BioDrugs最新文献

{"title":"Impact of Early Access Reform on Oncology Innovation in France: Approvals, Patients, and Costs","authors":"Tess Martin, Catherine Rioufol, Bertrand Favier, Nicolas Martelli, Isabelle Madelaine, Christos Chouaid, Isabelle Borget","doi":"10.1007/s40259-024-00658-1","DOIUrl":"https://doi.org/10.1007/s40259-024-00658-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>An ambitious reform of the early access (EA) process was set up in July 2021 in France, aiming to simplify procedures and accelerate access to innovative drugs.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>This study analyzes the characteristics of oncology drug approvals through the EA process and its impact on real-life data for oncology patients.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The number and characteristics of EA demands concerning oncology drugs submitted to the National Health Authority (HAS, Haute Autorité de Santé) were reviewed until 31 December 2022. A longitudinal retrospective study on patients treated with an EA oncology drug between 1 January 2019 and 31 December 2022 was also performed using the French nationwide claims database (Systeme National des Données de Santé [SNDS]) to assess the impact of the reform on the number of indications and patients, and the costs.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Among 110 published decisions, the HAS granted 88 (80%) EA indications within 70 days of assessment on average, including 46 (52%) in oncology (67% in solid tumors and 33% in hematological malignancies). Approved indications were mostly supported by randomized phase III trials (67%), whereas refused EA relied more on non-randomized (57%) trials. Overall survival was the primary endpoint of 28% of EA approvals versus none of denied EAs. In the SNDS data, the annual number of patients with cancer treated with an EA drug increased from 3137 patients in 2019 to 18,341 in 2022 (+ 484%), whereas the number of indications rose from 12 to 62, mainly in oncohematology (<i>n</i> = 17), lung (<i>n</i> = 12), digestive (<i>n</i> = 9) and breast cancer (<i>n</i> = 9). Reimbursement costs for EA treatments surged from €42 to €526 million (+ 1159%).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The French EA reform contributed to enabling rapid access to innovations in a wide range of indications for oncology patients. However, the findings highlight ongoing challenges in financial sustainability, warranting continued evaluation and adjustments.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"1 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140628451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CRISPR-Cas System: A New Dawn to Combat Antibiotic Resistance","authors":"Muhammad Shahzad Rafiq, Muhammad AbuBakar Shabbir, Ahmed Raza, Shoaib Irshad, Andleeb Asghar, Muhammad Kashif Maan, Mushtaq Ahmed Gondal, Haihong Hao","doi":"10.1007/s40259-024-00656-3","DOIUrl":"https://doi.org/10.1007/s40259-024-00656-3","url":null,"abstract":"<p>Antimicrobial resistance (AMR) can potentially harm global public health. Horizontal gene transfer (HGT), which speeds up the emergence of AMR and increases the burden of drug resistance in mobile genetic elements (MGEs), is the primary method by which AMR genes are transferred across bacterial pathogens. New approaches are urgently needed to halt the spread of bacterial diseases and antibiotic resistance. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), an RNA-guided adaptive immune system, protects prokaryotes from foreign DNA like plasmids and phages. This approach may be essential in limiting horizontal gene transfer and halting the spread of antibiotic resistance. The CRISPR-Cas system has been crucial in identifying and understanding resistance mechanisms and developing novel therapeutic approaches. This review article investigates the CRISPR-Cas system’s potential as a tool to combat bacterial AMR. Antibiotic-resistant bacteria can be targeted and eliminated by the CRISPR-Cas system. It has been proven to be an efficient method for removing carbapenem-resistant plasmids and regaining antibiotic susceptibility. The CRISPR-Cas system has enormous potential as a weapon against bacterial AMR. It precisely targets and eliminates antibiotic-resistant bacteria, facilitates resistance mechanism identification, and offers new possibilities in diagnostics and therapeutics.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"95 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140592503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Next-Generation Anti-TNFα Agents: The Example of Ozoralizumab","authors":"Kouhei Tsumoto, Tsutomu Takeuchi","doi":"10.1007/s40259-024-00648-3","DOIUrl":"https://doi.org/10.1007/s40259-024-00648-3","url":null,"abstract":"<p>Biologic therapy involving anti-tumor necrosis factor-α (anti-TNFα) agents has fundamentally changed the management of patients with immune-mediated inflammatory diseases, including rheumatoid arthritis, thus benefiting many patients. Nevertheless, the inability of some patients to achieve low disease activity or clinical remission remains a major concern. To address such concerns, next-generation anti-TNFα agents that differ from the immunoglobulin G-format anti-TNFα agents that have been used to date are being developed using antibody-engineering technology. Their unique design employing novel molecular characteristics affords several advantages, such as early improvement of clinical symptoms, optimization of drug bioavailability, enhancement of tissue penetration, and a reduction in side effects. This holds promise for a new paradigm shift in biologic therapy via the use of next-generation anti-TNFα agents. Ozoralizumab, a next-generation anti-TNFα agent that was recently approved in Japan, comprises a variable region heavy-chain format. It has a completely different structure from conventional therapeutic antibodies, such as a small molecular size, an albumin-binding module, and a unique format that produces an avidity effect. Ozoralizumab exhibited rapid biodistribution into joints, provided attenuation of Fcγ receptor-mediated inflammatory responses, and had a high binding affinity to TNFα in non-clinical studies. In clinical trials, ozoralizumab yielded an early improvement in clinical symptoms, a sustained efficacy for up to 52 weeks, and an acceptable tolerability in patients with rheumatoid arthritis. This review focuses on the results of pre-clinical and clinical trials for ozoralizumab and outlines the progress in next-generation antibody development.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"27 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140592233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Could a Long-Acting Prodrug of SN-38 be Efficacious in Sacituzumab Govitecan-Resistant Tumors?","authors":"Daniel V Santi, Gary W Ashley, Luc Cabel, Francois-Clement Bidard","doi":"10.1007/s40259-024-00643-8","DOIUrl":"10.1007/s40259-024-00643-8","url":null,"abstract":"<p><p>We previously proposed that sacituzumab govitecan (SG, Trodelvy®) likely acts as a simple prodrug of systemic SN-38 as well as an antibody drug conjugate (ADC). In the present commentary, we assess whether a long-acting SN-38 prodrug, such as PLX038, might be efficacious in SG-resistant patients. We first describe possible mechanisms of action of SG, with new insights on pharmacokinetics and TROP2 receptor occupancy. We argue that SG is not an optimal conventional ADC and that the amount of systemic SN-38 spontaneously hydrolyzed from the ADC is so high it must have activity. Then, we describe the concept of time-over-target as related to the pharmacology of SG and PLX038 as SN-38 prodrugs. To be clear, we are not in any way suggesting that PLX038 or any SN-38 prodrug is superior to SG as an anticancer agent. Clearly, SG has the benefit over antigen-independent SN-38 prodrugs in that it targets cells with the TROP2 receptor. However, we surmise that PLX038 should be a more efficacious and less toxic prodrug of systemic SN-38 than SG. Finally, we suggest possible mechanisms of SG resistance and how PLX038 might perform in the context of each. Taken together, we argue that-contrary to many opinions-SG does not exclusively act as a conventional ADC, and propose that PLX038 may be efficacious in some settings of SG-resistance.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"171-176"},"PeriodicalIF":6.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10912420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, Tolerability, and Preliminary Efficacy of Serplulimab, a Novel Anti-PD-1 Antibody, in Patients with Metastatic or Recurrent Solid Tumors: A Phase I Study.","authors":"Ching-Liang Ho, Tsu-Yi Chao, Chia-Lun Chang, Hsuan-Yu Lin","doi":"10.1007/s40259-023-00639-w","DOIUrl":"10.1007/s40259-023-00639-w","url":null,"abstract":"<p><strong>Background: </strong>Serplulimab is a novel, recombinant, humanized, monoclonal, anti-programmed death 1 antibody with a similar or better affinity and pre-clinical antitumor activity than pembrolizumab and nivolumab.</p><p><strong>Objective: </strong>This phase I, open-label, dose-escalation study evaluated serplulimab in patients with advanced solid tumors. The second interim analysis of the dose-finding phase is reported here.</p><p><strong>Methods: </strong>Adult patients with histologically confirmed metastatic/recurrent solid tumors who had progressed on, or were intolerant to/clinically unsuitable for standard treatment, were enrolled. Four intravenous serplulimab dose levels were evaluated: 0.3, 1.0, 3.0, and 10.0 mg/kg every 2 weeks in 28-day cycles for up to 2 years. Primary endpoints were the incidence of treatment-emergent adverse events and the maximum tolerated dose.</p><p><strong>Results: </strong>By 27 July, 2020 (data cut-off), 29 patients with stage IV disease (34.5% with lung cancer) received one or more doses of serplulimab. One (3.4%) patient had completed treatment and 26 (89.7%) had discontinued from the study. The maximum tolerated dose was not reached. Twenty-two (75.9%) patients experienced treatment-emergent adverse events related to serplulimab, most frequently nausea (24.1%), with no notable differences in incidence between dose cohorts; of these, grade ≥ 3 events occurred in four (13.8%) patients. Pharmacokinetic data demonstrated minimal accumulation of serplulimab after repeated administration. Functional programmed death 1 blockade was observed across dose levels. Objective response and disease control rates were 8.0 and 60.0%, respectively.</p><p><strong>Conclusions: </strong>Serplulimab was well tolerated and demonstrated antitumor activity. These data support further study of serplulimab in larger patient populations.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov NCT03468751 (19 March, 2018).</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"287-299"},"PeriodicalIF":6.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139401715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Biosimilar Paradox of Oncologists' Perceptions and Hesitations in South Korea: A Web-Based Survey Study.","authors":"Gyeongseon Shin, Byung Soo Kim, Do Yeun Kim, SeungJin Bae","doi":"10.1007/s40259-023-00640-3","DOIUrl":"10.1007/s40259-023-00640-3","url":null,"abstract":"<p><strong>Introduction: </strong>Biosimilars offer a cost-effective alternative to original biopharmaceuticals with comparable efficacy and safety. The perception and familiarity of prescribers toward biosimilars play a critical role in their market penetration. Yet, few studies have explored the perception of oncologists toward biosimilars, much less in Asia.</p><p><strong>Objectives: </strong>The objective of this study is to understand barriers of adopting biosimilars among oncologists and explore strategies to promote their use in clinical practice settings.</p><p><strong>Methods: </strong>A web-based survey was conducted among Korean oncologists from September to October 2022, assessing their perception of biosimilars and prescribing practices.</p><p><strong>Results: </strong>Among the 118 surveyed oncologists, 75.4% (89 out of 118) had previously prescribed biosimilars. When asked about their preference, 48.3% (57 out of 118) of the respondents preferred originators to biosimilars, whereas 16.1% (19 out of 118) favored biosimilars over the originators. The primary reason for preferring the originators was trust in safety and efficacy (94.7%, 54 out of 57). Still, a paradox was noted as 87.0% (47 out of 54) and 85.2% (46 out of 54) of these also acknowledged the comparable efficacy and safety of biosimilars. A relatively small number of the respondents (16.1%, 19 out of 118) did not consider prescribing biosimilars to biologic-naïve patients at all, and up to 56.8% (67 out of 118) expressed reluctance to switch prescriptions from originators to biosimilars. However, 90.7% (107 out of 118) of respondents considered changing their prescription to biosimilars if patients faced financial stress. Concerns regarding the efficacy when switching to biosimilars were expressed by 42.7% (38 out of 89) of oncologists with biosimilar prescribing experience, increasing to 69.0% (20 out of 29) among those without such experience.</p><p><strong>Conclusion: </strong>Korean oncologists perceived biosimilars to be as safe and effective as originators. However, there is a notable mismatch between this perception and their prescribing practices, particularly among those who have not prescribed biosimilars before. The financial burden of patients served as a significant driver for prescribing biosimilars, yet marginal price differences between originators and biosimilars may be associated with the low adoption rate of biosimilars in Korea. Active price competition may enhance market penetration of biosimilars.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"301-311"},"PeriodicalIF":6.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10912143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139429571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Is the Availability of Biosimilar Adalimumab Associated with Budget Saving? A Difference-in-Difference Analysis of 14 Countries.","authors":"Hyunjung Woo, Gyeongseon Shin, Donghwan Lee, Hye-Young Kwon, SeungJin Bae","doi":"10.1007/s40259-024-00645-6","DOIUrl":"10.1007/s40259-024-00645-6","url":null,"abstract":"","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"323"},"PeriodicalIF":6.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10912105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Splice-Modulating Antisense Oligonucleotides as Therapeutics for Inherited Metabolic Diseases.","authors":"Suxiang Chen, Saumya Nishanga Heendeniya, Bao T Le, Kamal Rahimizadeh, Navid Rabiee, Qurat Ul Ain Zahra, Rakesh N Veedu","doi":"10.1007/s40259-024-00644-7","DOIUrl":"10.1007/s40259-024-00644-7","url":null,"abstract":"<p><p>The last decade (2013-2023) has seen unprecedented successes in the clinical translation of therapeutic antisense oligonucleotides (ASOs). Eight such molecules have been granted marketing approval by the United States Food and Drug Administration (US FDA) during the decade, after the first ASO drug, fomivirsen, was approved much earlier, in 1998. Splice-modulating ASOs have also been developed for the therapy of inborn errors of metabolism (IEMs), due to their ability to redirect aberrant splicing caused by mutations, thus recovering the expression of normal transcripts, and correcting the deficiency of functional proteins. The feasibility of treating IEM patients with splice-switching ASOs has been supported by FDA permission (2018) of the first \"N-of-1\" study of milasen, an investigational ASO drug for Batten disease. Although for IEM, owing to the rarity of individual disease and/or pathogenic mutation, only a low number of patients may be treated by ASOs that specifically suppress the aberrant splicing pattern of mutant precursor mRNA (pre-mRNA), splice-switching ASOs represent superior individualized molecular therapeutics for IEM. In this work, we first summarize the ASO technology with respect to its mechanisms of action, chemical modifications of nucleotides, and rational design of modified oligonucleotides; following that, we precisely provide a review of the current understanding of developing splice-modulating ASO-based therapeutics for IEM. In the concluding section, we suggest potential ways to improve and/or optimize the development of ASOs targeting IEM.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"177-203"},"PeriodicalIF":6.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10912209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nano-Bio Interactions: Exploring the Biological Behavior and the Fate of Lipid-Based Gene Delivery Systems.","authors":"Seigo Kimura, Hideyoshi Harashima","doi":"10.1007/s40259-024-00647-4","DOIUrl":"10.1007/s40259-024-00647-4","url":null,"abstract":"<p><p>Gene therapy for many diseases is rapidly becoming a reality, as demonstrated by the recent approval of various nucleic acid-based therapeutics. Non-viral systems such as lipid-based carriers, lipid nanoparticles (LNPs), for delivering different payloads including small interfering RNA, plasmid DNA, and messenger RNA have been particularly extensively explored and developed for clinical uses. One of the most important issues in LNP development is delivery to extrahepatic tissues. To achieve this, various lipids and lipid-like materials are being examined and screened. Several LNP formulations that target extrahepatic tissues, such as the spleen and the lungs have been developed by adjusting the lipid compositions of LNPs. However, mechanistic details of how the characteristics of LNPs affect delivery efficiency remains unclear. The purpose of this review is to provide an overview of LNP-based nucleic acid delivery focusing on LNP components and their structures, as well as discussing biological factors, such as biomolecular corona and cellular responses related to the delivery efficiency.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"259-273"},"PeriodicalIF":6.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139721504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Engineering of Interleukin-2 for Enhanced Therapeutic Activity in Autoimmune Diseases.","authors":"Luke M Tomasovic, Kathy Liu, Derek VanDyke, Charina S Fabilane, Jamie B Spangler","doi":"10.1007/s40259-023-00635-0","DOIUrl":"10.1007/s40259-023-00635-0","url":null,"abstract":"<p><p>The interleukin-2 (IL-2) cytokine plays a crucial role in regulating immune responses and maintaining immune homeostasis. Its immunosuppressive effects have been harnessed therapeutically via administration of low cytokine doses. Low-dose IL-2 has shown promise in the treatment of various autoimmune and inflammatory diseases; however, the clinical use of IL-2 is complicated by its toxicity, its pleiotropic effects on both immunostimulatory and immunosuppressive cell subsets, and its short serum half-life, which collectively limit the therapeutic window. As a result, there remains a considerable need for IL-2-based autoimmune disease therapies that can selectively target regulatory T cells with minimal off-target binding to immune effector cells in order to prevent cytokine-mediated toxicities and optimize therapeutic efficacy. In this review, we discuss exciting advances in IL-2 engineering that are empowering the development of novel therapies to treat autoimmune conditions. We describe the structural mechanisms of IL-2 signaling, explore current applications of IL-2-based compounds as immunoregulatory interventions, and detail the progress and challenges associated with clinical adoption of IL-2 therapies. In particular, we focus on protein engineering approaches that have been employed to optimize the regulatory T-cell bias of IL-2, including structure-guided or computational design of cytokine mutants, conjugation to polyethylene glycol, and the development of IL-2 fusion proteins. We also consider future research directions for enhancing the translational potential of engineered IL-2-based therapies. Overall, this review highlights the immense potential to leverage the immunoregulatory properties of IL-2 for targeted treatment of autoimmune and inflammatory diseases.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"227-248"},"PeriodicalIF":6.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10947368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138298315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}