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Multiomics analysis reveals metabolic subtypes and identifies diacylglycerol kinase α (DGKA) as a potential therapeutic target for intrahepatic cholangiocarcinoma

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Cancer Communications 2024年第2期44卷 226-250页

作者： Weiren Liu Huqiang Wang Qianfu Zhao Chenyang Tao Weifeng Qu Yushan Hou Run Huang Zimei Sun Guiqi Zhu Xifei Jiang Yuan Fang Jun Gao Xiaoling Wu Zhixiang Yang Rongyu Ping Jiafeng Chen Rui Yang Tianhao Chu Jian Zhou Jia Fan Zheng Tang Dong Yang Yinghong Shi Department of liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityKey Laboratory of Carcinogenesis and Cancer Invasion of Ministry of EducationShanghaiP.R.China research Unit of liver cancer Recurrence and Metastasis Chinese Academy of Medical SciencesBeijingP.R.China State Key Laboratory of Medical Proteomics Beijing Proteome Research CenterNational Center for Protein Sciences(Beijing)Beijing Institute of LifeomicsBeijingP.R.China

Background:Intrahepatic cholangiocarcinoma(iCCA)is a highly heteroge-neous and lethal hepatobiliary tumor with few therapeutic *** metabolic reprogramming of tumor cells plays an essential role in the develop-ment of tumors,while the metabolic molecular classification of iCCA is largely ***,we performed an integrated multiomics analysis and metabolic classification to depict differences in metabolic characteristics of iCCA patients,hoping to provide a novel perspective to understand and treat ***:We performed integrated multiomics analysis in 116 iCCA samples,including whole-exome sequencing,bulk RNA-sequencing and proteome *** on the non-negative matrix factorization method and the protein abundance of metabolic genes in human genome-scale metabolic models,the metabolic subtype of iCCA was *** and prognostic gene analy-ses were used to compare overall survival(OS)differences between metabolic *** proliferation analysis,5-ethynyl-2’-deoxyuridine(EdU)assay,colony formation assay,RNA-sequencing and Western blotting were performed to investigate the molecular mechanisms of diacylglycerol kinaseα(DGKA)in iCCA ***:Three metabolic subtypes(S1-S3)with subtype-specific biomarkers of iCCA were *** metabolic subtypes presented with distinct prog-noses,metabolic features,immune microenvironments,and genetic *** S2 subtype with the worst survival showed the activation of some special metabolic processes,immune-suppressed microenvironment and Kirsten ratsar-coma viral oncogene homolog(KRAS)/AT-rich interactive domain 1A(ARID1A)*** the S2 subtype-specific upregulated proteins,DGKA was further identified as a potential drug target for iCCA,which promoted cell proliferation by enhancing phosphatidic acid(PA)metabolism and activating mitogen-activated protein kinase(MAPK)***:Viamultiomics analyses,we identified three metabolic subtypes of iCCA,revealing

关键词： diacylglycerol kinaseα intrahepatic cholangiocarcinoma MAPK signaling metabolic classifi-cation multiomics analysis phosphatidic acid metabolism

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Machine learning in liver surgery:Benefits and pitfalls

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World Journal of Clinical Cases 2024年第12期12卷 2134-2137页

作者： Rafael Calleja Manuel Durán María Dolores Ayllón Ruben Ciria Javier Briceño Hepatobiliary Surgery and liver Transplantation Unit Hospital Universitario Reina SofíaMaimonides Biomedical Research Institute of CordobaCórdoba 14004Spain

The application of machine learning(ML)algorithms in various fields of hepatology is an issue of ***,we must be cautious with the *** this letter,based on a published ML prediction model for acute kidney injury after liver surgery,we discuss some limitations of ML models and how they may be addressed in the *** the future faces significant challenges,it also holds a great potential.

关键词： Machine learning liver surgery Artificial intelligence Random forest Prediction model

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National guidelines for the diagnosis and treatment of hilar cholangiocarcinoma

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World Journal of Gastroenterology 2024年第9期30卷 1018-1042页

作者： Faisal Saud Dar Zaigham Abbas Irfan Ahmed Muhammad Atique Usman Iqbal Aujla Muhammad Azeemuddin Zeba Aziz Abu Bakar Hafeez Bhatti Tariq Ali Bangash Amna Subhan Butt Osama Tariq Butt Abdul Wahab Dogar Javed Iqbal Farooqi Faisal Hanif Jahanzaib Haider Siraj Haider Syed Mujahid Hassan Adnan Abdul Jabbar Aman Nawaz Khan Muhammad Shoaib Khan Muhammad Yasir Khan Amer Latif Nasir Hassan Luck Ahmad Karim Malik Kamran Rashid Sohail Rashid Mohammad Salih Abdullah Saeed Amjad Salamat Ghias-un-Nabi Tayyab Aasim Yusuf Haseeb Haider Zia Ammara Naveed Department of Hepatopancreatic Biliary Surgery&liver Transplant Pakistan Kidney and Liver Institute&Research CentreLahore 54000Pakistan Department of Hepatogastroenterology and liver Transplantation Dr.Ziauddin University HospitalKarachi 75600SindhPakistan University of Aberdeen Aberdeen B243FXUnited Kingdom Department of Pathology Pakistan Kidney and Liver Institute&Research CentreLahore 54000Pakistan Department of Gastroenterology&Hepatology Pakistan Kidney and Liver Institute&Research CentreLahore 54000Pakistan Department of Radiology Aga Khan UniversityKarachi 74800Pakistan Department of Oncology Hameed Latif HospitalLahore 54000Pakistan Division of Hepatopancreatic Biliary Surgery&liver Transplantation Shifa International HospitalIslamabad 44000Pakistan Department of Hepatopancreatic Biliary Surgery&liver Transplant Shaikh Zayed Hospital and Post Graduate Medical InstituteLahore 54000Pakistan Department of Medicine Aga Khan University HospitalKarachi 74800Pakistan Department of liver Transplant Pir Abdul Qadir Shah Jeelani Institute of Medical SciencesGambat 66020Pakistan Department of Medicine&Gastroenterology Lifecare Hospital and Research CentrePeshawar 25000Khyber PakhtunkhwaPakistan Department of Hepatopancreatobiliary&liver Transplant Bahria International HospitalLahore 54000Pakistan Department of Surgery Hepatopancreatobiliary&Liver TransplantDow University of Health SciencesKarachi 74800Pakistan Department of Gastroenterology Hepatology&NutritionPir Abdul Qadir Shah Jeelani Institute of Medical SciencesGambat 66020Pakistan Department of Oncology Dr.Ziauddin HospitalKarachi 74800Pakistan Department of Radiology Rehman Medical InstitutePeshawar 25000Pakistan Army liver Transplant Unit Pak Emirates Military HospitalRawalpindi 46000Pakistan Department of Gastroenterology Sindh Institute of Urology and TransplantationKarachi 75500Pakistan Rashid Nursing Home and Cancer Clinic Rashid Nursing Home and Cancer ClinicRawalpindi 46000Pakistan Department of Gastroentero

A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and liver institute&research Centre(PKLI&RC)after initial consultations with the *** Pakistan Society for the Study of liver Diseases(PSSLD)and PKLI&RC jointly organised this *** effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma(hCCA).The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these *** coordinated effort can minimise delays and give patients a chance for curative treatment and effective *** diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance *** cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for ***,histopathologic confirmation is not always required before *** ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for *** only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette *** patients with unresectable hCCA can be considered for liver *** chemotherapy should be offered to patients with a high risk of *** use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary *** with acute cholangitis can be drained with endoscopic or percutaneous biliary *** chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.

关键词： Hilar cholangiocarcinoma Bismuth-Corlette classification Memorial Sloan Kettering Cancer Centre Staging Preoperative biliary drainage Portal vein embolisation Surgical resection Hepatectomy

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Recent trends in the epidemiology and clinical outcomes of inflammatory bowel disease in South Korea,2010-2018

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World Journal of Gastroenterology 2024年第9期30卷 1154-1163页

作者： Seulji Kim Hyun Jung Lee Seung Woo Lee Sanghyun Park Seong-Joon Koh Jong Pil Im Byeong Gwan Kim Kyung-Do Han Joo Sung Kim Department of Internal Medicine Korea Institute of Radiological and Medical SciencesSeoul 01812South Korea Department of Internal Medicine and liver research institute Seoul National University College of MedicineSeoul 03080South Korea Department of Statistics and Actuarial Science Soongsil UniversitySeoul 06978South Korea

BACKGROUND Inflammatory bowel disease(IBD)was previously regarded as a Western disease;however,its incidence is increasing in the *** epidemiology of IBD in Asia differs significantly from the patterns in the *** To comprehensively investigate the epidemiology of IBD in South Korea,inclu-ding its incidence,prevalence,medication trends,and *** We analyzed claims data from the Health Insurance Review and Assessment Service and Rare and Intractable Diseases(RIDs),operated by the National Health Insurance Service of South *** with IBD were identified based on the International Classification of Diseases,Tenth Revision,and RID diagnostic codes for Crohn’s disease(CD)and ulcerative colitis(UC)from 2010 to *** In total,14498 and 31409 patients were newly diagnosed with CD and UC,respectively,between 2010 and *** annual average incidence of CD was 3.11 cases per 105 person-years,and that of UC was 6.74 cases per 10^(5) *** 2014,the incidence rate of CD has been stable,while that of UC has steadily increased,shifting the peak age group from 50-year-olds in 2010 to 20-year-olds in *** CD and UC prevalence increased consistently over the study period;the use of 5-aminosali-cylates and corticosteroids gradually decreased,while that of immunomodulators and biologics steadily increased in both CD and *** clinical outcomes of IBD,such as hospitalization and surgery,decreased during the study *** The CD incidence has been stable since 2014,but that of UC has increased with a shift to a younger age at peak incidence between 2010 and *** clinical outcomes improved over time,with increased use of immunomodu-lators and biologics.

关键词： Inflammatory bowel disease Crohn’s disease Ulcerative colitis Incidence Prevalence

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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science China Life Sciences 2024年

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key Laboratory of Carcinogenesis and Translational research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research Laboratory Peking University Cancer Hospital &Institute Department of Gastrointestinal Cancer Center Peking University Cancer Hospital & Institute Department of liver Surgery & Transplantation Liver Cancer Institute Zhongshan Hospital Fudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational Research Division of Gastrointestinal Cancer Translational Research Laboratory Peking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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A novel small-animal locomotor activity recording device for biological clock research

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Animal Models and Experimental Medicine 2024年第1期7卷 71-76页

作者： Yi-Long Wu Ming Zhong Jun Yin Wei-Jie Ou Yu-Bin Zhuang Nan-Wen Zhang Su Lin Yue-Yong Zhu Endoscopy Center The First Affiliated HospitalFujian Medical UniversityFuzhouChina Department of Endocrinology The First Affiliated HospitalFujian Medical UniversityFuzhouChina Chuangke Workshop Technology Co. LtdShenzhenChina Department of Digestive Nutrition Fujian Children's HospitalFuzhouChina Experimental Animal Center Fujian Medical UniversityFuzhouChina Department of Pharmacology Fujian Medical UniversityFuzhouChina Department of Hepatology Hepatology Research InstituteClinical Research Center for Liver and Intestinal Diseases of Fujian ProvinceThe First Affiliated HospitalFujian Medical UniversityFuzhouChina

The rodent running-wheel recording apparatus is a reliable approach for studying cir-cadian *** study demonstrated how to construct a simple and intelligent running-wheel recording *** running wheel was attached to the cage's base,whereas the Hall sensor was attached to the cage's ***,the RJ25 adaptor relayed the running signal to the main control ***,the main control board was connected to the USB port of the computer with the USB *** were collected using the online-accessible,self-created software *** Magturning,generated data were saved and exported in real ***,the device was validated by collecting data on the locomotor activities of mice under dif-ferent light *** conclusion,this new device can record circadian activity of *** device is appropriate for interdisciplinary investigations related to biological clock research.

关键词： biological clock circadian rhythm intelligent equipment locomotor activity running wheel

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Impact of metabolic dysfunction-associated steatotic liver disease on the efficacy of immunotherapy in patients with chronic hepatitis B-related hepatocellular carcinoma

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Cancer Biology & Medicine 2024年第9期21卷 813-825页

作者： Jiaxin Han Wentao Kuai Liu Yang Xuemei Tao Yuekui Wang Minghui Zeng Yuqin Li Yuqiang Mi Ningning Zhang Wei Lu Liang Xu Clinical School of the Tianjin Second People's Hospital Tianjin Medical University Department of Hepatology Tianjin Second People's Hospital Tianjin institute of Hepatology Department of Hepatobiliary Oncology Liver Cancer Center Tianjin Medical University Cancer Institute & Hospital National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer

Objective: To investigate the impact of metabolic dysfunction-associated steatotic liver disease(MASLD) on the efficacy of immune checkpoint inhibitor(ICI)-based therapy in patients with chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC).Methods: A total of 155 patients with CHB-related HCC who received ICI±based therapy(in the Department of Hepatology, Tianjin Second People's Hospital and Department of Hepatobiliary Oncology, Tianjin Medical University Cancer institute & Hospital) between April 2021 and December 2023 were *** were divided into two groups: MASLD concurrent with CHB [MASLD-CHB](n = 38), and CHB(n = 117).Results: The median progression-free survival(PFS, 6.9 months vs.9.3 months; P = 0.001), progressive disease(57.89% vs.37.61%; P = 0.028), and disease control rate(42.11% vs.62.39%; P = 0.028) in the MASLD-CHB group were significantly worse than the CHB *** median overall survival was not *** percentage of CD4+PD1+(17.56% vs.8.89%; P < 0.001) and CD8+PD1+ T cells(10.50% vs.7.42%; P = 0.005) in patient samples from the MASLD-CHB group were significantly higher than the CHB *** MASLD [hazard ratio(HR) = 1.921; 95% CI, 1.138±3.245; P = 0.015] and alpha-fetoprotein levels after 3 months of treatment(HR = 2.412; 95% CI, 1.360±4.279; P = 0.003) were independent risk factors for PFS in all ***: ICI-based therapy in patients with CHB-related HCC and concurrent MASLD resulted in poorer efficacy and shorter PFS compared to patients with CHB-related HCC alone.

关键词： Metabolic dysfunction-associated steatotic liver disease chronic hepatitis B efficacy hepatocellular carcinoma immunotherapy

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Diverse functions of sox9 in liver development and homeostasis and hepatobiliary diseases

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Genes & Diseases 2024年第4期11卷 170-187页

作者： Taiyu Shang Tianyi Jiang Xiaowen Cui Yufei Pan Xiaofan Feng Liwei Dong Hongyang Wang School of Life Sciences Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China National Center for liver Cancer The Naval Medical UniversityShanghai 201805China International Cooperation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery InstituteThe Second Military Medical UniversityShanghai 200438China Laboratory of Signaling Regulation and Targeting Therapy of liver Cancer Second Military Medical University&Ministryof EducationShanghai 200438China

The liver is the central organ for digestion and detoxification and has unique metabolic and regenerative *** hepatobiliary system originates from the foregut endoderm,in which cells undergo multiple events of cell proliferation,migration,and differentiation to form the liver parenchyma and ductal system under the hierarchical regulation of transcription *** on liver development and diseases have revealed that SRY-related high-mobility group box 9(SOx9)plays an important role in liver embryogenesis and the progression of hepatobiliary ***9 is not only a master regulator of cell fate determination and tissue morphogenesis,but also regulates various biological features of cancer,including cancer stemness,invasion,and drug resistance,making Sox9 a potential biomarker for tumor prognosis and *** review systematically summarizes the latest findings of sox9 in hepatobiliary development,homeostasis,and *** also highlight the value of sox9 as a novel biomarker and potential target for the clinical treatment of major liverdiseases.

关键词： Biliary system Cancer Homeostasis liver diseases SOX9

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Azathioprine does not reduce adenoma formation in a mouse model of sporadic intestinal tumorigenesis

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World Journal of Gastroenterology 2014年第44期20卷 16683-16689页

作者： Mattheus CB Wielenga Jooske F van Lidth de Jeude Sanne L Rosekrans Alon D Levin Monique Schukking Geert RAM D'Haens Jarom Heijmans Marnix Jansen Vanesa Muncan Gijs R van den Brink tytgat institute for liver and intestinal research and Department of Gastroenterology and Hepatology Academic Medical Center Department of Pathology Academic Medical Center

AIM: To investigate if azathioprine could reduce adenoma formation in ApcMin/+, a mouse model of sporadic intestinal tumorigenesis.

关键词： Azathioprine Thiopurine intestinal adenoma Polyp ApcMin Chemoprevention Lymphoma Colon cancer

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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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