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

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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Ciclopirox inhibits SARS-CoV-2 replication by promoting the degradation of the nucleocapsid protein

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2505-2519页

作者： Xiafei Wei Yuzheng Zhou Xiaotong Shen Lujie Fan Donglan Liu Xiang Gao Jian Zhou Yezi Wu Yunfei Li Wei Feng Zheng Zhang Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People's HospitalSouthern University of Science and TechnologyShenzhen 518112China Guangzhou Laboratory Guangzhou Medical UniversityGuangzhou 511495China State Key Laboratory of Respiratory disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China

The nucleocapsid protein(NP)plays a crucial role in SARS-CoV-2 replication and is the most abundant structural protein with a long *** its vital role in severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)assembly and host inflammatory response,it remains an unexplored target for drug *** this study,we identified a small-molecule compound(ciclopirox)that promotes NP degradation using an FDA-approved library and a drug-screening cell *** significantly inhibited SARS-CoV-2 replication both in vitro and in vivo by inducing NP *** induced abnormal NP aggregation through indirect interaction,leading to the formation of condensates with higher viscosity and lower *** condensates were subsequently degraded via the autophagy-lysosomal pathway,ultimately resulting in a shortened NP half-life and reduced NP *** results suggest that NP is a potential drug target,and that ciclopirox holds substantial promise for further development to combat SARS-CoV-2 replication.

关键词： SARS-CoV-2 Nucleocapsid protein Viral replication Ciclopirox Abnormal aggregation Protein degradation Autophagy-lysosome Drug target

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Effects of Lactobacillus paracasei N1115 on gut microbial imbalance and liver function in patients with hepatitis B-related cirrhosis

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World Journal of Gastroenterology 2024年第11期30卷 1556-1571页

作者： Yan-Chao Hu Xiang-Chun Ding Hui-Juan Liu Wan-Long Ma Xue-Yan Feng Li-Na Ma Department of infectious disease General Hospital of Ningxia Medical UniversityYinchuan 750004Ningxia Hui Autonomous RegionChina infectious disease clinical research center of Ningxia Yinchuan 750004Ningxia Hui Autonomous RegionChina

BACKGROUND Hepatitis B cirrhosis(HBC)is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic *** the relationship between certain single probiotics and HBC has been explored,the impact of the complex ready-to-eat Lactobacillus paracasei N1115(LP N1115)supplement on patients with HBC has not been *** To compare the changes in the microbiota,inflammatory factor levels,and liver function before and after probiotic treatment in HBC *** This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December *** were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment *** samples were collected at the onset and conclusion of the 12-wk intervention *** structure of the intestinal microbiota and the levels of serological indicators,such as liver function and inflammatory factors,were *** Following LP N1115 intervention,the intestinal microbial diversity significantly increased in the intervention group(P<0.05),and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful ***,the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors(P<0.05).CONCLUSION LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota,improving liver function,and reducing inflammatory factor levels.

关键词： Hepatitis B cirrhosis N1115 ready-to-eat lactobacillus Inflammation Liver function Lachnospiraceae incertae sedis Probiotic

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Epidemiological characteristics of tuberculosis incidence and its macro-influence factors in Chinese mainland during 2014–2021

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贫困所致传染病(英文) 2024年第3期13卷 43-57页

作者： Deng Le-le Zhao Fei Li Zhuo-wei Zhang Wei-wei He Guang-xue Ren Xiang national Institute for Viral disease Control and Prevention Chinese Center for Disease Control and Prevention Beijing China Department of Pharmacy Beijing Hospital national center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical Science Beijing Key Laboratory of Drug clinical Risk and Personalized Medication Evaluation Beijing China Miyun District center for disease Control and Prevention Beijing China School Of Public Health Binzhon Medical University Yantai China Division of infectious disease Key Laboratory of Surveillance and Early-Warning On Infectious Disease Chinese Center for Disease Control and Prevention Beijing China

Background Tuberculosis (TB) remains a pressing public health issue, posing a significant threat to individuals'' well-being and lives. This study delves into the TB incidence in Chinese mainland during 2014–2021, aiming to gain deeper insights into their epidemiological characteristics and explore macro-level factors to enhance control and *** TB incidence data in Chinese mainland from 2014 to 2021 were sourced from the national Notifiable disease Reporting System (NNDRS). A two-stage distributed lag nonlinear model (DLNM) was constructed to evaluate the lag and non-linearity of daily average temperature (℃, Atemp), average relative humidity (%, ARH), average wind speed (m/s, AWS), sunshine duration (h, SD) and precipitation (mm, PRE) on the TB incidence. A spatial panel data model was used to assess the impact of demographic, medical and health resource, and economic factors on TB *** A total of 6,587,439 TB cases were reported in Chinese mainland during 2014–2021, with an average annual incidence rate of 59.17/100,000. The TB incidence decreased from 67.05/100,000 in 2014 to 46.40/100,000 in 2021, notably declining from 2018 to 2021 (APC =-8.87%, 95%CI: -11.97, -6.85%). TB incidence rates were higher among males, farmers, and individuals aged 65 years and older. Spatiotemporal analysis revealed a significant cluster in Xinjiang, Qinghai, and Xizang from March 2017 to June 2019 (RR= 3.94,P 71.73%), low sunshine duration (< 6.18 h) increased the risk of TB incidence, while extreme low wind speed (< 2.79 m/s) decreased the risk. The spatial Durbin model showed positive associations between TB incidence rates and se

关键词： Tuberculosis Surveillance Epidemiological characteristics Incidence Influence factor Distributed lag nonlinear model (DLNM) Spatial panel model China

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UniBind:a novel artificial intelligence-based prediction model for SARS-CoV-2 infectivity and variant evolution

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Signal Transduction and Targeted Therapy 2024年第1期9卷 14-15页

作者： Qihong Yan Jincun Zhao State Key Laboratory of Respiratory disease National Clinical Research Center for Respiratory DiseaseGuangzhou Institute of Respiratory Healththe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina

In a recent study published in Nature Medicine,Wang et *** an excellent framework called UniBind based on artificial intelligence(AI),which enables accurately predicting infectivity of SARS-CoV-2 variants and evolutionary trends of future viral variants.1 This computational method holds the possibility to not only serve as a valuable early-warning tool for monitoring potential pathogenic SARS-CoV-2 variants but also facilitate fundamental research on protein-protein interactions(PPIs).

关键词： artificial Bind prediction

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Astragaloside IV Alleviates Acute Liver Failure Induced by D-GalN/LPS by Upregulating Autophagy and Reducing Inflammation

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infectious Microbes & diseases 2024年第1期6卷 20-28页

作者： Meng Hong Wenwen Lian Ying Yang Zhi Chen 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 MedicineHangzhouChina

Acute liver failure(ALF)is a life-threatening condition that manifests in an extremely serious manner and progresses *** following study investigated the protective effect of astragaloside IV(AS-IV),a traditional Chinese drug,on ALF,and its underlying mechanisms,focusing on autophagy and inflammation *** were randomly divided into a saline group,a D-galactosamine and lipopolysac-charide(D-GalN/LPS)group and an AS-IV *** analysis,immunohistochemistry,cytometric bead array,high-throughput quantitative PCR,flow cytometry and Western analysis were used to assess inflammation and liver damage 5 hours after D-GalN/LPS *** IV treatment reduced mortality by alleviating D-GalN/LPS–induced hepatic damage and decreasing inflammation(decreasing Ly6c+monocyte levels,reducing inflammatory cytokines and increasing anti-inflammatory factors)as well as upregulating ***,PCR array was used to detect expression of autophagy-related genes,which demonstrated a Log2 fold change in gene expression between the AS-IV and D-GalN/LPS groups ranging from 1.19 to-3.53,with Tnfsf10 showing the largest alteration be-tween the two *** data suggest that AS-IV may alleviate ALF by upregulating autophagy and reducing inflammation,and it may therefore be an interesting drug for alleviating ALF.

关键词： astragaloside IV acute liver failure inflammation autophagy

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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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Comparative Study on the Immunogenicity and Efficacy of Different Post-exposure Intramuscular Rabies Vaccination Regimens in China

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Biomedical and Environmental Sciences 2024年第2期37卷 178-186页

作者： SONG Yun HE Ying LU Xue Xin ZHANG Xiao Mei JIANG XIAO Lin SONG Qing HUANG Xue Yong MA Hong Xia YU Peng Cheng ZHU Wu Yang Henan Provincial center for disease Control and Prevention Infectious Disease Prevention and Control InstituteHenan Provincial Key Laboratory of Infectious Disease PathogensZhengzhou 450000HenanChina national Institute for Viral disease Control and Prevention China CDCKey Laboratory of BiosafetyNational Health CommissionBeijing 102206China Shandong Provincial center for disease Control and Prevention Jinan 250014ShandongChina Qingdao Chengyang District center for disease Control and Prevention Qingdao 266108ShandongChina

Objective This study aimed to compare the current Essen rabies post-exposure immunization schedule(0-3-7-14-28)in China and the simple 4-dose schedule(0-3-7-14)newly recommended by the World Health Organization in terms of their safety,efficacy,and *** Mice were vaccinated according to different immunization schedules,and blood was collected for detection of rabies virus neutralizing antibodies(RVNAs)on days 14,21,28,35,and 120after the first ***,different groups of mice were injected with lethal doses of the CVS-11 virus on day 0,subjected to different rabies immunization schedules,and assessed for morbidity and death *** a clinical trial,185 rabies-exposed individuals were selected for post-exposure vaccination according to the Essen schedule,and blood was collected for RVNAs detection on days 28and 42 after the first *** A statistically significant difference in RVNAs between mice in the Essen and 0-3-7-14 schedule groups was observed on the 35th day(P0.05)in RVNAs levels at any time *** post-exposure immune protective test showed that the survival rate of mice in the control group was 20%,whereas that in the immunization groups was 40%.In the clinical trial,the RVNAs positive conversion rates on days 28(14 days after 4 doses)and 42(14 days after 5 doses)were both 100%,and no significant difference in RVNAs levels was observed(P>0.05).Conclusion The simple 4-dose schedule can produce sufficient RVNAs levels,with no significant effect of a delayed fourth vaccine dose(14–28 d)on the immunization potential.

关键词： Rabies Post-exposure immunization Essen regimen RVNAs

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Association of acute glycemic parameters at admission with cardiovascular mortality in the oldest old with acute myocardial infarction

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Journal of Geriatric Cardiology 2024年第3期21卷 349-358页

作者： Hui-Hui LIU Meng ZHANG Yuan-Lin GUO Cheng-Gang ZHU Na-Qiong WU Ying GAO Rui-Xia XU Jie QIAN Ke-Fei DOU Jian-Jun LI Cardiometabolic center State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesNational Clinical Research Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

OBJECTIVES Stress-related glycemic indicators,including admission blood glucose(ABG),stress-hyperglycemia ratio(SHR),and glycemic gap(GG),have been associated with worse outcomes after acute myocardial infarction(AMI).However,data regarding their prognostic value in the oldest old with AMI are ***,this study aimed to investigate the association of stress-related glycemic indicators with short-and long-term cardiovascular mortality(CVM)in the oldest old(≥80 years)with *** In this prospective study,a total of 933 consecutive old patients with AMI admitted to FuWai hospital(Beijing,China)were *** admission,ABG,SHR,and GG were assessed and all participants were classified according to their ***-Meier,restricted cubic splines(RCS),and multivariate Cox regression analyses were performed to evaluate the association between these glycemic indicators and CVM within 30 days and long-term *** During an average of 1954 patient-years of follow-up,a total of 250 cardiovascular deaths were ***-Meier analyses showed the lowest CVM in quartile 1 of ABG and in quartile 2 of SHR and *** adjusting for potential covariates,patients in quartile 4 of ABG,SHR,and GG had a respective 1.67-fold(95%CI:1.03-2.69;P=0.036),1.80-fold(95%CI:1.16-2.79;P=0.009),and 1.78-fold(95%CI:1.14-2.79;P=0.011)higher risk of long-term CVM risk compared to those in the reference groups(quartile 1 of ABG and quartile 2 of SHR and GG).Furthermore,RCS suggested a J-shaped relationship of ABG and a Ushaped association of SHR and GG with long-term ***,we observed similar associations of these acute glycemic parameters with 30-day *** Our data first indicated that SHR and GG consistently had a U-shaped association with both 30-day and longterm CVM among the oldest old with AMI,suggesting that they may be useful for risk stratification in this special population.

关键词： admitted infarction shaped

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Prognostic value of ultrasound in early arterial complications post liver transplant

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 13-20页

作者： Ning-Bo Zhao Yi Chen Rui Xia Jian-Bo Tang Dong Zhao Department of Ultrasound National Clinical Research Centre for Infectious DiseaseShenzhen Third People's HospitalThe Second Affiliated Hospital of Southern University of Science and TechnologyNational Clinical Research Center for Infectious DiseaseShenzhen 518112Guangdong ProvinceChina Department of Thyroid and Hernia Surgery The Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510000Guangdong ProvinceChina Department of Biomedical Engineering Southern University of Science and TechnologyShenzhen 51800Guangdong ProvinceChina 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 518112Guangdong ProvinceChina

Liver transplantation is the primary therapeutic intervention for end-stage liver ***,vascular complications,particularly those involving the hepatic artery,pose significant risks to *** clinical manifestations associated with early arterial complications following liver transplantation are often *** timely intervention,these complications can result in graft fai-lure or patient ***,early diagnosis and the formulation of an op-timal treatment plan are *** examination remains the pre-dominant imaging modality for detecting complications post liver *** article comprehensively reviews common causes and clinical present-ations of early hepatic artery complications in the post-transplantation period and delineates abnormal sonographic findings for accurate diagnosis of these ***,ultrasound offers the advantages of convenience,safety,effect-iveness,and *** enables real-time,dynamic,and precise evalua-tion,making it the preferred diagnostic method for post-liver transplantation *** Liver transplantation stands as the primary therapeutic approach for end-stage liver *** advancements in surgical techniques and the application of novel immunosuppressive agents contribute to ongoing improvements in the success rate and overall survival in patients undergoing liver transplantation *** these advan-cements,vascular complications,particularly those involving the hepatic artery,pose significant risks to *** the early stages following liver transplantation(within the first 30 d),proper hepatic artery function is crucial for hepatic arterial blood *** later stages,collateral circulation,including arteries such as the phrenic artery,right gastric artery,and gastroduodenal artery,becomes important for maintaining hepatic blood *** is now understood that the establishment of effective collat

关键词： Liver transplantation Vascular complication Arterial complication Ultrasound

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