Expert Opinion on Orphan Drugs最新文献_第6页

Putative adjunct therapies to target mitochondrial dysfunction and oxidative stress in phenylketonuria, lysosomal storage disorders and peroxisomal disorders 针对苯丙酮尿症、溶酶体储存障碍和过氧化物酶体障碍的线粒体功能障碍和氧化应激的假定辅助疗法

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-11-01 DOI: 10.1080/21678707.2020.1850254

Nadia Turton, T. Rutherford, D. Thijssen, I. Hargreaves

{"title":"Putative adjunct therapies to target mitochondrial dysfunction and oxidative stress in phenylketonuria, lysosomal storage disorders and peroxisomal disorders","authors":"Nadia Turton, T. Rutherford, D. Thijssen, I. Hargreaves","doi":"10.1080/21678707.2020.1850254","DOIUrl":"https://doi.org/10.1080/21678707.2020.1850254","url":null,"abstract":"ABSTRACT Introduction: Oxidative stress (OS) and mitochondrial dysfunction are implicated in the pathogenesis of a number of metabolic diseases. OS occurs when there is an imbalance between the pro-oxidant/antioxidant homeostasis, leading to an increased generation of reactive oxidant species (ROS) with resultant cellular dysfunction. It is becoming apparent that increased ROS generation may be attributable to secondary mitochondrial dysfunction as a consequence of disease pathophysiology. Mitochondrial dysfunction occurs as a result of oxidative damage from enhanced ROS generation as well as the accumulation of toxic metabolites in some metabolic diseases. Areas covered: The present review will discuss evidence of OS and mitochondrial dysfunction in phenylketonuria (PKU), lysosomal storage disorders (LSDs), and peroxisomal disorders. In addition, potential adjunct therapies which have the potential to enhance mitochondrial functioning and mitigate OS will be explored. The databases utilized for this review were Pubmed and the Wed of science, with inclusive dates, 1988–2020. Expert opinion: There is an un-unified approach in the treatment of metabolic diseases. Agents including augmenters of mitochondrial function, antioxidants, and activators of mitochondrial biogenesis, may be beneficial. However, although successful in some cases, these adjunct therapies have yet to be incorporated into the clinical-management of metabolic diseases.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1850254","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42239288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibitory effect of Tunceli garlic (Allium tuncelianum) on blastocystis subtype 3 grown in vitro tuncelianum大蒜对体外培养的囊虫3亚型的抑制作用

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-11-01 DOI: 10.1080/21678707.2020.1857725

M. Aykur, Emrah Karakavuk, M. Karakavuk, M. Akıl, H. Can, M. Döşkaya, Y. Gürüz, H. Dağcı

{"title":"Inhibitory effect of Tunceli garlic (Allium tuncelianum) on blastocystis subtype 3 grown in vitro","authors":"M. Aykur, Emrah Karakavuk, M. Karakavuk, M. Akıl, H. Can, M. Döşkaya, Y. Gürüz, H. Dağcı","doi":"10.1080/21678707.2020.1857725","DOIUrl":"https://doi.org/10.1080/21678707.2020.1857725","url":null,"abstract":"ABSTRACT Objective: Blastocystis is a common protozoan parasite detected worldwide. This study aims to investigate the in vitro inhibitory effect of ethyl alcohol extracts of Tunceli garlic (Allium tuncelianum) on growth of Blastocystis ST3 subtype. Methods: Blastocystis ST3 were grown in 3 ml Jones’s medium containing A. tuncelianum prepared at five different concentrations for 72 hours at 37°C. Distilled water was used as negative control whereas metronidazole (MTZ) and trimethoprim-sulfamethoxazole (TMP-SMX) prepared in 0.1, 0.5 and 1 mg/ml of concentrations was used as the positive control. Results: According to the results, the MIC90 of the A. tuncelianum was 115 mg/ml at 72 hours. MIC90 of MTZ was 1 mg/ml at 72 hours (94.96%). TMP-SMX had the highest growth MIC90 effect which was reached at 1 mg/ml concentration during 24 hours (88.18%). The growth inhibitory effect of A. tuncelianum extract increased gradually in all doses and timepoints. Conclusion: In this study, obtained findings show the potential inhibitory effect of A. tuncelianum plant extract against Blastocystis ST3 which causes symptomatic diarrhea in humans. It may be recommended to consume the whole A. tuncelianum plant as food supplement. A. tuncelianum extract could be considered as an alternative for the potential treatment of Blastocystis infection.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1857725","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47005696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SOD1-targeting therapies for neurodegenerative diseases: a review of current findings and future potential sod1靶向治疗神经退行性疾病:当前研究结果和未来潜力的综述

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-10-02 DOI: 10.1080/21678707.2020.1835638

J. Franklin, M. Azzouz, P. Shaw

{"title":"SOD1-targeting therapies for neurodegenerative diseases: a review of current findings and future potential","authors":"J. Franklin, M. Azzouz, P. Shaw","doi":"10.1080/21678707.2020.1835638","DOIUrl":"https://doi.org/10.1080/21678707.2020.1835638","url":null,"abstract":"ABSTRACT Introduction: amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited effective treatments. Mutations in the SOD1 gene are causative in approximately 2% of ALS cases. As the first ALS-associated gene to be discovered, efforts in the development of therapies targeting SOD1 are advanced relative to other genetic causes of ALS. Silencing of the SOD1 gene, has recently shown preliminary evidence of disease-modifying activity in SOD1-ALS patients. Areas covered: 1) the pathophysiology of mutant SOD1-ALS, and the rationale for targeting the SOD1 gene; 2) the strategies that have been used to target mutant SOD1 in clinical and preclinical studies; 3) the role of misfolded wild-type SOD1 in sporadic ALS and other neurodegenerative diseases, and the potential for targeting SOD1 in these patients; 4) future avenues for research. A literature search of publications pertaining to SOD1-ALS and its treatment from 1992-present using the MEDLINE database form the basis for this review. Expert opinion: Central nervous system SOD1 knockdown is achievable in SOD1-ALS patients with intrathecal antisense oligonucleotide therapy, and is both safe and well-tolerated: phase III study outcomes are awaited. A wide array of other SOD1-targeting strategies have shown considerable promise in preclinical studies.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1835638","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48030538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Current state of developing advanced therapies for rare diseases in the European Union 欧盟开发罕见病先进疗法的现状

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-10-02 DOI: 10.1080/21678707.2020.1835640

T. Qiu, Yitong Wang, M. Dabbous, E. Hanna, Ru Han, S. Liang, M. Toumi

{"title":"Current state of developing advanced therapies for rare diseases in the European Union","authors":"T. Qiu, Yitong Wang, M. Dabbous, E. Hanna, Ru Han, S. Liang, M. Toumi","doi":"10.1080/21678707.2020.1835640","DOIUrl":"https://doi.org/10.1080/21678707.2020.1835640","url":null,"abstract":"ABSTRACT Objective Advanced Therapy Medicinal Products (ATMPs) present significant therapeutic advantages for inherited rare diseases. However, the development of orphan ATMPs is challenging due to their complexity and unpredictable biological activity. This study aims to comprehensively describe the current state of orphan ATMPs in Europe. Methods Orphan drugs (ODs) granted by European Commission until March 2020 were investigated. The characteristic of diseases and ATMPs were extracted from the public summary reports of ODs from Committee for Orphan Medicinal Products. The methodology for the pivotal studies of ATMPs was extracted. Results A total of 274 ATMPs were identified, covering 116 rare diseases, with metabolic, optical, and oncologic diseases being the most targeted. A total of 158 ATMPs were indicated for life-threatening diseases, 129 ATMPs targeted diseases currently lacking authorized or satisfactory treatment available. Twenty-eight ATMPs are being investigated in the phase II/IIII or phase III studies. The median patient size of pivotal studies was 127, 15 were open-label studies, 8 were single-arm trials, and 14 reported surrogate outcomes. Conclusion There are rapid growths in developing ATMPs for life-threatening diseases with high unmet clinical needs. Optimizing the study methodology and exploring innovative design to facilitate the market access is paramount.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1835640","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46434968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Clinical and economic assessment of nusinersen: the Bulgarian perspective 临床和经济评估的nusinersen:保加利亚的观点

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-10-02 DOI: 10.1080/21678707.2020.1835641

M. Kamusheva, M. Dimitrova

{"title":"Clinical and economic assessment of nusinersen: the Bulgarian perspective","authors":"M. Kamusheva, M. Dimitrova","doi":"10.1080/21678707.2020.1835641","DOIUrl":"https://doi.org/10.1080/21678707.2020.1835641","url":null,"abstract":"ABSTRACT Introduction Spinal muscular atrophy (SMA) is a very serious debilitating rare condition mainly affecting newborns and infants. Areas covered The aim of current chapter is to present the standard of care and treatment available in Bulgaria from both clinical and economic point of view. The authors are presenting the latest clinical studies in the area of this rare neuromuscular disorder as well as describing a very detailed economic evaluation from the perspective of Bulgarian healthcare insurance fund regarding Nusinersen. A systematic literature review of the published clinical studies of nusinersen for the period March 2015 – March 2019 was performed following predefined criteria. Expert opinion Nusinersen is a significant therapeutic advancement, and is the first option to delay the progression of the disease. A number of clinical trials have demonstrated the efficacy and tolerability of nusinersen and achieving better clinical outcomes after its use compared to placebo. Despite the expected significant increase of the budget for SMA, nusinersen provides new possibilities of treatment of children with SMA in Bulgaria and innovative disease-modifying approach to the unmet medical needs of the patients and their families.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1835641","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48704149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Advances in drug therapies for cytomegalovirus in transplantation: a focus on maribavir and letermovir 巨细胞病毒移植药物治疗进展：以马里巴韦和莱特莫韦为重点

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-10-02 DOI: 10.1080/21678707.2020.1835639

J. Bruminhent, R. Razonable

{"title":"Advances in drug therapies for cytomegalovirus in transplantation: a focus on maribavir and letermovir","authors":"J. Bruminhent, R. Razonable","doi":"10.1080/21678707.2020.1835639","DOIUrl":"https://doi.org/10.1080/21678707.2020.1835639","url":null,"abstract":"ABSTRACT Introduction Cytomegalovirus (CMV) challenges physicians who care for immunocompromised transplant recipients. Antiviral drugs are the cornerstone in the prevention and treatment of CMV disease, but they have toxicities that limit their effective clinical uses. Advances in antiviral therapeutics against CMV are needed. High antiviral efficacy, especially against drug-resistant CMV, and low risk of adverse toxicities are characteristics of an ideal drug for CMV infection. Areas covered A comprehensive review of novel drugs was conducted to provide a concise summary of the latest advances in antiviral therapeutics for the management of CMV infection in transplantation. This review focuses on the clinical efficacy and safety of maribavir and letermovir. All studies related to maribavir and letermovir were identified through a search of PubMed, citation chasing, and the author’s knowledge of the topic. Expert opinion Maribavir and letermovir are the ‘new kids on the block’ in the antiviral drug management of CMV. Both drugs provide novel and unique mechanisms of antiviral activity that are distinct from the traditional polymerase inhibitors. Clinical trials of maribavir and letermovir are reviewed, and their (potential) roles in prevention and treatment algorithms are discussed. Finally, the integration of these novel antiviral therapies with immunologic strategies is emphasized.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1835639","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48928594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Rare cancers, the continued agenda for progress – editor’s special foreword 罕见癌症，继续前进的议程-编辑的特别前言

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-09-01 DOI: 10.1080/21678707.2020.1821529

D. O’Connor

引用次数: 0

Multiple endocrine neoplasia type 1: a review of current diagnostic and treatment approaches 1型多发性内分泌瘤:目前诊断和治疗方法的综述

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-09-01 DOI: 10.1080/21678707.2020.1811086

F. Marini, F. Giusti, F. Tonelli, M. Brandi

{"title":"Multiple endocrine neoplasia type 1: a review of current diagnostic and treatment approaches","authors":"F. Marini, F. Giusti, F. Tonelli, M. Brandi","doi":"10.1080/21678707.2020.1811086","DOIUrl":"https://doi.org/10.1080/21678707.2020.1811086","url":null,"abstract":"ABSTRACT Introduction Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited syndrome, caused by heterozygote inactivating mutation of the MEN1 tumor suppressor gene, and characterized by the development of multiple tumors in target neuroendocrine tissues. Areas covered Authors reviewed, after targeted literature research, the main techniques and general protocols employed for tumor diagnosis in MEN1 patients, describing their positive aspects and limitations. Surgical approaches, conventional medical therapies, and novel molecular-based treatments of the main MEN1 tumors are also discussed. Expert opinion MEN1 lifelong cancer surveillance allows early tumor discovery and is fundamental in the reduction of morbidity and mortality of the syndrome. Diagnostic techniques, with increasing sensitivity and specificity, are constantly being improved, some taking advantage of the molecular characteristics of tumors. Surgery remains the therapy of choice for most MEN1 tumors, usually in association with medical therapies for the control of hormone-derived syndromes. Novel pharmacological treatments, based on molecular features of MEN1 tumors, are taking hold in the clinical management of patients in case of unresectable and/or advanced tumors. Specific clinical trials, not limited to single case reports, are a fundamental step to validate the efficacy of these treatments and establish the adequate posology for MEN1 tumors.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1811086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43085490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Tazemetostat as a treatment for epithelioid sarcoma Tazemetostat治疗上皮样肉瘤

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-09-01 DOI: 10.1080/21678707.2020.1809377

Mia C. Weiss, M. Agulnik

{"title":"Tazemetostat as a treatment for epithelioid sarcoma","authors":"Mia C. Weiss, M. Agulnik","doi":"10.1080/21678707.2020.1809377","DOIUrl":"https://doi.org/10.1080/21678707.2020.1809377","url":null,"abstract":"ABSTRACT Introduction Epithelioid Sarcomas is a rare aggressive subtype of soft tissue sarcomas that is most prevalent in young adult males. It is locally invasive and frequently metastasizes to regional lymph nodes and distant organ sites. Complete surgical resection is curative in early-stage disease; however, there remains a high recurrence rate and distant metastatic risk. Outcomes remain poor in patients that develop metastatic disease. These tumors are characterized by loss of INI-1/SMARCB1 expression, which opposes the enzymatic function of EZH2, a critical component of epigenetic regulation. Tazemetostat is a highly selective, orally available EZH2 inhibitor. The recommended dose of Tazemetostat is 800 mg twice daily for patients aged 16 years or older with advanced or metastatic epithelioid sarcomas not eligible for complete surgical resection. Areas covered Clinical studies investigating Tazemetostat in epithelioid sarcomas. Expert opinion Approval of the Tazemetostat New Drug Application represents the first FDA approval for the treatment of advanced epithelioid sarcomas. It is the first epigenetic therapy approved for solid tumors. The approval encourages investigation in epigenetic regulation as a targetable therapy in other tumor types. Clinical issues remaining post-approval include efficacy of Tazemetostat in combination with other approved agents, and follow up to assess the long-term safety risks.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1809377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46992139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Assessing prognosis of chronic lymphocytic leukemia using biomarkers and genetics 应用生物标志物和遗传学评估慢性淋巴细胞白血病的预后

IF 0.8 4区医学

Expert Opinion on Orphan Drugs Pub Date : 2020-08-16 DOI: 10.1080/21678707.2020.1804860

R. Moia, A. Patriarca, A. Mahmoud, V. Ferri, C. Favini, S. Rasi, C. Deambrogi, G. Gaidano

{"title":"Assessing prognosis of chronic lymphocytic leukemia using biomarkers and genetics","authors":"R. Moia, A. Patriarca, A. Mahmoud, V. Ferri, C. Favini, S. Rasi, C. Deambrogi, G. Gaidano","doi":"10.1080/21678707.2020.1804860","DOIUrl":"https://doi.org/10.1080/21678707.2020.1804860","url":null,"abstract":"ABSTRACT Introduction Chronic lymphocytic leukemia (CLL) is a clinically and genetically heterogenous disease. Genomic studies have deciphered the pathogenesis of CLL and has allowed the identification of prognostic and predictive biomarkers. During the last decade, the treatment options for CLL have expanded significantly, posing the need for the identification of molecular predictors for treatment tailoring. Areas covered This review focuses on biomarkers revealed by investigations of CLL molecular genetics and immunogenetics, and that may help optimizing therapy for individual patients. In addition, the manuscript discusses minimal residual disease (MRD) assessment and its potential application as a prognostic biomarker and as a new tool to guide treatment duration. Expert opinion The availability of a variety of treatment options, including chemoimmunotherapy (CIT) and biological drugs that inhibit the B cell receptor (BCR) and the B cell lymphoma 2 (BCL2) antiapoptotic protein, has significantly improved survival of CLL patients. In this therapeutic landscape, the identification of different CLL risk groups based on the presence of specific molecular lesions and/or immunogenetic features has allowed treatment tailoring in terms of choosing the most appropriate drug. The combination of genetic and immunogenetic biomarkers together with MRD assessment may allow one step forward in the precision medicine approach to CLL.","PeriodicalId":12118,"journal":{"name":"Expert Opinion on Orphan Drugs","volume":null,"pages":null},"PeriodicalIF":0.8,"publicationDate":"2020-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/21678707.2020.1804860","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42380521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2