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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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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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Advocating for the implementation of SonoVue microbubbles as pressure sensors: a call to action for clinical noninvasive pressure estimation

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Hepatobiliary Surgery and Nutrition 2024年第4期13卷 690-695页

作者： Ao Wen Lingxiao Yang Tao Lv Huayu Yang Fei Li Yilei Mao Gang Xu Jia-Yin Yang Liver transplant Center Organ Transplant CenterWest China Hospital of Sichuan UniversityChengduChina Laboratory of Liver transplantation Key Laboratory of Transplant Engineering and ImmunologyNational Health Commission(NHC)West China Hospital of Sichuan UniversityChengduChina West China Hospital West China School of MedicineSichuan UniversityChengduChina Department of Liver Surgery Peking Union Medical College(PUMC)HospitalPUMC and Chinese Academy of Medical SciencesBeijingChina Paul C.Lauterbur Research Center for Biomedical Imaging Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina

Pressure measurement within the body is of pivotal significance in the diagnosis of vascular and organ-related diseases associated with hydrostatic *** present,the most commonly used clinical method is to insert a catheter along with a pressure sensor and then guide it to the area of interest through vessels such as central venous pressure(CVP).However,the presence of sensors within the vessel of interest will inevitably cause alterations to the circulation and thus affect blood ***,the use of invasive methods does not allow monitoring of every area inside the body.

关键词： SonoVue microbubbles pressure estimation noninvasive

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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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Current status of liver transplantation for human immunodeficiency virus-infected patients in China's Mainland

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World Journal of Gastroenterology 2024年第14期30卷 1958-1962页

作者： Jian-Xin Tang Dong Zhao Department of Liver Surgery and organ transplantation Center Shenzhen Third People’s HospitalThe Second Affiliated Hospital of Southern University of Science and TechnologyNational Clinical Research Center for Infectious DiseaseShenzhen 518000Guangdong ProvinceChina

According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 *** overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in *** addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly *** often leads to the development of end-stage liver and kidney ***,organ transplantation has emerged as an important part of active treatment for HIV infected ***,the curative effect is not *** infection has been considered a contraindication for organ *** the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively *** prolonged survival,the failure of important organs has become the main cause of death among HIV ***,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive *** study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land *** date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have *** analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary co

关键词： Liver transplantation Human immunodeficiency virus Infection Hepatitis B virus End-stage liver disease China'Mainland

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Outcomes in pediatric recipients of single kidney transplantation from pediatric donors with acute kidney injury:A single-center pilot study

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Chinese Medical Journal 2024年第12期137卷 1489-1491页

作者： Qiang Zhang Yanxu Chen Haiyue Yu Jun Li Chenglin Wu Sizhe Long Pengan Li Qian Fu Huanxi Zhang Xiaojun Su Bowen Xu Longshan Liu Changxi Wang organ transplant Center The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080China Stomatological Hospital Southern Medical UniversityGuangzhouGuangdong 510280China Center for Information Technology and Statistics The First Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510080China Guangdong Provincial Key Laboratory of organ Donation and transplant Immunology GuangzhouGuangdong 510080China Guangdong Provincial Key Laboratory Guangdong Provincial International Cooperation Base of Science and Technology(organ transplantation) GuangzhouGuangdong 510080China

To the Editor:The shortage of deceased donor(DD)kidneys for transplantation remains a persistent *** the potential reversibility of acute kidney injury(AKI)lesions,kidneys from pediatric donors with AKI are often underutilized,especially in the context of pediatric *** implementing single kidney transplantation(SKT)from pediatric donors to pediatric recipients(PTP),we can optimize the utilization of available kidneys and increase the number of pediatric recipients.

关键词： pediatric kidney acute

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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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Clinical application of COVID-19 vaccine in liver transplant recipients

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 339-343页

作者： Feng-Chao Liu Man Xie Wei Rao Division of Hepatology Liver Disease CenterThe Affiliated Hospital of Qingdao UniversityQingdao 266000China organ transplantation Center The Affiliated Hospital of Qingdao UniversityQingdao 266000China Institute of organ Donation and transplantation of Qingdao University Qingdao 266000China Department of Gastroenterology The Affiliated Hospital of Qingdao UniversityQingdao 266000China

Background:Solid organ transplant(SOT)activities,such as liver transplant,have been greatly influenced by the pandemic of coronavirus disease 2019(COVID-19),a disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Immunosuppressed individuals of liver transplant recipients(LTRs)tend to have a high risk of COVID-19 infection and related ***,COVID-19 vaccination has been recommended to be administered as early as possible in *** sources:The keywords“liver transplant”,“SARS-CoV-2”,and“vaccine”were used to retrieve articles published in ***:The antibody response following the 1st and 2nd doses of vaccination was disappointingly low,and the immune responses among LTRs remarkably improved after the 3rd or 4th dose of *** the 3rd or 4th dose of COVID-19 vaccine increased the antibody titer,a proportion of patients remained ***,recent studies showed that SARS-CoV-2 vaccine could trigger adverse events in LTRs,including allograft rejection and liver ***:This review provides the recently reported data on the antibody response of LTRs following various doses of vaccine,risk factors for poor serological response and adverse events after vaccination.

关键词： Liver transplant COVID-19 SARS-CoV-2 Vaccine Antibody response

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Design and discovery of a highly potent ultralong-acting GLP-1 and glucagon co-agonist for attenuating renal fibrosis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1283-1301页

作者： Qian Zhao Jiale Dong Han Liu Hui Chen Huan Yu Shuyin Ye Shuangjin Yu Yu Li Longhui Qiu Nazi Song Hongjiao Xu Qi Liu Zhiteng Luo Yuyi Li Rui Wang Guodong Chen Xianxing Jiang School of Pharmaceutical Sciences Guangdong Provincial Key Laboratory of Chiral Molecule and Drug DiscoverySun Yat-sen UniversityGuangzhou 510006China organ transplant Center the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510006China Zhongshan School of Medicine Sun Yat-sen UniversityGuangzhou 510006China Shenzhen Turier Biotech.Co. Ltd.Shenzhen 518118China School of Life Sciences Key Laboratory of Preclinical Study for New Drugs of Gansu ProvinceSchool of Basic Medical Sciences&Research Unit of Peptide ScienceChinese Academy of Medical SciencesLanzhou UniversityLanzhou 730000China

The role of co-agonists of glucagon-like peptide-1 receptor(GLP-1R)and glucagon receptor(GCGR)in chronic kidney disease(CKD)remains *** we found that GLP-1R and GCGR expression levels were lower in the kidneys of mice with CKD compared to healthy mice and were correlated with disease ***,GLP-1R or GCGR knockdown aggravated the progression of kidney injury in both diabetic db/db mice and non-diabetic mice undergoing unilateral ureteral obstruction(UUO).Based on the importance of GLP-1R and GCGR in CKD,we reported a novel monomeric peptide,1907-B,with dual-agonism on both GLP-1R and *** data confirmed that 1907-B had a longer half-life than long-acting semaglutide in rats or cynomolgus monkeys(~2-3 fold)and exhibited better therapeutic contribution to CKD than best-in-class monoagonists,semaglutide,or glucagon,in db/db mice and UUO *** lock-of-function models,including selective pharmacological activation and genetic knockdown,confirmed that 1907-B’s effects on ameliorating diabetic nephropathy in db/db mice,as well as inhibiting kidney fibrosis in UUO mice,were mediated through GLP-1 and glucagon *** findings highlight that 1907-B,a novel GLP-1R and GCGR co-agonist,exerts multifactorial improvement in kidney injuries and is an effective and promising therapeutic option for CKD treatment.

关键词： GLP-1 receptor Glucagon receptor Chronic kidney disease Diabetic nephropathy Kidney fibrosis Dual-agonism

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