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Resolving the developmental mechanisms of cardiac microthrombosis of SARS-CoV-2 based on single-cell transcriptome analysis

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Science China Life Sciences 2025年第1期 103-115页

作者： Xizi Luo Nan Zhang Yuntao Liu Beibei Du Xuan Wang Tianxu Zhao Bingqiang Liu Shishun Zhao Jiazhang Qiu Guoqing Wang State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic infectious diseases Key Laboratory for Zoonosis Research of the Ministry of EducationCollege of Basic MedicineJilin University State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic infectious diseases Key Laboratory for Zoonosis Research of the Ministry of EducationCollege of Veterinary MedicineJilin University College of Mathematics Jilin University Bioinformatic Lab School of MathematicsShandong University Department of Cardiology China-Japan Union HospitalJilin University

The coronavirus disease 2019（COVID-19） outbreak caused by the severe acute respiratory syndrome coronavirus-2（SARS-CoV-2） developed into a global health emergency. Systemic microthrombus caused by SARS-CoV-2 infection is a common complication in patients with COVID-19. Cardiac microthrombosis as a complication of SARS-CoV-2 infection is the primary cause of cardiac injury and death in patietns with severe COVID-19. In this study, we performed single-cell sequencing analysis of the right ventricular free wall tissue from healthy donors,patients who died during the hypercoagulable period of characteristic coagulation abnormality（CAC）, and patients who died during the fibrinolytic period of CAC. We collected 61,187 cells enriched in 24 immune cell subsets and 13 cardiac-resident cell subsets. We found that in the course of SARS-CoV-2 infected heart microthrombus, MYO1EhighRASGEF1Bhighmonocyte-derived macrophages promoted hyperactivation of the immune system and initiated the extrinsic coagulation pathway by activating chemokines CCL3, CCL5. This series of events is the main cause of cardiac microthrombi following SARS-CoV-2 infection. In a SARS-CoV-2 infected heart microthrombus, excessive immune activation is accompanied by an increase in cellular iron content, which in turn promotes oxidative stress and intensifies intercellular competition. This induces cells to alter their metabolic environment, resulting in increased sugar uptake via the glycosaminoglycan synthesis pathway. In addition, high levels of reactive oxygen species generated by elevated iron levels promote increased endogenous malondialdehyde synthesis in a subpopulation of cardiac endothelial cells. This exacerbates endothelial cell dysfunction and exacerbates the coagulopathy process.

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Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng Fan Zhiwen Luo Xueran Kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han Beijie Qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu Shiyi Chen Department of Sport medicine Huashan HospitalFudan UniversityShanghaiChina Department of Orthopedic Surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina Department of Basic medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina Department of infectious diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural *** role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of *** used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other *** demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by *** underscores the intricate relationship between natural compounds such as nutlin-3 and immune *** comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma *** also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic ***-3a inhibited glioma cell proliferation and activated the p53 *** efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or *** using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway ***,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing *** results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma *** research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

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High frequency of thrombocytopenia in patients with acute-on-chronic liver failure treated with linezolid

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Hepatobiliary & Pancreatic diseases International 2015年第3期14卷 287-292页

作者： Yi-Min Zhang Wei Yu Ning Zhou Jian-Zhou Li Li-Chen Xu Zhong-Yang Xie Ying-Feng Lu Lan-Juan Li State Key Laboratory for Diagnosis and Treatment of infectious diseases Department of Infectious Diseases the First Affiliated Hospital Zhejiang University School of Medicine Collaborative Innovation Center for Diagnosis and Treatment of infectious diseases

BACKGROUND： Linezolid is an effective antibiotic reagent for Gram-positive bacterial infection; its most common side effect is thrombocytopenia. However, the incidence of throm- bocytopenia in patients with acute-on-chronic liver failure （ACLF） who underwent linezolid therapy was unclear. The present study was to evaluate the incidence of thrombocyto- penia in ACLF and non-ACLF patients treated with linezolid and the risk factors of thrombocytopenia in these patients.

关键词： acute-on-chronic liver failure linezolid thrombocytopenia

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Health and Disease:Akkermansia muciniphila,the Shining Star of the Gut Flora

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Research 2023年第4期2023卷 557-576页

作者： Chen Xue Ganglei Li Xinyu Gu Yuanshuai Su Qiuxian Zheng Xin Yuan Zhengyi Bao Juan Lu Lanjuan Li 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 MedicineHangzhouZhejiangChina Department of Neurosurgery The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Akkermansia muciniphila(***)has drawn much attention as an important gut microbe strain in recent *** can influence the occurrence and development of diseases of the endocrine,nervous,digestive,musculoskeletal,and respiratory systems and other *** can also improve immunotherapy for some *** is expected to become a new probiotic in addition to Lactobacillus and *** increase in *** abundance through direct or indirect *** supplementation may inhibit or even reverse disease ***,some contrary findings are found in type 2 diabetes mellitus and neurodegenerative diseases,where increased *** abundance may aggravate the *** enable a more comprehensive understanding of the role of *** in diseases,we summarize the relevant information on *** in different systemic diseases and introduce regulators of *** abundance to promote the clinical transformation of *** research.

关键词： muciniphila diseases respiratory

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Cryptococcosis in patients with liver cirrhosis:Death risk factors and predictive value of prognostic models

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Hepatobiliary & Pancreatic diseases International 2021年第5期20卷 460-468页

作者： Qi-Hui Zhou Cai-Qin Hu Yu Shi Feng-Tian Wu Qin Yang Jun Guan Ai-Chun Li Zhi Chen Department of infectious diseases State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesNational Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China

Background:Liver cirrhosis is associated with immune deficiency,which causes these patients to be susceptible to various infections,including cryptococcus *** in cirrhotic patients with cryptococcosis has *** present study was to explore the risk factors of mortality and the predictive ability of different prognostic ***:Forty-seven cirrhotic patients with cryptococcosis at a tertiary care hospital were included in this retrospective *** on demographics,clinical parameters,laboratory exams,diagnostic methods,medication during hospitalization,severity scores and prognosis were collected and ***’s t test and Mann-Whitney test were used to compare characteristics of survivors and non-survivors at a 90-day follow-up and cerebrospinal fluid(CSF)manifestations of cryptococcal *** Cox regression analysis was used to identify the independent risk factors for ***-Meier curves were used to analyze patient *** operating characteristic(ROC)curves were used to evaluate the different prognostic ***:The 30-and 90-day survival rates were 93.6%and 80.9%,respectively,in cirrhotic patients with *** liver diseases[hazard ratio(HR)=7.567,95%confidence interval(CI):1.616-35.428,P=0.010],activated partial thromboplastin time(APTT)(HR=1.117,95%CI:1.016-1.229,P=0.022)and Child-Pugh score(HR=2.146,95%CI:1.314-3.504,P=0.002)were risk factors for 90-day mortality in cirrhotic patients with *** count(HR=0.965,95%CI:0.940-0.991,P=0.008)was a protective ***(HR=1.120,95%CI:1.044-1.202,P=0.002)and Child-Pugh score(HR=1.637,95%CI:1.086-2.469,P=0.019)were risk factors for 90-day mortality in cirrhotic patients with cryptococcal *** was significant difference in the percentage of lymphocytes in CSF between survivors and non-survivors[60.0(35.0-75.0)vs.95.0(83.8-97.2),P<0.001].The model of end-stage liver disease-sodium(MELD-

关键词： Cryptococcosis Cirrhosis Risk factors Prognosis

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Anti-retroviral drugs: current state and development in the next decade

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Acta Pharmaceutica Sinica B 2018年第2期8卷 131-136页

作者： Xingquan Zhang Division of infectious diseases Department of Medicine School of Medicine University of CaliforniaSan Diego

The pace of discovery of new antiretroviral(ARV) drugs has slowed, although the efficacy and safety of once-daily fixed dose combinations have been extensively investigated. Several traditional ARV drugs remain in phase Ⅲ clinical trials. This review summarizes current information on ARV drugs in phase Ⅲ clinical trials and focuses on the development of ARV drugs in the next decade.

关键词： Antiretroviral drugs Long-acting formulations Attachment inhibitors Maturation inhibitors Nanomedicine

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Nosocomial spontaneous bacterial peritonitis antibiotic treatment in the era of multi-drug resistance pathogens: A systematic review

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World Journal of Gastroenterology 2017年第25期23卷 4654-4660页

作者： Marco Fiore Alberto Enrico Maraolo Ivan Gentile Guglielmo Borgia Sebastiano Leone Pasquale Sansone Maria Beatrice Passavanti Caterina Aurilio Maria Caterina Pace Department of Anaesthesiological Surgical and Emergency SciencesUniversity of Campania“Luigi Vanvitelli” Department of Clinical medicine and Surgery Section of Infectious DiseasesUniversity of Naples Federico II Division of infectious diseases “San Giuseppe Moscati”Hospital

To systematically review literature upon aetiology of nosocomial spontaneous bacterial peritonitis (N-SBP) given the rising importance of multidrug-resistant (MDR) bacteria. METHODSA literature search was performed on MEDLINE and Google Scholar databases from 2000 to 15th of November 2016, using the following search strategy: “spontaneous” AND “peritonitis”. RESULTSThe initial search through electronic databases retrieved 2556 records. After removing duplicates, 1958 records remained. One thousand seven hundred and thirty-five of them were excluded on the basis of the screening of titles and abstract, and the ensuing number of remaining articles was 223. Of these records, after careful evaluation, only 9 were included in the qualitative analysis. The overall proportion of MDR bacteria turned out to be from 22% to 73% of cases across the studies. CONCLUSIONN-SBP is caused, in a remarkable proportion, by MDR pathogens. This should prompt a careful re-assessment of guidelines addressing the treatment of this clinical entity.

关键词： Hospital-acquired infections Nosocomial spontaneous bacterial peritonitis Multidrug resistant bacteria Cirrhosis Critically ill patient

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Direct anti-HCV agents

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Acta Pharmaceutica Sinica B 2016年第1期6卷 26-31页

作者： Xingquan Zhang Division of infectious diseases University of CaliforniaSan Diego School of Medicine

Unlike human immunodeficiency virus(HIV)and hepatitis B virus(HBV),hepatitis C virus(HCV)infection is a curable *** direct antiviral agent(DAA)targets are focused on HCV NS3/4A protein(protease),NS5 B protein(polymerase)and NS5 A *** first generation of DAAs includes boceprevir and telaprevir,which are protease inhibitors and were approved for clinical use *** cure rate for genotype 1 patients increased from 45% to 70% when boceprevir or telaprevir was added to standard PEG-IFN/*** effective and less toxic second generation DAAs supplanted these drugs by *** second generation of DAAs includes sofosbuvir(Sovaldi),simeprevir(Olysio),and fixed combination medicines Harvoni and Viekira *** drugs increase cure rates to over 90%without the need for interferon and effectively treat all HCV *** these drugs the "cure HCV"goal has become a *** remain about drug resistance mutations and the high cost of these *** investigation of new HCV drugs is progressing rapidly;fixed dose combination medicines in phase III clinical trials include Viekirax,asunaprevirtdaclatasvirtbeclabuvir,grazoprevirtelbasvir and others.

关键词： Hepatitis C virus Cure HCV Sustained virologic response Direct antiviral agents NS3/4A protease inhibitor

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Notch signaling pathway in cancer:from mechanistic insights to targeted therapies

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2527-2563页

作者： Qingmiao Shi Chen Xue Yifan Zeng Xin Yuan Qingfei Chu Shuwen Jiang Jinzhi Wang Yaqi Zhang Danhua Zhu Lanjuan Li 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 310003China

Notch signaling,renowned for its role in regulating cell fate,organ development,and tissue homeostasis across metazoans,is highly conserved throughout *** Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences,typically necessitating receptor-ligand interaction to initiate classical Notch signaling *** evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer *** of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies,closely linked to cancer proliferation,invasion,and ***,the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells,thereby enhancing cancer *** regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive ***,the Notch signaling pathway is implicated in conferring chemoresistance to tumor ***,a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch *** review focuses on the research progress of the Notch signaling pathway in cancers,providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of ***,the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy,aiming to offer new insights into therapeutic strategies for human malignancies.

关键词： Notch invasion involvement

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Typical hemophagocytic syndrome associated with cytomegalovirus infection in an immunocompetent patient: a case report and literature review

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第12期24卷 1159-1164页

作者： Fangfang GENG Meifang YANG Xuan ZHANG Hong ZHAO De ZHOU Jianhua HU 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 DiseasesDepartment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Hematology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Cytomegalovirus(CMV)infection is currently prevalent in populations throughout the world,and 56%-94%of the global population is seropositive for *** infection mainly affects immunocompromised *** these cases,it can cause significant symptoms,tissue-invasive disease,and many sequelae including death(Dioverti and Razonable,2016).The vast majority of healthy adults with CMV infection experience an asymptomatic course;when symptomatic,it manifests as a mononucleosis-like syndrome in approximately 10%of patients(Sridhar et al.,2018).

关键词： infection immuno

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