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Decade of optimizing therapy with direct-acting antiviral drugs and the changing profile of patients with chronic hepatitis C

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World Journal of Gastroenterology 2023年第6期29卷 949-966页

作者： MichałBrzdęk Dorota Zarębska-Michaluk federica invernizzi Marta Cilla Krystyna Dobrowolska Robert Flisiak Collegium Medicum Jan Kochanowski UniversityKielce 25-516Poland of Infectious Diseases Jan Kochanowski UniversityKielce 25-516Poland Center for Liver Disease Division of Internal Medicine and HepatologyIRCCS Ospedale San RaffaeleMilan 20-132Italy Department of Infectious Diseases and Hepatology Medical University of BiałystokBiałystok 15-540Poland

Chronic infection with the hepatitis C virus(HCV)remains a major health problem affecting approximately 58 million people *** the era of interferon(IFN)-based regimens,patients particularly infected with genotypes 1 and 4 achieved a low response *** implementation of direct-acting antivirals changed the landscape of HCV *** increase in effectiveness provided us with the hope of eliminating HCV as a significant public threat by *** the following years,there was an observed improvement in the treatment of HCV with genotype-specific regimens and highly effective pangenotypic options that are the most recent stage of the *** optimization of therapy was accompanied by changes in the patient profile from the beginning of the IFN-free era over *** treated with antiviral therapies were younger in successive periods,less burdened with comorbidities and comedications,more frequently treatment-naïve and had less advanced liver *** the IFN-free era,specific subpopulations such as patients with HCV/HIV coinfection,those with a history of previous treatment,patients with renal impairment or with cirrhosis had lower chances for a virologic ***,these populations should no longer be considered difficult to *** the high effectiveness of HCV therapy,there is a small percentage of patients with treatment ***,they can be effectively retreated with pangenotypic rescue regimens.

关键词： Hepatitis C virus Interferon Direct-acting antiviral Epidemiology Chronic hepatitis C

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Rectal neuroendocrine tumors:Current advances in management,treatment,and surveillance

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World Journal of Gastroenterology 2022年第11期28卷 1123-1138页

作者： Camilla Gallo Roberta Elisa Rossi federica Cavalcoli Federico Barbaro Ivo Boškoski Pietro invernizzi Sara Massironi Division of Gastroenterology and Center for Autoimmune Liver Diseases Department of Medicine and SurgeryUniversity of Milano-BicoccaEuropean Reference Network on Hepatological DiseasesSan Gerardo HospitalMonza 20900Italy Division of HPB Surgery Hepatology and Liver TransplantationDepartment of Pathophysiology and TransplantationUniversity of MilanENETS Center of ExcellenceFondazione IRCCS Istituto Nazionale Tumori(INTNational Cancer Institute)Milan 20133Italy Diagnostic and Therapeutic Endoscopy Unit Fondazione IRCCS Istituto Nazionale TumoriMilan 20133Italy Digestive Endoscopy Unit UniversitàCattolica del Sacro Cuore di RomaCenter for Endoscopic Research Therapeutics and TrainingFondazione Policlinico Universitario Agostino Gemelli IRCSSRome 00168Italy

Rectal neuroendocrine neoplasms(r-NENs)are considered among the most frequent digestive NENs,together with small bowel *** incidence has increased over the past few years,and this is probably due to the widespread use of endoscopic screening for colorectal cancer and the advanced endoscopic procedures available *** to the current European Neuroendocrine Tumor Society(ENETS)guidelines,well-differentiated r-NENs smaller than 10 mm should be endoscopically removed in view of their low risk of local and distant invasion.R-NENs larger than 20 mm are candidates for surgical resection because of their high risk of distant spreading and the involvement of the muscularis *** is an area of uncertainty regarding tumors between 10 and 20 mm,in which the metastatic risk is intermediate and the endoscopic treatment can be *** removed,the indications for surveillance are scarce and poorly codified by international guidelines,therefore in this paper,a possible algorithm is proposed.

关键词： Rectal neuroendocrine tumors Endoscopy Endoscopic submucosal dissection Resectable advanced disease Systemic therapy

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Any role for transarterial radioembolization in unresectable intrahepatic cholangiocarcinoma in the era of advanced systemic therapies?

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World Journal of Hepatology 2023年第12期15卷 1284-1293页

作者： Alessandra Elvevi Alice Laffusa federica Elisei Sabrina Morzenti Luca Guerra Antonio Rovere Pietro invernizzi Sara Massironi Division of Gastroenterology and Center for Autoimmune Liver Diseases Department of Medicine and SurgeryUniversity of Milano-Bicocca and European Reference Network on Hepatological Diseases(ERN RARELIVER)Fondazione IRCCS San Gerardo dei Tintori HospitalMonza 20900Italy Department of Nuclear Medicine Fondazione IRCCS San Gerardo dei Tintori University of Milano BicoccaMonza 20900Italy Medical Physics Fondazione IRCCS San Gerardo dei TintoriMonza 20900Italy Department of Radiology and Interventional Radiology Fondazione IRCCS San Gerardo dei Tintori HospitalMonza 20900Italy

Intrahepatic cholangiocarcinoma(iCCA)is recognized as the second most frequently diagnosed liver malignancy,following closely after hepatocellular *** incidence has seen a global upsurge in the past several ***,due to the lack of well-defined risk factors and limited diagnostic tools,iCCA is often diagnosed at an advanced stage,resulting in a poor *** surgery is the only potentially curative option,it is rarely ***,there are ongoing investigations into various treatment approaches for unresectable iCCA,including conventional chemotherapies,targeted therapies,immunotherapies,and locoregional *** study aims to explore the role of transarterial radioembolization(TARE)in the treatment of unresectable iCCA and provide a comprehensive *** findings suggest that TARE is a safe and effective treatment option for unresectable iCCA,with a median overall survival(OS)of 14.9 months in the study *** on TARE for unresectable iCCA,both as a first-line treatment(as a neo-adjuvant down-staging strategy)and as adjuvant therapy,have reported varying median response rates(ranging from 34%to 86%)and median OS(12-16 mo).These differences can be attributed to the heterogeneity of the patient population and the limited number of participants in the *** studies have identified tumor burden,portal vein involvement,and the patient’s performance status as key prognostic ***,a phase 2 trial evaluated the combination of TARE and chemotherapy(cisplatin-gemcitabine)as a first-line therapy for locally advanced unresectable *** results showed promising outcomes,including a median OS of 22 mo and a 22%achievement in down-staging the *** conclusion,TARE represents a viable treatment option for unresectable iCCA,and its combination with systemic chemotherapy has shown promising ***,it is important to consider treatment-independent factors that can influence ***

关键词： Intrahepatic cholangiocarcinoma Transarterial radioembolization Locoregional treatment Overall Survival Response rates Neo-adjuvant therapy Combined Therapies Prognostic factors

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Comprehensive review of autoantibodies in patients with hyper-IgM syndrome

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Cellular & Molecular Immunology 2018年第6期15卷 610-617页

作者： Mohamed-Ridha Barbouche Qubo Chen Marco Carbone Imen Ben-Mustapha Zakera Shums Mehdi Trifa federica Malinverno Francesca Bernuzzi Haiyan Zhang Nourhen Agrebi Gary L Norman Christopher Chang M Eric Gershwin Pietro invernizzi Laboratory of Immunology Institute Pasteur de Tunis and Faculty of MedicineUniversity Tunis El Manar1002 TunisTunisia Humanitas Clinical and Research Center 20089 RozzanoItaly Clinical Laboratory Guangdong Provincial Hospital of Chinese medicine510000 GuangzhouChina Division of Gastroenterology and Center for Autoimmune Liver Diseases Department of Medicine and SurgeryUniversity of Milan-Bicocca20900 Monza(MB)Italy Department of Research and Development Inova Diagnostics92131 San DiegoCAUSA Department of Anesthesia and Intensive Care Children Hospital Bechir HamzaTunis and Faculty of MedicineUniversity Tunis El Manar1007 TunisTunisia Division of Gastroenterology and Hepatology Key Laboratory of Gastroenterology and HepatologyMinistry of HealthStateKey Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive Disease200001 ShanghaiChina Division of Rheumatology Allergy and Clinical ImmunologyUniversity of California at Davis95616 DavisCAUSA

Hyper-immunoglobulin M syndrome is an X-linked primary immunodeficiency disease caused by mutations in the CD40 ligand *** CD40 ligand has been recently highlighted as playing a key role in the pathogenesis of primary biliary *** the present study,we assessed an extensive set of serum autoantibodies in a series of well-defined patients with hyper-immunoglobulin M ***,liver-related and liver-not-related autoantibodies IgG,IgM and IgA were tested by ELISA and standard indirect immunofluorescence in HEp-2 cells in 13 Tunisian patients(8 males and 5 females,aged 1–12 years)with hyper-immunoglobulin M syndrome during 1995–2012 and,as controls,21 age-and gender-matched blood *** level of IgM antibody against MIT3 was significantly higher in patients than in controls(35.8 vs 10.7,P=0.002).Half of the hyperimmunoglobulin M syndrome patients were found to be anti-MIT3 IgM positive vs none of the controls(Po0.0001).Twenty-three percent of patients were found to be anti-sp100 antibody positive vs only 0.05%of *** immunofluorescence,92.3%of patients were MIT3 IgM positive vs none of the *** conclusion,the IgM class of anti-MIT3 antibodies was shown to be present by both ELISA and immunofluorescence in most of the patients with hyper-immunoglobulin M *** presence of the hallmark of primary biliary cholangitis,a disease where the CD40 ligand is a key player,in an immunodeficiency disease caused by mutations in the CD40 ligand gene is very intriguing and opens new scenarios in understanding the immune pathogenesis of primary biliary cholangitis.

关键词： immunoglobulin M autoantibodies immunodeficiency hyper-immunoglobulin M syndrome primary biliary cholangitis

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Insights on ZEB1-AS1:emerging role from cancer to neurodegeneration

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Neural Regeneration Research 2024年第6期19卷 1187-1188页

作者： Stephana Carelli federica Rey Erika Maghraby Cristina Cereda Pediatric Research Center“Romeo ed Enrica invernizzi” Department of Biomedical and Clinical SciencesUniversity of MilanMilanItaly Center of Functional Genomics and Rare Diseases Department of PediatricsBuzzi Children’s HospitalMilanItaly Department of Biology and Biotechnology“L.Spallanzani” University of PaviaPaviaItaly

Implications for lncRNAs in the central nervous system:Transcriptional dysregulation is a key contributor to the pathogenesis of a wide range of diseases and long non-coding RNAs(lncRNAs)are highly expressed in the nervous ***,amongst the over 50,000 lncRNAs expressed in the human genome,more than 40%are specifically expressed in the brain where their roles in brain development,neuron functions,maintenance.

关键词： ZEB1 diseases pathogenesis

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Mitochondrial dysfunctions in neurodegenerative diseases:role in disease pathogenesis,strategies for analysis and therapeutic prospects

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Neural Regeneration Research 2022年第4期17卷 754-758页

作者： federica Rey Sara Ottolenghi Gian Vincenzo Zuccotti Michele Samaja Stephana Carelli Department of Biomedical and Clinical Sciences“L.Sacco” University of MilanMilanoItaly Paediatric Clinical Research Centre Fondazione“Romeo ed Enrica invernizzi” University of MilanoMilanoItaly Laboratory of Biochemistry Department of Health SciencesUniversity of MilanMilanoItaly Department of Paediatrics Children’s Hospital“V.Buzzi”MilanoItaly

Fundamental organelles that occur in every cell type with the exception of mammal erythrocytes,the mitochondria are required for multiple pivotal processes that include the production of biological energy,the biosynthesis of reactive oxygen species,the control of calcium homeostasis,and the triggering of cell *** disruption of anyone of these processes has been shown to impact strongly the function of all cells,but especially of *** this review,we discuss the role of the mitochondria impairment in the development of the neurodegenerative diseases Amyotrophic Lateral Sclerosis,Parkinson's disease and Alzheimer's *** highlight how mitochondria disruption revolves around the processes that underlie the mitochondria's life cycle:fusion,fission,production of reactive oxygen species and energy *** genetic and sporadic forms of neurodegenerative diseases are unavoidably accompanied with and often caused by the dysfunction in one or more of the key mitochondrial ***,in order to get in depth insights into their health status in neurodegenerative diseases,we need to focus into innovative strategies aimed at characterizing the various mitochondrial *** techniques include Mitostress,Mitotracker,transmission electron microscopy,oxidative stress assays along with expression measurement of the proteins that maintain the mitochondrial *** will also discuss a panel of approaches aimed at mitigating the mitochondrial *** include canonical drugs,natural compounds,supplements,lifestyle interventions and innovative approaches as mitochondria transplantation and gene *** conclusion,because mitochondria are fundamental organelles necessary for virtually all the cell functions and are severely impaired in neurodegenerative diseases,it is critical to develop novel methods to measure the mitochondrial state,and novel therapeutic strategies aimed at improving their health.

关键词： Alzheimer's disease amyotrophic lateral sclerosis mitochondria mitochondria modulation mitochondrial dysfunction mitochondrial health Mitostress Mitotracker neurodegenerative disease Parkinson's disease

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Characterization of the molecular dysfunctions occurring in Aicardi-Goutieres syndrome patients with mutations in ADAR1

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Genes & Diseases 2024年第3期11卷 116-119页

作者： Sofan Al wardat Loredana Frasinlli Elisa Orecchini federica Rey Silvia Anna Ciafre Silvia Galardi Jessica Garau Stella Gagliardi Simona Orcesi Davide Tonduti Stephana Carelli Cristina Cereda Ernesto Picardi Alessandro Michienzi Department of Biomedicine and Prevention University of Rome Tor VergataRome 00133Italy Pediatric Clinical Research Center"Romeo ed Enrica invernizzi" Department of Biomedical and Clinical SciencesUniversity of MilanoMilano 20157Italy Center of Functional Genomics and Rare Diseases Department of PediatricsBuzzi Children's HospitalMilano20154Italy Department of Child Neurology and Psychiatry IRccs Mondino FoundationPavia 27100Italy Unit of Pediatric Neurology C.O.A.L.A(Center for Diagnosis and Treatment of Leukodystrophies)Buzzi Children's HospitalMilano 20154Italy Department of Biosciences Biotechnologies and EnvironmentUniversityof Bari"AldoMoro"Bari 70125Italy Institute of Biomembranes Bioenergetics and Molecular Biotechnologies(IBIOM)National Research Council(CNR)Bari 70126Italy Biostructures and Biosystems National Institute(INBB) Rome00136Italy Institute of Biochemistry and Cell Biology IBBC-CNRCampus Adriano Buzzati TraversoRome 00015Italy

Aicardi-Goutieres syndrome(AGS)is a systemic inflammatory disorder caused by mutations in any one of the nine different genes,whose deficiency provokes a type I(interferon)IFN response probably central to pathogenesis.^(1) ADAR1,one of the genes mutated in AGS(AGS6),encodes for an enzyme that belongs to the ADAR family(ADAR1,ADAR2,and ADAR3)that catalyzes the conversion of adenosine to inosine within double-stranded RNAs(dsRNAs)(RNA editing A-to-1).

关键词： ADAR1 interferon res

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