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Gut microbiota dysbiosis in patients with nonalcoholic fatty liver disease

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Hepatobiliary & Pancreatic Diseases International 2017年第4期16卷 375-381页

作者： Feng Shen rui-dan zheng Xing-Qiang Sun Wen-Jin Ding Xiao-Ying Wang Jian-Gao Fan Department of Gastroenterology Xinhua HospitalShanghai Jiaotong University School of MedicineShanghai 200092China Department of Pathology Xinhua HospitalShanghai Jiaotong University School of MedicineShanghai 200092China Research and Therapy Centre for Liver Disease Zhengxing HospitalZhangzhou 363000China Department of Microbial Genomics Research BGI ShenzhenShenzhen 518083China

BACKGROUND: Gut microbiota plays a significant role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). This study aimed to assess the contribution of gut microbiota dysbiosis to the pathogenesis of NAFLD. METHODS: Forty-seven human feces samples (25 NAFLD patients and 22 healthy subjects) were collected and 16S rDNA amplicon sequencing was conducted on Hiseq 2000 platform. Discrepancy of species composition between controls and NAFLD group was defined by Metastats analysis under P value dant in NAFLD patients. Additionally, the Lachnospiraceae (21.90%), Enterobacteriaceae (12.02%), Erysipelotrichaceae (3.83%), and Streptococcaceae (1.39%) families, as well as the Escherichia_Shigella (10.84%), Lachnospiraceae_Incertae_Sedis (7.79%), and Blautia (4.95%) genera were enriched in the NAFLD group. However, there was a lower abundance of Prevotella in the NAFLD group than that in the control group (5.83% vs 27.56%, Pdant in healthy subjects, and the families Prevotellaceae (28.66%) and Ruminococcaceae (26.44%) followed the same trend. Compared to those without non-alcoholic steatohepatitis (NASH), patients with NASH had higher abundance of genus Blautia (5.82% vs 2.25%; P=0.01) and the corresponding Lachnospiraceae family (24.33% vs 14.21%; Pdance of genus Escherichia_Shigella (12.53% vs 1.97%; P<0.01) and the corresponding Enterobacteriaceae family (13.92% vs 2.07%; P<0.01) compared to those with F0/F1 fibrosis. CONCLUSIONS: NAFLD patients and healthy subjects harbor varying gut microbiota. In contrast to the results of previous research on children, decreased levels of Prevotella might be detrimental for adults with NAFLD. Th

关键词： gut microbiota fatty liver disease non-alcoholic steatohepatitis fibrosis

The pathologic relevance of metabolic criteria in patients with biopsy-proven nonalcoholic fatty liver disease and metabolic dysfunction associated fatty liver disease:A multicenter cross-sectional study in China

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Hepatobiliary & Pancreatic Diseases International 2021年第5期20卷 426-432页

作者： rui-Xu Yang zheng-Sheng Zou Bi-Hui Zhong Hong Deng Fang-Ping He Jun-Ping Shi Cai-Yan Zhao Yu-Qiang Mi Yong-Jian Zhou Fu-Sheng Di rui-dan zheng Qin Du Jia Shang Branko Popovic Jin Jun Chen Jian-Gao Fan Center for Fatty Liver Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghai 200092China Department of Liver Disease Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China Department of Gastroenterology the First Affiliated HospitalSun Yat-Sen UniversityGuangzhou 510080China Department of Infectious Diseases the Third Affiliated HospitalSun Yat-Sen UniversityGuangzhou 510630China Department of Gastroenterology II the First Affiliated Hospital of Xinjiang Medical UniversityXinjiang Uygur Autonomous RegionsUrumqi 830011China The Affiliated Hospital of Hangzhou Normal University Hangzhou 310015China Department of Infectious Disease the Third Hospital of Hebei Medical UniversityShijiazhuang 050051China Department of Infectious Diseases Tianjin Second People's HospitalTianjin 300192China Department of Gastroenterology and Hepatology Guangzhou First People's HospitalSchool of MedicineSouth China University of TechnologyGuangzhou 510180China Department of Endocrinology and Metabolism The Third Central Hospital of TianjinTianjin 300170China Diagnosis and Treatment Center for Liver Diseases Zhengxing HospitalZhangzhou 363000China Department of Gastroenterology the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Department of Infectious Diseases Henan Provincial People's HospitalZhengzhou 450003China Sanofi-Aventis Deutschland GmbH Frankfurt 65929Germany Hepatology Unit Department of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhou 510515China

Background:This study aimed to assess the association between metabolic syndrome(Met S)and severity of nonalcoholic fatty liver disease(NAFLD),and to discuss the pathological relevance of the diagnostic criteria in metabolic(dysfunction)associated fatty liver disease(MAFLD).Methods:This was a multicenter,cross-sectional *** with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of *** and metabolic parameters were collected to assess the pathological ***:Of 246 enrolled patients with NAFLD,150(61.0%)had the comorbidity of Met *** the increase of metabolic components,the proportions of nonalcoholic steatohepatitis(NASH)and significant fibrosis were notably *** comorbid three metabolic components significantly increased the proportion of NASH,and further increase of metabolic components did not increase the proportion of ***,the increase of metabolic components was parallel to the increase of the proportion of liver *** the 246 patients,239(97.2%)met the diagnostic criteria of *** non-MAFLD patients had less NASH,they present with similar proportion of significant fibrosis and *** the diagnostic criteria of MAFLD,BMI≥23 kg/m2 was related to NASH(Mantel-Haenszel Common Estimate OR:2.975;95%CI:1.037–8.538;P=0.043),and T2 DM was related to significant fibrosis(Mantel-Haenszel Common Estimate OR:2.531;95%CI:1.388–4.613;P=0.002).The homeostasis model assessment of insulin resistance(HOMA-IR)≥2.5 was the most significant factor for NASH(OR:4.100;95%CI:1.772–9.487;P=0.001)and significant factor for liver fibrosis(OR:2.947;95%CI:1.398–6.210;P=0.004)after the adjustments of the BMI and ***:Metabolic dysregulations are important risk factors in NAFLD *** insulin resistance status may play a predominant role in the progression in MAFLD patients.

关键词： Nonalcoholic fatty liver disease Metabolic syndrome Insulin resistance

Metabolic Disorders Combined with Noninvasive Tests to Screen Advanced Fibrosis in Nonalcoholic Fatty Liver Disease

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Journal of Clinical and Translational Hepatology 2021年第5期9卷 607-614页

作者： Yi-Wen Shi Fang-Ping He Jin-Jun Chen Hong Deng Jun-Ping Shi Cai-Yan Zhao Yu-Qiang Mi zheng-Sheng Zou Yong-Jian Zhou Fu-Sheng Di rui-dan zheng Qin Du Jia Shang rui-Xu Yang Branko Popovic Bi-Hui Zhong Jian-Gao Fan Center for Fatty Liver Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghaiChina Department of Gastroenterology II The First Affiliated Hospital of Xinjiang Medical UniversityXinjiang Uygur Autonomous RegionsÜrümqiChina Hepatology Unit Department of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhouChina Department of Infectious Diseases the Third Affiliated HospitalSun Yat-Sen UniversityGuangzhouChina The Affiliated Hospital of Hangzhou Normal University HangzhouChina Department of Infectious Disease The Third Hospital of Hebei Medical UniversityShijiazhuangChina Department of Infectious Diseases Tianjin Second People’s HospitalTianjinChina Department of Liver Disease Chinese PLA General Hospitalthe Fifth Medical Center of Chinese PLA General HospitalBeijingChina Department of Gastroenterology and Hepatology Guangzhou First People’s HospitalSchool of MedicineSouth China University of TechnologyGuangzhouChina Department of Endocrinology and Metabolism The Third Central Hospital of TianjinTianjinChina Diagnosis and Treatment Center for Liver Diseases Zhengxing HospitalZhangzhouChina Department of Gastroenterology the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Department of Infectious Diseases Henan Provincial Peoples’Hospital Zhengzhou ZhengzhouChina Sanofi-Aventis Deutschland GmbH FrankfurtGermany Department of Gastroenterology The First Affiliated HospitalSun Yat-Sen UniversityGuangzhouChina

Background and Aims:Nonalcoholic fatty liver disease(NAFLD)is associated with metabolic *** study aimed to explore the role of metabolic disorders in screening advanced fibrosis in NAFLD ***:A total of 246 histologically-proven NAFLD patients were enrolled across 14 *** compared the severity of fibrosis in patients with different components of metabolic *** on standard noninvasive tests and metabolic disorders,we developed new algorithms to identify advanced ***:Metabolic syndrome(MetS)was frequent in NAFLD patients(133/246,54%).Patients with MetS had a higher proportion of significant fibrosis(p=0.014)and higher LSM values(9.2 kPa,vs.7.4 kPa,p=0.002)than those without *** with more metabolic disorders had higher fibrosis stages(p=0.017).Reduced highdensity lipoprotein cholesterol(odds ratio[OR]:2.241,95%confidence interval[CI]:1.004–5.002,p=0.049)and raised fasting glucose(OR:4.500,95%CI:2.083–9.725,p<0.001)were significantly associated with advanced *** these two metabolic disorders as a screening tool,a sensitivity,specificity and accuracy of 92%,81%and 83%was achieved,*** the new algorithms combining metabolic disorders with noninvasive measurements,the number of patients requiring liver biopsy was reduced,especially in combination with the Fibrosis-4 score and metabolic disorders(36%to 17%,p<0.001).In addition,this stepwise algorithm could achieve a high accuracy(85%)and high negative predictive value(93%).Conclusions:Metabolic disorders should be taken into consideration in the diagnosis of advanced *** further validation and investigation,new algorithms could be recommended in primary care units to spare patients from unnecessary referral and liver biopsies.

关键词： Nonalcoholic fatty liver disease Liver fibrosis Metabolic syndrome Noninvasive measurement

Controlled attenuation parameter for non-invasive assessment of hepatic steatosis in Chinese patients

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World Journal of Gastroenterology 2014年第16期20卷 4702-4711页

作者： Feng Shen rui-dan zheng Yu-Qiang Mi Xiao-Ying Wang Qin Pan Guang-Yu Chen Hai-Xia Cao Ming-Li Chen Liang Xu Jian-Neng Chen Yi Cao rui-Nan Zhang Lei-Ming Xu Jian-Gao Fan Department of Gastroenterology Xinhua HospitalShanghai Jiaotong University School of Medicine Research and Therapy Center for Liver Diseases The Affiliated Dongnan Hospital of Xiamen University Tianjin Research Institute of Liver Diseases Tianjin Hospital of Infectious Diseases Department of Pathology Xinhua HospitalShanghai Jiaotong University School of Medicine Department of UItrasound Xinhua HospitalShanghai Jiaotong University School of Medicine

AIM: To evaluate the performance of a novel non-invasive controlled attenuation parameter (CAP) to assess liver steatosis.

关键词： Fatty liver Nonalcoholic Controlled attenuation parameter Transient elastography Chronic hepatitis B

Linked PNPLA3 polymorphisms confer susceptibility to nonalcoholic steatohepatitis and decreased viral load in chronic hepatitis B

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World Journal of Gastroenterology 2015年第28期21卷 8605-8614页

作者： Qin Pan rui-Nan Zhang Yu-Qin Wang rui-dan zheng Yu-Qiang Mi Wen-Bin Liu Feng Shen Guang-Yu Chen Jia-Fa Lu Chan-Yan Zhu Shu-Yi Zhang Yi-Ming Chen Wan-Lu Sun Jian-Gao Fan Department of Gastroenterology Xinhua Hospital Shanghai Jiaotong University School of Medicine Diagnosis and Treatment Center for Liver Diseases Zhengxing HospitalZhangzhou Department of Infectious Diseases Tianjin Infectious Disease Hospital Wu-Jiao-Chang Community Health Center Clinical Epidemiology Center Shanghai Jiaotong University School of Medicine Shanghai Key Laboratory of Children’s Digestion and Nutrition

AIM:To investigate the association of PNPLA3 polymorphisms with concurrent chronic hepatitis B(CHB) and nonalcoholic fatty liver disease(NAFLD).METHODS:A cohort of Han patients with biopsyproven CHB,with or without NAFLD(CHB group,n = 51;CHB + NAFLD group,n = 57),and normal controls(normal group,n = 47) were recruited from Northern(Tianjin),Central(Shanghai),and Southern(Zhangzhou) *** PNPLA3 polymorphisms were genotyped by gene *** association between PNPLA3 polymorphisms and susceptibility to NAFLD,and clinical characteristics of NAFLD were evaluated on the basis of physical indices,liver function tests,glycolipid metabolism,and histopathologic *** association of PNPLA3 polymorphisms and hepatitis B virus(HBV) load was determined by the serum level of HBV ***:After adjusting for age,sex,and body mass index,we found that four linked single nucleotide polymorphisms(SNPs) of PNPLA3,including the rs738409 G allele(CHB + NAFLD group vs CHB group:odds ratio[OR]= 2.77,95%confidence interval[CI]:1.18-6.54;P = 0.02),rs3747206 T allele(CHB+ NAFLD group vs CHB group:OR = 2.77,95%CI:1.18-6.54;P = 0.02),rs4823173 A allele(CHB +NAFLD group vs CHB group:OR = 2.73,95%CI:1.16-6.44;P= 0.02),and rs2072906 G allele(CHB+ NAFLD group vs CHB group:OR = 3.05,95%CI:1.28-7.26;P = 0.01),conferred high risk to NAFLD in CHB *** patients with both CHB and NAFLD,these genotypes of PNPLA3 polymorphisms were associated with increased susceptibility to nonalcoholic steatohepatitis(NASH)(NAFLD activity score ≥3;P =0.01-0.03) and liver fibrosis(>1 Metavir grading;P =0.01-0.04).As compared to those with C/C and C/G at rs738409,C/C and C/T at rs3747206,G/G and G/A at rs4823173,and A/A and A/G at rs2072906,patients in the CHB + NAFLD group with G/G at rs738409,T/T at rs3747206,A/A at rs4823173,and G/G at rs2072906 showed significantly lower serum levels of HBV DNA(P< 0.01-0.05).CONCLUSION:Four linked SNPs of PNPLA3(rs738409,rs3747206,rs4823173,and rs2072906) a

关键词： Chronic hepatitis B Hepatitis B virus Nonalcoholic fatty liver disease PNPLA3 Singlenucleotidepolymorphism

Nodular Regenerative Hyperplasia of Liver Mimicking Cirrhosis: a Case Report

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国际感染病学（电子版） 2013年第3期2卷 137-140页

作者： rui-dan zheng Zhuo-ran Chen Jian-neng Chen Hui-yong Zhang Research and Therapy Center for Liver Diseases Dongnan Affiliated Hospital of Xiamen University

A 34-year-old man with no history of any abdominal pain or fatigue was admitted to our hospital in June 2008 due to the cirrhosis found incidentally during a physical examination. Laboratory examination, electrocardiograph, abdominal ultrasonography and magnetic resonance imaging were carried out during his hospitalization. However, according to the results of the above measures, the diagnosis of nodular regenerative hyperplasia of the liver (NRHL) could not be made. The result of electrocardiograph showed there was no sinus bradycardia. The abdominal ultrasonography showed evidence of hepatosplenomegaly, and magnetic resonance imaging showed multiple non-enhancing hepatic nodules. Histologic conifrmation was available by means of liver biopsy and the deifnitive diagnosis of NRHL was conifrmed histologically by liver biopsy. NRHL always presents with signs of portal hypertension with little evidence of obvious liver disease, NRHL may mimick the cirrhosis of liver and be easily confused with cirrhosis of the liver nodules, so liver biopsy should be recommended for correct diagnosis. The clinical, radiological and pathologic features of this case with NRHL was reported in order to familiarize the physicians with its clinical manifestations.

关键词： Nodular regenerative hyperplasia of the liver Cirrhosis Case report

Experimental Study on Diesel Spray and Flame Asymmetry Characteristics of Dual-Orifice Nozzles for a Medium-Speed Engine

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Journal of Thermal Science 2025年第1期34卷 303-322页

作者： JU Dehao LIU rui zheng Liang DENG Jiahui ZHANG Wenzheng HUO Jinlu HUANG Li Shanghai Marine Diesel Engine Research Institute National Key Laboratory of Marine Engine Science and Technology Key Laboratory for Power Machinery and Engineering Ministry of EducationShanghai Jiao Tong University

The asymmetry of the multi-orifice spray will cause uneven heat load of the marine diesel engine,thereby affecting its working performance and service ***,an in-depth understanding of the spray and flame characteristics of multi-orifice nozzles will guide the optimization of the nozzle structure,needle design and diesel atomization and combustion *** this reason,four groups of dual-orifice nozzles with different hole diameters(0.1-0.55 mm) and mass flow rates covering the typical marine medium-speed diesel injections are designed and customized,and the constant volume chamber(CVC) with high temperature and pressure is used to simulate the actual in-cylinder working conditions of the diesel engine for the spray visualization *** study the asymmetry of the fuel sprays discharged from a diesel injector,the multi-orifice nozzle is simplified as a dual-orifice nozzle in this *** with X-ray Computed Tomography(CT) imaging technology,the influences of the nozzle internal structure on the spray and flame asymmetry are studied in the constructed supercritical *** is found that the asymmetry of the inlet angle and the equivalent length-diameter ratio is positively correlated with the inconsistency of the dual *** an increase in the injection pressure and nozzle diameter,the asymmetry of the dual spray becomes more pronounced,resulting in greater disparities in the ignition delay times and ignition positions of the two ***,the increase in nozzle diameter also leads to combustion instability,resulting in a flame with a serrated *** the increase of ambient temperature,the proportion of liquid phase in the jet decreases and the relative density of spray front decreases.

关键词： atomization dual-orifice nozzle nozzle structure spray flame asymmetry

中国制造业产业结构演进的区域分异与环境效应

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经济地理 2017年第10期37卷 108-115页

作者：石敏俊逄瑞郑丹杨晶中国人民大学经济学院中国北京100872 中国科学院大学经济与管理学院中国北京100190 中化集团中国北京100031

文章应用全局主成分分析方法(GPCA),基于地级行政单元数据分析了2001—2008年中国制造业产业空间分布演进趋势,结果表明:东南沿海核心区率先推进产业结构优化,产业结构向深加工化和技术密集化发展;北部沿海核心区的产业结构优化滞后于... 详细信息

文章应用全局主成分分析方法(GPCA),基于地级行政单元数据分析了2001—2008年中国制造业产业空间分布演进趋势,结果表明:东南沿海核心区率先推进产业结构优化,产业结构向深加工化和技术密集化发展;北部沿海核心区的产业结构优化滞后于东南沿海核心区;中部地区的产业结构演进处于从重化工化向加工化过渡的阶段;西部地区产业发展主要集中于重点开发区域,产业结构演进尚处于工业化初期阶段。文章进一步检验了制造业产业结构演进和产业转移对各地区环境污染的影响,发现制造业转入会加剧地区环境污染。不同类型的产业转移对环境污染的影响不同,日用消费品产业、农业资源型产业、重化工业的转入会显著加剧地区污染物排放,而技术密集型产业和耐用消费品产业的转入则会减缓本地污染排放的增加,但作用在统计上并不显著。

关键词：产业空间分布产业集聚产业转移环境效应中国

Engineering high-performance chemiluminescent probes via enzymatic pocket targeting: high-throughput screening for ultralong afterglow imaging of orthotopic hepatocellular carcinoma

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Science China Chemistry 2025年

作者： Shuai Huang Shuaige Bai Ting Luo Bin Feng Min Liu Fan zheng Shuang Huang Yanpeng Fang dan Ding Wenbin Zeng Xiangya School of Pharmaceutical Sciences Central South University College of Life Sciences Nankai University

Hepatocellular carcinoma （HCC） is a highly aggressive liver malignancy and the main form of liver cancer. Early diagnosis and treatment of HCC can effectively reduce mortality. Carboxylesterase （CE）-specific detection and imaging can be used for early diagnosis and image-guided surgical of HCC. However, traditional optical probes suffer from poor selectivity and low imaging signal-to-noise ratio. Here, we have constructed a series of chemiluminescent probes for carboxylesterase detection based on the strategy of enzymatic pocket-oriented steric tailoring techniques. The probes with different unique and excellent properties have been obtained through the structure-based steric hindrance adjustment on the recognition site. Here, CE-2 has been successfully used for high-throughput screening of rapid carboxylesterase inhibitors due to its extremely low detection limit (2.5×10-4U mL-1) and fast recognition ability. CE-3 has been successfully used for image-guided surgery of orthotopic hepatocellular carcinoma due to its ultra-long chemiluminescence imaging （over 12 h） of hepatocellular carcinoma. This study may promote advances in the rapid detection and screening of inhibitory drugs for CE and the field of surgical navigation in HCC.

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