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TRPC6 Knockout Alleviates Renal Fibrosis through PI3K/AKT/GSK3B Pathway

Current Medical Science 2024年第3期44卷 589-602页

作者： An-bang SUN Fang-hua LI Lin ZHU Xi-xi ZENG Min ZHU Qing-hua LEI yan-hong LIAO Department of Anatomy School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Transfusion Medicine Wuhan Hospital of Traditional Chinese and Western MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Nephrology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Department of Thoracic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China National Basic Medical Teaching Demonstration Center Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Key Laboratory of Neurological Diseases of Ministry of Education Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective Renal fibrosis is the ultimate pathway of various forms of acute and chronic kidney ***,the knockout of transient receptor potential channel 6(TRPC6)has shown promise in alleviating renal ***,the regulatory impact of TRPC6 on renal fibrosis remains *** In vivo,TRPC6 knockout(TRPC6−/−)mice and age-matched 129 SvEv(WT)mice underwent unilateral renal ischemia-reperfusion(uIR)injury surgery on the left renal pedicle or sham *** and serum were collected on days 7,14,21,and 28 after *** vitro,primary tubular epithelial cells(PTECs)were isolated from TRPC6−/−and WT mice,followed by treatment with transforming growth factorβ1(TGFβ1)for 72 *** anti-fibrotic effect of TRPC6−/−and the underlying mechanisms were assessed through hematoxylin-eosin staining,Masson staining,immunostaining,qRT-PCR,and Western *** Increased TRPC6 expression was observed in uIR mice and PTECs treated with TGFβ***6−/−alleviated renal fibrosis by reducing the expression of fibrotic markers(Col-1,α-SMA,and vimentin),as well as decreasing the apoptosis and inflammation of PTECs during fibrotic progression both in vivo and in ***,we found that the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase 3 beta(GSK3β)signaling pathway,a pivotal player in renal fibrosis,was down-regulated following TRPC6 *** These results suggest that the ablation of TRPC6 may mitigate renal fibrosis by inhibiting the apoptosis and inflammation of PTECs through down-regulation of the PI3K/AKT/GSK3β*** TRPC6 could be a novel therapeutic strategy for preventing chronic kidney disease.

关键词： transient receptor potential channel 6 ischemia-reperfusion injury renal fibrosis renal tubular epithelial cells

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Terminalic Acid, a New Tannin from the Fruit of Terminalia chebula

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Chinese Chemical Letters 1998年第9期9卷 827-828页

作者： yan Ze LIU Bing Wu YU Gang DING (Department of Phytochemistry, Henan College of Traditional ChineseMedicine, zhengzhou 450003),yang Jie WU (Department of Organic Chemistry, zhengzhou University zhengzhou, 450052) Department of Phytochemistry Henan Coll. Traditional Chinese Med. Zhengzhou 450003 China Department of Organic Chemistry Zhengzhou University Zhengzhou 450052 China

Terminalic acid 1, a new hydrolysable tannin, was isolated from the fruit of Terminalia chebula. Its structure was found to be 1-O-galloyl-2,4-chebuloyl-beta-D-glucopyranose by chemical method and H-1-NMR, C-13-NMR, H... 详细信息

关键词： Terminalia chebula hydrolysable tannins terminalic acid

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Characteristics and source apportionment of ambient volatile organic compounds and ozone generation sensitivity in urban Jiaozuo,China

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Journal of Environmental Sciences 2024年第4期138卷 607-625页

作者： Pengzhao Li Chun Chen Dan Liu Jie Lian Wei Li Chuanyi Fan Liangyu yan Yue Gao Miao Wang Hang Liu Xiaole Pan Jing Mao State Centre for International Cooperation on Designer Low-Carbon and Environmental Materials School of Materials Science and EngineeringZhengzhou UniversityZhengzhou 450001China Henan Key Laboratory of Environmental Monitoring Technology Henan Ecological Environment Monitoring and Safety CenterZhengzhou 450046China Jiaozuo Ecological Environment Monitoring Center of Henan Province Jiaozuo 454003China State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China

In recent years,many cities have taken measures to reduce volatile organic compounds(VOCs),an important precursor of ozone(O_(3)),to alleviate O_(3) pollution in China.116 VOC species were measured by online and offline methods in the urban area of Jiaozuo from May to October in 2021 to analyze the compositional *** sources were analyzed by a positive matrix factorization(PMF)model,and the sensitivity of ozone generation was determined by ozone isopleth plotting research(OZIPR)*** results showed that the average volume concentration of total VOCs was 30.54 ppbv and showed a bimodal feature due to the rush-hour traffic in the morning and at *** most dominant VOC groups were oxygenated VOCs(OVOCs,29.3%)and alkanes(26.7%),and the most abundant VOC species were acetone and ***,based on the maximum incremental reactivity(MIR)method,the major VOC groups in terms of ozone formation potential(OFP)contribution were OVOCs(68.09μg/m^(3),31.5%),aromatics(62.90μg/m^(3),29.1%)and alkene/alkynes(54.90μg/m^(3),25.4%).This indicates that the control of OVOCs,aromatics and alkene/alkynes should take *** sources of VOCs were quantified by PMF,including fixed sources of fossil fuel combustion(27.8%),industrial processes(25.9%),vehicle exhaust(19.7%),natural and secondary formation(13.9%)and solvent usage(12.7%).The empirical kinetic modeling approach(EKMA)curve obtained by OZIPR on O_(3) exceedance days indicated that the O_(3) sensitivity varied in different *** results provide theoretical support for O_(3) pollution prevention and control in Jiaozuo.

关键词： Volatile organic compounds(VOCs) Online and offline measurement Ozone formation potential(OFP) Positive matrix factorization(PMF) Ozone isopleth plotting research(OZIPR) Jiaozuo

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A novel route to enhance high-temperature mechanical property and thermal shock resistance of low-carbon Mgo-C bricks by introducing ZrSiO_(4)

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Journal of Iron and Steel Research International 2024年第6期31卷 1436-1448页

作者： Chun-hui Sun Ling-ling Zhu Hao yan Wei Zhao Jing-xuan Liu Lin Ren Xian-tang Zhao Xiao-song Tong Shu-wen Yu Beijing Lirr High-Temperature Materials Co. Ltd.Beijing 102211China School of Materials Science and Engineering Henan Province Industrial Technology Research Institute of Resources and MaterialsZhengzhou UniversityZhengzhou 450001HenanChina School of Chemistry and Chemical Engineering Suzhou UniversitySuzhou 234000AnhuiChina

Conventional MgO-C bricks(graphite content>14 wt.%)produce a great deal of greenhouse gas emission,while low-carbon MgO-C bricks have serious thermal shock resistance during high-temperature *** enhance the high-temperature mechanical property and thermal shock resistance of low-carbon MgO-C bricks,a novel route of introducing ZrSiO_(4) powder into low-carbon MgO-C bricks was reported in such refractories with 2 wt.% flaky *** results indicate that the low-carbon MgO-C brick with 0.5 wt.%ZrSiO_(4) addition has the maximum hot modulus of rupture at 1400℃ and the corresponding specimen fired in the carbon embedded atmosphere has the maximum residual strength ratio(98.6%)after three thermal shock *** is found that some needle-like AlON and plate-like Al_(2)O_(3)-ZrO_(2) composites were in situ formed in the matrices after the low-carbon MgO-C bricks were coked at 1400℃,which can enhance the high-temperature mechanical property and thermal shock resistance due to the effect of fiber toughening and particle ***,CO_(2) emission of the newly developed low-carbon MgO-C bricks is reduced by 58.3% per ton steel after using them as the working lining of a 90 t vacuum oxygen decarburization ladle.

关键词： Low-carbon MgO-C brick ZrsiO_(4) Synergistic toughening effect High-temperature mechanical property Thermal shock resistance Vacuum oxygen decarburization ladle

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Rab18 maintains homeostasis of subcutaneous adipose tissue to prevent obesity-induced metabolic disorders

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Science China(Life Sciences) 2024年第6期67卷 1170-1182页

作者： Jiaming Liu Liangkui Li Dijin Xu Yuqi Li Tao Chen Yeyang Liu Yuqian Bao yan Wang Longyan yang Peng Li Li Xu State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences Beijing Advanced Innovation Center for Structural BiologySchool of Life SciencesTsinghua UniversityBeijing 100084China Shanghai Qi Zhi Institute Shanghai 200232China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Tianjian Laboratory of Advanced Biomedical Sciences Zhengzhou UniversityZhengzhou 450001China Department of Physiology School of Basic Medical SciencesGannan Medical UniversityGanzhou 341000China Department of Endocrinology and Metabolism Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s HospitalShanghai 200025China Center for Endocrine Metabolism and Immune Diseases Beijing Luhe HospitalCapital Medical UniversityBeijing 101149China Beijing Key Laboratory of Diabetes Research and Care Beijing 101149China

Metabolically healthy obesity refers to obese individuals who do not develop metabolic *** people store fat in subcutaneous adipose tissue(SAT)rather than in visceral adipose tissue(VAT).However,the molecules participating in this specific scenario remain ***18,a lipid droplet(LD)-associated protein,mediates the contact between the endoplasmic reticulum(ER)and LDs to facilitate LD growth and *** the present study,we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and ***18 adipocyte-specific knockout(Rab18 AKO)mice had a decreased volume ratio of SAT to VAT compared with wildtype *** subjected to high-fat diet(HFD),Rab18 AKO mice had increased ER stress and inflammation,reduced adiponectin,and decreased triacylglycerol(TAG)accumulation in *** contrast,TAG accumulation in VAT,brown adipose tissue(BAT)or liver of Rab18AKO mice had a moderate increase without ER stress ***18 AKO mice developed insulin resistance and systematic ***18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT,similar to the counterpart ***,Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress,indicating the involvement of Rab18 in alleviating lipid ***18 AKO mice provide a good animal model to investigate metabolic disorders such as impaired *** conclusion,our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.

关键词： Rab18 subcutaneous adipose tissue(SAT) metabolically healthy obesity(MHO) lipotoxicity ER stress ectopic lipid storage LD-ER contact

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CD146,a therapeutic target involved in cell plasticity

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Science China(Life Sciences) 2024年第8期67卷 1563-1578页

作者： Zhenzhen Wu Yuzhe Zang Chuyi Li Zhiheng He Jingyu Liu Zhaoqi Du Xinran Ma Lin Jing Hongxia Duan Jing Feng Xiyun yan CAS Engineering Laboratory for Nanozyme Key Laboratory of BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China College of Life Sciences University of Chinese Academy of SciencesBeijing 100049China Nanozyme Laboratory in Zhongyuan Henan Academy of Innovations in Medical ScienceZhengzhou 451163China Joint Laboratory of Nanozymes in zhengzhou University School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001China

Since its identification as a marker for advanced melanoma in the 1980s,CD146 has been found to have multiple functions in both physiological and pathological processes,including embryonic development,tissue repair and regeneration,tumor progression,fibrosis disease,and *** research has revealed that CD146 is involved in various signaling pathways as a receptor or coreceptor in these *** correlation between CD146 and multiple diseases has sparked interest in its potential applications in diagnosis,prognosis,and targeted *** better comprehend the versatile roles of CD146,we have summarized its research history and synthesized findings from numerous reports,proposing that cell plasticity serves as the underlying mechanism through which CD146 contributes to development,regeneration,and various *** CD146 would consequently halt cell state shifting during the onset and progression of these related ***,the development of therapy targeting CD146 holds significant practical value.

关键词： CD146 cell plasticity therapeutic target

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sTREM-1 as promising prognostic biomarker for acute-on-chronic liver failure and mortality in patients with acute decompensation of cirrhosis

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World Journal of Gastroenterology 2024年第9期30卷 1177-1188页

作者： Song-Man Yu Hai Li Guo-Hong Deng Xian-Bo Wang Xin Zheng Jin-Jun Chen Zhong-Ji Meng Yu-Bao Zheng yan-Hang Gao Zhi-Ping Qian Feng Liu Xiao-Bo Lu Yu Shi Jia Shang Ruo-Chan Chen yan Huang Department of Infectious Diseases Xiangya HospitalCentral South UniversityChangsha 410000Hunan ProvinceChina Department of Gastroenterology Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Department of Infectious Diseases Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Center of Integrative Medicine Beijing Ditan HospitalCapital Medical UniversityBeijing 100020China Department of Infectious Diseases Institute of Infection and ImmunologyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430020Hubei ProvinceChina Department of Infectious Diseases Nanfang HospitalSouthern Medical UniversityGuangzhou 510515Guangdong ProvinceChina Department of Infectious Disease Taihe HospitalHubei University of MedicineShiyan 442009Hubei ProvinceChina Department of Infectious Diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina Department of Hepatology The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina Department of Liver Intensive Care Unit Shanghai Public Health Clinical CentreFudan UniversityShanghai 200093China Tianjin Institute of Hepatology Nankai University Second People's HospitalTianjin 300192China Infectious Disease Center The First Affiliated Hospital of Xinjiang Medical UniversityUrumqi 830054Xinjiang Uygur Autonomous RegionChina The State Key Laboratory for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital of School of MedicineZhejiang UniversityHangzhou 310003Zhejiang ProvineChina Department of Infectious Diseases Henan Provincial People's HospitalZhengzhou 463599Henan ProvineChina Department of Infectious Diseases Hunan Key Laboratory of Viral HepatitisXiangya HospitalCentral South UniversityChangsha 110051Hunan ProvineChina

BACKGROUND Acute decompensation(AD)of cirrhosis is associated with high short-term mortality,mainly due to the development of acute-on-chronic liver failure(ACLF).Thus,there is a need for biomarkers for early and accurate identification of AD patients with high risk of development of ACLF and *** triggering receptor expressed on myeloid cells-1(sTREM-1)is released from activated innate immune cells and correlated with various inflammatory *** To explore the prognostic value of sTREM-1 in patients with AD of *** A multicenter prospective cohort of 442 patients with cirrhosis hospitalized for AD was divided into a study cohort(n=309)and validation cohort(n=133).Demographic and clinical data were collected,and serum sTREM-1 was measured at *** enrolled patients were followed-up for at least 1 *** In patients with AD and cirrhosis,serum sTREM-1 was an independent prognosis predictor for 1-year survival and correlated with liver,coagulation,cerebral and kidney failure.A new prognostic model of AD(P-AD)incorporating sTREM-1,blood urea nitrogen(BUN),total bilirubin(TBil),international normalized ratio(INR)and hepatic encephalopathy grades was established and performed better than the model for end-stage liver disease(MELD),MELD-sodium(MELD-Na),chronic liver failure-consortium(CLIF-C)ACLF and CLIF-C AD ***,sTREM-1 was increased in ACLF and predicted the development of ACLF during first 28-d *** ACLF risk score incorporating serum sTREM-1,BUN,INR,TBil and aspartate aminotransferase levels was established and significantly superior to MELD,MELD-Na,CLIF-C ACLF,CLIF-C AD and P-AD in predicting risk of ACLF *** Serum sTREM-1 is a promising prognostic biomarker for ACLF development and mortality in patients with AD of cirrhosis.

关键词： Soluble triggering receptor expressed on myeloid cell-1 Acute decompensation Cirrhosis Acute-on-chronic liver failure Prognostic biomarker

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MicroRNAs:A novel signature in the metastasis of esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2024年第11期30卷 1497-1523页

作者： Qi-Ying Wei Feng Jin Zhong-Yu Wang Bing-Jie Li Wen-Bo Cao Zhi-yan Sun Sai-Jun Mo Department of Pathophysiology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001Henan ProvinceChina Department of Perioperative Medicine The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Division of Special Service Department of Basic OncologySchool of Basic MedicineZhengzhou UniversityZhengzhou 450001Henan ProvinceChina Department of Basic Science of Oncology School of Basic Medical SciencesZhengzhou UniversityZhengzhou 450001Henan ProvinceChina

Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths *** increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered,coupled with higher risk of metastasis,which is an exceedingly malignant charac-teristic of cancer,frequently leading to a high mortality ***,there is currently no specific and effective marker to predict and treat metastasis in ***(miRNAs)are a class of small non-coding RNA molecules,approximately 22 nucleotides in *** are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence,progression,and prognosis of ***,we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis,and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic *** review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis,with the ultimate aim of reducing the mortality rate among patients with ESCC.

关键词： MicroRNAs Esophageal squamous cell carcinoma Metastasis Signaling pathway Epigenetics mechanism

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NOX4 promotes tumor progression through the MAPK-MEK1/2-ERK1/2 axis in colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1421-1436页

作者： Yu-Jie Xu Ya-Chang Huo Qi-Tai Zhao Jin-yan Liu Yi-Jun Tian Lei-Lei yang Yi Zhang Biotherapy Center and Cancer Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Department of Oncology Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityPeople’s Hospital of Henan UniversityZhengzhou 450003Henan ProvinceChina

BACKGROUND Metabolic reprogramming plays a key role in cancer progression and clinical outcomes;however,the patterns and primary regulators of metabolic reprogramming in colorectal cancer(CRC)are not well *** To explore the role of nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)in promoting progression of *** We evaluated the expression and function of dysregulated and survival-related metabolic genes using Gene Ontology and Kyoto Encyclopedia of Genes and *** clustering was used to cluster CRC based on dysregulated metabolic genes.A prediction model was constructed based on survival-related metabolic *** formation,migration,invasion,proliferation,apoptosis and clone formation was used to evaluate the biological function of NOX4 in *** sequencing was utilized to explore the alterations of gene expression NOX4 over-expression tumor *** vivo subcutaneous and lung metastasis mouse tumor model was used to explore the effect of NOX4 on tumor *** We comprehensively analyzed 3341 metabolic genes in CRC and identified three clusters based on dysregulated metabolic *** these genes,NOX4 was highly expressed in tumor tissues and correlated with worse *** vitro,NOX4 overexpression induced clone formation,migration,invasion,and stemness in CRC ***,RNA-sequencing analysis revealed that NOX4 overexpression activated the mitogen-activated protein kinase-MEK1/2-ERK1/2 signaling ***,a MEK1/2 inhibitor,abolished the NOX4-mediated tumor *** vivo,NOX4 overexpression promoted subcutaneous tumor growth and lung metastasis,whereas trametinib treatment can reversed the *** Our study comprehensively analyzed metabolic gene expression and highlighted the importance of NOX4 in promoting CRC metastasis,suggesting that trametinib could be a potential therapeutic drugs of CRC clinical therapy targeting NOX4.

关键词： Colorectal cancer Metabolic reprogramming Metastasis Nicotinamide adenine dinucleotide phosphate oxidase 4 Mitogen-activated protein kinase signaling

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Cumulative effects of excess high-normal alanine aminotransferase levels in relation to new-onset metabolic dysfunction-associated fatty liver disease in China

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World Journal of Gastroenterology 2024年第10期30卷 1346-1357页

作者： Jing-Feng Chen Zhuo-Qing Wu Hao-Shuang Liu Su yan You-Xiang Wang Miao Xing Xiao-Qin Song Su-Ying Ding Health Management Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Institute of Systems Engineering Dalian University of TechnologyDalian 116024Liaoning ProvinceChina College of Public Health Zhengzhou UniversityZhengzhou 450001Henan ProvinceChina School of Basic Medicine and Forensic Medicine Henan University of Science and TechnologyLuoyang 471003Henan ProvinceChina

BACKGROUND Within the normal range,elevated alanine aminotransferase(ALT)levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease(MAFLD).AIM To investigate the associations between repeated high-normal ALT measurements and the risk of new-onset MAFLD *** A cohort of 3553 participants followed for four consecutive health examinations over 4 years was *** incidence rate,cumulative times,and equally and unequally weighted cumulative effects of excess high-normal ALT levels(ehALT)were *** proportional hazards regression was used to analyse the association between the cumulative effects of ehALT and the risk of new-onset *** A total of 83.13%of participants with MAFLD had normal ALT *** incidence rate of MAFLD showed a linear increasing trend in the cumulative ehALT *** with those in the low-normal ALT group,the multivariate adjusted hazard ratios of the equally and unequally weighted cumulative effects of ehALT were 1.651[95%confidence interval(CI):1.199-2.273]and 1.535(95%CI:1.119-2.106)in the third quartile and 1.616(95%CI:1.162-2.246)and 1.580(95%CI:1.155-2.162)in the fourth quartile,*** Most participants with MAFLD had normal ALT ***-term high-normal ALT levels were associated with a cumulative increased risk of new-onset MAFLD.

关键词： Metabolic dysfunction-associated fatty liver disease High-normal alanine aminotransferase level Cumulative effect Cox proportional hazards regression Cohort study

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