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Key role of interferon regulatory factor 1(IRF-1)in regulating liver disease:progress and outlook

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第6期25卷 451-470页

作者： Tao CHEN Shipeng LI Dewen DENG Weiye ZHANG Jianjun ZHANG Zhongyang SHEN First Central Clinical School Tianjin Medical UniversityTianjin 300192China department of organ transplant Tianjin First Central HospitalTianjin 300192China Research Institute of transplant medicine Nankai UniversityTianjin 300192China department of Hepatobiliary Surgery Henan Provincial People’s HospitalZhengzhou 450000China Key Laboratory of organ transplant Tianjin First Central HospitalTianjin 300192China

Interferon regulatory factor 1(IRF-1)is a member of the IRF *** is the first transcription factor to be identified that could bind to the interferon-stimulated response element(ISRE)on the target gene and displays crucial roles in the interferoninduced signals and ***-1,as an important medium,has all of the advantages of full cell cycle regulation,cell death signaling transduction,and reinforcing immune surveillance,which are well *** studies indicate that IRF-1 is of vital importance to the occurrence and evolution of multifarious liver diseases,including but not limited to inhibiting the replication of the hepatitis virus(A/B/C/E),alleviating the progression of liver fibrosis,and aggravating hepatic ischemiareperfusion injury(HIRI).The tumor suppression of IRF-1 is related to the clinical characteristics of liver cancer patients,which makes it a potential indicator for predicting the prognosis and recurrence of liver cancer;additionally,the latest studies have revealed other effects of IRF-1 such as protection against alcoholic/non-alcoholic fatty liver disease(AFLD/NAFLD),cholangiocarcinoma suppression,and uncommon traits in other liver diseases that had previously received little ***,several compounds and drugs have featured a protective function in specific liver disease models in which there is significant involvement of the IRF-1 *** this paper,we hope to propose a prospective research basis upon which to help decipher translational medicine applications of IRF-1 in liver disease treatment.

关键词： Interferon regulatory factor(IRF-1) Hepatitis virus Liver fibrosis Hepatic ischemia-reperfusion injury(HIRI) Liver cancer

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Bio-analysis of Saliva Using Paper Devices and Colorimetric Assays

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Journal of Analysis and Testing 2024年第1期8卷 114-132页

作者： Adhan Narasimhan Harshil Jain Kowshika Muniandy Raja Chinnappan Naresh Kumar Mani Microfluidics Sensors and Diagnostics(μSenD)LaboratoryCentre for MicrofluidicsBiomarkersPhotoceutics&Sensors(μBioPS)Department of BiotechnologyManipal Institute of TechnologyManipal Academy of Higher EducationManipalKarnataka 576104India College of medicine Alfaisal UniversityRiyadh 11533SaudiArabia Tissue/organ Bioengineering&BioMEMS Lab Organ Transplant Centre of ExcellenceTransplant Research&Innovation DepartmentKing Faisal Specialist Hospital and Research CentreRiyadhSaudi Arabia

In light of the evolving nature of various diseases,time becomes a crucial factor in diagnosis and identifying the underlying causes.A point-of-care device provides a rapid diagnosis of a disease without using complex and advanced instruments,which are costly and difficult to transport.A paper-based device is a relatively frugal solution wherein the paper is used as a substratum in which the reactions are carried *** methods are non-invasive,and the sample collection is relatively *** is one such body fluid in which various biomarkers are present for numerous *** of saliva has attracted more attention recently due to its non-invasiveness and *** the discovery of clinical biomarkers from salivary analysis has the potential to revolutionize the healthcare sector by providing crucial information to monitor the health status of individuals and disease progression which enables personalized *** review provides the limitation of the traditional methods in clinical applications and highlights the significance of saliva as a non-invasive biological fluid that is a source of multiple biomarkers associated with various *** also provides insights into the different paper-based colorimetric microfluidic devices developed against salivary biomarkers in the past *** major challenges in the point-of-care application and the future prospects have been discussed as ***,we also emphasize the importance of this approach in dental disease diagnosis which is least explored and holds potential applications.

关键词： Paper-based assay Salivary analysis Non-invasive Point-of-care Body fluids Biomarkers Qualitative detection

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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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FGF21-mediated autophagy:Remodeling the homeostasis in response to stress in liver diseases

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Genes & Diseases 2024年第3期11卷 264-274页

作者： Wei Shen Modan Yang Hao Chen Chiy He Huigang Li Xinyu Yang Jianyong Zhuo Zuyuan Lin Zhihang Hu Di Lu Xiao Xu Zhejiang University School of medicine HangzhouZhejiang 310058China Key Laboratory of Integrated Oncology and Intelligent medicine of Zhejiang Province Department of Hepatobiliary and Pancreatic SurgeryAffiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhouZhejiang 310006China The Institute for organ Repair and Regenerative medicine of Hangzhou HangzhouZhejiang 310006China Institute of organ transplantation Zhejiang UniversityHangzhouZhejiang 310003China National Center for Healthcare Quality Management in Liver transplant HangzhouZhejiang 310003China

Liver diseases are worldwide problems closely associated with various stresses,such as endoplasmic reticulum *** exact interplay between stress and liver diseases remains *** plays an essential role in maintaining homeostasis,and recent studies indicate tight crosstalk between stress and autophagy in liver *** the bal-ance between damage and autophagy is broken,autophagy can no longer resist injury or main-tain *** recent years,FGF21(fibroblast growth factor 21)-induced autophagy has attracted much ***21 is regarded as a stress hormone and can be up-regulated by an abundance of signaling pathways in response to ***,increased FGF21 activates autophagy by a complicated signaling network in which mTOR plays a pivotal *** review summarizes the mechanism of FGF21-mediated autophagy and its derived application in the defense of stress in liver diseases and offers a glimpse into its promising prospect in future clinical practice.

关键词： Autophagy Fibroblast growth factor 21 Liver diseases mTOR Stress

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Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

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World Journal of Gastroenterology 2024年第7期30卷 759-769页

作者： Maja Cigrovski Berkovic Alessandro Coppola Vibor Sesa Anna Mrzljak Quirino Lai department for Sport and Exercise medicine Faculty of Kinesiology University of ZagrebZagreb 10000Croatia department of Surgery Sapienza University of RomeRome 00185Italy department of Gastroenterology and Hepatology Liver Transplant CenterUniversity Hospital Centre ZagrebZagreb 10000Croatia department of medicine School of MedicineZagreb 10000Croatia General Surgery and organ transplantation Unit Department of SurgerySapienza University of RomeRome 00018Italy

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor ***,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is *** this perspective,metformin is emerging as a molecule of *** studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR *** systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with *** To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of *** A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free *** A total of 13 studies(5674 patients)were included in this *** of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of *** T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS

关键词： Pancreatic neuroendocrine tumors Type 2 diabetes mellitus Prognosis Treatment Metformin

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Downstaging strategies for unresectable hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第20期30卷 2731-2733页

作者： Georgia Sofia Karachaliou Nikolaos Dimitrokallis Dimitrios P Moris Division of Gastroenterology Department of MedicineDuke University Medical CenterDurhamNC 27710United States First department of Surgery&organ transplant Unit Evangelismos General HospitalAthens 10676Greece department of Surgery Duke University Medical CenterDurhamNC 27710United States

A significant number of patients with hepatocellular carcinoma(HCC)are usually diagnosed in advanced stages,that leads to inability to achieve *** options are focusing on downstaging a locally advanced *** is wellsupported in the literature that patients with HCC who undergo successful conversion therapy followed by curative-intent surgery may achieve a significant survival benefit compared to those who receive chemotherapy alone or those who are successfully downstaged with conversion therapy but not treated with *** artery infusion chemotherapy can be a potential downstaging strategy,since recent studies have demonstrated excellent outcomes in patients with colorectal liver metastatic disease as well as primary liver malignancies.

关键词： Unresectable hepatocellular carcinoma Hepatic arterial infusion chemotherapy Downstaging Hepatocellular carcinoma

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Pleural empyema with endobronchial mass due to Rhodococcus equi infection after renal transplantation: A case report and review of literature

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World Journal of Clinical Cases 2024年第1期12卷 224-231页

作者： Guo-Fu Liang Sheng Chao Zhou Sun Ke-Jing Zhu Qian Chen Lei Jia Yu-Lin Niu department of organ transplantation School of Clinical MedicineGuizhou Medical UniversityGuiyang 550025Guizhou ProvinceChina department of organ transplantation The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550000Guizhou ProvinceChina

BACKGROUND Kidney transplantation is the best option for patients with end-stage renal ***,the need for lifelong immunosuppression results in renal transplant recipients being susceptible to various *** equi(***)is a rare opportunistic pathogen in humans,and there are limited reports of infection with *** in post-renal transplant recipients and no uniform standard of *** article reports on the diagnosis and treatment of a renal transplant recipient infected with *** 21 mo postoperatively and summarizes the charac-teristics of infection with *** after renal transplantation,along with a detailed review of the ***,we present the case of a 25-year-old man who was infected with *** 21 mo after renal *** the clinical features at the time of presentation were not specific,chest computed tomography(CT)showed a large volume of pus in the right thoracic cavity and right middle lung atelectasis,and fiberoptic bronchoscopy showed an endobronchial mass in the right middle and lower lobe *** culture and metagenomic next-generation sequen-cing sequencing of the pus were suggestive of *** *** immunosup-pressive drugs were immediately suspended and intravenous vancomycin and azithromycin were administered,along with adequate drainage of the *** endobronchial mass was then *** the patient’s clinical symptoms and chest CT presentation resolved,he was switched to intravenous ciprofloxacin and azithromycin,followed by oral ciprofloxacin and *** patient was re-hospitalized 2 wk after discharge for recurrence of *** *** recovered after another round of adequate abscess drainage and intravenous ciprofloxacin and *** Infection with *** in renal transplant recipients is rare and complex,and the clinical presentation lacks *** antibiotic therapy is required,and adequate abscess drainage and s

关键词： Kidney transplantation Rhodococcus equi Pleural empyema Pulmonary atelectasis Immunosuppression Case report

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Mitochondrial dysfunction affects hepatic immune and metabolic remodeling in patients with hepatitis B virus-related acute-onchronic liver failure

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World Journal of Gastroenterology 2024年第8期30卷 881-900页

作者： Yu Zhang Xiao-Ling Tian Jie-Qun Li Dong-Sheng Wu Qiang Li Bin Chen department of Hepatology Institute of HepatologyThe First Affiliated Hospital of Hunan University of Chinese MedicineChangsha 410021Hunan ProvinceChina department of Liver transplant Transplant Medical Research CenterThe Second Xiangya Hospital of Central South UniversityChangsha 410011Hunan ProvinceChina department of Surgery The First Affiliated Hospital of Hunan University of Chinese MedicineChangsha 410021Hunan ProvinceChina

BACKGROUND Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).However,the mechanisms underlying immune and metabolic derangement in patients with advanced HBV-ACLF are *** To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic *** Liver samples were collected from 16 healthy donors(HDs)and 17 advanced HBV-ACLF patients who were eligible for liver *** mitochondrial ultrastructure,metabolic characteristics,and immune microenvironment of the liver were *** focus was given to organic acid metabolism as well as the function and subpopulations of macrophages in patients with *** Compared with HDs,there was extensive hepatocyte necrosis,immune cell infiltration,and ductular reaction in patients with *** patients,the liver suffered severe hypoxia,as evidenced by increased expression of hypoxia-inducible factor-1α.Swollen mitochondria and cristae were observed in the liver of *** number,length,width,and area of mitochondria were adaptively increased in *** metabolomics analysis revealed that mitochondrial oxidative phosphorylation decreased,while anaerobic glycolysis was enhanced in patients with *** findings suggested that,to a greater extent,hepa-tocytes used the extra-mitochondrial glycolytic pathway as an energy *** with HBV-ACLF had elevated levels of chemokine C-C motif ligand 2 in the liver homogenate,which stimulates peripheral monocyte infiltration into the *** and functional analysis of macrophage subsets revealed that patients with ACLF had a high abundance of CD68^(+)HLA-DR^(+)macrophages and elevated levels of both interleukin-1βand transforming growth factor-β1 in their *** abundance of CD206^(+)CD163^(+)macrophag

关键词： Acute-on-chronic liver failure Hypoxia-inducible factor-1α Mitochondria Metabolic phenotype Immune cells

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An acoustofluidic device for the automated separation of platelet-reduced plasma from whole blood

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Microsystems & Nanoengineering 2024年第3期10卷 293-303页

作者： Zhehan Ma Jianping Xia Neil Upreti Emeraghi David Joseph Rufo Yuyang Gu Kaichun Yang Shujie Yang Xiangchen Xu Jean Kwun Eileen Chambers Tony Jun Huang Thomas Lord department of Mechanical Engineering and Materials Science Duke UniversityDurhamNCUSA department of Biomedical Engineering Duke UniversityDurhamNCUSA department of Pediatrics Duke UniversityDurhamNCUSA Duke transplant Center Department of SurgeryDuke University School of MedicineDurhamNCUSA

Separating plasma from whole blood is an important sample processing technique required for fundamental biomedical research,medical diagnostics,and therapeutic *** protocols for plasma isolation require multiple centrifugation steps or multiunit microfluidic processing to sequentially remove large red blood cells(RBCs)and white blood cells(WBCs),followed by the removal of small ***,we present an acoustofluidic platform capable of efficiently removing RBCs,WBCs,and platelets from whole blood in a single *** leveraging differences in the acoustic impedances of fluids,our device generates significantly greater forces on suspended particles than conventional microfluidic approaches,enabling the removal of both large blood cells and smaller platelets in a single *** a result,undiluted human whole blood can be processed by our device to remove both blood cells and platelets(>90%)at low voltages(25 Vpp).The ability to successfully remove blood cells and platelets from plasma without altering the properties of the proteins and antibodies present creates numerous potential applications for our platform in biomedical research,as well as plasma-based diagnostics and ***,the microfluidic nature of our device offers advantages such as portability,cost efficiency,and the ability to process small-volume samples.

关键词： remove separation removing

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Influence of sex on outcomes of liver transplantation for hepatocellular carcinoma:a multicenter cohort study in China

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Cancer Biology & medicine 2024年第4期21卷 347-362页

作者： Jian Chen Zhe Yang Fengqiang Gao Zhisheng Zhou Junli Chen Di Lu Kai Wang Meihua Sui Zhengxin Wang Wenzhi Guo Guoyue Lyu Haizhi Qi Jinzhen Cai Jiayin Yang Shusen Zheng Xiao Xu Zhejiang University School of medicine Hangzhou 310030China Institute of organ transplantation Zhejiang UniversityHangzhou 310030China department of Hepatobiliary and Pancreatic Surgery Shulan Hospital of HangzhouHangzhou 310006China National Center for Healthcare Quality Management in Liver transplant Hangzhou 310003China department of General Surgery Huashan HospitalFudan UniversityShanghai 200040China department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China department of Hepatobiliary and Pancreatic Surgery The First Hospital of Jilin UniversityChangchun 130021China department of Liver transplantation Second Xiangya HospitalCentral South UniversityChangsha 410008China department of organ transplantation Center The Affiliated Hospital of Qingdao UniversityQingdao 266003China department of Liver Surgery and Liver transplantation Center West China HospitalSichuan UniversityChengdu 610044China NHC Key Laboratory of Combined Multi-organ transplantation Hangzhou 310003China department of Hepatobiliary and Pancreatic Surgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Objective:Sex-specific differences are observed in various liver diseases,but the influence of sex on the outcomes of hepatocellular carcinoma(HCC)after liver transplantation(LT)remains to be *** study is the first Chinese nationwide investigation of the role of sex in post-LT outcomes in patients with ***:Data for recipients with HCC registered in the China Liver transplant Registry between January 2015 and December 2020 were *** associations between donor,recipient,or donor-recipient transplant patterns by sex and the post-LT outcomes were studied with propensity score matching(PSM).The survival associated with different sex-based donor-recipient transplant patterns was further ***:Among 3,769 patients enrolled in this study,the 1-,3-,and 5-year overall survival(OS)rates of patients with HCC after LT were 96.1%,86.4%,and 78.5%,respectively,in female recipients,and 95.8%,79.0%,and 70.7%,respectively,in male recipients after PSM(P=0.009).However,the OS was comparable between recipients with female donors and male *** analysis indicated that male recipient sex was a risk factor for post-LT survival(HR=1.381,P=0.046).Among the donor-recipient transplant patterns,the male-male donor-recipient transplant pattern was associated with the poorest post-LT survival(Ptransplant pattern was associated with the poorest post-LT *** from male donors may provide the most benefit to female *** results indicate that sex should be considered as a critical factor in organ allocation.

关键词： Sex liver transplantation hepatocellular carcinoma outcome recipient donor

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