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A prognostic four-gene signature and a therapeutic strategy for hepatocellular carcinoma:Construction and analysis of a circRNA-mediated competing endogenous RNA network

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 272-287页

作者： Hai-Yan Zhang Jia-Jie Zhu Zong-Ming Liu Yu-Xuan Zhang Jia-Jia Chen Ke-Da Chen zhejiang Chinese Medical University Hangzhou 310053China Shulan International Medical College Zhejiang Shuren UniversityHangzhou 310015China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

Background:Hepatocellular carcinoma(HCC)has a poor long-term prognosis.The competition of circular RNAs(circRNAs)with endogenous RNA is a novel tool for predicting HCC prognosis.Based on the alterations of circRNA regulatory networks,the analysis of gene modules related to HCC is feasible.Methods:Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC.Gene function,pathway,and protein interaction analyses were performed for the differentially expressed genes(DEGs)in this regulatory network.In the proteinprotein interaction network,hub genes were identified and subjected to regression analysis,producing an optimized four-gene signature for prognostic risk stratification in HCC patients.Anti-HCC drugs were excavated by assessing the DEGs between the low-and high-risk groups.A circRNA-microRNA-hub gene subnetwork was constructed,in which three hallmark genes,KIF4A,CCNA2,and PBK,were subjected to functional enrichment analysis.Results:A four-gene signature(KIF4A,CCNA2,PBK,and ZWINT)that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas(TCGA)cohort and International Cancer Genome Consortium(ICGC)cohort was developed.CDK inhibitors,PI3K inhibitors,HDAC inhibitors,and EGFR inhibitors were predicted as four potential mechanisms of drug action(MOA)in high-risk HCC patients.Subsequent analysis has revealed that PBK,CCNA2,and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion,regulating microsatellite instability(MSI),and exerting an impact on HCC progression.Conclusions:The present study highlights the role of the circRNA-related regulatory network,identifies a four-gene prognostic signature and biomarkers,and further identifies novel therapy for HCC.

关键词： Hepatocellular carcinoma circRNA-related ceRNA network Biomarker Least absolute shrinkage and selection operator Bioinformatics

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Possible Role of Cellular Polyamine Metabolism in Neuronal Apoptosis

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Current Medical science 2024年第2期44卷 281-290页

作者： Xin-tong JI Wen-lei YU Meng-jia JINI Lin-jie LU Hong-ping YIN Huan-huan WANG School of Basic Medical sciences Affiliated Hospital of Hangzhou Normal UniversityHangzhou Normal UniversityHangzhou 311121China School of Medicine Chongqing UniversityChongqing 400030China Department of Stomatology Huzhou Wuxing District People's HospitalHuzhou Wuxing District Maternal and Child Health HospitalHuzhou 313008China School of Pharmacy Zhejiang UniversityHangzhou 310030 China'Department of Stomatology Haining Hospital of Traditional Chinese MedicineJiaxing 314400China

Recent studies have shown that cellular levels of polyamines(PAs)are significantly altered in neurodegenerative diseases.Evidence from in vivo animal and in vitro cell experiments suggests that the cellular levels of various PAs may play important roles in the central nervous system through the regulation of oxidative stress,mitochondrial metabolism,cellular immunity,and ion channel functions.Dysfunction of PA metabolism related enzymes also contributes to neuronal injury and cognitive impairment in many neurodegenerative diseases.Therefore,in the current work,evidence was collected to determine the possible associations between cellular levels of PAs,and related enzymes and the development of several neurodegenerative diseases,which could provide a new idea for the treatment of neurodegenerative diseases in the future.

关键词： polyamine apoptosis mitochondria neurodegenerative disease

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Mechanisms of liver injuries caused by traditional Chinese medicines

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 310-312页

作者： Shui-Fang Jin Qi Pan Jin-Peng Zhou Xiao-Ping Pan Intensive Care Unit The First Affiliated Hospital of Zhejiang Chinese Medical University(Zhejiang Provincial Hospital of Chinese Medicine)Hangzhou 310006China Institute of Liver Diseases College of Basic Medical SciencesZhejiang Chinese Medical UniversityHangzhou 310053China The Second Clinical Medical College of zhejiang Chinese Medical University Hangzhou 310056China

Drug-induced liver injury(DILI)is a common adverse drug reaction,which can even result in liver failure[1,2].The Chinese Medical Association issued the Guidelines for the Diagnosis and Treatment of DILI based on the Roussel Uclaf Causality Assessment Method(RUCAM)in 2015[3].A previous study reported that traditional Chinese medicines(TCMs),herbal and dietary supplements,and antituberculosis drugs were the main causes of DILI in China[4].Herb-induced liver injury(HILI)refers to liver injury caused by TCMs,natural drugs,and their related preparations[5].

关键词： drugs tuberculosis TCM

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Genome sequencing provides insights into Caprifoliaceae genome evolution and the mechanism underlying second blooming phenomenon in Heptacodium miconioides

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Horticultural Plant Journal 2024年第3期10卷 897-910页

作者： Yueling Li Zhongshuai Sun Zexin Jin Junmin Li zhejiang provincial Key Laboratory of Plant Evolutionary Ecology and Conservation Taizhou UniversityTaizhouZhejiang 318000China Institute of Ecology Taizhou UniversityTaizhouZhejiang 318000China School of Life sciences Taizhou UniversityTaizhouZhejiang 318000China

Plants of the Caprifoliaceae family are widely cultivated worldwide as ornamental plants owing to their numerous,sweet-smelling,beautiful flowers and fruits.Heptacodium miconioides Rehd.,a member of the family,is endemic to eastern China and is cultivated as a popular ornamental plant in North America and European countries.It has a rather novel and beautiful trait of high horticultural value,that is,its sepals persist and enlarge,turning purplish red.Here,we report the chromosome-level genome assembly of H.miconioides to understand its evolution and floral characteristics.The 622.28 Mb assembled genome harbored a shared whole-genome duplication with a related species,Lonicera japonica.Comparative genomic analysis suggested that chromosome fission events following genome duplication underlie the unusual chromosome number of these two species,as well as chromosome fission of another five chromosomes in H.miconioides,giving rise to a haploid chromosome number of 14(versus 9 in L.japonica).In addition,based on transcriptome and chloroplast genome analysis of 17 representative species in the Caprifoliaceae,we assumed that large structural variations in the chromosomes of H.miconioides were not caused by hybridization.Changes in the candidate genes of the MADS-box family were detected in the H.miconioides genome,including AP1-,AP3-,and SEPexpanded,which might underlie the sepal elongation and development in this species.The current findings provided a critical resource for genome evolution studies in Caprifoliaceae and it was an example of how multi-omics data can elucidate the regulation of important ornamental traits.

关键词： Heptacodium miconioides Genome assembly Caprifoliaceae Chromosome fusion Sepal traits

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from Acupoints to Mylohyoid: Revealing the Neural Circuitry Basis of Electroacupuncture for Dysphagia

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Neuroscience Bulletin 2024年第1期40卷 139-142页

作者： Xiaoli Da Xuhong Jiang Lihong Li Cenglin Xu Zhong Chen Key Laboratory of Neuropharmacology and Translational Medicine of zhejiang Province School of Pharmaceutical ScienceZhejiang Chinese Medical UniversityHangzhou 310053China Department of Neurology the First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310003China Department of Acupuncture the Second Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310000China

Acupuncturea representative and historical treatment in traditional Chinese medicine(TCM),has been used to cure diseases for Chinese people in the past centuries.Since the late 1990s,acupuncture has been further accepted worldwide.The World Health Organization(WHO)proposed Clinical Research Specification for acupuncture in 1995 and the US Food and Drug Administration(FDA)approved acupuncture as a complementary and alternative therapy for various kinds of diseases in 1996,with clinical advantages such as convenience and effectiveness[1].Cumulative evidence has proved that acupuncture could produce different degrees of efficacy for treating various kinds of diseases(such as neuropathic pain,migraine,Parkinson's disease et al.)and alleviate symptoms[2-4].However,unlike its evidence-based efficacies.

关键词： medicine(TCM) acupuncture Acupuncture

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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 signaling.However,increasing evidences indicate that BCL9 also plays multiple Wnt-independent roles.Herein,we summarized the updates of the canonical and non-canonical functions of BCL9 in cellular,physiological,or pathological processes.Moreover,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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Recent advances in cancer-associated fibroblast:Biomarkers,signaling pathways,and therapeutic opportunities

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Chinese Medical Journal 2024年第6期137卷 638-650页

作者： Donger Zhou Lei Zheng Department of Hepatobiliary-Pancreatic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Sidney Kimmel Comprehensive Cancer Center The Skip Viragh Pancreatic Cancer Center for Clinical Research and Careand The Bloomberg-Kimmel Institute for Immunotherapy at Johns Hopkins University School of MedicineBaltimoreMD 21287USA

Anti-cancer therapies usually focus on tumor cells,but non-tumor stromal components in the tumor microenvironment also play vital roles in tumor initiation and progression,which may be the prognostic factors and potential therapeutic targets.Cancer-associated fibroblasts(CAFs)are the essential component in the tumor environment,exhibiting high heterogeneity in their cell origin and phenotype with diverse functions that influence tumor angiogenesis,immune systems,and metabolism.Single-cell RNA sequencing and genetically engineered mouse models have increased our understanding of CAF diversity,and many subtypes have been defined.However,the precise functions of these subtypes need to be studied and validated.Studies of signaling pathways and epigenetic changes in CAFs facilitate understanding of the phenotypes of CAFs and the crosstalk between tumor cells and CAFs to provide potential therapeutic targets.Some clinical trials,including phase III trials targeting CAFs,have been performed recently.However,few of these trials have generated promising results,which indicates that the complexity of CAFs in the tumor microenvironment remains largely unknown,and in-depth investigations of CAFs should be performed.This review summarizes the research on CAFs,focusing on the heterogeneity of their phenotypes and functions,specific signaling pathways,and the therapeutic strategies involving CAFs.Additionally,we briefly discuss the current technologies commonly used in CAF studies and describe the challenges and future perspectives of CAF research.

关键词： Cancer-associated fibroblasts Tumor microenvironment Anti-cancer therapy Targeted therapy

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Safety and efficacy of omalizumab for antihistamine-resistant chronic urticaria in children:a case series and literature review

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World Journal of Pediatrics 2024年第3期20卷 294-298页

作者： Wei-Fang Zhu Chen Wang Jian-Jun Qiao Lan-Juan Li Department of Dermatology First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Chronic urticaria(CU)is a common skin disease characterized by the occurrence of wheals,with or without angioedema,lasting more than 6 weeks.The prevalence of CU is about 0.7%[1],but higher in children,with an incidence of 1.38%[1].The occurrence of severe pruritus and unpredictable wheals may severely impact patients'quality of life,cause psychological problems,including sleep disorders and depression,and lead to economic burden due to limitation on daily life and work[2,3].

关键词： edema prevalence children

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Pancreatic panniculitis as the first presentation of pancreatic ductaladenocarcinoma

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 106-108页

作者： Wei-Fang Zhu Shan Fang Jian-Jun Qiao Department of Dermatology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

To the Editor:Pancreatic panniculitis,also known as pancreatic fat necrosis or enzymatic panniculitis,is a rare type of panniculitis that occurs in 0.3%−3%of patients with pancreatic disease such as acute or chronic pancreatitis and pancreatic carcinoma,especially acinar cell carcinoma[1,2].The clinical manifestations are nonspecific erythema tender nodules.

关键词： Pancreatic acute adenocarcinoma

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Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 25-34页

作者： Hai-Li Bao Chuan-Zhi Chen Chang-Zhen Ren Ke-Yan Sun Hao Liu Shao-Hua Song Zhi-Ren Fu Department of Organ Transplantation Shanghai Changzheng HospitalNavy Military Medical UniversityShanghai 200003China Department of Surgical Oncology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Cardiology Shanghai Changzheng HospitalNaval Military Medical UniversityShanghai 200003China Department of General Surgery Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various diseases.However,little is known about its effect on hepatic ischemia-reperfusion(I/R)injury.This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism.Methods:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R procedure.Serum alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver injury.The severity related to the inflammatory response and reactive oxygen species(ROS)production was also investigated.Furthermore,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages.Results:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis.The oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin treatment.In addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro.Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway.Conclusions:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling.

关键词： Hepatic ischemia-reperfusion injury Polydatin Macrophage Polarization Inflammation

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