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Lecithin-cholesterol acyltransferase is a potential tumor suppressor and predictive marker for hepatocellular carcinoma metastasis

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3651-3671页

作者： Yan Li Li-Na Jiang Bo-Kang Zhao Mei-Ling Li Yi-Yun Jiang Yi-Si Liu Shu-Hong Liu Li Zhu Xin Ye Jing-Min Zhao department of Pathology and Hepatology The Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China department of Hepatology Center of Infectious Diseases and Pathogen BiologyThe First Hospital of Jilin UniversityChangchun 130061Jilin ProvinceChina First department of Liver Disease Center Beijing Youan HospitalCapital Medical UniversityBeijing 100069China Key Laboratory of Pathogenic microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China Savaid Medical School University of Chinese Academy of SciencesBeijing 100190China department of Pathology The Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China

BACKGROUND Hepatocellular carcinoma(HCC)is a major cause of cancer mortality worldwide,and metastasis is the main cause of early recurrence and poor ***,the mechanism of metastasis remains poorly *** To determine the possible mechanism affecting HCC metastasis and provide a possible theoretical basis for HCC *** The candidate molecule lecithin-cholesterol acyltransferase(LCAT)was screened by gene microarray and bioinformatics *** expression levels of LCAT in clinical cohort samples was detected by quantitative realtime polymerase chain reaction and western *** proliferation,migration,invasion and tumor-forming ability were measured by Cell Counting Kit-8,Transwell cell migration,invasion,and clonal formation assays,*** formation was detected in nude mice after LCAT gene knockdown or *** immunohistochemistry for Ki67,E-cadherin,N-cadherin,matrix metalloproteinase 9 and vascular endothelial growth factor were performed in liver tissues to assess the effect of LCAT on *** set enrichment analysis(GSEA)on various gene signatures were analyzed with GSEA version *** machine-learning algorithms(random forest,support vector machine,and logistic regression)were applied to predict HCC metastasis in The Cancer Genome Atlas and GEO *** LCAT was identified as a novel gene relating to HCC metastasis by using gene microarray in HCC *** was significantly downregulated in HCC tissues,which is correlated with recurrence,metastasis and poor outcome of HCC *** analysis indicated that LCAT inhibited HCC cell proliferation,migration and invasion both in vitro and in *** data showed that LCAT was negatively associated with HCC size and metastasis(HCC size≤3 cm vs 3-9 cm,P9 cm,P<0.01;metastatic-free HCC vs extrahepatic metastatic HCC,P<0.05).LCAT suppressed the growth,migration and invasion of HCC cell lines via PI3K/A

关键词： Lecithin-cholesterol acyltransferase Tumor suppressor gene Hepatocellular carcinoma PI3K/AKT/mTOR Predicting model

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The immune response to SARS-CoV-2 in people with HIV

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Cellular & Molecular Immunology 2024年第2期21卷 184-196页

作者： Maxine A.Höft Wendy A.Burgers Catherine Riou Institute of infectious Disease and Molecular Medicine University of Cape TownCape TownSouth Africa Division of Medical Virology Department of PathologyUniversity of Cape TownCape TownSouth Africa Wellcome Centre for infectious Diseases Research in Africa University of Cape TownCape TownSouth Africa

This review examines the intersection of the HIV and SARS-CoV-2 *** with HIV(PWH)are a heterogeneous group that differ in their degree of immune suppression,immune reconstitution,and viral *** COVID-19 in those with wellcontrolled HIV infection poses no greater risk than that for HIV-uninfected individuals,people with advanced HIV disease are more vulnerable to poor COVID-19 ***-19 vaccines are effective and well tolerated in the majority of PWH,though reduced vaccine efficacy,breakthrough infections and faster waning of vaccine effectiveness have been demonstrated in *** is likely a result of suboptimal humoral and cellular immune responses after *** with advanced HIV may also experience prolonged infection that may give rise to new epidemiologically significant variants,but initiation or resumption of antiretroviral therapy(ART)can effectively clear persistent ***-19 vaccine guidelines reflect these increased risks and recommend prioritization for vaccination and additional booster doses for PWH who are moderately to severely *** recommend continued research and monitoring of PWH with SARS-CoV-2 infection,especially in areas with a high HIV burden.

关键词： SARS-CoV-2 HIV Immune dysfunction Vaccine efficacy Prolonged infection Immunogenicity

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Identification of novel small-molecule inhibitors of SARS-CoV-2 by chemical genetics

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4028-4044页

作者： Chris Chun-Yiu Chan Qian Guo Jasper Fuk-Woo Chan Kaiming Tang Jian-Piao Cai Kenn Ka-Heng Chik Yixin Huang Mei Dai Bo Qin Chon Phin Ong Allen Wing-Ho Chu Wan-Mui Chan Jonathan Daniel Ip Lei Wen Jessica Oi-Ling Tsang Tong-Yun Wang Yubin Xie Zhenzhi Qin Jianli Cao Zi-Wei Ye Hin Chu Kelvin Kai-Wang To Xing-Yi Ge Tao Ni Dong-Yan Jin Sheng Cui Kwok-Yung Yuen Shuofeng Yuan State Key Laboratory of Emerging infectious Diseases Carol Yu Centre for InfectionDepartment of MicrobiologySchool of Clinical MedicineLi Ka Shing Faculty of Medicinethe University of Hong KongPokfulamHong Kong SAR 999077China department of infectious Diseases and microbiology the University of Hong Kong-Shenzhen HospitalShenzhen 518000China Centre for Virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong Kong SAR 999077China Academician Workstation of Hainan Province Hainan Medical University-the University of Hong Kong Joint Laboratory of Tropical Infectious DiseasesHaikou 571100China School of Biomedical Sciences Li Ka Shing Faculty of Medicinethe University of Hong KongPokfulamHong Kong SAR 999077China NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen Biology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China College of Biology Hunan Provincial Key Laboratory of Medical VirologyHunan UniversityChangsha 410082China

There are only eight approved small molecule antiviral drugs for treating *** them,four are nucleotide analogues(remdesivir,JT001,molnupiravir,and azvudine),while the other four are protease inhibitors(nirmatrelvir,ensitrelvir,leritrelvir,and simnotrelvir-ritonavir).Antiviral resistance,unfavourable drug‒drug interaction,and toxicity have been reported in previous *** there is a dearth of new treatment options for *** this work,a three-tier cell-based screening was employed to identify novel compounds with anti-SARS-CoV-2 *** compound,designated 172,demonstrated broad-spectrum antiviral activity against multiple human pathogenic coronaviruses and different SARS-CoV-2 variants of *** studies validated by reverse genetics showed that compound 172 inhibits the 3-chymotrypsin-like protease(3CLpro)by binding to an allosteric site and reduces 3CLpro dimerization.A drug synergistic checkerboard assay demonstrated that compound 172 can achieve drug synergy with nirmatrelvir in *** vivo studies confirmed the antiviral activity of compound 172 in both Golden Syrian Hamsters and K18 humanized ACE2 ***,this study identified an alternative druggable site on the SARS-CoV-23CLpro,proposed a potential combination therapy with nirmatrelvir to reduce the risk of antiviral resistance and shed light on the development of allosteric protease inhibitors for treating a range of coronavirus diseases.

关键词： SARS-CoV-2 High throughput screening Broad-spectrum antiviral treatment 3CLpro inhibitor Allosteric-site inhibitor Animal models Chemical genetics Reverse genetics

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Plasma Metabonomics of Human Adenovirus-infected Patients with Pneumonia and Upper Respiratory Tract Infection

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Current Medical Science 2024年第1期44卷 121-133页

作者： Ting-ting WEI Wen XU Bo TU Wan-xue ZHANG Xin-xin YANG Yiguo ZHOU Shan-shan ZHANG Jun-lian YANG Ming-zhu XIE Juan DU Wei-wei CHEN Qing-bin LU department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijing 100191China department of infectious Disease The Fifth Medical Center of Chinese PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijing 100039China department of Laboratorial Science and Technology&Vaccine Research Center School of Public HealthPeking UniversityBeijing 100191China department of Health Policy and Management School of Public HealthPeking UniversityBeijing 100191China Global Center for infectious Disease and Policy Research&Global Health and infectious Diseases Group Peking UniversityBeijing 100191China Key Laboratory of Epidemiology of Major Diseases(Peking University) Ministry of EducationBeijing 100191China

Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains *** the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were *** In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had *** samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted *** Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and *** metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid *** sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI *** and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.

关键词： human adenovirus metabonomic lipids pneumonia upper respiratory tract infection

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Carrimycin in the treatment of acute promyelocytic leukemia combined with pulmonary tuberculosis: A case report

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World Journal of Clinical Cases 2024年第3期12卷 623-629页

作者： Fu-Yu Yang Lei Shao Jie Su Zhen-Meng Zhang department of infectious Diseases The Affiliated Central Hospital of Shandong First Medical UniversityJinan 250013Shandong ProvinceChina

BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic *** treatment for acute promyelocytic leukemia(APL)combined with PTB is *** patients show an extremely poor ***,studies should establish efficient treatment options to improve patient survival and *** SUMMARY A 60-year-old male with pain in the right side of his chest and a fever for 4 d visited the outpatient department of our *** blood smear revealed 54%*** bone marrow examinations,variant APL with TNRC18-RARA fusion gene was *** computed tomography scan showed bilateral pneumonitis with bilateral pleural effusions,partial atelectasis in the lower lobes of both lungs,and the bronchoalveolar lavage fluid gene X-Pert test was positive,indicative of ***,ethambutol(EMB),and isoniazid(INH)were administered since he could not receive chemotherapy as the WBC count decreased *** one week of treatment with carrimycin,the patient recovered from fever and received *** was very effective and his white blood cells counts got back to *** being given five months with rifampin,EMB and INH and chemotherapy,the patient showed complete remission from pneumonia and *** We report a case of PTB treated successfully with carrimycin with APL that requires chemotherapy.

关键词： Carrimycin Hematologic disease Acute myeloid leukemia Acute promyelocytic leukemia Pulmonary tuberculosis Case report

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Inhibiting HMGCR represses stemness and metastasis of hepatocellular carcinoma via Hedgehog signaling

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Genes & Diseases 2024年第5期11卷 470-483页

作者： Zhirong Zhang Jiayao Yang Rui Liu Jing Ma Kai Wang Xiaojun Wang Ni Tang Key Laboratory of Molecular Biology for infectious Diseases(Ministry of Education) Institute for Viral HepatitisDepartment of Infectious DiseasesThe Second Affiliated HospitalChongqing Medical UniversityChongqing 400016China Institute of Hepatobiliary Surgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China

Cancer stem cells(CSCs)play a crucial role in tumor initiation,recurrence,metastasis,and drug ***,the current understanding of CSCs in hepatocellular carcinoma(HCC)remains *** a comprehensive analysis of the database,it has been observed that 3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGCR),a critical enzyme involved in cholesterol synthesis,is up-regulated in HCC tissues and liver ***,high expression of HMGCR is associated with a poor prognosis in patients with ***,HMGCR promotes the stemness and metastasis of HCC both in vitro and in *** screening various signaling pathway inhibitors,we have determined that HMGCR regulates stemness and metastasis by activating the Hedgehog signaling in ***,HMGCR positively correlates with the expression of the Smoothened receptor and facilitates the nuclear translocation of the transcriptional activator GLI family zinc finger *** of the Hedgehog pathway can reverse the stimulatory effects of HMGCR on stemness and metastasis in ***,simvastatin,an FDA-approved cholesterol-lowering drug,has been shown to inhibit stemness and metastasis of HCC by targeting *** together,our findings suggest that HMGCR promotes the regeneration and metastasis of HCC through the activation of Hedgehog signaling,and simvastatin holds the potential for clinical suppression of HCC metastasis.

关键词： Cancer stem cells Hedgehog Hepatocellular carcinoma Metastasis Statin

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FibroScan-aspartate transaminase:A superior non-invasive model for diagnosing high-risk metabolic dysfunction-associated steatohepatitis

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World Journal of Gastroenterology 2024年第18期30卷 2440-2453页

作者： Jing-Ya Yin Tian-Yuan Yang Bing-Qing Yang Chen-Xue Hou Jun-Nan Li Yue Li Qi Wang Center of Liver Diseases Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China department of Pathology Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Beijing institute of infectious disease Beijing 100015China Beijing Key Laboratory of Emerging infectious Diseases Institute of Infectious DiseasesBeijing Ditan HospitalCapital Medical UniversityBeijing 100015China

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)with hepatic histological NAFLD activity score≥4 and fibrosis stage F≥2 is regarded as“at risk”non-alcoholic steatohepatitis(NASH).Based on an international consensus,NAFLD and NASH were renamed as metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH),respectively;hence,we introduced the term“high-risk MASH”.Diagnostic values of seven non-invasive models,including FibroScan-aspartate transaminase(FAST),fibrosis-4(FIB-4),aspartate transaminase to platelet ratio index(APRI),*** high-risk MASH have rarely been studied and compared in *** To assess the clinical value of seven non-invasive models as alternatives to liver biopsy for diagnosing high-risk *** A retrospective analysis was conducted on 309 patients diagnosed with NAFLD via liver biopsy at Beijing Ditan Hospital,between January 2012 and December *** screening for MASLD and the exclusion criteria,279 patients wereincluded and categorized into high-risk and non-high-risk MASH *** threshold values of each model,sensitivity,specificity,positive predictive value(PPV),and negative predictive values(NPV),were *** operating characteristic curves were constructed to evaluate their diagnostic efficacy based on the area under the curve(AUROC).RESULTS MASLD diagnostic criteria were met by 99.4%patients with *** MASLD population was analyzed in two cohorts:Overall population(279 patients)and the subgroup(117 patients)who underwent liver transient elastography(FibroScan).In the overall population,FIB-4 showed better diagnostic efficacy and higher PPV,with sensitivity,specificity,PPV,NPV,and AUROC of 26.9%,95.2%,73.5%,72.2%,and ***,Forns index,and aspartate transaminase to alanine transaminase ratio(ARR)showed moderate diagnostic efficacy,whereas S index and gamma-glutamyl transpeptidase to platelet ratio(GPR)were relatively *** the sub

关键词： Metabolic dysfunction-associated steatotic liver disease High-risk metabolic dysfunction-associated steatohepatitis Non-invasive models Liver biopsy Diagnostic value

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Link between mutations in ACVRL1 and PLA2G4A genes and chronic intestinal ulcers:A case report and review of literature

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 932-943页

作者： Yong-Jing Tang Jian Zhang Jie Wang Ren-Dong Tian Wei-Wei Zhong Ben-Sheng Yao Bing-Yu Hou Ying-Hua Chen Wei He Yi-Huai He department of infectious Diseases The Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina department of Gastroenterology Dafang County People's HospitalBijie 551600Guizhou ProvinceChina department of Internal Medicine Puchang BranchMedical CommunitySuiyang County People's HospitalZunyi 563300Guizhou ProvinceChina department of infectious Diseases Jingmen Central HospitalJingmen 448000Hubei ProvinceChina department of infectious Diseases Dafang County People's HospitalBijie 551600Guizhou ProvinceChina

BACKGROUND Genetic factors of chronic intestinal ulcers are increasingly garnering *** present a case of chronic intestinal ulcers and bleeding associated with mu-tations of the activin A receptor type II-like 1(ACVRL1)and phospholipase A2 group IVA(PLA2G4A)genes and review the available relevant *** SUMMARY A 20-year-old man was admitted to our center with a 6-year history of recurrent abdominal pain,diarrhea,and dark *** the onset 6 years ago,the patient had received treatment at a local hospital for abdominal pain persisting for 7 d,under the diagnosis of diffuse peritonitis,acute gangrenous appendicitis with perforation,adhesive intestinal obstruction,and pelvic *** surgical treat-ment included exploratory laparotomy,appendectomy,intestinal adhesiolysis,and pelvic abscess *** patient’s condition improved and he was ***,the recurrent episodes of abdominal pain and passage of black stools started again one year after *** the basis of these features and results of subsequent colonoscopy,the clinical diagnosis was established as in-flammatory bowel disease(IBD).Accordingly,aminosalicylic acid,immunotherapy,and related symptomatic treatment were administered,but the symptoms of the patient did not improve *** investigations revealed mutations in the ACVRL1 and PLA2G4A ***1 and PLA2G4A are involved in angiogenesis and coagulation,*** suggests that the chronic intestinal ulcers and bleeding in this case may be linked to mutations in the ACVRL1 and PLA2G4A *** Kangfuxin liquid was administered to promote healing of the intestinal mucosa and effectively manage clinical *** Mutations in the ACVRL1 and PLA2G4A genes may be one of the causes of chronic intestinal ulcers and bleeding in *** administered Kangfuxin liquid may have therapeutic potential.

关键词： Intestinal ulcers Crohn’s disease Ulcerative colitis Activin A receptor type II-like 1 Phospholipase A2 group 4A Case report

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Approach from the laboratory to the field: New strategies in the control of mosquito-borne infectious diseases

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Science China Life Sciences 2024年

作者： Ziqian Xu Lianpan Dai Jun Liu National Key Laboratory of Intelligent Tracking and Forecasting for infectious Diseases (NITFID) National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention CAS Key Laboratory of Pathogen microbiology and Immunology Institute of Microbiology Chinese Academy of Sciences

Vector-borne viruses, transmitted among humans and animal hosts through bites of vectors such as mosquitoes and ticks,pose a great and ongoing threat to public health and biosafety (Yang et al., 2022).Among them, dengue virus-induced epidemics, have dramatically increased worldwide in recent decades. The report released by the World Health Organization (WHO) at the end of 2023 showed that dengue epidemic globally surged in2023, with the number of reported cases nearing a historical peak.

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Emerging role of galectin 3 in neuroinflammation and neurodegeneration

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Neural Regeneration Research 2024年第9期19卷 2004-2009页

作者： Brian M.Lozinski Khanh Ta Yifei Dong department of Clinical Neuroscience University of CalgaryCalgaryABCanada Deparment of Biochemistry Microbiology&ImmunologyUniversity of SaskatchewanSaskatoonSKCanada

Neuroinflammation and neurodegeneration are key processes that mediate the development and progression of neurological ***,the mechanisms modulating these processes in different diseases remain incompletely *** in single cell based multi-omic analyses have helped to identify distinct molecular signatures such as Lgals3 that is associated with neuroinflammation and neurodegeneration in the central nervous system(CNS).Lgals3 encodes galectin-3(Gal3),aβ-galactoside and glycan binding glycoprotein that is frequently upregulated by reactive microglia/macrophages in the CNS during various neurological *** Gal3 has previously been associated with non-CNS inflammatory and fibrotic diseases,recent studies highlight Gal3 as a prominent regulator of inflammation and neuroaxonal damage in the CNS during diseases such as multiple sclerosis,Alzheimer’s disease,and Parkinson’s *** this review,we summarize the pleiotropic functions of Gal3 and discuss evidence that demonstrates its detrimental role in neuroinflammation and neurodegeneration during different neurological *** also consider the challenges of translating preclinical observations into targeting Gal3 in the human CNS.

关键词： Alzheimer’s disease Galectin 3 microglia multiple sclerosis neurodegeneration neuroinflammation Parkinson’s disease therapeutics

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