、11-甲氧基-3,7,11-三甲基十二碳-2,4-二烯酸硫代乙酯和11-甲氧基-3,7,11-三甲基十二碳-2,4-二烯酸异丙酯。

关键词：保幼激素类似物白蚁激素杀虫剂兵蚁工蚁

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UV-3D打印材料研究进展

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绿色包装 2021年第2期 33-37页

作者：袁昊蒋小珊林达理程光耀刘云轩王泰北京印刷学院机电工程学院北京102600 北京印刷学院数字化印刷装备北京市重点实验室北京102600 北京印刷学院印刷装备北京市高等工程研究中心北京102600 漳州理工职业学院漳州363000

UV-3D打印作为增材技术新的发展方向,具有设计自由,节约材料以及快速成型等优点,被广泛研究。本文通过分析立体光刻技术(SLA),数字光处理技术(DLP)和UV直写技术等,并研究了UV技术在3D打印领域的应用与发展。然后分析UV-3D打印常用的一... 详细信息

UV-3D打印作为增材技术新的发展方向,具有设计自由,节约材料以及快速成型等优点,被广泛研究。本文通过分析立体光刻技术(SLA),数字光处理技术(DLP)和UV直写技术等,并研究了UV技术在3D打印领域的应用与发展。然后分析UV-3D打印常用的一些材料,包括环氧树脂和丙烯酸树脂以及其发展现状。最后通过介绍UV技术在3D打印的应用现状提出发展对策。

关键词： 3D打印 UV固化光聚合材料

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基于地基Lidar高度指标的小麦生物量监测研究

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农业机械学报 2019年第10期50卷 159-166页

作者：邱小雷方圆郭泰程涛朱艳姚霞南京农业大学国家信息农业工程技术中心

为探讨Li dar监测作物生物量的可行性和方法,以小麦为研究对象,通过田间试验获取关键生育期的小麦Li dar点云高度指标和地上部生物量,基于幂函数回归与支持向量回归、利用十折交叉验证法分别进行特征选择和模型构建,选取各算法最优的全... 详细信息

为探讨Li dar监测作物生物量的可行性和方法,以小麦为研究对象,通过田间试验获取关键生育期的小麦Li dar点云高度指标和地上部生物量,基于幂函数回归与支持向量回归、利用十折交叉验证法分别进行特征选择和模型构建,选取各算法最优的全生育期小麦地上部生物量监测模型,并在测试集上对模型的预测能力进行检验与比较。结果表明:利用H95和生育期特征所构建的全生育期支持向量回归模型精度最高,训练集上决定系数R2达到0.814,测试集结果(R^2=0.821,RMSE为1.730 t/hm^2,RRMSE为32.77%)表明,模型具有较好的准确性;利用Hmean所构建的全生育期幂函数回归模型决定系数R2达到0.809,测试集结果(R^2=0.815,RMSE为1.760 t/hm^2,RRMSE为33.33%)也表明模型具有较好的准确性;高度指标估测小麦生物量具有先天局限性,所构建模型较适宜于监测小麦地上部生物量小于10 t/hm^2的情况,在超过10 t/hm^2的样本集上,95%的模型预测值被低估,RMSE呈指数增长;生育期特征有利于提升监测模型预测精度。

关键词：小麦生物量地基Lidar 高度指标

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