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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

The frst avian infuenza A (H7N9) viral infection in humans in Zhejiang Province, China: a death report

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Frontiers of Medicine 2013年第3期7卷 333-344页

作者： Enfu Chen Fenjuan Wang Huakun Lv Yanjun Zhang Hua Ding Shelan Liu Jian Cai Li Xie Xiaoping Xu Chengliang Chai Haiyan Mao Jimin Sun Junfen Lin Zhao Yu Lianhong Li Zhiping Chen Shichang Xia Department of infectious diseases Zhejiang Center for Disease Control and Prevention Department of infectious diseases Xiaoshan District Center for Disease Control and Prevention Department of infectious diseases Hangzhou Center for Disease Control and Prevention Department of infectious diseases Jiande Center for Disease Control and Prevention

This study reports the frst death caused by a novel avian infuenza A(H7N9)virus in Zhejiang Province,*** patient had chronic hepatitis B and history of exposure to *** patient initially complained of diarrhea and infuenza-like symptoms on March 7 and 14 *** disease progressed to severe pneumonia,sustained hypoxia,and coagulation *** patient died on March 27 because of respiratory failure,multiple organ failure,and disseminated intravascular coagulation without oseltamivir *** H7N9 virus from Zhejiang is highly similar to isolates obtained from Shanghai,Jiangsu,Anhui,*** of hemagglutinin,neuramidinase,and matrix genes indicated that the isolates share the same avian origin,have low virulence,and are sensitive to oseltamivir,but are resistant to *** the isolate that caused the fatality exhibited substitution of Q226I in the HA gene,which indicates a potentially enhanced human *** secondary transmission rate was 1.6%(2/125).Only two health workers presented with infuenza-like symptoms,and they subsequently tested negative for H7N9 *** conclusion,underlying disease,late diagnosis,and untimely antiviral treatment are possible high-risk factors for infections and death caused by the lowpathogenicity avian infuenza A(H7N9).Person-to-person transmission of the H7N9 virus was not detected among close contacts,but such transmission should be investigated in the *** and enhancing surveillance will help in the early discovery and diagnosis of suspected cases,which will reduce the number of severe cases and deaths.

关键词： avian influenza A (H7N9) virus epidemiology contacts person-to-person transmission

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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Advances in the Treatment of Autoimmune Hepatitis

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Journal of Clinical and Translational Hepatology 2024年第10期12卷 878-885页

作者： Zelu Meng Yida Yang 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 MedicineHangzhouZhejiangChina

Autoimmune hepatitis(AIH)is a chronic,progressive inflammatory liver disease caused by autoimmune reactions,with an unknown *** left untreated,it can progress to cirrhosis,liver failure,or even *** most patients respond well to first-line treatments,a significant number experience poor responses or intolerance,requiring the use of second-or third-line *** research into the pathogenesis of AIH is leading to the development of novel therapeutic *** review summarized recent advancements in the treatment of AIH both domestically and internationally.

关键词： Hepatitis,Autoimmune Immunosuppression Treatment Management Update Remission Induction Long-term Prognosis

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

Progress in hepatitis B virus-related acute-on-chronic liver failure treatment in China:A large,multicenter,retrospective cohort study using a propensity score matching analysis

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Hepatobiliary & Pancreatic diseases International 2021年第6期20卷 535-541页

作者： Lan-Lan Xiao Xiao-Xin Wu Jia-Jia Chen Dong Yan Dong-Yan Shi Jian-Rong Huang Xiao-Wei Xu Lan-Juan Li 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 UniversityHangzhou 310003China

Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term ***,the treatment progression for HBV-ACLF in China in the past decade has not been well *** present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past ***:This study retrospectively compared short-term(28/56 days)survival rates of two different nationwide cohorts(cohort I:2008-2011 and cohort II:2012-2015).Eligible HBV-ACLF patients were enrolled *** in the cohorts I and II were assigned either to the standard medical therapy(SMT)group(cohort I-SMT,cohort II-SMT)or artificial liver support system(ALSS)group(cohort IALSS,cohort II-ALSS).Propensity score matching analysis was conducted to eliminate baseline differences,and multivariate logistic regression analysis was used to explore the independent factors for 28-day ***:Short-term(28/56 days)survival rates were significantly higher in the ALSS group than those in the SMT group(P<0.05)and were higher in the cohort II than those in the cohort I(P<0.001).After propensity score matching,short-term(28/56 days)survival rates were higher in the cohort II than those in the cohort I for both SMT(60.7%vs.53.0%,50.0%vs.39.8%,P<0.05)and ALSS(66.1%vs.56.5%,53.0%vs.44.4%,P<0.05)*** 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments(P=0.046).Multivariate logistic regression analysis revealed that ALSS(OR=0.962,95%CI:0.951-0.973,P=0.038),nucleos(t)ide analogs(OR=0.927,95%CI:0.871-0.983,P=0.046),old age(OR=1.028,95%CI:1.015-1.041,P<0.001),total bilirubin(OR=1.002,95%CI:1.001-1.003,P=0.004),INR(OR=1.569,95%CI:1.044-2.358,P<0.001),COSSH-ACLF grade(OR=2.683,95%CI:1.792-4.017,P<0.001),and albumin(OR=0.952,95%CI:0.924-0.982,P=0.002)were independent factors for 28-day ***:The treatment for patients with HBV-ACLF has improved

关键词： Hepatitis B virus-related acute-on-chronic liver failure Propensity score matching analysis Short-term survival rate Standard medical therapy Artificial liver support system

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Risk factors for congenital nasolacrimal duct obstruction in children under two years of age

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国际眼科杂志 2025年第1期25卷 17-23页

作者： Rozhin Kasiri Gholamreza Khataminia Ali Kasiri Mohammad Sadegh Mirdehghan Mohammad Armin Kasiri infectious Ophthalmologic Research center Ahvaz Jundishapur University of Medical SciencesAhvaz ***Iran Islamic Azad University Tehran Medical Sciences Tehran ***Iran

·AIM:To identify various risk factors that may play a significant role in the development of congenital nasolacrimal duct obstruction(CNLDO).·METHODS:This observational case-control study included a case group of 122 children less than two years of age with CNLDO who underwent probing and irrigation treatment at the ophthalmology department of Imam Khomeini Hospital in Ahvaz,Iran,from June 2022 to June2024.A control group of 122 age-matched children without CNLDO was also included for *** was collected from the children's medical records.·RESULTS:The study found a significant correlation between the occurrence of CNLDO and several maternal factors,such as preeclampsia,the use of levothyroxine,hypothyroidism,having more than three pregnancies(gravidity>3),natural pregnancy,and gestational diabetes ***,in children,factors,such as oxygen therapy,anemia,reflux,jaundice,and a family history of CNLDO in first-degree relatives were associated with CNLDO,and maternal preeclampsia and hypothyroidism were found to significantly increase the risk of developing CNLDO in children.·CONCLUSION:Given that CNLDO affects both premature and full-term children,the present findings may potentially facilitate the early identification of children and infants at risk of nasolacrimal duct obstruction,thereby preventing the onset of chronic dacryocystitis.

关键词： risk factors congenital nasolacrimal duct obstruction children

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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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