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Prognostic and predictive biomarkers in metastatic colorectal cancer anti-EGFR therapy

World Journal of Gastroenterology 2016年第30期22卷 6944-6954页

作者： Cristiana Lo Nigro vincenzo ricci Daniela Vivenza Cristina Granetto Teresa Fabozzi Emanuela Miraglio Marco C Merlano Department of Oncology S. Croce and Carle Teaching Hospital Department of Oncology San Raffaele Institute

AIM: To reviewing genetic and epigenetic make-up of metastatic colorectal cancers (mCRCs) addicted to epidermal growth factor receptor (EGFR) ***: The present study summarizes the potential value of prognostic and predictive biomarkers in selecting mCRC patients treated with anti-EGFR therapy. A meta-analysis was performed using a systematic search of PubMed, Medline and Web of Science to identify eligible papers until March 21st, 2016 using these following terms: ‘‘colorectal cancer’’, “predictive biomarkers’’, “anti-EGFR therapy”, “KRAS”, “NRAS’’, “PIK3CA”, “TP53”, “PTEN”, ‘‘EGFR”, “MET”, “HER2”, “epiregulin”, “amphiregulin”, “prognostic biomarkers”, “BRAF”, “miRNA” and “antibody-dependent cell-mediated cytotoxicity (ADCC) activity”. Two investigators independently evaluated and extracted data from each identified studies based on selected criteria of inclusion and ***: The introduction of agents targeting EGFR such as cetuximab and panitumumab increased overall survival of mCRCs. Nevertheless, it has firstly became evident that response rates to cetuximab regimens in unselected patient populations were typically lower than 30%. Clinical data confirmed the predictive value of RAS mutations for resistance to cetuximab and panitumumab leading to the license of these monoclonal antibodies exclusively for the management of patients with RAS-wild type colorectal cancers. So far the identification of predictive biomarkers have generated interesting, though preliminary and, at times, conflicting data on the importance of tumour mRNA levels of EGFR ligands, of activating mutations in other genes such as NRAS and PIK3CA. The pr

关键词： Metastatic colorectal cancer Anti-epidermal growth factor receptor therapy KRAS Biomarkers Antibody-dependent cell-mediated cytotoxicity

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Circulating cytokines and outcome in metastatic colorectal cancer patients treated with regorafenib

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World Journal of Gastrointestinal Oncology 2020年第3期12卷 301-310页

作者： vincenzo ricci Cristina Granetto Antonella Falletta Matteo Paccagnella Andrea Abbona Elena Fea Teresa Fabozzi Cristiana Lo Nigro Marco Carlo Merlano Medical Oncology and Laboratory of Translational Oncology Oncology DepartmentS.Croce and Carle Teaching Hospital CuneoCuneo 12100Italy Arco Cuneo Foundation Cuneo 12100Italy Medical Oncology S.G.Bosco HospitalTorino 10154Italy S.Croce and Carle Teaching Hospital Cuneo Cuneo 12100Italy

BACKGROUND Regorafenib is an oral small-molecule multikinase inhibitor approved in third or later line of treatment for patients with metastatic colorectal cancer(mCRC).Regorafenib has shown significant benefits in overall survival and progression free survival in two phase III trials compared to placebo in patients with mCRC who had progressed on previous *** To identify an immune profile that might specifically correlate with the outcome in patients treated with *** Blood samples were collected from 17 patients before treatment with regorafenib and from 6 healthy *** proteins evaluated(TNF-α,TGF-β,VEGF,CCL-2,CCL-4,and CCL-5)were selected on the basis of their roles in angiogenesis and colorectal cancer *** We found that TNF-αbasal level was significantly higher in mCRC patients compared to healthy *** Responder(NR)patients showing progression of disease(n=12)had higher basal level of TGF-β,TNF-α,VEGF,CCL-2 and CCL-5 compared to Responder(R)patients(complete response CR,n=1;partial response PR,n=1;Stable Disease SD,n=3).On the contrary,plasma basal level of CCL-4 was higher in R compared to NR *** values of TGF-βand TNF-αnegatively correlated with progression free *** These results suggest a cytokine signature potentially able to discriminate between R and NR patients to treatment with regorafenib.

关键词： Colorectal cancer Multikinase inhibitor Cytokines Angiogenesis

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Intellectual Capital and Business Performance in Professional Football Clubs： Evidence From a Longitudinal Analysis

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Journal of Modern Accounting and Auditing 2015年第9期11卷 450-465页

作者： Federica ricci vincenzo Scafarto Domenico Celenza Ida Samantha Gilvari University of Cassino and Southern Lazio Cassino Italy

This paper aims to explore the impact of intellectual capital efficiency （ICE） on firm performance in the context of professional football clubs. In particular, our aim is twofold：（1） to provide measures of ICE specifically tailored to professional football businesses; and （2） to empirically investigate whether some dimensions of ICE, namely, human capital and relational capital efficiency, are positively associated with sporting performance, here used as a proxy for business performance. This paper develops a quantitative analysis of club-level panel data using the statistical technique known as mixed-effects linear regression for longitudinal analysis. The research spans a time period of five years and specifically the sporting seasons from 2007/2008 up to 2011/2012. The empirical findings of this study provide tentative evidence that ICE, especially as far as relational capital is concerned, is positively associated with on-pitch performance of professional football businesses. On the counterpart, results for the impact of human capital efficiency （HCE） do not consistently come out with the （positive） expected signs. More specifically, our findings suggest that relational capital efficiency, meaning the ability to develop and nurture positive business relationship with relevant external stakeholders, is a significant consideration for football club managers; on the other, they might shed light on the actual business model of professional football clubs that, in our analysis, does not appear consistent with the long-held hypothesis of winning maximization. The main limitation of this study lies in the fact that our indicators do not fully capture all relevant dimensions of the intellectual capital （IC） construct.

关键词： intellectual capital efficiency (ICE) firm performance professional football clubs

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Evaluation of antibody-dependent cell-mediatedcy totoxicity activity and cetuximab response in KRAS wildtype metastatic colorectal cancer patients

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World Journal of Gastrointestinal Oncology 2016年第2期8卷 222-230页

作者： cristiana lo nigro vincenzo ricci daniela vivenza martino monteverde giuliana strola francesco lucio federica tonissi emanuela miraglio cristina granetto mirella fortunato marco carlo merlano laboratory of cancer genetics and translational oncology oncology departments.croce and carle teaching hospital12100 Cuneo Italy medical oncology oncology departments.croce and carle teaching hospital12100 Cuneo Italy laboratory department s.croce and carle teaching hospital12100 Cuneo Italy radiotherapy department s.croce and carle teaching hospital12100 Cuneo Italy pathology department s.croce and carle teaching hospital12100 Cuneo Italy

AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with ***: Forty-one KRAS wt mC RC patients,treated with cetuximab and irinotecan-based chemotherapy in Ⅱ and Ⅲ lines were analyzed. Genotyping of single nucleotide polymorphism(SNP)s in the FCGR2A,FCGR3A and in the 3' untranslated regions of KRAS and mutational analysis for KRAS,BRAF and NRAS genes was determined either by sequencing or allelic discrimination assays. Enriched NK cells were obtained from lymphoprepperipheral blood mononuclear cell and iN KT cells were defined by co-expression of CD3,TCRVα24,TCRVβ11. ADCC was evaluated as ex vivo NK-dependent activity,measuring lactate dehydrogenase ***: At basal,mCRC patients performing ADCC activity above the median level(71%) showed an improved overall survival(OS) compared to patients with ADCC below(median 16 vs 8 mo;P=0.026). We did not find any significant correlation of iN KT cells with OS(P=0.19),albeit we observed a trend to a longer survival after 10 mo in patients with iN KT above median basal level(0.382 cells/microliter). Correlation of OS and progression-free survival(PFS) with interesting SNPs involved in ADCC ability revealed not to be significant. Patients carrying alleles both with A in FCGR2 A and TT in FCGR3A presented a trend of longer PFS(median 9 vs 5 mo;P=0.064). Chemotherapy impacted both iN KT cells and ADCC activity. Their prognostic values get lost when we analysed them after 2 and 4 mo of ***: Our results suggest a link between iN KT cells,basal ADCC activity,genotypes in FCGR2A and FCGR3A,and efficacy of cetuximab in KRAS wt mC RC patients.

关键词： Metastatic colorectal cancer Single nucleotidepolymorphism in Fc-γ receptors Cetuximab RAS family Antibody-dependent cell-mediated cytotoxicity Invariantnatural killer T cells

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Potential role of an athlete-focused echocardiogram in sports eligibility

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World Journal of Cardiology 2021年第8期13卷 271-297页

作者： Stefano Palermi Alessandro Serio Marco Vecchiato Felice Sirico Francesco Gambardella Fabrizio ricci Franco Iodice Juri Radmilovic vincenzo Russo Antonello D'Andrea Department University of Naples Federico IINaples 80131Italy Sport and Exercise Medicine Division Department of MedicineUniversity Hospital of PadovaPadova 35128Italy Department of Neuroscience Imaging and Clinical Sciences“G.d’Annunzio”University of Chieti-PescaraChieti 66100Italy Department of Clinical Sciences Faculty of MedicineLund UniversityClinical Research CenterMalmö21428Sweden Casa di Cura Villa Serena Pescara 65013Italy Unit of Cardiology Department of Translational Medical SciencesUniversity of Campania“Luigi Vanvitelli”Monaldi HospitalNaples 80131Italy Unit of Cardiology and Intensive Coronary Care “Umberto I”HospitalNocera Inferiore 84014Italy

Sudden cardiac death(SCD)of an athlete is a rare but tragic event and sport activity might play a trigger role in athletes with underlying structural or electrical heart *** screenings(PPs)have been conceived for the potential to prevent SCD in young athletes by early identification of cardiac *** European Society of Cardiology protocol for PPs includes history collection,physical examination and baseline electrocardiogram,while further examinations are reserved to individuals with abnormalities at first-line ***,transthoracic echocardiography has been hypothesized to have a primary role in the *** review aims to describe how to approach an athlete-focused echocardiogram,highlighting what is crucial to focus on for the different diseases(cardiomyopathies,valvulopathies,congenital heart disease,myocarditis and pericarditis)and when is needed to pay attention to overlap diagnostic zone(“grey zone”)with the athlete's *** properly tested,focused echocardiography by sports medicine physicians may become standard practice in larger screening practices,potentially available during first-line evaluation.

关键词： Echocardiogram Athletes Sport eligibility Pre-participation screening Sudden cardiac death Sport cardiology

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Locoregional therapy and systemic cetuximab to treat colorectal liver metastases

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World Journal of Gastrointestinal Oncology 2015年第6期7卷 47-54页

作者： Giammaria Fiorentini Camillo Aliberti Donatella Sarti Paolo Coschiera Massimo Tilli Luca Mulazzani Paolo Giordani Francesco Graziano Alfonso Marqués Gonzalez Raul García Marcos Fernando Gómez Mugnoz Maurizio Cantore Stefano ricci vincenzo Catalano Andrea Mambrini Oncology Unit Azienda Ospedaliera "Ospedali Riuniti Marche Nord"San Salvatore Hospital Oncology Radiodiagnostics Oncology Institute of VenetoInstitute for the Research and Treatment of Cancer (IRCC) Diagnostics for Images Unit and Interventional Radiology Azienda Ospedaliera "Ospedali Riuniti Marche Nord" Diagnostics for Images and Interventional Radiology Azienda USL of FerraraDelta Hospital Unit of Anestesiology La Fe University Hospital and Polytechnic Medical Imaging and Interventional and Vascular Radiology La Fe University Hospital and Polytechnic Medical Imaging Center (CDIC) Provincial Clinic Hospital Oncology Unit Azienda Ospedaliera "Carlo Poma" Department of Vascular and Interventional Radiology INRCA Hospital-IRCCS Oncology Unit Carrara General Hospital

AIM: To investigate efficacy and safety of second-line treatment with irinotecan-loaded drug-eluting beads(DEBIRI) and cetuximab(DEBIRITUX) of unresectable colorectal liver ***: Patients with the following characteristics were included in the study: unresectable hepatic metastases from colorectal carcinoma(CRC-LM), progression after first line chemotherapy(any type of chemotherapeutic drug and combination was allowed), second line treatment(mandatory), which included for each patient(unregarding the KRas status) two cycles of DEBIRI(using 100-300 μm beads loaded with irinotecan at a total dose 200 mg) followed by 12 cycles of cetuximab that was administered weekly at a first dose of 400 mg/m2 and then 250 mg/m2; good performance status(0-2) and liver functionality(alanine aminotransferase and gamma-glutamyl transferase not exceeding three times the upper limit of normal, total bilirubin not exceeding 2.5 mg/m L). Data were collected retrospectively and included: tumor response(evaluated monthly for 6 mo then every 3 mo), overall response rate(ORR), KRas status, type and intensity of adverse events(G according to the Common Terminology Criteria for Adverse Events v3.0, CTCAE), overall survival(OS) and progression free survival(PFS).RESULTS: Forty consecutive cases of CRC hepatic metastases were included in the study. Median duration of DEBIRITUX was 4.4 mo(range, 4.0-6.5). Sixteen patients(40%) received the planned 2 cycles of DEBIRI and an average of 10 cetuximab cycles. ORR of the whole sample was 50%, in particular 4 patients were complete responders(10%) and 16(40%) partial responders. The most observed side effects(G2) were: post-embolization syndrome(30%), diarrhea(25%), skin rushes(38%) and asthenia(35%). The retrospective evaluation of KRas status(24 wild type, 16 mutated) showed that the group of patients with wild type KRas had ORR significantly higher than mutant KRas. Median follow-up was 29 mo(8-48 range); median PFS was 9.8 mo and OS was

关键词： Cetuximab Irinotecan-loaded drug-elutingbeads Hepatic metastases Chemoembolization Colonrectal tumor Irinotecan

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Effects of viremia and CD4 recovery on gut“microbiome-immunity”axis in treatment-na?ve HIV-1-infected patients undergoing antiretroviral therapy

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World Journal of Gastroenterology 2022年第6期28卷 635-652页

作者： Edda Russo Giulia Nannini Gaetana Sterrantino Seble Tekle Kiros vincenzo Di Pilato Marco Coppi Simone Baldi Elena Niccolai Federica ricci Matteo Ramazzotti Marco Pallecchi Filippo Lagi Gian Maria Rossolini Alessandro Bartoloni Gianluca Bartolucci Amedeo Amedei Department of Clinical and Experimental Medicine University of FlorenceFlorence 50134Italy Department of Surgical Sciences and Integrated Diagnostics University of GenoaGenoa 16126Italy Department of Biomedical Experimental and Clinical"Mario Serio"University of FlorenceFlorence 50134Italy Microbiology and Virology Unit Florence Careggi University HospitalUniversity of FlorenceFlorence 50134Italy Department of Neurosciences PsychologyDrug Research and Child HealthUniversity of FlorenceFlorence 50019Italy

BACKGROUND Human immunodeficiency virus type 1(HIV-1)infection is characterized by persistent systemic inflammation and immune activation,even in patients receiving effective antiretroviral therapy(ART).Converging data from many cross-sectional studies suggest that gut microbiota(GM)changes can occur throughout including human immunodeficiency virus(HIV)infection,treated by ART;however,the results are *** the first time,we compared the fecal microbial composition,serum and fecal microbial metabolites,and serum cytokine profile of treatment-na?ve patients before starting ART and after reaching virological suppression,after 24 wk of ART *** addition,we compared the microbiota composition,microbial metabolites,and cytokine profile of patients with CD4/CD8 ratio1(immunological responders[IRs]),after 24 wk of ART *** To compare for the first time the fecal microbial composition,serum and fecal microbial metabolites,and serum cytokine profile of treatment-na?ve patients before starting ART and after reaching virological suppression(HIV RNA<50 copies/m L)after 24 wk of *** We enrolled 12 treatment-na?ve HIV-infected patients receiving ART(mainly based on integrase inhibitors).Fecal microbiota composition was assessed through next generation *** addition,a comprehensive analysis of a blood broad-spectrum cytokine panel was performed through a multiplex *** the same time,serum free fatty acid(FFA)and fecal short chain fatty acid levels were obtained through gas chromatography-mass *** We first compared microbiota signatures,FFA levels,and cytokine profile before starting ART and after reaching virological *** alterations were observed in microbiota composition,in particular in the viral suppression condition,we detected an increase of Ruminococcus and Succinivibrio and a decrease of ***,in the same condition,we also obser

关键词： HIV Antiretroviral therapy Microbiome-immunity axis Microbiota Cytokines Short chain fatty acid Inflammation Immunological responders Viremia

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The HEPD particle detector of the CSES satellite mission for investigating seismo-associated perturbations of the Van Allen belts

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Science China(Technological Sciences) 2018年第5期61卷 643-652页

作者： AMBROSI Giovanni BARTOCCI Simona BASARA Laurent BATTISTON Roberto BURGER William J. CARFORA Luca CASTELLINI Guido CIPOLLONE Piero CONTI Livio CONTIN Andrea DE DONATO Cinzia DE SANTIS Cristian FOLLEGA Francesco M. GUANDALINI Cristina IONICA Maria IUPPA Roberto LAURENTI Giuliano LAZZIZZERA Ignazio LOLLI Mauro MANEA Christian MARCELLI Laura MASCIANTONIO Giuseppe MERGE Matteo OSTERIA Giuseppe PACINI Lorenzo PALMA Francesco PALMONARI Federico PANICO Beatrice PATRIZII Laura PERFETTO Francesco PICOZZA Piergiorgio POZZATO Michele PUEL Matteo RASHEVSKAYA Irina ricci Ester ricci Marco ricciARINI Sergio Bruno SCOTTI Valentina SOTGIU Alessando SPARVOLI Roberta SPATARO Bruno VITALE vincenzo Istituto Nazionale di Fisica Nucleare (INFN) Sezione di Perugia Perugia 06123 Italy Uninettuno University Rome 00186 Italy Istituto Nazionale di Fisica Nucleare (INFN) Sezione di Roma Tor Vergata Rome 00133 Italy Istituto Nazionale di Fisica Nucleare (INFN) TIFPA Povo (TN) 38123 Italy Dipartimento di Fisica Universita di Trento Povo (TN) 38123 Italy Dipartimento di Fisica Universita di Roma Tor Vergata Rome 00133 Italy IFAC-CNR Sesto Fiorentino (FI) 50019 Italy Dipartimento di Fisica e Astronomia Universita di Bologna Bologna 40127 Italy Istituto Nazionale di Fisica Nucleare (INFN) Sezione di Bologna Bologna 40127 Italy Istituto Nazionale di Fisica Nucleare (INFN) Sezione di Napoli Naples 80126 Italy Istituto Nazionale di Fisica Nucleare (INFN) LNE Frascati (RM) 00044 Italy Agenzia Spaziale Italiana (ASI) SSDC Rome 00133 Italy

CSES(China Seismo-Electromagnetic Satellite) is a mission developed by CNSA(Chinese National Space Administration) and ASI(Italian Space Agency), to investigate the near-Earth electromagnetic, plasma and particle environment, for studying the seismo-associated disturbances in the ionosphere-magnetosphere transition zone. The anthropogenic and electromagnetic noise,as well as the natural non-seismic electromagnetic emissions is mainly due to tropospheric activity. In particular, the mission aims to confirming the existence of possible temporal correlations between the occurrence of earthquakes for medium and strong magnitude and the observation in space of electromagnetic perturbations, plasma variations and precipitation of bursts with highenergy charged particles from the inner Van Allen belt. In this framework, the high energy particle detector(HEPD) of the CSES mission has been developed by the Italian LIMADOU Collaboration. HEPD is an advanced detector based on a tower of scintillators and a silicon tracker that provides good energy and angular resolution and a wide angular acceptance, for electrons of 3–100 Me V, protons of 30–200 Me V and light nuclei up to the oxygen. CSES satellite has been launched on February 2^(nd), 2018 from the Jiuquan Satellite Launch Center(China).

关键词： earthquake seismic-precursors particle detector Van Allen belts magnetosphere ionosphere space weather cosmic rays

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意大利汉语教学的历史和现状考察

意大利汉语教学的历史和现状考察

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作者：意杰作（vincenzo Iannotta）上海外国语大学

学位级别：硕士

本研究专注于探讨意大利汉语教学的历史和现状,对其发展进程进行了考察。自意大利汉学诞生之初直至目前,许多重要意大利汉学家、意籍中国学者,以及相关教育机构对于汉语教学的发展,以及中国文化的推广,均作出了卓著的贡献。本文基于大... 详细信息

本研究专注于探讨意大利汉语教学的历史和现状,对其发展进程进行了考察。自意大利汉学诞生之初直至目前,许多重要意大利汉学家、意籍中国学者,以及相关教育机构对于汉语教学的发展,以及中国文化的推广,均作出了卓著的贡献。本文基于大量相关文史记载和参考资料,对此进行了全面系统的回顾。与此同时,本文作者针对意大利在校高中生和汉学教师进行了调查和数据收集,对于意大利汉语教学现状也进行了观察和分析。本文旨在对意大利的汉语研究和教学的历史与现状进行全面的探讨,并对于意大利汉语教学体系的发展前景进行一定的讨论和展望。论文分为以下三章:第一章揭示了意大利的汉学起源,着重探讨早期汉语研究。马可波罗(Marco Polo)最早来到中国,开启了意大利人对中国文化的兴趣。早期意大利汉学领域最重要的先驱人物为耶稣会士利玛窦(Matteo ricci)和罗明坚(Michele Ruggieri),他们在传教的目标之外,获取了更伟大的成就,也即在欧洲和中国之间建立了跨文化对话关系。他们当时用一门欧洲语言编写最早解释和翻译汉语著作之一,特别是用拉丁语或者葡萄牙语。他们的相关著作还是开启了新一代传教士汉学家的研究和教学活动。在第二代意大利汉学家中,如卫匡国(Martino Martini)、殷铎泽(Prospero Intorcetta)等,都对于建立系统的汉语教学体系同样做出了持续的贡献。第二章对于意大利历史中最重要的汉学重镇、那不勒斯中华书院进行了详细介绍。书院的建立与其创始人、18世纪耶稣会士马国贤(Matteo Ripa)的传教活动密切相关。他建校的初衷是培养来自中国本土的神职人员,书院的建立为中意人士之间的跨文化交流和相互理解铺平了道路。1861年意大利统一以后,书院逐渐成为公立教育机构,并发展出了自己的学术特色。那不勒斯中华书院的两位华人学者王佐才(Francesco Saverio Wan)和郭栋臣(Giuseppe Maria Kuo)是优秀的教师、口译者,以及教材编纂者,在意大利汉语教学法的发展当中起到了关键性作用,本章也对于他们编著的教材进行了评价和分析。第三章回溯了意大利教育体系中的汉语教学课程的缘起,介绍了早期的中国文化和语言课程的教学者,以及不同时期的汉语教学在大学和高中的发展。近期中国经济快速发展,大量中国移民进入意大利,这些因素都对不同层次的汉语教学班级的建立起到了促进作用。本章对于在意大利率先开设汉语课程的一所高中进行了调查,就该校学生对于学习中国语言和文化的态度、观点与视角进行了讨论,并以一本常用教材为例,对目前意大利汉语教学的特点进行了探讨。

关键词：意大利汉语教学历史与现状意大利汉语学者那不勒斯中华书院高中汉语课程

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