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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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clinical management of acute liver failure: Results of an international multi-center survey

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World Journal of Gastroenterology 2016年第33期22卷 7595-7603页

作者： Liane Rabinowich Julia Wendon William Bernal Oren Shibolet liver Unit Department of GastroenterologyTel-Aviv Medical Center and Tel-Aviv University liver Intensive Therapy Unit Institute of Liver StudiesKing’s College Hospital

AIM To assess the practice of caring for acute liver failure(ALF) patients in varying geographic locations and medical *** Members of the European Acute liver Failure Consortium completed an 88-item questionnaire detailing management of ALF. Responses from 22 transplantation centers in 11 countries were analyzed,treating between 300 and 500 ALF cases and performing over 100 liver transplants(LT) for ALF annually. The questions pertained to details of the institution and their clinical activity,standards of care,referral and admission,wardbased care versus intensive care unit(ICU) as well as questions regarding liver transplantation- including criteria,limitations,and perceived performance. clinical data was also collected from 13 centres over a 3 mo period. RESULTS The interval between referral and admission of ALF patients to specialized units was usually less than 24 h and once admitted,treatment was provided by a multidisciplinary team. Principles of care of patients with ALF were similar among centers,particularly in relation to recognition of severity and care of the more critically ill. centers exhibited similarities in thresholds for ICU admission and management of severe hepatic encephalopathy. Over 80% of centers administered n-acetyl-cysteine to ICU patients for non-paracetamolrelated ALF. There was significant divergence in the use of prophylactic antibiotics and anti-fungals,lactulose,nutritional support and imaging investigations in admitted patients and in the monitoring and treatment of intra-cranial pressure(ICP). ICP monitoring was employed in 12 centers,with the most common indications being papilledema and renal failure. Most patients listed for transplantation underwent surgery within an average waiting time of 1-2 d. Over a period of 3 mo clinical data from 85 ALF patients was collected. Overall patient survival at 90-d was 76%. Thirty six percent of patients underwent emergency LT,with a 90% post transplant survival to hospital disc

关键词： Acute liver failure liver transplantation Intra-cranial pressure Hepatic encephalopathy

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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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Three-dimensional cell-based strategies for liver regeneration

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BIOCELL 2024年第7期48卷 1023-1036页

作者： DAN GUO XI XIA JIAN YANG liver Transplant center Transplant CenterWest China HospitalSichuan UniversityChengdu610041China Frontiers Medical center Tianfu Jincheng LaboratoryChengdu610212China

liver regeneration and the development of effective therapies for liver failure remain formidable challenges in modern *** recent years,the utilization of 3D cell-based strategies has emerged as a promising approach for addressing these urgent clinical *** review provides a thorough analysis of the application of 3D cell-based approaches to liver regeneration and their potential impact on patients with end-stage liver ***,we discuss various 3D culture models that incorporate hepatocytes and stem cells to restore liver function and ameliorate the consequences of liver ***,we explored the challenges in transitioning these innovative strategies from preclinical studies to clinical *** collective insights presented herein highlight the signiﬁcance of 3D cell-based strategies as a transformative paradigm for liver regeneration and improved patient care.

关键词： Three-Dimensional liver regeneration Organoids Stem cells Cell therapy

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Development of a new Cox model for predicting long-term survival in hepatitis cirrhosis patients underwent transjugular intrahepatic portosystemic shunts

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World Journal of Gastrointestinal Surgery 2024年第2期16卷 491-502页

作者： Yi-Fan Lv Bing Zhu Ming-Ming Meng Yi-Fan Wu Cheng-Bin Dong Yu Zhang Bo-Wen Liu Shao-Li You Sa Lv Yong-Ping Yang Fu-Quan Liu liver Disease Minimally Invasive Diagnosis and Treatment center Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China liver Vascular Disease Diagnosis and Treatment center The Fifth Medical Center of Chinese People's Liberation Army General HospitalBeijing 100039China

BACKGROUND Transjugular intrahepatic portosystemic shunt(TIPS)placement is a procedure that can effectively treat complications of portal hypertension,such as variceal bleeding and refractory ***,there have been no specific studies on predicting long-term survival after TIPS *** To establish a model to predict long-term survival in patients with hepatitis cirrhosis after *** A retrospective analysis was conducted on a cohort of 224 patients who un-derwent TIPS *** univariate and multivariate Cox regression analyses,various factors were examined for their ability to predict survival at 6 years after ***,a composite score was formulated,encompassing the indication,shunt reasonability,portal venous pressure gradient(PPG)after TIPS,percentage decrease in portal venous pressure(PVP),indocyanine green retention rate at 15 min(ICGR15)and total bilirubin(Tbil)***,the performance of the newly developed Cox(NDC)model was evaluated in an in-ternal validation cohort and compared with that of a series of existing *** The indication(variceal bleeding or ascites),shunt reasonability(reasonable or unreasonable),ICGR15,post-operative PPG,percentage of PVP decrease and Tbil were found to be independent factors affecting long-term survival after TIPS *** NDC model incorporated these parameters and successfully identified patients at high risk,exhibiting a notably elevated mortality rate following the TIPS procedure,as observed in both the training and validation ***,in terms of predicting the long-term survival rate,the performance of the NDC model was significantly better than that of the other four models[Child-Pugh,model for end-stage liver disease(MELD),MELD-sodium and the Freiburg index of post-TIPS survival].CONCLUSION The NDC model can accurately predict long-term survival after the TIPS procedure in patients with hepatitis cirrhosis,help identify high-risk patients

关键词： Transjugular intrahepatic portosystemic shunt Long-term survival Predictive model

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Comprehensive characterization of cell disulfidptosis in human cancers:An integrated pan-cancer analysis

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Genes & Diseases 2024年第4期11卷 5-8页

作者： Guo Zhao Yale Jiang Yuning Wang Shuhang Wang Ning Li clinical Trial center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Excessive accumulation of disulfide molecules,like cystine,can induce disulfide stress and high toxicity in cells,but the reduced form of nicotinamide adenine dinucleotide phosphate can reverse this process and mitiga... 详细信息

关键词： disulfide cancer characterization

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Pulmonary Bacterial Infection and liver Cirrhosis: Current Status and Treatment

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Infectious Microbes & Diseases 2024年第1期6卷 5-10页

作者： Yingying Zhao Song Yang Huichun Xing center of liver Diseases Division 3 Beijing Ditan HospitalCapital Medical UniversityBeijingChina

liver cirrhosis has a higher incidence rate and mortality when complicated with bacterial *** bacterial infections,especially bacterial pneumonia,increase the susceptibility of cirrhotic patients to decompensation,with a higher likelihood of *** pneu-monia is often overlooked in patients with liver cirrhosis,although it can impact the clinical progress and *** diagnosis and inappropriate antibiotic treatments are associated with poor prognosis and increased *** understanding of mechanisms and appropriate antibiotic treatments for cirrhosis-related bacterial pneumonia remain ***,we reviewed the epidemiology,clinical characteristics and treatment of pulmonary bacterial infections in cirrhotic patients to provide suggestions for clinical practice.

关键词： bacterial pneumonia liver cirrhosis epidemiology characteristics treatment

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Development and validation of a novel non-invasive test for diagnosing nonalcoholic fatty liver disease in Chinese children

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World Journal of Pediatrics 2024年第4期20卷 413-421页

作者： Zhe-Wen Qin Qian-Nan Ren Hong-Xi Zhang Ya-Ru Liu Ke Huang Wei Wu Guan-Ping Dong Yan Ni Jun-Fen Fu Division of Endocrinology National Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalDepartment of EndocrinologyNational Clinical Research Center for Child HealthNational Children’s Regional Medical CenterThe Children’s HospitalZhejiang University School of MedicineHangzhou310052China

With the exploding prevalence of obesity,many children are at risk of developing nonalcoholic fatty liver *** anthropometric and laboratory parameters,our study aimed to develop a model to quantitatively evaluate liver fat content(LFC)in children with *** A well-characterized cohort of 181 children between 5 and 16 years of age were recruited to the study in the Endocrinology Department as the derivation *** external validation cohort comprised 77 *** assessment of liver fat content was performed using proton magnetic resonance *** and laboratory metrics were measured in all subjects.B-ultrasound examination was carried out in the external validation *** Kruskal-Wallis test,Spearman bivariate correlation analyses,univariable linear regressions and multivariable linear regression were used to build the optimal predictive *** The model was based on indicators including alanine aminotransferase,homeostasis model assessment of insulin resistance,triglycerides,waist circumference and Tanner *** adjusted R^(2)of the model was 0.589,which presented high sensitivity and specificity both in internal[sensitivity of 0.824,specificity of 0.900,area under curve(AUC)of 0.900 with a 95%confidence interval:0.783–1.000]and external validation(sensitivity of 0.918 and specificity of 0.821,AUC of 0.901 with a 95%confidence interval:0.818–0.984).Conclusions Our model based on five clinical indicators was simple,non-invasive,and inexpensive;it had high sensitivity and specificity in predicting LFC in ***,it may be useful for identifying children with obesity who are at risk for developing nonalcoholic fatty liver disease.

关键词： Biochemical markers Children Magnetic resonance spectroscopy Nonalcoholic fatty liver disease Pediatric obesity

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Differentiation and immunosuppressive function of CD19^(+)CD24^(hi)CD27^(+) regulatory B cells are regulated through the miR-29a-3p/NFAT5 pathway

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 472-480页

作者： Jin-Yang Li Tian-Shuo Feng Ji Gao Xin-Xiang Yang Xiang-Cheng Li Zhen-Hua Deng Yong-Xiang Xia Zheng-Shan Wu Hepatobiliary center the First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Key Laboratory of liver Transplantation Chinese Academy of Medical SciencesNanjing 210029China NHC Key Laboratory of Living Donor liver Transplantation Nanjing Medical UniversityNanjing 210029China

Background: Regulatory B cells(Bregs) is an indispensable element in inducing immune tolerance after liver transplantation. As one of the microRNAs(miRNAs), mi R-29a-3p also inhibits translation by degrading the target mRNA, and yet the relationship between Bregs and mi R-29a-3p has not yet been fully explored. This study aimed to investigate the impact of miR-29a-3p on the regulation of differentiation and immunosuppressive functions of memory Bregs(m Bregs) and ultimately provide potentially effective therapies in inducing immune tolerance after liver transplantation. Methods: Flow cytometry was employed to determine the levels of Bregs in peripheral blood mononuclear cells. TaqMan low-density array miRNA assays were used to identify the expression of different miRNAs, electroporation transfection was used to induce mi R-29a-3p overexpression and knockdown, and dual luciferase reporter assay was used to verify the target gene of miR-29a-3p. Results: In patients experiencing acute rejection after liver transplantation, the proportions and immunosuppressive function of m Bregs in the circulating blood were significantly impaired. mi R-29a-3p was found to be a regulator of m Bregs differentiation. Inhibition of miR-29a-3p, which targeted nuclear factor of activated T cells 5(NFAT5), resulted in a conspicuous boost in the differentiation and immunosuppressive function of m Bregs. The inhibition of mi R-29a-3p in CD19~+ B cells was capable of raising the expression levels of NFAT5, thereby promoting B cells to differentiate into m Bregs. In addition, the observed enhancement of differentiation and immunosuppressive function of m Bregs upon mi R-29a-3p inhibition was abolished by the knockdown of NFAT5 in B cells. Conclusions: mi R-29a-3p was found to be a crucial regulator for m Bregs differentiation and immunosuppressive function. Silencing mi R-29a-3p could be a potentially effective therapeutic strategy for inducing immune tolerance after liver transplantation.

关键词： Regulatory B cells miR-29a-3p NFAT5 liver transplantation

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Molecular mechanisms underlying microglial sensing and phagocytosis in synaptic pruning

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Neural Regeneration Research 2024年第6期19卷 1284-1290页

作者： Anran Huo Jiali Wang Qi Li Mengqi Li Yuwan Qi Qiao Yin Weifeng Luo Jijun Shi Qifei Cong clinical Research center of Neurological Disease The Second Affiliated Hospital of Soochow UniversityInstitute of Neuroscience and Jiangsu Key Laboratory of Neuropsychiatric Diseases Soochow University Department of Neurology and clinical Research center of Neurological Disease The Second Affiliated Hospital of Soochow University

Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits. In brain physiology, highly dynamic microglial processes are facilitated to sense the surrounding environment and stimuli. Once the brain switches its functional states, microglia are recruited to specific sites to exert their immune functions, including the release of cytokines and phagocytosis of cellular debris. The crosstalk of microglia between neurons, neural stem cells, endothelial cells, oligodendrocytes, and astrocytes contributes to their functions in synapse pruning, neurogenesis, vascularization, myelination, and blood-brain barrier permeability. In this review, we highlight the neuron-derived “find-me,” “eat-me,” and “don’t eat-me” molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain development. This review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease, thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.

关键词： complement immune signals microglia molecular signal synapse elimination synapse formation synapse refinement synaptic pruning

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