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Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB

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Biomedical and Environmental Sciences 2024年第3期37卷 303-314页

作者： YANG Liu WANG Shi Yu JIANG Ting Ting DENG Wen CHANG Min WU Shu Ling CAO Wei Hua LU Yao SHEN Ge LIU Ru Yu GAO Yuan Jiao XU Meng Jiao HU Lei Ping ZHANG Lu XIE Yao LI Ming Hui Department of hepatology division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Center for Infectious diseases Second Affiliated Hospital of Air Force Medical UniversityXi'an 710038ShaanxiChina Department of hepatology division 2 Peking University Ditan Teaching HospitalBeijing 100015China

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and *** This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow *** In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<*** Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

关键词： CHB Dendritic Cells Intermittent Interferon Therapy Plateau Phase

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Pretreating and normalizing metabolomics data for statistical analysis

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Genes & diseases 2024年第3期11卷 188-205页

作者： Jun Sun Yinglin Xia division of Gastroenterology and hepatology Department of MedicineDepartment of Microbiology/ImmunologyUIC Cancer CenterUniversity of Illinois ChicagoJesse Brown VA Medical Center Chicago(537)ChicagoIL 60612USA division of Gastroenterology and hepatology Department of MedicineUniversity of Illinois ChicagoChicagoIL 60612USA

Metabolomics as a research field and a set of techniques is to study the entire small molecules in biological *** is emerging as a powerful tool generally for pre-cision ***,integration of microbiome and metabolome has revealed the mechanism and functionality of microbiome in human health and ***,metabo-lomics data are very ***/pretreating and normalizing procedures on metabolomics data are usually required before statistical *** this review article,we comprehensively review various methods that are used to preprocess and pretreat metabolo-mics data,including MS-based data and NMR-based data preprocessing,dealing with zero and/or missing values and detecting outliers,data normalization,data centering and scaling,data *** discuss the advantages and limitations of each *** choice for a suitable preprocessing method is determined by the biological hypothesis,the characteristics of the data set,and the selected statistical data analysis *** then provide the perspective of their applications in the microbiome and metabolome research.

关键词： Data centering and scaling Data normalization Data transformation Missing values MS-Baseddata preprocessing NMRData preprocessing Outliers Preprocessing/pretreatment

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The Wnt-dependent and Wnt-independent functions of BCL9 in development,tumorigenesis,and immunity:Implications in therapeutic opportunities

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Genes & diseases 2024年第2期11卷 701-710页

作者： Minjie Wu Heng Dong Chao Xu Mengqing Sun Haojin Gao Fangtian Bu Jianxiang Chen College of Pharmacy and Department of hepatology Institute of Hepatology and Metabolic DiseasesThe Affiliated Hospital of Hangzhou Normal UniversityHangzhou Normal UniversityHangzhouZhejiang 311121China Laboratory of Cancer Genomics Division of Cellular and Molecular ResearchNational Cancer CentreSingapore 169610Singapore Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhouZhejiang 311121China

B-cell CLL/lymphoma 9(BCL9)is considered a key developmental regulator and a well-established oncogenic driver in multiple cancer types,mainly through potentiating the Wnt/β-catenin ***,increasing evidences indicate that BCL9 also plays multiple Wnt-independent ***,we summarized the updates of the canonical and non-canonical functions of BCL9 in cellular,physiological,or pathological ***,we also concluded that the targeted inhibitors disrupt the interaction ofβ-catenin with BCL9 reported recently.

关键词： BCL9 Development Immunity Multifaceted functions Therapeutic target Tumorigenesis

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The gut microbiome modulate response to immunotherapy in cancer

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Science China Life Sciences 2024年

作者： Shan-Shan Jiang Zi-Ran Kang Ying-Xuan Chen Jing-Yuan Fang division of Gastroenterology and hepatology Shanghai Institute of Digestive Disease NHC Key Laboratory of Digestive Diseases State Key Laboratory for Oncogenes and Related Genes Renji Hospital School of Medicine Shanghai Jiao Tong University

Gut microbiota have been reported to play an important role in the occurrence and development of malignant tumors. Currently, clinical studies have identified specific gut microbiota and its metabolites associated with efficacy of immunotherapy in multiple types of *** investigations have elucidated that gut microbiota modulate the antitumor immunity and affect the efficacy of cancer immunotherapy. Certain microbiota and its metabolites may favorably remodel the tumor microenvironment by engaging innate and/or adaptive immune cells. Understanding how the gut microbiome interacts with cancer immunotherapy opens new avenues for improving treatment strategies. Fecal microbial transplants, probiotics, dietary interventions, and other strategies targeting the microbiota have shown promise in preclinical studies to enhance the immunotherapy. Ongoing clinical trials are evaluating these approaches. This review presents the recent advancements in understanding the dynamic interplay among the host immunity, the microbiome, and cancer immunotherapy, as well as strategies for modulating the microbiome, with a view to translating into clinical applications.

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Sarcopenia and metabolic dysfunction associated steatotic liver disease:Time to address both

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World Journal of hepatology 2024年第6期16卷 871-877页

作者： Rochelle Wong Li-Yun Yuan division of gastrointestinal and Liver diseases Keck School of Medicine of University of Southern CaliforniaLos AngelesCA 90033United States

Sarcopenia and metabolic dysfunction associated steatotic liver disease(MASLD)are closely ***,traditionally a disease of the older adult and chronic disease population,has been closely studied as one of the pathophysiologic conditions at play in the development of *** share similar risk factors of insulin resistance and physical *** similar pathophysiology along the liver-muscle axis,sarcopenia has been studied as a risk factor for MASLD,and vice *** research suggests a bidirectional *** the chronicity of MASLD as a chronic inflammatory liver disease,it can break down muscle mass and lead to sarcopenia,while sarcopenia promotes intramuscular lipid accumulation that releases cytokines that can aggravate inflammation in the ***,for the longest time,a lack of consensus definition for MASLD and sarcopenia made it difficult to study their relationship and outcomes.A recent nomenclature update to diagnosing MASLD has made it easier for researchers to identify cohorts for ***,no gold standard technique to measure muscle mass or consensus sarcopenia definition has been identified *** studies are needed to reach a consensus and reduce diagnostic *** similar pathophysiology and shared risk factors between the two diseases,future research may also identify potential therapeutic targets along the liver-muscle axis that would benefit both sarcopenia and MASLD in order to maximize their outcomes.

关键词： Sarcopenia Steatotic liver disease Metabolic dysfunction Insulin resistance Liver-muscle axis

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STAT3-Dependent Effects of Polymeric Immunoglobulin Receptor in Regulating Interleukin-17 Signaling and Preventing Autoimmune Hepatitis

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Engineering 2024年第5期36卷 209-222页

作者： Ting Li Tongtong Pan Nannan Zheng Xiong Ma Xiaodong Wang Fang Yan Huimian Jiang Yuxin Wang Hongwei Lin Jing Lin Huadong Zhang Jia Huang Lingming Kong Anmin Huang Qingxiu Liu Yongping Chen Dazhi Chen hepatology Diagnosis and Treatment Center The First Affiliated Hospital of Wenzhou Medical University&Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver DiseasesWenzhou 325035China Department of Clinical Medicine Hangzhou Medical CollegeHangzhou 310053China State Key Laboratory for Oncogenes and Related Genes Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200001China Wenzhou Medical University Wenzhou 325035China division of Infectious diseases Lishui People’s HospitalLishui 323000China

One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of *** relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic *** of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse ***,there is a direct relationship between pIgR expression and transaminase levels in patients with *** this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of ***3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota ***,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota *** sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through ***,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in *** this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.

关键词： Autoimmune hepatitis Polymeric immunoglobulin receptor Regenerating islet-derived 3 beta Intestinal microbiota Signal transducer and activator of transcription 3

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Innovative pathways allow safe discharge of mild acute pancreatitis from the emergency room

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World Journal of Gastroenterology 2024年第11期30卷 1475-1479页

作者： Darshan J Kothari Sunil G Sheth division of Gastroenterology Duke University Medical CenterDurhamNC 27710United States division of Gastroenterology&hepatology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02215United States

Acute pancreatitis(AP)is a leading cause of gastrointestinal-related hospitalizations in the United States,resulting in 300000 admissions per year with an estimated cost of over$2.6 billion *** severity of AP is determined by the presence of pancreatic complications and end-organ *** moderate/severe pancreatitis can be associated with significant morbidity and mortality,the majority of patients have a mild presentation with an uncomplicated course and mortality rate of less than 2%.Despite favorable outcomes,the majority of mild AP patients are admitted,contributing to healthcare cost and *** this Editorial we review the performance of an emergency department(ED)pathway for patients with mild AP at a tertiary care center with the goal of reducing hospitalizations,resource utilization,and costs after several years of implementation of the *** discuss the clinical course and outcomes of mild AP patients enrolled in the pathway who were successfully discharged from the ED compared to those who were admitted to the hospital,and identify predictors of successful ED discharge to select patients who can potentially be triaged to the *** conclude that by implementing innovative clinical pathways which are established and reproducible,selected AP patients can be safely discharged from the ED,reducing hospitalizations and healthcare costs,without compromising clinical *** also identify a subset of patients most likely to succeed in this pathway.

关键词： Emergency department Mild pancreatitis Pathways Hospitalization Predictors

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FGF4 protects the liver from immune-mediated injury by activating CaMKKβ-PINK1 signal pathway to inhibit hepatocellular apoptosis

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Acta Pharmaceutica Sinica B 2024年第6期14卷 1605-1623页

作者： Zhifeng Huang Tongtong Pan Liang Xu Lu Shi Xiong Ma Liya Zhou Luyao Wang Jiaojiao Wang Guoqing Zhu Dazhi Chen Lingtao Song Xiaomin Pan Xiaodong Wang Xiaokun Li Yongde Luo Yongping Chen hepatology Diagnosis and Treatment Center Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseasesthe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325035China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)&School of Pharmaceutical SciencesWenzhou Medical UniversityWenzhou 325035China School of Laboratory Medicine and Life Sciences Wenzhou Medical University&Key Laboratory of Laboratory MedicineMinistry of EducationWenzhou Medical UniversityWenzhou 325035China division of Gastroenterology and hepatology Key Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200001China Hangzhou Medical College Hangzhou 311300China

Immune-mediated liver injury (ILI) is a condition where an aberrant immune response due to various triggers causes the destruction of hepatocytes. Fibroblast growth factor 4 (FGF4) was recently identified as a hepatoprotective cytokine;however, its role in ILI remains unclear. In patients with autoimmune hepatitis (type of ILI) and mouse models of concanavalin A (ConA)- or S-100-induced ILI, we observed a biphasic pattern in hepatic FGF4 expression, characterized by an initial increase followed by a return to basal levels. Hepatic FGF4 deficiency activated the mitochondria-associated intrinsic apoptotic pathway, aggravating hepatocellular apoptosis. This led to intrahepatic immune hyper-reactivity, inflammation accentuation, and subsequent liver injury in both ILI models. Conversely, administration of recombinant FGF4 reduced hepatocellular apoptosis and rectified immune imbalance, thereby mitigating liver damage. The beneficial effects of FGF4 were mediated by hepatocellular FGF receptor 4, which activated the Ca^(2+)/calmodulin-dependent protein kinasekinase 2 (CaMKKβ) and its downstream phosphatase and tensin homologue-induced putative kinase 1 (PINK1)-dependent B-cell lymphoma 2-like protein 1-isoform L (Bcl-XL) signalling axis in the mitochondria. Hence, FGF4 serves as an early response factor and plays a protective role against ILI, suggesting a therapeutic potential of FGF4 and its analogue for treating clinical immune disorder-related liver injuries.

关键词： Fibroblast growthfactor 4 Fibroblast growth factor receptor 4 Immune liver injury Ca^(2+)/Calmodulin dependent protein

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Nano-revolution in hepatocellular carcinoma:A multidisciplinary odyssey-Are we there yet?

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World Journal of hepatology 2024年第5期16卷 684-687页

作者： Howard D Lee Li-Yun Yuan Department of Medicine Division of Gastrointestinal and Liver DiseasesKeck School of Medicine of University of Southern CaliforniaLos AngelesCA 90033United States

In this editorial we comment on the review by Zhou et al reviewing the landscape of nanomedicine in the treatment of hepatocellular carcinoma(HCC).We focus on the immense potential of nanotechnology,particularly ligand-receptor mediated nanotherapy,in revolutionizing the treatment landscape of *** advan-cements in multidisciplinary treatment,HCC remains a significant global health ***-mediated nanotherapy offers the opportunity for precise drug delivery to tumor sites,targeting specific receptors overexpressed in HCC cells,thereby enhancing efficacy and minimizing side *** drug resistance and aggressive tumor biology is facilitated by nanomedicine,bypassing traditional hurdles encountered in *** include targeting glypican-3,asialoglycoprotein,transferrin receptor or folic acid receptors,capitalizing on their over-expression in tumor *** ability for multi-receptor targeting through dual-ligand nanoparticle modification holds the prospect of further enhancement in specificity and efficacy of directed ***,challenges including immune responses,reproducibility in nanoparticle synthesis,and production scalability *** directions involve refining targeting strategies,improving drug release mechanisms,and streamlining production processes to enable personalized and multifunctional ***,the integration of nanotherapy in HCC treatment holds immense promise,but continued partnership and effort are needed in offering hope for more effective,precise,and accessible clinical care in the management of HCC.

关键词： Hepatocellular carcinoma Nanomedicine Ligand-receptor mediated nanotherapy Precision medicine Personalized medicine Targeting

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Role of endoscopic-ultrasound-guided biliary drainage with electrocautery-enhanced lumen-apposing metal stent for palliation of malignant biliary obstruction

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World Journal of gastrointestinal Surgery 2024年第7期16卷 1981-1985页

作者： Smit S Deliwala Emad Qayed Department of Medicine Division of Digestive DiseasesEmory University School of MedicineAtlantaGA 30303United States

In this editorial,we discuss the article by Peng et al in the recent issue of the World Journal of gastrointestinal Surgery,focusing on the evolving role of endoscopicultrasound-guided biliary drainage(EUS-BD)with electrocautery lumen apposing metal stent(LAMS)for distal malignant biliary *** endoscopy has rapidly advanced in decompression techniques,with growing evidence of its safety and efficacy surpassing percutaneous and surgical *** endoscopic retrograde cholangiopancreatography(ERCP)has been the gold standard for biliary decompression,its failure rate approaches 10.0%,prompting the exploration of alternatives like *** random-effects meta-analysis demonstrated high technical and clinical success of over 90.0% and an adverse event rate of 17.5%,mainly in the form of stent *** based on stent size were not reported but the majority used 6 mm and 8 mm *** the body of literature continues to demonstrate the effectiveness of this technique,the challenges of stent dysfunction need to be addressed in future *** strategy that has shown promise is placement of double-pigtail stents,only 18% received the prophylactic intervention in this *** expect this to improve with time as the technique continues to be refined and *** results above establish EUS-BD with LAMS as a reliable alternative after failed ERCP and considering EUS to ERCP upfront in the same session is an effective *** the promising results,studies must explore the role of EUS-BD as first-line therapy for biliary decompression.

关键词： Endoscopic-ultrasound Malignant biliary obstruction Lumen apposing metal stent Choledochoduodenostomy Hepaticogastrostomy

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