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Heparin is an effective treatment for preventing liver failure after hepatectomy

World Journal of Gastroenterology 2024年第22期30卷 2881-2892页

作者： Zhi-Ying Xu Min Peng Ming-Ming Fan Qi-Fei Zou Yi-Ran Li Dong Jiang hepatic surgery IV Shanghai Eastern Hepatobiliary Surgery HospitalThe Third Affiliated Hospital of Naval Medical UniversityShanghai 200433China Ultrasound Diagnosis PLA Naval Medical CenterShanghai 200437China Department of Ultrasound Eastern Hepatobiliary Surgery HospitalThe Third Affiliated Hospital of Naval Medical UniversityShanghai 200433China

BACKGROUND Posthepatectomy liver failure(PHLF)is one of the most important causes of death following liver ***,an established anticoagulant,can protect liver function through a number of mechanisms,and thus,prevent liver *** To look at the safety and efficacy of heparin in preventing hepatic dysfunction after *** The data was extracted from Multiparameter Intelligent Monitoring in Intensive Care III(MIMIC-III)v1.4 pinpointed patients who had undergone hepatectomy for liver cancer,subdividing them into two cohorts:Those who were injected with heparin and those who were *** statistical evaluations used were unpaired ttests,Mann-Whitney U tests,chi-square tests,and Fisher’s exact tests to assess the effect of heparin administration on PHLF,duration of intensive care unit(ICU)stay,need for mechanical ventilation,use of continuous renal replacement therapy(CRRT),incidence of hypoxemia,development of acute kidney injury,and ICU *** regression was utilized to analyze the factors related to PHLF,with propensity score matching(PSM)aiming to balance the preoperative disparities between the two *** In this study,1388 patients who underwent liver cancer hepatectomy were *** yielded 213 matched pairs from the heparin-treated and control *** univariate analyses indicated that heparin potentially reduces the risk of PHLF in both matched and unmatched *** analysis in the matched cohorts confirmed a significant association,with heparin reducing the risk of PHLF(odds ratio:0.518;95%confidence interval:0.295-0.910;P=0.022).Additionally,heparin treatment correlated with improved short-term postoperative outcomes such as reduced ICU stay durations,diminished requirements for respiratory support and CRRT,and lower incidences of hypoxemia and ICU *** Liver failure is an important hazard following hepatic *** ICU care heparin administration has been proved to decr

关键词： Liver resection Posthepatectomy liver failure Prophylactic treatment Heparin Prognosis of hepatectomy

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Computed tomography-based radiomics to predict early recurrence of hepatocellular carcinoma post-hepatectomy in patients background on cirrhosis

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World Journal of Gastroenterology 2024年第15期30卷 2128-2142页

作者： Gui-Xiang Qian Zi-Ling Xu Yong-Hai Li Jian-Lin Lu Xiang-Yi Bu Ming-Tong Wei Wei-Dong Jia Department of hepatic surgery Anhui Provincial HospitalThe First Affiliated Hospital of USTCDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina Department of hepatic surgery Anhui Provincial Hospital Affiliated to Anhui Medical UniversityAnhui Medical UniversityHefei 230001Anhui ProvinceChina Department of Anorectal surgery the First People’s Hospital of HefeiHefei 230001Anhui ProvinceChina

BACKGROUND The prognosis for hepatocellular carcinoma(HCC)in the presence of cirrhosis is unfavourable,primarily attributable to the high incidence of *** To develop a machine learning model for predicting early recurrence(ER)of posthepatectomy HCC in patients with cirrhosis and to stratify patients’overall survival(OS)based on the predicted risk of *** In this retrospective study,214 HCC patients with cirrhosis who underwent curative hepatectomy were *** feature selection was conducted using the least absolute shrinkage and selection operator and recursive feature elimination ***-radiologic features were selected through univariate and multivariate logistic regression *** machine learning methods were used for model comparison,aiming to identify the optimal *** model’s performance was evaluated using the receiver operating characteristic curve[area under the curve(AUC)],calibration,and decision curve ***,the Kaplan-Meier(K-M)curve was used to evaluate the stratification effect of the model on patient *** Within this study,the most effective predictive performance for ER of post-hepatectomy HCC in the background of cirrhosis was demonstrated by a model that integrated radiomics features and clinical-radiologic *** the training cohort,this model attained an AUC of 0.844,while in the validation cohort,it achieved a value of *** K-M curves illustrated that the combined model not only facilitated risk stratification but also exhibited significant discriminatory ability concerning patients’*** The combined model,integrating both radiomics and clinical-radiologic characteristics,exhibited excellent performance in HCC with *** K-M curves assessing OS revealed statistically significant differences.

关键词： Machine learning Radiomics Hepatocellular carcinoma Cirrhosis Early recurrence Overall survival Computed tomography Prognosis Risk factor Delta-radiomics

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Genetic landscape and clinical significance of cuproptosis-related genes in liver hepatocellular carcinoma

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Genes & Diseases 2024年第2期11卷 516-519页

作者： Dingtao Hu Yichuan Wang Xu Shen Tiantian Mao Xijun Liang Tengjiao Wang Weifeng Shen Yugang Zhuang Jin Ding Clinical Cancer Institute Center for Translational MedicineNaval Medical UniversityShanghai 200433China Department of Emergency Shanghai Tenth People's HospitalTongji UniversitySchool of MedicineShanghai 200072China Bioinformatics Analysis Laboratory Center for Translational MedicineNaval Medical UniversityShanghai 200433China The Department of hepatic surgery Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200433China

Recently,Peter et al reported a novel form of cell death(cuproptosis)that was different from other known death mechanisms.1 They found that accumulation of copper ions could induce destabilization of Fe-S cluster proteins and aggregation of mitochondrial lipoylated proteins,ultimately resulting in cuproptosis.1 of note,ten genes were identified as cuproptosis-related genes(CRGs)in copper ion-induced cell death,including PDHB,PDHA1,DLAT,DLD,LIPT1,LIAS,FDX1,CDKN2A,GLS,and MTF1.1 Since dysregulation of copper metabolism is involved in many cancers,cuproptosis and CRGs may play vital roles in cancer development and treatment.1.2 Herein,our pancancer analysis revealed the coordinated upregulation of 9 of 10 CRGs in human liver hepatocellular carcinoma(LIHC)across 33 solid tumors(Fig.S1A;Fig.1A),suggesting the distinct role of CRGs in *** then explored the genetic landscape,biological function,and clinical significance of CRGs in LIHC,and validated our bioinformatic findings by in vitro experiments and clinical *** detailed methods were described in the supplementary material.

关键词： clinical metabolism hepatocellular

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Autophagy in hepatic progenitor cells modulates exosomal miRNAs to inhibit liver fibrosis in schistosomiasis

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Frontiers of Medicine 2024年第3期18卷 538-557页

作者： Yue Yuan Jiaxuan Li Xun Lu Min Chen Huifang Liang Xiao-ping Chen Xin Long Bixiang Zhang Song Gong Xiaowei Huang Jianping Zhao Qian Chen Division of Gastroenterology Department of Internal Medicine at Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China hepatic surgery center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Hubei Key Laboratory of Hepato–Pancreato–Biliary Diseases Wuhan430030China Department of Trauma surgery Tongji Trauma CenterTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Schistosoma infection is one of the major causes of liver *** roles of hepatic progenitor cells(HPCs)in the pathogenesis of liver fibrosis have been ***,the precise mechanism underlying the role of HPCs in liver fibrosis in schistosomiasis remains *** study examined how autophagy in HPCs affects schistosomiasis-induced liver fibrosis by modulating exosomal *** activation of HPCs was verified by immunohistochemistry(IHC)and immunofluorescence(IF)staining in fibrotic liver from patients and mice with Schistosoma japonicum *** coculturing HPCs with hepatic stellate cells(HSCs)and assessing the autophagy level in HPCs by proteomic analysis and in vitro phenotypic assays,we found that impaired autophagy degradation in these activated HPCs was mediated by lysosomal *** autophagy by the autophagy inhibitor chloroquine(CQ)significantly diminished liver fibrosis and granuloma formation in ***-infected ***-secreted extracellular vehicles(EVs)were further isolated and studied by miRNA ***-1306-3p,miR-493-3p,and miR-34a-5p were identified,and their distribution into EVs was inhibited due to impaired autophagy in HPCs,which contributed to suppressing HSC *** conclusion,we showed that the altered autophagy process upon HPC activation may prevent liver fibrosis by modulating exosomal miRNA release and inhibiting HSC activation in *** the autophagy degradation process may be a therapeutic strategy for liver fibrosis during Schistosoma infection.

关键词： schistosomiasis hepatic progenitor cell autophagy extracellular vesicle fibrosis miRNA

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METTL14 downregulation drives S100A4^(+)monocyte-derived macrophages via MyD88/NF-κB pathway to promote MAFLD progression

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2176-2192页

作者： Yue-fan Wang Wen-li Zhang Zhi-xuan Li Yue Liu Jian Tan Hao-zan Yin Zhi-chao Zhang Xian-jie Piao Min-hao Ruan Zhi-hui Dai Si-jie Wang Chen-yang Mu Ji-hang Yuan Shu-han Sun Hui Liu Fu Yang The Third Department of hepatic surgery Eastern Hepatobiliary Surgery Hospital Affiliated to Naval Medical University200438 ShanghaiChina The Department of Medical Genetics Naval Medical University200433 ShanghaiChina Translational Medicine Research center Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital100048 BeijingChina The Department of Pharmaceutical Analysis School of PharmacyNaval Medical University200433 ShanghaiChina Key Laboratory of Biosafety Defense Ministry of Education200433 ShanghaiChina Shanghai Key Laboratory of Medical Biodefense 200433 ShanghaiChina

Without intervention,a considerable proportion of patients with metabolism‐associated fatty liver disease(MAFLD)will progress from simple steatosis to metabolism‐associated steatohepatitis(MASH),liver fibrosis,and even hepatocellular ***,the molecular mechanisms that control progressive MAFLD have yet to be fully ***,we unraveled that the expression of the N6-methyladenosine(m6A)methyltransferase METTL14 is remarkably downregulated in the livers of both patients and several murine models of MAFLD,whereas hepatocyte-specific depletion of this methyltransferase aggravated lipid accumulation,liver injury,and ***,hepatic Mettl14 overexpression alleviated the above pathophysiological changes in mice fed on a high-fat diet(HFD).Notably,in vivo and in vitro mechanistic studies indicated that METTL14 downregulation decreased the level of GLS2 by affecting the translation efficiency mediated by YTHDF1 in an m6A-depedent manner,which might help to form an oxidative stress microenvironment and accordingly recruit Cx3cr1^(+)Ccr2^(+)monocyte-derived macrophages(Mo-macs).In detail,Cx3cr1^(+)Ccr2^(+)Mo-macs can be categorized into M1-like macrophages and S100A4-positive macrophages and then further activate hepatic stellate cells(HSCs)to promote liver *** experiments revealed that CX3CR1 can activate the transcription of S100A4 via CX3CR1/MyD88/NF-κB signaling pathway in Cx3cr1^(+)Ccr2^(+)*** of METTL14 or GLS2,or interfering with this signal transduction pathway such as inhibiting MyD88 could ameliorate liver injuries and *** together,these findings indicate potential therapies for the treatment of MAFLD progression.

关键词： S100A4 MyD88 metabolism

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The role of N-glycosylation in cancer

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1098-1110页

作者： Yu Lin David M.Lubman Department of surgery University of Michigan Medical CenterAnn ArborMI 48109USA

Despite advances in understanding the development and progression of cancer in recent years,there remains a lack of comprehensive characterization of the cancer *** play an important role in medicine and are involved in various human disease conditions including ***-moieties participate in fundamental cancer processes like cell signaling,invasion,angiogenesis,and *** N-glycosylation significantly impacts cancer processes and targeted therapies in ***,understanding N-glycosylation in a tumor is essential for comprehending disease progression and discovering anti-cancer targets and biomarkers for therapy monitoring and *** review presents the fundamental process of protein N-glycosylation and summarizes glycosylation changes in tumor cells,including increased terminal sialylation,N-glycan branching,and ***,the role of N-glycosylation in tumor signaling pathways,migration,and metabolism are *** and glycopeptides as potential biomarkers for early detection of cancer based on site specificity have been ***,understanding and exploring the cancer glycoproteome,along with its role in medicine,implication in cancer and other human diseases,highlights the significance of N-glycosylation in tumor processes,necessitating further research for potential anticancer targets and biomarkers.

关键词： N-Glycosylated proteins Cancer signaling Cancer angiogenesis Cancer metabolism Cancer biomarkers

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Biotin-modified Galactosylated Chitosan-gene Carrier in Hepatoma Cells Targeting Delivery

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Journal of Wuhan University of Technology(Materials Science) 2024年第2期39卷 522-531页

作者：程明荣张锋李清王华 Department of General surgery Nanxiang Branch of Ruijin HospitalShanghai 201802China Minhang District Pujin Community Health Service center Shanghai 201112China Hepatobiliary surgery center Tongji Hospital Affiliated to Tongji UniversityShanghai 200065China

Our previous studies have successfully grafted biotin and galactose onto chitosan(CS)and synthesized biotin modified galactosylated chitosan(Bio-GC).The optimum N/P ratio of Bio-GC and plasmid DNA was 3:*** this N/P ratio,the transfection efficiency in the hepatoma cells was the highest with a slow release ***-GC nanomaterials exhibit the protective effect of preventing the gene from nuclease degradation,and can target the transfection into hepatoma cells by combination with galactose and biotin *** transfection rate was inhibited by the competition of galactose and ***-GC nanomaterials were imported into cells’cytoplasm by their receptors,followed by the imported exogenous gene transfected into the ***-GC nanomaterials can also cause inhibitory activity in the hepatoma cells in the model of orthotopic liver transplantation in mice,by carrying the gene through the blood to the hepatoma *** together,bio-GC nanomaterials act as gene vectors with the activity of protecting the gene from DNase degradation,improving the rate of transfection in hepatoma cells,and transporting the gene into the cytoplasm in vitro and in ***,they are efficient hepatoma-targeting gene carriers.

关键词： gene vector hepatocellular carcinoma nanoparticles sustained release gene therapy

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Transcriptomic and machine learning analyses identify hub genes of metabolism and host immune response that are associated with the progression of breast capsular contracture

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Genes & Diseases 2024年第3期11卷 427-437页

作者： Yukun Mao Xueying Hou Su Fu Jie Luan Breast Plastic and Reconstructive surgery center Plastic Surgery HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100144China

Capsular contracture is a prevalent and severe complication that affects the post-operative outcomes of patients who receive silicone breast *** present,prosthesis replacement is the major treatment for capsular contracture after both breast augmentation procedures and breast reconstruction following breast cancer ***,the mecha-nism(s)underlying breast capsular contracture remains *** study aimed to identify the biological features of breast capsular contracture and reveal the potential underlying mechanism using RNA *** tissues from 12 female patients(15 breast capsules)were divided into low capsular contracture(LCC)and high capsular contracture(HCC)groups based on the Baker ***,41 lipid metabolism-related genes were identified through enrichment analysis,and three of these genes were identified as candidate genes by SVM-RFE and LASSO *** then compared the proportions of the 22 types of im-mune cells between the LCC and HCC groups using a CIBERSORT analysis and explored the Cor-relation between the candidate hub features and immune ***,PRKAR2B was positively correlated with the differentially clustered immune cells,which were M1 macro-phages and follicular helper T cells(area under the ROC=0.786).In addition,the expression of PRKAR2B at the mRNA or protein level was lower in the HCC group than in the LCC *** molecular mechanisms were identified based on the expression levels in the high and low PRKAR2B *** findings indicate that PRKAR2B is a novel diagnostic biomarker for breast capsular contracture and might also influence the grade and progression of capsularcontracture.

关键词： Biomarker Breastcapsular contracture Immune infiltration Machinelearning algorithms PRKAR2B

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Hippo(YAP)-autophagy axis protects against hepatic ischemia-reperfusion injury through JNK signaling

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Chinese Medical Journal 2024年第6期137卷 657-668页

作者： Shuguang Zhu Xiaowen Wang Haoqi Chen Wenfeng Zhu Xuejiao Li Ruiwen Cui Xiaomeng Yi Xiaolong Chen Hua Li Genshu Wang Department of hepatic surgery Liver TransplantationThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Hepatology lab The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of General surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Organ Transplantation The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of Renal Transplantation Guangdong Provincial Hospital of Chinese MedicineGuangzhouGuangdong 510630China Department of Surgical Intensive Care Unit The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China Department of hepatic surgery Liver TransplantationGuangdong Provincial Hospital of Chinese MedicineGuangzhouGuangdong 510630China

Background:hepatic ischemia-reperfusion injury(HIRI)remains a common complication during liver transplantation(LT)in *** a key downstream effector of the Hippo pathway,Yes-associated protein(YAP)has been reported to be involved in various physiological and pathological ***,it remains elusive whether and how YAP may control autophagy activation during ***:Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy *** an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of ***:Autophagy was activated in the post-perfusion liver grafts during LT in patients,and the expression of YAP positively correlated with the autophagic level of ***-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI(P<0.05).YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models(P<0.05).Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with *** addition,inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species(P<0.05).Moreover,the regulation of autophagy by YAP during HIRI was mediated by AP1(c-Jun)N-terminal kinase(JNK)signaling through binding to the transcriptional enhanced associate domain(TEAD).Conclusions:YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of *** Hippo(YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

关键词： YAP-signaling proteins Autophagy c-Jun N-terminal kinase Ischemia-reperfusion injury Liver transplantation

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Strategy and technique for surgical treatment of Ebstein’s anomaly

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Chinese Medical Journal 2024年第10期137卷 1218-1224页

作者： Qingyu Wu Xiaoya Zhang Mingkui Zhang Hongyin Li Dongya Zhang Lianyi Wang Qingfeng Wu Cardiac center Division of Cardiac SurgeryThe First Hospital of Tsinghua UniversityBeijing 100016China

Background:Ebstein’s anomaly(EA)is a rare and complex congenital heart anomaly,and the effect of surgical treatment is not *** study aims to introduce our experience in management strategies,surgical techniques,and operative indications for patients with Ebstein’s ***:A retrospective study of 258 operations was performed in 253 patients by the same cardiac surgeon in The First Hospital of Tsinghua University between March 2004 and January 2020.32 patients had previously received cardiac surgery in other *** clinical data including diagnosis,operative indications,techniques,pathological changes,and survival rates were collected and ***:Anatomical correction was performed in 203(78.7%)operations,1½ventricle repair in 38(14.7%)operations,tricuspid valve repair only in four operations(1.6%),tricuspid valve replacement in ten(3.9%),total cavopulmonary connection(TCPC)in two(0.8%),and Glenn operation in one operation(0.4%).Reoperation was performed in five patients(2.0%)during *** them,tricuspid valve replacement was performed in one patient,1½ventricle repair in two patients,and tricuspid valve annulus reinforcement in two *** patients died with an early mortality rate of 2.0%.Complete atrioventricular conduction block was complicated in one patient(0.4%).A total of 244 patients was followed up(four in the 253 patients lost)with a duration of 3.0-168.0(87.6±38.4)*** function of 244 patients improved significantly with mean New York Heart Association(NYHA)functional class recovery from 3.5 to *** mean grade of tricuspid valve regurgitation improved from 3.6 to *** late deaths(1.2%)*** survival rates at five and ten years after surgery were 98.6%and 98.2%,*** was performed in five patients(2.0%)during the follow-up ***:Based on our management strategies and operative principles and techniques,anatomical correction of EA is capable of achiev

关键词： Ebstein’s anomaly Anatomical repair Surgical treatment Long-term result

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