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Validation and performance of three scoring systems for predicting primary non-function and early allograft failure after liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 463-471页

作者： Yu Nie Jin-Bo Huang Shu-Jiao He Hua-Di Chen Jun-Jun Jia Jing-Jing Li Xiao-Shun He Qiang Zhao General Surgery center Department of Hepatobiliary Surgery IIResearch Center for Artificial Organ and Tissue EngineeringGuangzhou Clinical Research and Transformation Center for Artificial LiverInstitute of Regenerative MedicineZhujiang HospitalSouthern Medical UniversityGuangzhou 510515China Organ Transplant center the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Guangdong Provincial Key Laboratory of Organ Donation and Transplant Immunology Guangzhou 510080China Guangdong Provincial International Cooperation Base of Science and Technology Guangzhou 510080China Division of Hepatobiliary Pancreatic Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Background: Primary non-function(PNF) and early allograft failure(EAF) after liver transplantation(LT) seriously affect patient outcomes. In clinical practice, effective prognostic tools for early identifying recipients at high risk of PNF and EAF were urgently needed. Recently, the Model for Early Allograft Function(MEAF), PNF score by King's College(King-PNF) and Balance-and-Risk-Lactate(BAR-Lac) score were developed to assess the risks of PNF and EAF. This study aimed to externally validate and compare the prognostic performance of these three scores for predicting PNF and EAF. Methods: A retrospective study included 720 patients with primary LT between January 2015 and December 2020. MEAF, King-PNF and BAR-Lac scores were compared using receiver operating characteristic(ROC) and the net reclassification improvement(NRI) and integrated discrimination improvement(IDI) analyses. Results: Of all 720 patients, 28(3.9%) developed PNF and 67(9.3%) developed EAF in 3 months. The overall early allograft dysfunction(EAD) rate was 39.0%. The 3-month patient mortality was 8.6% while 1-year graft-failure-free survival was 89.2%. The median MEAF, King-PNF and BAR-Lac scores were 5.0(3.5–6.3),-2.1(-2.6 to-1.2), and 5.0(2.0–11.0), respectively. For predicting PNF, MEAF and King-PNF scores had excellent area under curves(AUCs) of 0.872 and 0.891, superior to BAR-Lac(AUC = 0.830). The NRI and IDI analyses confirmed that King-PNF score had the best performance in predicting PNF while MEAF served as a better predictor of EAD. The EAF risk curve and 1-year graft-failure-free survival curve showed that King-PNF was superior to MEAF and BAR-Lac scores for stratifying the risk of EAF. Conclusions: MEAF, King-PNF and BAR-Lac were validated as practical and effective risk assessment tools of PNF. King-PNF score outperformed MEAF and BAR-Lac in predicting PNF and EAF within 6 months. BAR-Lac score had a huge advantage in the prediction for PNF without post-transplant variables. Proper use

关键词： Primary non-function Early allograft failure Risk predicting model liver transplantation

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Advancements in Barrett's esophagus detection:The role of artificial intelligence and its implications

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World Journal of Gastroenterology 2024年第11期30卷 1494-1496页

作者： Sara Massironi Division of Gastroenterology and center for Autoimmune liver Diseases Department of Medicine and SurgeryFondazione IRCCS San Gerardo dei TintoriUniversity of Milano-BicoccaMonza 20900Italy

Artificial intelligence(AI)is making significant strides in revolutionizing the detection of Barrett's esophagus(BE),a precursor to esophageal *** the research article by Tsai et al,researchers utilized endoscopic images to train an AI model,challenging the traditional distinction between endoscopic and histological *** approach yielded remarkable results,with the AI system achieving an accuracy of 94.37%,sensitivity of 94.29%,and specificity of 94.44%.The study's extensive dataset enhances the AI model's practicality,offering valuable support to endoscopists by minimizing unnecessary ***,questions about the applicability to different endoscopic systems *** study underscores the potential of AI in BE detection while highlighting the need for further research to assess its adaptability to diverse clinical settings.

关键词： Barrett's esophagus Artificial intelligence Endoscopic images Artificial intelligence model Early cancer detection Endoscopy

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STING-mediated IL-6 Inhibits OATP1B1 Expression via the TCF4 Signaling Pathway in Cholestasis

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Journal of Clinical and Translational Hepatology 2024年第8期12卷 701-712页

作者： Yan Guo Hongjia Zhang Nan Zhao Ying Peng Dongya Shen Yubin Chen Xiaoxun Zhang Can-E Tang Jin Chai Department of Endocrinology Xiangya HospitalCentral South UniversityChangshaHunanChina Department of Gastroenterology Institute of Digestive Diseases of PLACholestatic Liver Diseases Center and Center for Metabolic Associated Fatty Liver DiseaseThe First Affiliated Hospital(Southwest Hospital)to Third Military Medical University(Army Medical University)ChongqingChina Department of Clinical Pharmacology Xiangya HospitalCentral South UniversityChangshaHunanChina Department of Cardiac Surgery Xiangya HospitalCentral South UniversityChangshaHunanChina National Clinical research center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunanChina

Background and Aims Organic anion-transporting polypeptides(OATPs)play a crucial role in the transport of bile acids and *** our previous study,interleukin 6(IL-6)reduced OATP1B3 levels in cholestatic ***,it remains unclear whether IL-6 inhibits OATP1B1 expression in cholestatic *** study aimed to investigate whether IL-6 can inhibit OATP1B1 expression and explore the underlying *** The effect of stimulator of interferon genes(STING)signaling on inflammatory factors was investigated in a cholestatic mouse model using RT-qPCR and enzyme-linked immunosorbent *** assess the impact of inflammatory factors on OATP1B1 expression in hepatocellular carcinoma,we analyzed OATP1B1 expression by RT-qPCR and Western Blot after treating PLC/PRF/5 cells with TNF-α,IL-1β,and *** elucidate the mechanism by which IL-6 inhibits OATP1B1 expression,we examined the expression of the OATP1B1 regulator TCF4 in PLC/PRF/5 and HepG2 cells using RT-qPCR and Western *** interaction mechanism betweenβ-catenin/TCF4 and OATP1B1 was investigated by knocking downβ-catenin/TCF4 through siRNA *** The STING inhibitor decreased inflammatory factor levels in the cholestatic mouse model,with IL-6 exhibiting the most potent inhibitory effect on ***-6 downregulatedβ-catenin/TCF4,leading to decreased OATP1B1 ***-downβ-catenin/TCF4 counteracted theβ-catenin/TCF4-mediated repression of *** STING-mediated IL-6 up-regulation may inhibit OATP1B1,leading to reduced transport of bile acids and bilirubin by *** may contribute to altered pharmacokinetics in patients with diseases associated with increased IL-6 production.

关键词： Inflammation Bile acid Bilirubin Cholestasis STING IL-6 β-catenin TCF4

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RAMP1 Protects Hepatocytes against Ischemia-reperfusion Injury by Inhibiting the ERK/YAP Pathway

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Journal of Clinical and Translational Hepatology 2024年第4期12卷 357-370页

作者： Yongsheng Tang Zenan Yuan Xu Lu Yingqiu Song Shuguang Zhu Chunhui Qiu Qi zhang Binsheng Fu Changchang Jia Hua Li Department of Hepatic Surgery Liver Transplantation CenterThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Gastrointestinal Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Cell-Gene Therapy Translational Medicine research center The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina

Background and Aims:Hepatic ischemia-reperfusion injury(HIRI)is a prevalent complication of liver transplantation,partial hepatectomy,and severe infection,necessitating the development of more effective clinical *** activity–modifying protein 1(RAMP1),a member of the G protein–coupled receptor adapter family,has been implicated in numerous physiological and pathological *** study aimed to investigate the pathogenesis of RAMP1 in ***:We established a 70%liver ischemia-reperfusion model in RAMP1 knockout(KO)and wild-type *** and blood samples were collected after 0,6,and 24 h of hypoxia/*** histological and serological analyses were performed to evaluate liver *** also conducted in-vitro and in-vivo experiments to explore the molecular mechanism underlying RAMP1 ***:liver injury was exacerbated in RAMP1-KO mice compared with the sham group,as evidenced by increased cell death and elevated serum transaminase and inflammation *** was promoted in RAMP1-KO mice via the induction of hepatocyte apoptosis and inhibition of *** absence of RAMP1 led to increased activation of the extracellular signal–regulated kinase(ERK)/mitogen-activated protein kinase(MAPK)pathway and yes-associated protein(YAP)phosphorylation,ultimately promoting ***772984,an ERK/MAPK phosphorylation inhibitor,and PY-60,a YAP phosphorylation inhibitor,reduced apoptosis in in-vitro and in-vivo ***:Our findings suggest that RAMP1 protects against HIRI by inhibiting ERK and YAP phosphorylation signal transduction,highlighting its potential as a therapeutic target for HIRI and providing a new avenue for intervention.

关键词： Hepatic ischemia-reperfusion injury(HIRI) Receptor activity-modifying protein 1(RAMP1) YES-Associated Protein(YAP) Extracellular signalregulated kinase(ERK)

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MicroRNAs in thyroid cancer with focus on medullary thyroid carcinoma:potential therapeutic targets and diagnostic/prognostic markers and web based tools

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Oncology research 2024年第6期32卷 1011-1019页

作者： ELHAM SHAKIBA SETI BOROOMAND SIMA KHERADMAND KIA MEHDI HEDAYATI Department of Biochemistry Faculty of Biological SciencesNorth Tehran BranchIslamic Azad UniversityTehran***Iran Department of Pathology and Laboratory Medicine Vancouver General HospitalVancouverV5Z 1M9Canada Department of Blood Cell research Laboratory for Red Blood Cell DiagnosticsSanquinAmsterdam1006 ANThe Netherlands Cellular and Molecular Endocrine research center Research Institute for Endocrine SciencesShahid Beheshti University of Medical SciencesTehran***Iran

This review aimed to describe the inculpation of microRNAs(miRNAs)in thyroid cancer(TC)and its subtypes,mainly medullary thyroid carcinoma(MTC),and to outline web-based tools and databases for bioinformatics analysis of miRNAs in ***,the capacity of miRNAs to serve as therapeutic targets and biomarkers in TC management will be *** review is based on a literature search of relevant articles on the role of miRNAs in TC and its subtypes,mainly ***,web-based tools and databases for bioinformatics analysis of miRNAs in TC were identified and *** can perform as oncomiRs or antioncoges,relying on the target mRNAs they *** replacement therapy using miRNA mimics or antimiRs that aim to suppress the function of certain miRNAs can be applied to correct miRNAs aberrantly expressed in diseases,particularly in *** are involved in the modulation of fundamental pathways related to cancer,resembling cell cycle checkpoints and DNA repair *** are also rather stable and can reliably be detected in different types of biological materials,rendering them favorable diagnosis and prognosis biomarkers as *** have emerged as promising tools for evaluating medical outcomes in TC and as possible therapeutic *** contribution of miRNAs in thyroid cancer,particularly MTC,is an active area of research,and the utility of web applications and databases for the biological data analysis of miRNAs in TC is becoming increasingly important.

关键词： Thyroid cancer MicroRNAs Biomarker Bioinformatics analysis Medullary thyroid carcinoma(MTC) OncomiRs Antioncoges

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Biosafe,rapid,and ultrahigh-capacity endotoxin purification in blood by a sustainable and recyclable MOF-functionalized chitin microsphere adsorbent

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SusMat 2024年第5期4卷 163-177页

作者： Anxiong Liu Lu Chen Luhe Qi Jing Huang Yongkang Zou Zhiwen Hu Le Yu Zibiao Zhong Qifa Ye Chaoji Chen National Quality Control center for Donated Organ Procurement Hubei Key Laboratory of Medical Technology on TransplantationHubei Clinical Research Center for Natural Polymer Biological LiverHubei Engineering Center of Natural Polymer-Based Medical MaterialsZhongnan Hospital of Wuhan UniversityInstitute of Hepatobiliary Diseases ofWuhan UniversityTransplant Center of Wuhan UniversityWuhanChina School of Resource and Environmental Science Hubei Biomass-Resource Chemistry and Environmental Biotechnology Key LaboratoryWuhan UniversityWuhanChina

Sepsis is responsible for approximately 5.3 million deaths globally each ***,we constructed hierarchical chitin microspheres loaded with MOF-919(Ch/metal–organic frameworks[MOFs])for the rapid and efficient removal of lipopolysaccharide(LPS)in complex blood ***,abun-dant active sites on MOF-919(Sc)also enable a record-high adsorption capacity of 9.56 mg/g in biomass-based adsorbents due to the coordination interactions between endotoxin and MOF-919(Sc).The LPS level of sepsis rabbits was less than 2 EU/mL(clearance rate>95%)after 90-min hemoperfusion,showing no adverse effect on the rabbit ***,compared to the commonly used LPS scrubber Toraymyxin(polymethyl methacrylate),the chitin adsorbent is significantly more cost-effective and environmentally *** prepara-tion strategy for hierarchical porous microspheres offers notable advantages in designability,recyclability,and renewability,providing a new approach to sepsis treatment and promising prospects for the biomedical application of sustainable biomass materials.

关键词： biomass blood purification chitin endotoxin removal hemoperfusion metal–organic frameworks

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Chinese expert consensus on refined diagnosis,treatment,and management of advanced primary liver cancer(2023 edition)

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肝脏研究（英文） 2024年第2期8卷 61-71页

作者： Xiufeng Liu Feng Xia Yue Chen Huichuan Sun Zhengqiang Yang Bo Chen Ming Zhao Xinyu Bi Tao Peng Aizier Ainiwaer Zhiwen Luo Fusheng Wang Yinying Lu National Clinical research center for Infectious Diseases Society of Hepatology,Beijing Medical Association Translational Medicine Branch,China Association of Gerontology and Geriatrics Department of Medical Oncology Bayi Hospital Affiliated to Nanjing Chinese Medical University NanjingJiangsuChina Department of Hepatobiliary Surgery Southwest HospitalArmy Medical University ChongqingChina Senior Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijingChina Department of liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghaiChina Department of Interventional Therapy National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Minimally Invasive Interventional Therapy Liver Cancer Study and Service GroupSun Yat-sen University Cancer CenterGuangzhouGuangdongChina Department of Hepatobiliary Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Hepatobiliary Surgery The First Affiliated Hospital of Guangxi Medical UniversityNanningGuangxiChina Senior Department of Infectious Diseases The Fifth Medical Center of PLA General HospitalBeijingChina Comprehensive liver Cancer center The Fifth Medical Center of PLA General HospitalBeijingChina

Hepatocellular carcinoma(HCC),commonly known as primary liver cancer,is a major cause of malignant tumors and cancer-related deaths in China,accounting for approximately 85％of all cancer cases in the *** guidelines have been used to diagnose and treat liver ***,these guidelines provide a broad definition for classifying advanced liver cancer,with an emphasis on a singular approach,without considering treatment options for individual ***,it is necessary to establish a comprehensive and practical expert consensus,specifically for China,to enhance the diagnosis and treatment of HCC using the Delphi *** classification criteria were refined for Chinese patients with HCC,and the corresponding optimal treatment regimen recommendations were *** recommendations took into account various factors,including tumor characteristics,vascular tumor thrombus grade,distant metastasis,liver function status,portal hypertension,and the hepatitis B virus replication status of patients with primary HCC,along with treatment *** findings and rec-ommendations provide detailed,scientific,and reasonable individualized diagnosis and treatment strategies for clinicians.

关键词： Hepatocellular carcinoma (HCC) Targeted therapy Immunotherapy Refined diagnosis and treatment Expert consensus

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Immune remodulation in pediatric inherited metabolic liver diseases

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World Journal of Hepatology 2024年第9期16卷 1258-1268页

作者： Yi-Chi Wu Xue-Lin Xiang June-Kong Yong Meng Li Lin-Man Li Zi-Cheng Lv Yi Zhou Xi-Cheng Sun Zi-Jie Zhang Huan Tong Xiao-Ying He Qiang Xia Hao Feng Department of liver Surgery Renji Hospital(Punan Branch)School of MedicineShanghai Jiao Tong UniversityShanghai 200127China Department of liver Surgery Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Department of liver Surgery Renji Hospital Affiliated to Shanghai Jiao Tong UniversityShanghai Institute of TransplantationShanghai Engineering Research Center of Transplantation and ImmunologyShanghai 200127China Department of Gynecology Shanghai First Maternity and Infant HospitalShanghai 200012China

Inherited metabolic liver diseases arise from genetic mutations that lead to dis-ruptions in liver metabolic pathways and are predominantly observed in pedia-tric *** spectrum of genetic metabolic liver disorders is diverse,encompassing a range of conditions associated with aberrations in iron,copper,carbohydrate,lipid,protein,and amino acid ***,research in the domain of genetic metabolic liver diseases has predominantly concentrated on hepatic parenchymal cell ***,emerging studies suggest that inherited metabolic liver diseases exert significant influences on the immune microenvironment,both within the liver and *** review endeavors to encapsulate the immunological features of genetic metabolic liver diseases,aiming to expand the horizons of researchers in this discipline,and to elucidate the underlying pathophysiological mechanisms pertinent to hereditary metabolic liver diseases and to propose innovative therapeutic approaches.

关键词： liver transplantation Inherited metabolic liver diseases Immune microen-vironment Genetic metabolic liver diseases Immunotherapy

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Retrospective study of the incidence, risk factors, treatment outcomes of bacterial infections at uncommon sites in cirrhotic patients

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World Journal of Hepatology 2024年第3期16卷 418-427页

作者： Sophie Schneitler Christina Schneider Markus Casper Frank Lammert Marcin Krawczyk Sören L Becker Matthias Christian Reichert Institute of Medical Microbiology and Hygiene Saarland UniversityHomburg 66421Germany Department of Medicine II Saarland University Medical CenterHomburg 66421Germany Health Sciences Hannover Medical SchoolHannover 30625Germany Laboratory of Metabolic liver Diseases Department of GeneralTransplant and Liver SurgeryCentre for Preclinical ResearchMedical University of WarsawWarsaw 02-097Poland

BACKGROUND Bacterial infections(BI)negatively affect the natural course of *** most frequent BI are urinary tract infections(UTI),pneumonia,and spontaneousbacterial peritonitis(SBP).AIM To assess the relevance of bacterial infections beyond the commonly recognized types in patients with cirrhosis and to investigate their relationship with other clinical *** We retrospectively analyzed patients with cirrhosis and BI treated between 2015 and 2018 at our tertiary care *** were classified as typical and atypical,and clinical as well as laboratory parameters were compared between the two *** In a cohort of 488 patients with cirrhosis,we identified 225 typical BI(95 UTI,73 SBP,72 pulmonary infections)and 74 atypical BIs,predominantly cholangitis and soft tissue infections(21 each),followed by intra-abdominal BIs(n=9),cholecystitis(n=6),head/throat BIs(n=6),osteoarticular BIs(n=5),and endocarditis(n=3).We did not observe differences concerning age,sex,or etiology of cirrhosis in patients with typical vs atypical *** BIs were more common in patients with more advanced cirrhosis,as evidenced by Model of End Stage liver Disease(15.1±7.4 vs 12.9±5.1;P=0.005)and Child-Pugh scores(8.6±2.5 vs 8.0±2;P=0.05).CONCLUSION Atypical BIs in cirrhosis patients exhibit a distinct spectrum and are associated with more advanced stages of the ***,the work-up of cirrhosis patients with suspected BI requires detailed work-up to elucidate whether typical BI can be identified.

关键词： Bacterial infection Empirical antibiotic therapy End-stage liver disease Escherichia coli Multi-resistant pathogens

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Impact of Proteinuria on liver Enzyme Levels

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Journal of Clinical and Translational Hepatology 2024年第9期12卷 759-760页

作者： David Yardeni Asif Hitawala Lilian Howard Theo Heller Meryl Waldman Department of Gastroenterology and liver Diseases Soroka University Medical CenterBeer-ShevaIsrael liver Diseases Branch National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaMDUSA Kidney Diseases Branch National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaMDUSA

Dear Editors,We read with great interest the recently published article“Subnormal Serum liver Enzyme Levels:A Review of Pathophysiology and Clinical Significance”by Youssef and colleagues.1 While much attention is given to elevations of liver enzymes,the authors highlight clinically important,often unrecognized reasons leading to low liver enzyme *** example,chronic kidney disease was cited as a cause of low serum aspartate aminotransferase(AST)proportional to the progression of the disease,but the cause(s)are not well *** is known about the possible influence of nephrotic syndrome(NS)on liver enzymes.

关键词： Impact liver Levels

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