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Multi-tissue transcriptomics of a unique monozygotic discordant twin case of severe progressive osseous heteroplasia

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Genes & Diseases 2024年第3期11卷 22-25页

作者： Alberto Gomez-Carballa Maria Jose Curras-Tuala Sara Pischedda Miriam Cebey-Lopez Jose Gomez-Rial Irene Rivero-Cale Jacobo Pardo-seco Xabier Bello Sandra Viz-Lasheras Antonio Justicia-Grande Julian Montoto-Louzao Alba Camino-Mera Isabel Ferreiros-Vidal Maximo Fraga Jose RAntunez Rodolfo Gomez Federico Martinon-Torres Antonio Salas Genetics Vaccines and Infections Research Group(GENVIP)Instituto de Investigacion Sanitaria de SantiagoSantiagode CompostelaGalicia 15706Spain Translational Pediatrics and Infectious Diseases Department of PediatricsHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Laboratorio de Inmunologia Servicio de Andlisis ClinicosHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Unidade de Xenetica Instituto de Ciencias Forenses(INCIFOR)Facultade de MedicinaUniversidade de Santiago de Compostelaand GenPoB Research GroupInstituto de Investigacion SanitariaHospital Clinico Universitario de Santiago de CompostelaServicio Galego de Saude(SERGAS)Galicia 15706Spain Musculoskeletal Pathology Group Instituto de Investigacion Sanitaria de SantiagoServicio Galego de Saude(SERGAS)Santiago de CompostelaGalicia 15706Spain Department of Pathology Hospital Clinico Universitario de Santiago de Compostela(SERGAS)Galicia 15706Spain Unidad Integrada de BiobancosBiomodelos 3D y Modelos Animales IDIS(lnstituto de Investigacion Sanitaria de Santiagode Compostela)Galicia15706Spain centro de Investigacion Biomedica en Red de Enfermedades Respiratorias(CIBER-ES) MadridSpain

Progressive osseous heteroplasia(POH)is an ultra-rare autosomal dominant disabling disorder characterized by heterotopic ossification(HO).It is caused by heterozygous inactivating mutations in the GNAS(guanine nucleotide-binding protein alpha-stimulating activity polypeptide)***,the molecular mechanisms underlying HO remain poorly *** a treatment for POH is not yet available,the identification of the mechanisms driving POH in affected tissues using gene expression may be of great help to underestand the molecular basis of POH and develop new therapeutic approaches.

关键词： stimulating driving asi

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Role of hepatitis B virus in development of hepatocellular carcinoma:Focus on covalently closed circular DNA

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World Journal of Hepatology 2022年第5期14卷 866-884页

作者： Claryssa Bianca Elizabeth Sidhartha Claudio Tiribelli Korri Elvanita El-Khobar Caecilia H C Sukowati Department of Biomedicine Indonesia International Institute for Life SciencesJakarta 13210Indonesia centro studi fegato Fondazione Italiana Fegato ONLUSTrieste 34149Italy Eijkman Center for Molecular Biology National Research and Innovation Agency(BRIN)Jakarta 10340Indonesia

Chronic infection with hepatitis B virus(HBV)remains a major global health problem,especially in developing *** may lead to prolonged liver damage,fibrosis,cirrhosis,and hepatocellular *** chronic HBV infection is related to host immune response and the stability of the covalently closed circular DNA(cccDNA)in human *** addition to being essential for viral transcription and replication,cccDNA is also suspected to play a role in persistent HBV infections or hepatitis relapses since cccDNA is very stable in non-dividing human *** the pathogenicity and oncogenicity of HBV components would be essential in the development of new diagnostic tools and treatment *** review summarizes the role and molecular mechanisms of HBV cccDNA in hepatocyte transformation and hepatocarcinogenesis and current efforts to its detection and targeting.

关键词： Hepatitis B virus Covalently closed circular DNA Hepatocellular carcinoma Hepatocarcinogenesis

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Immunotherapy against programmed death-1/programmed death ligand 1 in hepatocellular carcinoma: Importance of molecular variations, cellular heterogeneity, and cancer stem cells

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World Journal of Stem Cells 2021年第7期13卷 795-824页

作者： Caecilia H C Sukowati Korri Elvanita El-Khobar Claudio Tiribelli centro studi fegato Fondazione Italiana Fegato ONLUSTrieste 34149Italy Hepatitis Unit Eijkman Institute for Molecular BiologyJakarta 10430Indonesia

Hepatocellular carcinoma(HCC)is a heterogeneous malignancy related to diverse etiological *** oncogenic mechanisms and genetic variations lead to multiple HCC molecular ***,an immune-based strategy using immune checkpoint inhibitors(ICIs)was presented in HCC therapy,especially with ICIs against the programmed death-1(PD-1)and its ligand ***,despite the success of anti-PD-1/PD-L1 in other cancers,a substantial proportion of HCC patients fail to *** this review,we gather current information on biomarkers of anti-PD-1/PD-L1 treatment and the contribution of HCC heterogeneity and hepatic cancer stem cells(CSCs).Genetic variations of PD-1 and PD-L1 are associated with chronic liver disease and progression to ***-L1 expression in tumoral tissues is differentially expressed in CSCs,particularly in those with a close association with the tumor *** information will be beneficial for the selection of patients and the management of the ICIs against PD-1/PD-L1.

关键词： Hepatocellular carcinoma Programmed death-1 Programmed death ligand 1 Cancer stem cells Cancer heterogeneity Genetic variants

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Non-invasive prenatal testing can detect silent cancers in expecting mothers

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Genes & Diseases 2024年第2期11卷 585-588页

作者： Alessandro Ottaiano Monica Ianniello Nadia Petrillo Mariachiara Santorsola Luigia De Falco Salvatore Giovanni Castaldi Maria Antonietta Castaldi Valentina Giudice Carmine Selleri Giovanni Savarese Unit of Innovative Therapies for Abdominal Metastases Istituto Nazionale Tumori di NapoliIRCCS “G.Pascale”Via Mariano SemmolaNapoli 80131Italy AMES Centro Polidiagnostico Strumentale SRLVia Padre Carmine Fico 24Casalnuovo Di Napoli 80013Italy Specialization School of Clinical Pathology Università degli Studi di SalernoVia Giovanni Paolo II 132Fisciano 84084Italy Unit of High-Risk Pregnancy and Prenatal Diagnosis University Hospital “San Giovanni di Dio e Ruggi d'Aragona”Via San LeonardoSalerno 84125Italy Hematology and Transplant Center University Hospital “San Giovanni di Dio e Ruggi d'Aragona”Via San LeonardoSalerno 84125Italy Department of Medicine Surgery and Dentistry“Scuola Medica Salernitana”Via Salvador Allende 43Baronissi 84081Italy

Pregnancy is a unique physiological state in which several changes *** of the most important aspects is the maternal immune system,which sets to tolerate the presence of thedeveloping fetus(a semi-allogeneic organism),while at the same time providing protection against pathogens.1 Pregnancy has long been known to affect the risk of certain cancers including breast cancer in the short term,gestational trophoblastic disease(GTD),cervical cancer,and melanoma.2,3 The reasons for the increased risk of these cancers during pregnancy are not fully understood,but several hypotheses have been proposed as the hormonal and immune system changes.

关键词： mother cancers fetus

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Radioisotope production using lasers:From basic science to applications

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Matter and Radiation at Extremes 2024年第3期9卷 31-44页

作者： M.R.D.Rodrigues A.Bonasera M.Scisciò J.A.Pérez-Hernández M.Ehret F.Filippi P.L.Andreoli M.Huault H.Larreur D.Singappuli D.Molloy D.Raffestin M.Alonzo G.G.Rapisarda D.Lattuada G.L.Guardo C.Verona Fe.Consoli G.Petringa A.McNamee M.La Cognata S.Palmerini T.Carriere M.Cipriani G.Di Giorgio G.Cristofari R.De Angelis G.A.P.Cirrone D.Margarone L.Giuffrida D.Batani P.Nicolai K.Batani R.Lera L.Volpe D.Giulietti S.Agarwal M.Krupka S.Singh Fa.Consoli Cyclotron Institute Texas A&M UniversityCollege StationTexas 77840USA Laboratori Nazionali del Sud Istituto Nazionale di Fisica Nucleare(LNS-INFN)CataniaItaly ENEA Fusion and Technologies for Nuclear Safety and Security Department-CFrascatiItaly centro de Láseres Pulsados(clpu) VillamayorSpain Universidad de Salamanca SalamancaSpain Centre Lasers Intenses et Applications(CELIA) Universitéde BordeauxCNRSCEATalenceFrance HB11 Energy Holdings Pty FreshwaterNew South WalesAustralia School of Mathematics and Physics Queen’s University BelfastBelfastUnited Kingdom Dipartimento di Fisica e Astronomia“E.Majorana ”Università di CataniaCataniaItaly Facoltàdi Ingegneria e Architettura Universitàdegli Studi di Enna“Kore”EnnaItaly Dipartimento di Ingegneria Industriale Universitàdi Roma“Tor Vergata”RomaItaly Dipartimento di Fisica e Geologia Universitàdegli Studi di PerugiaPerugiaItaly Istituto Nazionale di Fisica Nucleare Sezione di PerugiaPerugiaItaly ELI Beamlines Facility the Extreme Light Infrastructure ERICDolni BrezanyCzech Republic ETSIA Universidad Politécnica de MadridMadridSpain Dipartimento Fisica “E.Fermi”Universitàdi Pisa and INFNPisaItaly FZU–Institute of Physics of Czech Academy of Sciences PragueCzech Republic Institute of Plasma Physics of Czech Academy of Sciences PragueCzech Republic

The discovery of chirped pulse amplification has led to great improvements in laser technology,enabling energetic laser beams to be compressed to pulse durations of tens of femtoseconds and focused to a few *** with energies of tens of MeV can be accelerated using,for instance,target normal sheath acceleration and focused on secondary *** such conditions,nuclear reactions can occur,with the production of radioisotopes suitable for medical *** use of high-repetition lasers to produce such isotopes is competitive with conventional methods mostly based on *** this paper,we study the production of^(67)Cu,^(63)Zn,^(18)F,and^(11)C,which are currently used in positron emission tomography and other *** the same time,we study the reactions^(10)B(p,α)^(7)Be and^(70)Zn(p,4n)^(67)Ga to put further constraints on the proton distributions at different angles,as well as the reaction^(11)B(p,α)^(8)Be relevant for energy *** experiment was performed at the 1 PW laser facility at VegaⅢin Salamanca,*** distributions of radioisotopes in the forward(with respect to the laser direction)and backward directions were measured using a high purity germanium *** results are in reasonable agreement with numerical estimates obtained following the approach of Kimura and Bonasera[*** ***.,Sect.A 637,164–170(2011)].

关键词： purity estimates backward

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The challenge of molecular selection in liver-limited metastatic colorectal cancer for surgical resection: a systematic review and meta-analysis in the context of current and future approaches

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Oncology Research 2024年第9期32卷 1407-1422页

作者： ROSSANA RONCATO JERRY POLESEL FEDERICA TOSI ELENA PERUZZI ERIKA BRUGUGNOLI CLAUDIA LAURIA PANTANO MARIA FURFARO FILIPPO DI GIROLAMO ALESSANDRO NANI ARIANNA PANI NOEMI MILAN ELENA DE MATTIA ANDREA SARTORE-BIANCHI ERIKA CECCHIN Experimental and Clinical Pharmacology Unit Centro di Riferimento Oncologico di Aviano(CRO)IRCCSAviano33081Italy Department of Medicine(DMED) University of UdineUdine33100Italy Unit of Cancer Epidemiology Centro di Riferimento Oncologico di Aviano(CRO)IRCCSAviano33081Italy Department of Oncology and Hemato-Oncology Universitàdegli Studi di MilanoMilan20122Italy Department of Hematology Oncologyand Molecular MedicineGrande Ospedale Metropolitano NiguardaMilan20122Italy Oncology Pharmacy Unit IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino AmadoriMeldola47014Italy Pharmacy Unit Fondazione IRCCS Istituto Tumori di MilanoMilan20122Italy Department of Pharmacy Ca’Foncello Treviso Regional HospitalPiazzale Ospedale 1Treviso31100Italy Department of Medical Surgical and Health Sciences University of TriesteTrieste34127Italy Hospital Pharmacy Cattinara HospitalAzienda Sanitaria Universitaria Giuliano IsontinaTrieste34148Italy Department of Oncology and Onco-Hematology Postgraduate School of Clinical Pharmacology and ToxicologyUniversity of MilanMilan20122Italy

Objectives:Treatment of metastatic colorectal cancer(mCRC)includes resection of liver metastases(LM),however,no validated biomarker identifies patients most likely to benefit from this *** meta-analysis aimed to assess the impact of the most relevant molecular alterations in cancer-related genes of CRC(i.e.,RAS,BRAF,SMAD4,PIK3CA)as prognostic markers of survival and disease recurrence in patients with mCRC surgically treated by LM ***:A systematic literature review was performed to identify studies reporting data regarding survival and/or recurrence in patients that underwent complete liver resection for CRC LM,stratified according to RAS,BRAF,PIK3CA,and SMAD4 mutational *** ratios(HRs)from multivariate analyses were pooled in the meta-analysis and various adjustment strategies for confounding factors were *** search was conducted in numerous databases,including MEDLINE(PubMed),Embase,Cumulative Index to Nursing and Allied Health Literature(CINAHL)(EBSCO host),and WHO Global Index Medicus,through March 18th,***-analyses,editorials,letters to the editor,case reports,studies on other primary cancers,studies with primary metastatic sites other than the liver,studies lacking specific oncological outcome variables or genetic data,non-English language studies,and studies omitting residual disease data from liver metastasectomy were *** remaining 47 studies were summarized in a descriptive table which outlines the key characteristics of each study and final results were graphically ***:RAS mutation status was negatively associated with overall survival(OS)(HR,1.68;95%CI,1.54–1.84)and recurrence free survival(RFS)(HR,1.46;95%CI,1.33–1.61).A negative association was also found for BRAF regarding OS(HR,2.64;95%CI,2.15–3.24)and RFS(HR,1.89;95%CI,1.32–2.73)and SMAD4 regarding OS(HR,1.93;95%CI,1.56–2.38)and RFS(HR,1.95;95%CI,1.31–2.91).For PIK3CA only three studies were eligible and no significant associati

关键词： Metastasectomy Liver metastases RAS BRAF SMAD4 PIK3CA Colorectal

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Hepatic cancer stem cells and drug resistance: Relevance in targeted therapies for hepatocellular carcinoma

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World Journal of Hepatology 2010年第3期2卷 114-126页

作者： Caecilia HC Sukowati Natalia Rosso Lory S Crocè Claudio Tiribelli centro studi fegato AREA Science Park Basovizza centro clinico studi fegato University of Trieste

Hepatocellular carcinoma (HCC) is one of most common malignancies in the world. Systemic treatments for HCC, particularly for advanced stages, are limited by the drug resistance phenomenon which ultimately leads to therapy failure. Recent studies have indicated an association between drug resistance and the existence of the cancer stem cells (CSCs) as tumor initiating cells. The CSCs are resistant to conventional chemotherapies and might be related to the mechanisms of the ATP Binding Cassette (ABC) transporters and alterations in the CSCs signaling pathways. Therefore, to contribute to the development of new HCC treatments, further information on the characterization of CSCs, the modulation of the ABC transporters expression and function and the signaling pathway involved in the self renewal, initiation and maintenance of the cancer are required. The combination of transporters modulators/inhibitors with molecular targeted therapies may be a potent strategy to block the tumoral progression. This review summarizes the association of CSCs, drug resistance, ABC transporters activities and changes in signaling pathways as a guide for future molecular therapy for HCC.

关键词： Hepatocellular carcinoma Liver Cancer stem cells Drug resistance Hepatocellular carcinoma therapy

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Management of restless legs syndrome in chronic liver disease:A challenge for the correct diagnosis and therapy

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World Journal of Hepatology 2018年第3期10卷 379-387页

作者： Rita Moretti Paola Caruso Marzia Tecchiolli Silvia Gazzin Claudio Tiribelli Department of Medical Surgical and Health SciencesUniversity of TriesteTrieste 34149Italy Italian Liver Foundation Centro Studi FegatoTrieste 34149Italy

AIM To investigate the association between restless legs syndrome(RLS) and well-defined chronic liver disease, and the possible therapeutic options. METHODS Two hundred and eleven patients with chronic liver disease, complaining of sleep disturbances, painful leg sensation and daily sleepiness, were included. Patients with persistent alcohol intake, recent worsening of clinical conditions, or hepatitis C virus were excluded. Diagnosis of RLS was suggested by the Johns Hopkins questionnaire and verified by fulfilling the diagnostic criteria by Allen. All patients were tested, both at baseline and during follow-up, with the Hamilton rating scale for depression, sleep quality assessment(PSQI), Epworth sleepiness scale(ESS), International Restless Legs Syndrome Study Group evaluation, and international RLS severity(IRLS) scoring system. Ironfree level, ferritin, folate, vitamin B12 and D-OH25 were detected. Neurological examinations and blood testoccurred at the beginning of the therapy, after 2 wk, and at the 28^(th), 75 th, 105 th, 135 th, 165 th and 205 th day. Regarding therapy, pramipexole or gabapentin were *** Patients were moderately depressed, with evident nocturnal sleep problems and concomitant daily sleepiness. Sleep problems and involuntary leg movements had been underestimated, and RLS s yndrome had not be e n c ons ide re d be fore t he neurological visit. All(211/211) patients fulfilled the RLS diagnostic criteria. Twenty-two patients considered their symptoms as mild, according to IRSL, but 189 found them moderate to very severe. No correlation was found between ammonium level and ESS or PSQI. Augmentation was rather precocious in our patients(135 th day), and more frequent(35%) than previous data(8.3%-9.1%). The dosage of dopamine agonists was found to be associated with augmentation and appears in range with the literature. Previous intake of alcohol and lower levels of vitamins have been related to the phenomenon in our *** RLS

关键词： Restless legs syndrome Chronic liver disease Dopamine agonist treatment Augmentation

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MutL homolog 1 methylation and microsatellite instability in sporadic colorectal tumors among Filipinos

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World Journal of Gastrointestinal Oncology 2021年第12期13卷 2101-2113页

作者： Loraine Kay D Cabral Cynthia A Mapua Filipinas F Natividad Caecilia H C Sukowati Edgardo R Cortez Ma Luisa D Enriquez Research and Biotechnology Group St.Luke's Medical CenterQuezon City 1112Philippines centro studi fegato Fondazione Italiana Fegato ONLUSTrieste 34149Italy Department of Surgery St.Luke's Medical CenterQuezon City 1112Philippines Center for Natural Science and Environmental Research De La Salle UniversityManila 1004Philippines

BACKGROUND Colorectal cancer(CRC)ranks third in terms of incidence and second in mortality *** CRC,the silencing of mismatch repair genes,including the mutL homolog 1(hMLH1)has been linked to microsatellite instability(MSI),the lengthening or shortening of microsatellite *** limited data have been presented so far on the link of hMLH1 methylation and MSI in Southeast Asia populations with sporadic CRC,and on its clinical *** To investigate the significance of the MSI status and hMLH1 methylation in CRC Filipino *** Fifty-four sporadic CRC patients with complete clinical data were included in this *** DNA from CRC tumor biopsies and their normal tissue counterparts were profiled for MSI by high resolution melting(HRM)analysis using the Bethesda Panel of Markers(BAT25,BAT26,D2S123,D5S346,and D17S250).hMLH1 methylation screening was performed using bisulfite conversion and methylation specific polymerase chain *** analysis was conducted to calculate their associations to clinicopathological characteristics and survival relevance(Kaplan-Meier curves and the log-rank test).RESULTS hMLH1 methylation was observed in 9%and 35%of CRC and normal samples,*** incidence of consistently methylated hMLH1 found in both normal and CRC was noticed for relation to location of tumor(P<0.05).As for MSI status,D2S123 the most common unstable microsatellite and MSI-high(MSIH)was the most common MSI profile,counted for 46%and 50%of normal and CRC tissues,*** presence of MSI-low(MSI-L)and microsatellite stable(MSS)was 43%and 11%for normal,and 31%and 19%for CRC *** mean month of patients’survival was shorter in patients whose normal and tumor tissues had methylated compared to those with unmethylated hMLH1 and with MSI-H compared to those with MSI-L/MSS(P<0.05).This was supported by significant difference in Kaplan-Meier with log-rank *** data indicated that hMLH1 methylation

关键词： Sporadic colorectal cancer DNA methylation Microsatellite instability Population genetic Colorectal cancer

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Comparison between hepatocellular carcinoma prognostic scores:A 10-year single-center experience and brief review of the current literature

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World Journal of Hepatology 2020年第12期12卷 1239-1257页

作者： Michele Campigotto Mauro Giuffrè Anna Colombo Alessia Visintin Alessandro Aversano Martina Budel Flora Masutti Cristiana Abazia Lory Saveria Croce Dipartimento Universitario clinico di Scienze Mediche Chirurgiche e Della SaluteUniversitàdegli Studi di TriesteTrieste 34149Italy Clinica Patologie del fegato Azienda Sanitaria Universitaria Giuliano IsontinaTrieste 34149Italy

BACKGROUND Hepatocellular carcinoma(HCC)represents the most common primitive liver malignancy.A relevant concern involves the lack of agreement on staging systems,prognostic scores,and treatment allocation *** To compare the survival rates among already developed prognostic *** We retrospectively evaluated 140 patients with HCC diagnosed between February 2006 and November *** were categorized according to 15 prognostic scoring systems and estimated median survivals were compared with those available from the current medical *** The median overall survival of the cohort of patients was 35(17;67)mo,and it was statistically different in relation to treatment choice,ultrasound surveillance,and serum *** Italian Liver Cancer(***)tumor staging system performed best in predicting survival according to stage allocation among all 15 evaluated prognostic *** the *** prognostic system,28.6%,40.7%,22.1%,and 8.6%of patients fell within stages 0-1,2-3,4-5 and>5 *** median survival was 57.9 mo for stages 0-1,43 mo for stages 2-3,21.7 mo for stages 4-5,and 10.4 mo for stage>*** 1-,3-,and 5-year survival rates were respectively 95%,65%,and 20%,for stages 0-1;94.7%,43.9%and 26.3%for stages 2-3;71%,25.8%and 16.1%for stages 4-5;and 50%,16.7%and 8.3%for stage>*** the same time,although statistically significant in prognostic stratification,the most commonly used Barcelona Clinic Liver Cancer system showed one of the most relevant differences in median survival,especially for stages A and C,when compared to the medical *** fact,10.7%,59.3%,27.1%,1.4%,and 0%of patients were stratified into stages 0,A,B,C,and D *** median survival was>81.1 mo for stage 0,44.9 mo for stage A,21.3 mo for stage B,and 3.1 mo for stage *** 1-,3-,and 5-year survival rates were respectively 86.7%,60%,and 46.7%for stage 0;91.6%,50.6%,and 20.5%for stage A;73.7%,23.7%and 13.2%for stage B;and

关键词： Hepatocellular carcinoma Prognostic score system Prognostic factors Survival analysis Barcelona Clinic Liver Cancer score system Italian Liver Cancer score system

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