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

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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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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Real-world effectiveness and safety of direct-acting antivirals in hepatitis C virus patients with mental disorders

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World Journal of Gastroenterology 2023年第25期29卷 4085-4098页

作者： Dorota Dybowska Dorota Zarebska-Michaluk Piotr Rzymski Hanna Berak Beata Lorenc Marek Sitko Michal Dybowski Wlodzimierz Mazur Magdalena Tudrujek-Zdunek Justyna Janocha-Litwin Ewa Janczewska Jakub Klapaczynski Anna Parfieniuk-Kowerda Anna Piekarska Barbara Sobala-Szczygiel Krystyna Dobrowolska Malgorzata Pawlowska Robert Flisiak Department of infectious diseases and hepatology Faculty of MedicineNicolaus Copernicus UniversityBydgoszcz 85-030Poland Department of infectious diseases and Allergology Jan Kochanowski UniversityKielce 25-317Poland Department of infectious diseases Provincial HospitalKielce 25-317Poland Department of Environmental Medicine University of Medical SciencesPoznań60-806Poland Integrated Science Association Universal Scientific Education and Research NetworkPoznań60-806Poland Outpatient Clinic Hospital for Infectious Diseases in WarsawWarsaw 01-201Poland Pomeranian Center of infectious diseases Medical UniversityGdańsk 80-214Poland Department of infectious and Tropical diseases Jagiellonian UniversityKraków 31-088Poland Utrecht University School of Economics Utrecht UniversityUtrecht 3584 ECNetherlands Clinical Department of infectious diseases Medical University of SilesiaChorzów 41-500Poland Department of infectious diseases Medical University of LublinLublin 20-059Poland Department of infectious diseases and hepatology Medical University of WrocławWrocław 50-367Poland Department of Basic Medical Sciences Faculty of Public Health in BytomMedical University of SilesiaKatowice 40-007Poland Department of Internal Medicine and hepatology Central Clinical Hospital of the Ministry of Internal Affairs and AdministrationWarsaw 00-241Poland Department of infectious diseases and hepatology Medical University of BiałystokBiałystok 15-089Poland Department of infectious diseases and hepatology Medical University ofŁódźŁódź91-347Poland Department of infectious diseases and hepatology Medical University of SilesiaBytom 41-902Poland Collegium Medicum Jan Kochanowski UniversityKielce 25-317Poland

BACKGROUND It is estimated that 58 million people worldwide are infected with the hepatitis C virus(HCV).Patients with severe psychiatric disorders could not be treated with previously available interferon-based therapies due to their unfavorable side effect *** has changed with the introduction of direct-acting antivirals(DAA),although their real-life tolerance and effectiveness in patients with different psychiatric disorders remain to be *** To evaluate the effectiveness and safety of DAA in patients with various mental *** This was a retrospective observational study encompassing 14272 patients treated with DAA for chronic hepatitis C in 22 Polish hepatology centers,including 942 individuals diagnosed with a mental disorder(anxiety disorder,bipolar affective disorder,depression,anxiety-depressive disorder,personality disorder,schizophrenia,sleep disorder,substance abuse disorder,and mental illness without a specific diagnosis).The safety and effectiveness of DAA in this group were compared to those in a group without psychiatric illness(n=13330).Antiviral therapy was considered successful if serum ribonucleic acid(RNA)of HCV was undetectable 12 wk after its completion[sustained virologic response(SVR)].Safety data,including the incidence of adverse events(AEs),serious AEs(SAEs),and deaths,and the frequency of treatment modification and discontinuation,were collected during therapy and up to 12 wk after treatment *** entire study population was included in the intent-to-treat(ITT)***-protocol(PP)analysis concerned patients who underwent HCV RNA evaluation 12 wk after completing *** Among patients with mental illness,there was a significantly higher percentage of men,treatmentnaive patients,obese,human immunodeficiency virus and hepatitis B virus-coinfected,patients with cirrhosis,and those infected with genotype 3(GT3)while infection with GT1b was more frequent in the population without psychia

关键词： Hepatitis C Mental disorders Direct-acting antivirals

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sFRP-4, a potential novel serum marker for chronic hepatitis B-related hepatocellular carcinoma

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Hepatobiliary & Pancreatic diseases International 2015年第2期14卷 164-170页

作者： Cheng Xu Xiang-Hua Zeng Li Wang Shi-Qi Tao Quan-Xin Wu Peng Zhu Guo-Hong Deng Yu-Ming Wang Institute of infectious diseases Southwest HospitalThird Military Medical University Chongqing Key Laboratory for Research of infectious diseases

BACKGROUND：The current methods used for diagnosing hepatocellular carcinoma（HCC）are ***,we assessed the serum levels of secreted frizzled related protein 4（s FRP-4）for diagnosing HCC in patients infected with chronic hepatitis B（CHB）.METHODS：In 272 patients with CHB enrolled,142 were pa tients with ***-three healthy subjects were recruited as healthy *** CHB patients were assigned to a test group or a validation group based on the time of enrollment. Human antibody arrays were used to screen 15 patients （8 CHB-related HCC patients, 7 CHB patients） for serum mark- ers. Four markers and one candidate marker were assessed in the test group and validation group, respectively. RESULTS： Human antibody assays indicated that the serum levels of sFRP-4 in HCC patients were significantly higher than those in CHB patients （P〈0,05）. Additionally, serum sFRP-4 levels were significantly higher in the HCC patients than those in the non-HCC patients in both test group （79.7 vs 41.3 ng/mL; P〈0.001） and validation group （89.0 vs 39.0 ng/mL; P〈0.001）. Areas under the Receiver Operating Charac- teristic curves （AUCs） for alpha-fetoprotein （AFP） and sFRP-4 were similar in both test group and validation group. In the test group, the combination of sFRP-4 （a sensitivity of 94.4%, a specificity of 60.5% at 46.4 ng/mL） and AFP （a sensitivity of 75.0%, a specificity of 87.2% at 11.3 ng/mL） showed better performance for diagnosing HCC （a sensitivity of 79.2% and a specificity of 95.3%）. The AUC for combined sFRP-4 and AFP increased to 0.941 （95% CI： 0.908-0.975）, and similar results were seen in the validation group. CONCLUSION： sFRP-4 is a candidate serum marker for diagnosing HCC in CHB patients, and the combination of sFRP-4 with AFP may improve the diagnostic accuracy of HCC.

关键词： chronic hepatitis B hepatocellular carcinoma s FRP-4 serum marker

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Is liver biopsy still needed in children with chronic viral hepatitis?

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World Journal of Gastroenterology 2015年第42期21卷 12141-12149页

作者： Maria Pokorska-?piewak Barbara Kowalik-Miko?ajewska Ma?gorzata Aniszewska Magdalena Pluta Magdalena Marczyńska Department of Children’s infectious diseases Medical University of Warsaw Warsaw Hospital for infectious diseases

Liver biopsy is a standard method used for obtaining liver tissue for histopathological evaluation. Since reliable serological and virological tests are currently available, liver biopsy is no longer needed for the etiological diagnosis of chronic hepatitis B and C. However, liver histology remains the gold standard as a prognostic tool, providing information about the liver disease progression(grading of necroinflammatory activity and staging of fibrosis) and serving clinicians in the management and therapeutic decisions. In general, histopathological evaluation is indicated before starting the antiviral treatment. Main limitations of the liver biopsy include its invasive and painful procedure, sampling errors and the inter- and intra-observer variability. In addition, indications for the liver biopsy in pediatric patients with chronic viral hepatitis were questioned recently, and efforts have been made toward the development of non-invasive methods as an alternative to the liver biopsy. The most commonly used methods are novel imaging studies(elastography) and combinations of biomarkers. However, to date, none of these tests was validated in children with chronic viral hepatitis. In this review, we present the current status of the liver biopsy in the management of chronic viral hepatitis B and C in pediatric population, including specific indications, complications, contraindications, problems, limitations, and alternative non-invasive methods.

关键词： Liver biopsy Hepatitis B Hepatitis C Pathology Ela

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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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MicroRNAs as non-invasive diagnostic biomarkers for gastric cancer:Current insights and future perspectives

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World Journal of Gastroenterology 2018年第30期24卷 3313-3329页

作者： Alexander Link Juozas Kupcinskas Department of Gastroenterology Hepatology and Infectious DiseasesOtto-von-Guericke University Institute for Digestive Research and Department of Gastroenterology Lithuanian University of Health Sciences

Non-invasive diagnostic biomarkers may contribute to an early identification of gastric cancer(GC) and improve the clinical ***,no sensitive and specific screening biomarkers are available yet and the currently available approaches are limited by the nature of the *** is a heterogenic disease with various distinct genetic and epigenetic events that occur during the multifactorial cascade of *** RNAs(mi RNAs) are commonly deregulated in gastric mucosa during the Helicobacter pylori infection and in stepwise manner from chronic gastritis,through preneoplastic conditions such as atrophic gastritis and intestinal metaplasia,to early dysplasia and invasive *** of mi RNAs in blood in 2008 led to a great interest on mi RNA-based diagnostic,prognostic biomarkers in *** this review,we provide the most recent systematic review on the existing studies related to mi RNAs as diagnostic biomarkers for ***,we systematically evaluate 75 studies related to differential expression of circulating mi RNAs in GC patients and provide novel view on various heterogenic aspects of the existing data and summarize the methodological ***,we highlight several important aspects crucial to improve the future translational and clinical research in the field.

关键词： microRNA biomarkers screening stomach gastric cancer systematic review blood serum plasma

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Dual-sugar tests of small intestinal permeability are poor predictors of bacterial infections and mortality in cirrhosis: a prospective study

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World Journal of Gastroenterology 2016年第11期22卷 3275-3284页

作者： Anika Vogt Philipp A Reuken Sven Stengel Andreas Stallmach Tony Bruns Department of Internal Medicine IV (Gastroenterology Hepatologyand Infectious Diseases)Jena University Hospital Center for Sepsis Control and Care Jena University Hospital

AIM: To prospectively analyze the impact of increased intestinal permeability (IP) on mortality and the occurrence of infections in patients with ***: IP was quantified using the lactulose/mannitol (L/M) test in 46 hospitalized patients with cirrhosis (25 Child-Pugh A/B, 21 Child-Pugh C) and in 16 healthy controls. Markers of inflammation [LPS-binding protein, Interleukin-6 (IL-6)] and enterocyte death [intestinal fatty-acid binding protein (I-FABP)] were determined in serum using enzyme-linked immunosorbent assays. Patients were followed for one year and assessed for survival, liver transplantation, the necessity of hospitalization and the occurrence of bacterial infections. The primary endpoint of the study was defined as differences in survival between patients with pathological and without pathological lactulose/mannitol ***: Thirty-nine (85%) patients with cirrhosis had a pathologically increased IP index (L/M ratio > 0.07) compared to 4 (25%) healthy controls (P < 0.0001). The IP index correlated with the Child-Pugh score (r = 0.484, P = 0.001) and with serum IL-6 (r = 0.342, P = 0.02). Within one year, nineteen (41%) patients developed a total of 33 episodes of hospitalization with bacterial or fungal infections. Although patients who developed spontaneous bacterial peritonitis (SBP) (n = 7) had a higher IP index than patients who did not (0.27 vs 0.14, P = 0.018), the baseline IP index did not predict time to infection, infection-free survival or overall survival, neither when assessed as linear variable, as tertiles, nor dichotomized using an established cut-off. In contrast, model for end-stage liver disease score, Child-Pugh score, the presence of ascites, serum IL-6 and I-FABP were univariate predictors of infection-free ***: Although increased IP is a frequent phenomenon in advanced cirrhosis and may predispose to SBP, it failed to predict infection-free and overall survival in this prospective coho

关键词： Intestinal permeability Liver cirrhosis Lactulose/mannitol ratio Spontaneous bacterial peritonitis Bacterial translocation

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Recombinant adenovirus containing hyper-interleukin-6 and hepatocyte growth factor ameliorates acute-on-chronic liver failure in rats

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World Journal of Gastroenterology 2016年第16期22卷 4136-4148页

作者： Dan-Dan Gao Jia Fu Bo Qin Wen-Xiang Huang Chun Yang Bei Jia Chongqing Key Laboratory of infectious diseases and Parasitic diseases Department of Infectious Diseases The First Affiliated Hospital of Chongqing Medical University

AIM: To investigate the protective efficacy of recombinant adenovirus containing hyper-interleukin-6 (Hyper-IL-6, HIL-6) and hepatocyte growth factor (HGF) (Ad-HGF-HIL-6) compared to that of recombinant adenovirus containing either HIL-6 or HGF (Ad-HIL-6 or Ad-HGF) in rats with acute-on-chronic liver failure (ACLF).METHODS: The recombinant adenoviruses containing HIL-6 and/or HGF were constructed. We established an ACLF model, and rats were randomly assigned to control, model, Ad-GFP, Ad-HIL-6, Ad-HGF or Ad-HGF-HIL-6 group. We collected serum and liver tissue samples to test pathological changes, biochemical indexes and molecular biological ***: Attenuated alanine aminotransferase, prothrombin time, high-mobility group box 1 (HMGB1), endotoxin, tumour necrosis factor (TNF)-α and interferon-γ were observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. Likewise, reduced hepatic damage and apoptotic activity, as well as reduced HMGB1 and Bax proteins, but raised expression of Ki67 and Bcl-2 proteins and Bcl-2/Bax ratio were also observed in the Ad-HGF-, Ad-HIL-6- and Ad-HGF-HIL-6-treated rats with ACLF. More significant changes were observed in the Ad-HGF-HIL-6 treatment group without obvious side effects. Furthermore, caspase-3 at the protein level decreased in the Ad-HIL-6 and Ad-HGF-HIL-6 treatment groups, more predominantly in the latter ***: This study identifies that the protective efficacy of Ad-HGF-HIL-6 is more potent than that of Ad-HGF or Ad-HIL-6 in ACLF rats, with no significant side effects.

关键词： Acute-on-chronic liver failure Recombinant adenovirus Hyper-interleukin-6 Hepatocyte growth factor Inflammatory cytokines

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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

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