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Establishment of a cholangiocarcinoma risk evaluation model based on mucin expression levels

World Journal of Gastrointestinal Oncology 2024年第4期16卷 1344-1360页

作者： Chun-Yuan Yang Li-Mei Guo Yang Li Guang-Xi Wang Xiao-Wei Tang Qiu-Lu Zhang Ling-Fu Zhang Jian-Yuan Luo department of Pathology Institute of Systems BiomedicineSchool of Basic Medical Sciences Peking UniversityPeking University Third HospitalPeking University Health Science CenterBeijing 100191China department of General Surgery Peking University Third HospitalBeijing 100191China department of Medical Genetics Department of Biochemistry and BiophysicsSchool of Basic Medical Sciences Peking UniversityPeking University Health Science CenterBeijing 100191China

BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant cancer,characterized by frequent mucin ***1 has been identified as a critical oncogene in the progression of ***,the comprehensive understanding of how the mucin family influences CCA progression and prognosis is still *** To investigate the functions of mucins on the progression of CCA and to establish a risk evaluation formula for stratifying CCA *** Single-cell RNA sequencing data from 14 CCA samples were employed for elucidating the roles of mucins,complemented by bioinformatic ***-quent validations were conducted through spatial transcriptomics and *** construction of a risk evaluation model utilized the least absolute shrinkage and selection operator regression algorithm,which was further confirmed by independent cohorts and diverse data *** CCA tumor cells with elevated levels of MUC1 and MUC4 showed activated nucleotide metabolic pathways and increased ***5AC-high cells were found to promote CCA progression through WNT ***5B-high cells exhibited robust cellular oxidation activities,leading to resistance against antitumoral ***13-high cells were observed to secret chemokines,recruiting and transforming macrophages into the M2-polarized state,thereby suppressing antitumor ***16-high cells were found to promote tumor progression through interleukin-1/nuclear factor kappa-light-chain-enhancer of activated B cells signaling upon interaction with *** the expression levels of these mucins,a risk factor evaluation formula for CCA was developed and validated across multiple *** samples with higher risk factors exhibited stronger metastatic potential,chemotherapy resistance,and poorer *** Our study elucidates the functional mechanisms through which mucins contribute to CCA development,and provides tools for risk stratification in CCA.

关键词： Mucin Cholangiocarcinoma Single-cell RNA sequencing Spatial transcriptomics Prognosis

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Follicle stimulating hormone controls granulosa cell glutamine synthesis to regulate ovulation

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Protein & Cell 2024年第7期15卷 512-529页

作者： Kai-Hui Zhang Fei-Fei Zhang Zhi-Ling Zhang Ke-Fei Fang Wen-Xing Sun Na Kong Min Wu Hai-Ou Liu Yan Liu Zhi Li Qing-Qing Cai Yang Wang Quan-Wei Wei Peng-Cheng Lin Yan Lin Wei Xu Cong-Jian Xu Yi-Yuan Yuan Shi-Min Zhao The Obstetrics&Gynecology hospital of Fudan university State Key Laboratory of Genetic EngineeringFudan UniversityShanghai 200090China Shanghai Key Laboratory of metabolic Remodeling and Children’s Hospital of Fudan UniversityShanghai 200032China School of Life Sciences and Institutes of Biomedical Sciences Fudan UniversityShanghai 200438China department of Nutrition and Food Hygiene School of Public HealthNantong UniversityNantong 226019China Reproductive Medicine center The Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Shanghai Fifth People’s hospital of Fudan university Fudan UniversityShanghai 200240China department of Animal Science and Technology Nanjing Agricultural UniversityNanjing 210014China Key Laboratory for Tibet Plateau Phytochemistry of Qinghai Province College of PharmacyQinghai University for NationalitiesXining 810007China Pediatric Research Institute Children’s Hospital Affiliated to Shandong University(Jinan Children’s Hospital)Jinan 250022China

Polycystic ovary syndrome(PCOS)is the leading cause of anovulatory *** understanding of the ovulation drivers hinders PCOS ***,we report that follicle stimulating hormone(FSH)controls follicular fluid(FF)glutamine levels to determine *** ovulation starts from FF-exposing granulosa cell(GC)*** glutamine,which decreases in pre-ovulation porcine FF,elevates in PCOS patients ***-glutamine chow to elevate FF glutamine inhibits mouse GC apoptosis and induces hormonal,metabolic,and morphologic PCOS ***,follicle-development-driving FSH promotes GC glutamine synthesis to elevate FF glutamine,which maintain follicle wall integrity by inhibiting GC apoptosis through inactivating ASK1-JNK apoptotic *** and glutamine inhibit the rapture of cultured murine *** removal or ASK1-JNK pathway activation with metformin or AT-101 reversed PCOS traits in PCOS models that are induced with either glutamine or *** suggest that glutamine,FSH,and ASK1-JNK pathway are targetable to alleviate PCOS.

关键词： ovulation glutamine granulosa cells PCOS FSH

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Innovative mesenchymal stem cell treatments for fatty liver disease

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World Journal of Stem Cells 2024年第9期16卷 846-853页

作者： Fei-Qiong Gao Jia-Qi Zhu Xu-Dong Feng department of Endocrinology Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhou 310003Zhejiang ProvinceChina Laboratory Medicine center Department of Clinical LaboratoryZhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHangzhou 310014Zhejiang ProvinceChina department of Clinical Laboratory Ningbo Medical Center Lihuili HospitalAffiliated Lihuili Hospital of Ningbo UniversityNingbo 315000Zhejiang ProvinceChina

The incidence of non-alcoholic fatty liver disease(NAFLD)and alcohol-associated liver disease(ALD)is increasing year by year due to changes in the contemporary environment and dietary structure,and is an important public health problem *** is an urgent need to continuously improve the understanding of their disease mechanisms and develop novel therapeutic *** stem cells(MSCs)have shown promise as a potential therapeutic strategy in therapeutic studies of NAFLD and *** and ALD have different triggers and their specific mechanisms of disease progression are different,but both involve disease processes such as hepatocellular steatosis and potential fibrosis,cirrhosis,and even hepatocellular *** have metabolic regulatory,anti-apoptotic,antioxidant,and immunomodulatory effects that together promote liver injury repair and functional recovery,and have demonstrated positive results in preclinical *** editorial is a continuum of Jiang et al’s review focusing on the advantages and limitations of MSCs and their derivatives as therapeutics for NAFLD and *** detail how MSCs attenuate the progression of NAFLD by modulating molecular pathways involved in glucolipid metabolism,inflammation,oxidative stress,endoplasmic reticulum stress,and *** on recent advances,we discuss MSCs and their derivatives as therapeutic strategies for NAFLD and ALD,providing useful information for their clinical application.

关键词： Alcohol-associated liver disease Non-alcoholic fatty liver disease Mesenchymal stem cells Cell therapy Inflammation

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T2-weighted imaging-based radiomic-clinical machine learning model for predicting the differentiation of colorectal adenocarcinoma

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 819-832页

作者： Hui-Da Zheng Qiao-Yi Huang Qi-Ming Huang Xiao-Ting Ke Kai Ye Shu Lin Jian-Hua Xu department of Gastrointestinal Surgery The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina department of Gynaecology and Obstetrics The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina department of Computed Tomography/Magnetic Resonance Imaging The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Centre of Neurological and metabolic Research The Second Affiliated Hospital of Fujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Group of Neuroendocrinology Garvan Institute of Medical ResearchSydneyNSW 2010Australia

BACKGROUND The study on predicting the differentiation grade of colorectal cancer(CRC)based on magnetic resonance imaging(MRI)has not been reported *** a non-invasive model to predict the differentiation grade of CRC is of great *** To develop and validate machine learning-based models for predicting the differ-entiation grade of CRC based on T2-weighted images(T2WI).METHODS We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July *** were randomly assigned to a training cohort(n=220)or a validation cohort(n=95)at a 7:3 *** were delineated layer by layer on high-resolution *** absolute shrinkage and selection operator regression was applied to screen for radiomic *** and clinical models were constructed using the multilayer perceptron(MLP)*** radiomic features and clinically relevant variables(selected based on a significance level of P<0.05 in the training set)were used to construct radiomics-clinical *** performance of the three models(clinical,radiomic,and radiomic-clinical model)were evaluated using the area under the curve(AUC),calibration curve and decision curve analysis(DCA).RESULTS After feature selection,eight radiomic features were retained from the initial 1781 features to construct the radiomic *** different classifiers,including logistic regression,support vector machine,k-nearest neighbours,random forest,extreme trees,extreme gradient boosting,light gradient boosting machine,and MLP,were used to construct the model,with MLP demonstrating the best diagnostic *** AUC of the radiomic-clinical model was 0.862(95%CI:0.796-0.927)in the training cohort and 0.761(95%CI:0.635-0.887)in the validation *** AUC for the radiomic model was 0.796(95%CI:0.723-0.869)in the training cohort and 0.735(95%CI:0.604-0.866)in the validation *** clinical model achieved an AUC of 0.7

关键词： Radiomics Colorectal cancer Differentiation grade Machine learning T2-weighted imaging

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Real-world Effectiveness and Tolerability of Interferonfree Direct-acting Antiviral for 15,849 Patients with Chronic Hepatitis C:A Multinational Cohort Study

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Journal of Clinical and Translational Hepatology 2024年第7期12卷 646-658页

作者： Fanpu Ji Sally Tran Eiichi Ogawa Chung-Feng Huang Takanori Suzuki Yu Jun Wong Hidenori Toyoda Dae Won Jun Liu Li Haruki Uojima Akito Nozaki Makoto Chuma Cheng-Hao Tseng Yao-Chun Hsu Masatoshi Ishigami Takashi Honda Masanori Atsukawa Hiroaki Haga Masaru Enomoto Huy Trinh Carmen Monica Preda Phillip Vutien Charles Landis Dong Hyun Lee Tsunamasa Watanabe Hirokazu Takahashi Hiroshi Abe Akira Asai Yuichiro Eguchi Jie Li Xiaozhong Wang Jia Li Junping Liu Jing Liang Carla Pui-Mei Lam Rui Huang Qing Ye Hongying Pan Jiajie Zhang Dachuan Cai Qi Wang Daniel Q.Huang Grace Wong Vincent Wai-Sun Wong Junyi Li Son Do Norihiro Furusyo Makoto Nakamuta Hideyuki Nomura Eiji Kajiwara Eileen L.Yoon Sang Bong Ahn Koichi Azuma Kazufumi Dohmen Jihyun An Do Seon Song Hyun Chin Cho Akira Kawano Toshimasa Koyanagi Aritsune Ooho Takeaki Satoh Kazuhiro Takahashi Ming-Lun Yeh Pei-Chien Tsai Satoshi Yasuda Yunyu Zhao Yishan Liu Tomomi Okubo Norio Itokawa Mi Jung Jun Toru Ishikawa Koichi Takaguchi Tomonori Senoh Mingyuan Zhang Changqing Zhao Raluca Ioana Alecu Wei Xuan Tay Pooja Devan Joanne Kimiko Liu Ritsuzo Kozuka Elena Vargas-Accarino Ai-Thien Do Mayumi Maeda Wan-Long Chuang Jee-Fu Huang Chia-Yen Dai Ramsey Cheung Maria Buti Junqi Niu Wen Xie Hong Ren Seng Gee Lim Chao Wu Man-Fung Yuen Jia Shang Qiang Zhu Yoshiyuki Ueno Yasuhito Tanaka Jun Hayashi Ming-Lung Yu Mindie H.Nguyen department of Infectious diseases The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxiChina Division of Gastroenterology and Hepatology Department of MedicineStanford University Medical CenterPalo AltoCAUSA department of General Internal Medicine Kyushu University HospitalFukuokaJapan Hepatobiliary Division Department of Internal MedicineKaohsiung Medical University HospitalKaohsiung Hepatitis Research center College of Medicine and Center for Liquid Biopsy and Cohort ResearchKaohsiung Medical UniversityKaohsiung department of Gastroenterology and Metabolism Nagoya City University Graduate School of Medical SciencesNagoyaJapan Gastroenterology&Hepatology Changi General HospitalSinghealthSingapore Singhealth Duke-NUS Medicine Academic Clinical Program Singapore department of Gastroenterology Ogaki Municipal HospitalOgakiJapan department of Internal Medicine Hanyang UniversityCollege of MedicineSeoulKorea Hanyang Institute of Bioscience and Biotechnology Hanyang UniversitySeoulKorea department of Hepatology The Third People's Hospital of Kunming CityKunmingYunnanChina department of Gastroenterology Internal MedicineKitasato University School of MedicineSagamiharaJapan Gastroenterological center Yokohama City University Medical CenterYokohamaJapan Division of Gastroenterology and Hepatology Department of Internal MedicineE-Da Cancer HospitalKaohsiung department of Gastroenterology and Hepatology Nagoya University Graduate School of MedicineNagoyaJapan Division of Gastroenterology and Hepatology Nippon Medical SchoolTokyoJapan department of Gastroenterology Yamagata University Faculty of MedicineYamagataJapan department of Transfusion Medicine and department of Hepatology Osaka Metropolitan University Graduate School of MedicineOsakaJapan San Jose Gastroenterology San JoseCAUSA Gastroenterology&Hepatology department Clinic Fundeni InstituteBucharestRomania Division of Gastroenterology and Hepatology University of WashingtonSeattleWAUSA department of

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 *** 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 ***: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/***:The mean age was 62±13 years,with 49.6%*** 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/***,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 ***12 for GT3 was 95.1%overall,98.2%for GT3a,and 94.0%for ***12 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 *** 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 ***: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/***12 for GT3/6 with cirrhosis and TE was lower but st

关键词： Hepatitis C virus Liver cirrhosis Hepatocellular carcinoma Genotype DAA REAL-C

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评价散寒化湿颗粒与奈玛特韦-利托那韦对照治疗轻型/中型新型冠状病毒感染有效性和安全性的随机、开放、多中心临床研究

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Science Bulletin 2024年第12期69卷 1954-1963页

作者：邹晓辉常康范国辉郑欢伟神和正唐亮杨映映王业明赵林华吕红周昕沈小明陈利强仝小林曹彬 National center for Respiratory Medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesLaboratory of Clinical Microbiology and Infectious DiseasesDepartment of Pulmonary and Critical Care MedicineCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China National center for Respiratory Medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesDepartment of Clinical Research and Data Management Center of Respiratory MedicineCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Shijiazhuang hospital of Traditional Chinese Medicine Shijiazhuang 050051China Linyi Traditional Chinese Medicine hospital Linyi 276000China Wuxi Traditional Chinese Medicine hospital Wuxi 214071China National center for Respiratory Medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesDepartment of Traditional Chinese Medicine for Pulmonary DiseasesCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Institute of metabolic diseases Guang’anmen Hospital of ChinaAcademy of Chinese Medical SciencesBeijing 100053China Taicang Traditional Chinese Medicine hospital Taicang 215400China The First hospital of Qiqihar Qiqihar 161005China The Second Affiliated hospital of Jiaxing university Jiaxing 314000China Huizhou First hospital Huizhou 516003China National center for Integrated Traditional Chinese Medicine and Western Medicine China-Japan Friendship HospitalBeijing 100029China

Sanhan Huashi granules(SHG)demonstrated therapeutic effects against coronavirus disease 2019(COVID-19)in observational *** order to compare the effectiveness and safety of SHG and nirmatrelvir–ritonavir in treating adults with mild-to-moderate COVID-19,we conducted a randomized,activecontrolled,open-label,multi-center trial conducted between February and July in *** patients were randomized in a 1:1 ratio to the SHG group and the nirmatrelvir–ritonavir group.A total of 400participants were randomized,among which 200 participants ultimately received SHG and 198 received nirmatrelvir–*** primary outcome was time to sustained clinical recovery through day *** significantly shortened the median time to sustained clinical recovery compared to nirmatrelvir–ritonavir(6.0(95%CI,5.0 to 6.0)vs.8.0(95%CI,6.0 to 9.0)d;P=0.001),particularly for individual symptoms including fever,sore throat,cough and *** participants in either group died and incidence of severe COVID-19 showed no difference between two *** who received nirmatrelvir–ritonavir demonstrated a higher rate of virus clearance on day 5 compared to those received SHG(46.4%(95%CI,39.1 to 53.7)vs.65.6%(95%CI,58.3 to 72.4);P<0.001).Most adverse events were mild in both *** summary,SHG was superior to nirmatrelvir–ritonavir in shortening the time to sustained clinical recovery in participants with mild-to-moderate COVID-19,despite a lower virus clearance rate observed after 5 d of treatment(Chinese Clinical Trial Registry Identifier:Chi CTR2300067872).

关键词： Traditional Chinese medicine COVID-19 Nirmatrelvir-Ritonavir Sustained clinical recovery

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Dysfunction of the adhesion G protein-coupled receptor latrophilin 1(ADGRL1/LPHN1)increases the risk of obesity

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2298-2311页

作者： Heba ZabriTorsten Schöneberg AndréNguyen Dietzsch Hadi Al-Hasani Joachim Altschmied Katharina Bottermann Jana Brendler Judith Haendeler Susanne Horn Isabell Kaczmarek Antje Körner Kerstin Krause Kathrin Landgraf Diana Le Duc Laura Lehmann Stefan Lehr Stephanie Pick Albert Ricken Rene Schnorr Angela Schulz Martina Strnadová Akhil Velluva Heba Zabri Torsten Schöneberg Doreen Thor Simone Prömel Rudolf Schönheimer Institute of Biochemistry Medical FacultyLeipzig UniversityLeipzigGermany Institute for Clinical Biochemistry and Pathobiochemistry Medical FacultyGerman Diabetes CenterLeibniz Center for Diabetes Research at Heinrich Heine University DüsseldorfDüsseldorfGermany German center for Diabetes Research(DZD e.V.) Munich-NeuherbergGermany Cardiovascular Degeneration Clinical Chemistry and Laboratory DiagnosticsMedical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Cardiovascular Research Institute(CARID) Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Pharmacology Medical FacultyUniversity Hospital and Heinrich Heine University DüsseldorfDüsseldorfGermany Institute of Anatomy Medical FacultyLeipzig UniversityLeipzigGermany center for Pediatric Research Hospital for Children and AdolescentsMedical FacultyLeipzig UniversityLeipzigGermany Helmholtz Institute for metabolic Obesity and Vascular Research(HI-MAG)of the Helmholtz Zentrum München at the University of Leipzig and University Hospital LeipzigLeipzigGermany department of Endocrinology NephrologyRheumatologyLeipzig University Medical CenterLeipzigGermany Institute of Human Genetics Leipzig University Medical CenterLeipzigGermany Institute of Cell Biology Department of BiologyHeinrich Heine University DüsseldorfDüsseldorfGermany School of Medicine University of Global Health EquityKigaliRwanda

Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide *** the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity.G protein-coupled receptors(GPCRs)are among the main modulators of metabolism and energy ***,for instance,regulate appetite and satiety in certain hypothalamic neurons,as well as glucose and lipid metabolism and hormone secretion from *** in some GPCRs,such as the melanocortin receptor type 4(MC4R),have been associated with early-onset ***,we identified the adhesion GPCR latrophilin 1(ADGRL1/LPHN1)as a member of the regulating network governing food intake and the maintenance of energy *** of the highly conserved receptor in mice results in increased food consumption and severe obesity,accompanied by dysregulation of glucose ***,we identified a partially inactivating mutation in human ADGRL1/LPHN1 in a patient suffering from ***,we propose that LPHN1 dysfunction is a risk factor for obesity development.

关键词： obesity metabolism intake

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Hepatic Zbtb18 (Zinc Finger and BTB Domain Containing 18) alleviates hepatic steatohepatitis via FXR (Farnesoid X Receptor)

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Signal Transduction and Targeted Therapy 2024年第2期9卷 766-781页

作者： Lei Zhang Jiabing Chen Xiaoying Yang Chuangpeng Shen Jiawen Huang Dong Zhang Naihua Liu Chaonan Liu Yadi Zhong Yingjian Chen Kaijia Tang Jingyi Guo Tianqi Cui Siwei Duan Jiayu Li Shangyi Huang Huafeng Pan Huabing Zhang Xiaoqiang Tang Yongsheng Chang Yong Gao State Key Laboratory of Traditional Chinese Medicine Syndrome Science and Technology Innovation CenterGuangzhou University of Chinese MedicineGuangzhouChina Key Laboratory of Immune Microenvironment and Disease(Ministry of Education) Tianjin Key Laboratory of Cellular Homeostasis and DiseaseDepartment of Physiology and PathophysiologyTianjin Medical UniversityTianjinChina Jiangsu Key Laboratory of Immunity and Metabolism Department of Pathogen Biology and ImmunologyJiangsu International Laboratory of Immunity and MetabolismXuzhou Medical UniversityXuzhouChina department of Endocrinology The First Clinical CollegeGuangzhou University of Chinese MedicineGuangdongChina The Fourth Clinical Medical College of Guangzhou university of Chinese Medicine ShenzhenChina Jiangsu Collaborative Innovation center of Traditional Chinese Medicine in Prevention and Treatment of Tumor Nanjing University of Chinese MedicineNanjingChina department of Biochemistry and Molecular Biology Metabolic Disease Research CenterSchool of Basic MedicineAnhui Medical UniversityHefeiChina Key Laboratory of Birth Defects and Related diseases of Women and Children of MOE State Key Laboratory of BiotherapyWest China Second University HospitalSichuan UniversityChengduChina

A lasting imbalance between fatty acid synthesis and consumption leads to non-alcoholic fatty liver disease(NAFLD),coupled with hepatitis and insulin *** the details of the underlying mechanisms are not fully ***,we unraveled that the expression of the transcription factor Zbtb18 is markedly decreased in the livers of both patients and murine models of *** Zbtb18 knockout promoted NAFLD features like impaired energy expenditure and fatty acid oxidation(FAO),and induced insulin ***,hepatic Zbtb18 overexpression alleviated hepato-steatosis,insulin resistance,and hyperglycemia in mice fed on a high-fat diet(HFD)or in diabetic ***,in vitro and in vivo mechanistic studies revealed that Zbtb18 transcriptional activation of Farnesoid X receptor(FXR)mediated FAO and Clathrin Heavy Chain(CLTC)protein hinders NLRP3 inflammasome *** key mechanism by which hepatocyte’s Zbtb18 expression alleviates NAFLD and consequent liver fibrosis was further verified by FXR’s deletion and forced expression in mice and cultured mouse primary hepatocytes(MPHs).Moreover,CLTC deletion significantly abrogated the hepatic Zbtb18 overexpression-driven inhibition of NLRP3 inflammasome activity in ***,Zbtb18 transcriptionally activates the FXR-mediated FAO and CLTC expression,which inhibits NLRP3 inflammasome’s activity alleviating inflammatory stress and insulin resistance,representing an attractive remedy for hepatic steatosis and fibrosis.

关键词： hepatic Hepatic impaired

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Targeted metabolomics study of fatty-acid metabolism in lean metabolic-associated fatty liver disease patients

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World Journal of Gastroenterology 2024年第27期30卷 3290-3303页

作者： Pei-Qi Sun Yi-Fu Yuan Qin Cao Xiao-Yan Chen Yuan-Ye Jiang Wen-Min Dong Li-Li Guo department of Gastroenterology Putuo HospitalShanghai University of Traditional Chinese MedicineShanghai 200062China department of Pharmacy Shanghai Pudong HospitalFudan University Pudong Medical CenterShanghai 201399China Central Laboratory Shanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China

BACKGROUND The annual incidence of metabolic-associated fatty liver disease(MAFLD)in China has been increasing and is often overlooked owing to its insidious *** 50%of the patients have a normal weight or are not *** are said to have lean-type MAFLD,and few studies of such patients are *** MAFLD is associated with abnormal lipid metabolism,lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and *** and analyze metabolic ***-Q-Orbitrap/MS content determination was used to determine serum palmitic acid(PA),oleic acid(OA),linoleic acid(LA),and arachidonic acid(AA)levels in lean-type MAFLD *** Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals(P*** levels of PA,OA,LA,and AA were significantly increased compared with healthy *** The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly,yielding 65 identified ***,OA,LA,and AA exhibited the most significant changes,offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.

关键词： Lean-type metabolic-associated fatty liver disease Targeted serum metabolomics Fatty acids Principal component analysis Orthogonal partial least squares-discriminant analysis

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Comparative associations of non-alcoholic fatty liver disease and metabolic dysfunction-associated steatotic liver disease with risk of incident chronic kidney disease:a cohort study

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Hepatobiliary Surgery and Nutrition 2024年第5期13卷 801-813,I0003-I0005页

作者： Ji Hye Heo Mi Yeon Lee Seong Hwan Kim Ming-Hua Zheng Christopher D.Byrne Giovanni Targher Ki-Chul Sung department of Internal Medicine Hallym University College of MedicineChuncheonRepublic of Korea Division of Biostatistics Department of R&D ManagementKangbuk Samsung HospitalSungkyunkwan University School of MedicineSeoulRepublic of Korea Division of Cardiology Department of Internal MedicineKorea University Ansan HospitalAnsanRepublic of Korea MAFLD Research center Department of HepatologyThe First Affiliated Hospital of Wenzhou Medical UniversityWenzhouChina Wenzhou Key Laboratory of Hepatology WenzhouChina Institute of Hepatology Wenzhou Medical UniversityWenzhouChina Key Laboratory of Diagnosis and Treatment for the Development of Chronic Liver Disease in Zhejiang Province WenzhouChina Nutrition and Metabolism Faculty of MedicineUniversity of SouthamptonSouthamptonUK Southampton National Institute for Health and Care Research Biomedical Research CentreUniversity Hospital SouthamptonSouthamptonUK metabolic diseases Research Unit IRCCS Sacro Cuore-Don Calabria HospitalNegrar di ValpolicelleItaly Division of Cardiology Department of Internal MedicineKangbuk Samsung HospitalSungkyunkwan University School of MedicineSeoulRepublic of Korea

Background:We examined the comparative associations between non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated steatotic liver disease(MASLD)definitions with risk of developing chronic kidney disease(CKD)and abnormal ***:We conducted a cohort study of 214,145 Korean adults with normal kidney function at baseline who underwent liver *** were further subdivided into no steatotic liver disease(no-SLD),NAFLD-only,MASLD-only,both NAFLD and MASLD,and SLD not categorized as NAFLD or MASLD *** proportional hazards models were used to analyze the risk of incident CKD and ***:Compared with either the no-NAFLD or no-MASLD groups,the NAFLD and MASLD groups were associated with a higher risk of incident CKD(NAFLD:adjusted hazard ratio(HR),1.18[95%CI,1.01-1.38];MASLD:adjusted HR,1.21[95%CI,1.04-1.39]).Among the five subgroups,both NAFLD and MASLD group had the strongest association with risk of incident CKD(adjusted HR,1.21[95%CI,1.04-1.42]).The MASLD-only group had the strongest association with incident abnormal albuminuria,with an adjusted HR comparable to that of the both NAFLD and MASLD group(adjusted HR 1.96[95%CI,1.44-2.67]for the MASLD-only,and adjusted HR 1.98[95%CI,1.58-2.49]for the both NAFLD and MASLD group versus the no-SLD group).The NAFLD-only group was not independently associated with risk of CKD or abnormal ***:These findings suggest that MASLD definition identifies individuals at high risk of developing incident CKD or abnormal albuminuria better than NAFLD definition.

关键词： metabolic dysregulation non-alcoholic fatty liver disease(NAFLD) metabolic syndrome chronic kidney disease(CKD) albuminuria

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