Pulmonary pharmacology & therapeutics最新文献

{"title":"Experimental modeling of pulmonary fibrosis and combined emphysema in mice using repeated doses of bleomycin and cigarette smoke extract","authors":"Jung Hur ,&nbsp;Chin Kook Rhee ,&nbsp;Joon Young Choi ,&nbsp;Yong Suk Jo","doi":"10.1016/j.pupt.2025.102376","DOIUrl":"10.1016/j.pupt.2025.102376","url":null,"abstract":"<div><h3>Rationale</h3><div>A high prevalence of smoking among idiopathic pulmonary fibrosis (IPF) patients increases the risk of emphysema. Combined pulmonary fibrosis and emphysema (CPFE) occurs predominantly in males, characterized by severe exercise-induced dyspnea, decreased diffusing capacity, and increased lung cancer risk. The exclusion of CPFE patients from clinical studies has limited understanding of its pathophysiology, treatment, and prognosis. This study aimed to close this knowledge gap by comparing CPFE with pure IPF in animal models, with the intent of developing phenotype-directed therapeutic strategies.</div></div><div><h3>Methods</h3><div>Eight-week-old female C57BL/6J mice received biweekly intratracheal bleomycin (BLM, 2 U/kg/100 μL) for 3 doses. For the CPFE model, additional intranasal cigarette smoke extract (CSE) was administered twice weekly. Inflammation and fibrosis were evaluated through bronchoalveolar lavage fluid (BALF), proinflammatory cytokines, fibrosis markers, and lung histology.</div></div><div><h3>Results</h3><div>BALF analysis showed increased cell counts in all BLM-treated groups, primarily macrophages, with elevated interleukin (IL)-6, transforming growth factor (TGF)-β1, and matrix metalloproteinases (MMP 3 and MMP 8). The BLM and CSE treated group displayed higher macrophages and lymphocytes counts than BLM alone. Lung tissue analysis revealed increased hydroxyproline, inflammation scores, Ashcroft scores, and higher α-smooth muscle actin (SMA) and collagen 1 expression in BLM-treated groups. The BLM and CSE treated group demonstrated notably higher emphysema formation as measured by mean linear intercept (MLI).</div></div><div><h3>Conclusions</h3><div>Through repeated BLM administrations and CSE exposure, an effective model for persistent pulmonary fibrosis and emphysema was established, enabling preclinical studies on CPFE and IPF and exploration of phenotype-directed therapeutic strategies for pulmonary fibrosis.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"90 ","pages":"Article 102376"},"PeriodicalIF":3.3,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144523904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The era of multiple biologics: Is combination and switching an option in the management of severe asthma?","authors":"Emmanuel Oshiogwe Okwuofu ,&nbsp;Audrey Chee Hui Yong ,&nbsp;Jonathan Chee Woei Lim ,&nbsp;Johnson Stanslas","doi":"10.1016/j.pupt.2025.102375","DOIUrl":"10.1016/j.pupt.2025.102375","url":null,"abstract":"<div><h3>Background and objective</h3><div>The introduction of biologics therapies targeting specific cytokines relevant to asthma pathophysiology has changed the landscape in the treatment of severe asthma in both adults and children. However, the availability of multiple agents, inclusion criteria for randomised control trials (RCTs), variation in national and international guidelines, instances of treatment failures, and the potential of switching or combining biologic therapies, highlight the need for real-world evidence. Data from real-world studies of biologics in severe asthma may complement efficacy data obtained from RCTs and provide important post-marketing safety information. Additionally, these studies may help inform the design of future clinical trials, characterise the natural history of the disease, and support important translational research. This review highlights current evidence for the combination and switching of biologics in severe asthma and comorbid diseases that may serve as pointers for optimal clinical outcomes.</div></div><div><h3>Method</h3><div>Pubmed, Scopus, and Web of Science were searched using specified search strategies.</div></div><div><h3>Results</h3><div>Available evidence suggests that patients with severe asthma who received combination or switched biologics (omalizumab, benralizumab, reslizumab, mepolizumab, dupilumab, and Tezepelumab) in real-world settings experienced significant improvement in asthma control, exacerbation, and lung function. Although combining biologics is not currently a common practice, there are cases where biologic therapies were combined, discontinued, or switched.</div></div><div><h3>Conclusion</h3><div>Patients may benefit from the early and systematic consideration of combination and switching of biologic therapies in severe asthma.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"90 ","pages":"Article 102375"},"PeriodicalIF":3.3,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of EP395, a novel macrolide, on acute neutrophilic airway inflammation","authors":"Jennifer Ann Kricker ,&nbsp;Virginia Norris ,&nbsp;Clive Page ,&nbsp;Michael John Parnham","doi":"10.1016/j.pupt.2025.102364","DOIUrl":"10.1016/j.pupt.2025.102364","url":null,"abstract":"<div><div>Macrolide antibiotics have been shown to reduce exacerbations of respiratory diseases, including chronic obstructive pulmonary disease (COPD) and asthma. This effect is believed to be due to the immunomodulatory properties of macrolides rather than their antimicrobial activity. However, prolonged use of macrolide antibiotics can result in the development of antimicrobial resistance, which prompted us to develop EP395, a compound with similar pharmacological actions to macrolides, but without antimicrobial activity. We investigated EP395 in several established models of neutrophilic airway inflammation in male BALB/c mice. Oral pretreatment with EP395 for 2 weeks had significant anti-inflammatory effects, reducing cytokines and neutrophil infiltration into bronchoalveolar lavage fluid (BAL) induced by either lipopolysaccharide (LPS), tobacco smoke or respiratory syncytial virus (RSV). EP395 had comparable inhibitory effects to azithromycin in all three models. The PDE4 inhibitor, roflumilast, was also included as a positive control in the LPS model, with comparable effects on neutrophil numbers. In vitro assays on neutrophil function revealed both stimulatory and inhibitory effects of treatment with EP395. These data demonstrate the beneficial pharmacological activity of EP395, a macrolide with negligible antimicrobial activity, in models of acute neutrophilic inflammation and on neutrophil activity and supported its progression into clinical development as a potential treatment for COPD.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"90 ","pages":"Article 102364"},"PeriodicalIF":3.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144221986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of EP395, a novel anti-inflammatory macrolide, in an inhaled lipopolysaccharide challenge model in healthy volunteers: a randomised controlled trial","authors":"Jens M. Hohlfeld ,&nbsp;Philipp Badorrek ,&nbsp;Olof Breuer ,&nbsp;Kate Hanrott ,&nbsp;Jennifer Kricker ,&nbsp;Michael J. Parnham ,&nbsp;Virginia Norris","doi":"10.1016/j.pupt.2025.102365","DOIUrl":"10.1016/j.pupt.2025.102365","url":null,"abstract":"<div><div>EP395, a macrolide with negligible antimicrobial activity but with anti-inflammatory effects in murine lipopolysaccharide (LPS) challenge model, is being developed as a potential treatment to reduce COPD exacerbations. This double-blind, placebo-controlled clinical study evaluated the pharmacodynamics of EP395 in response to inhaled LPS, an established clinical model for assessing anti-inflammatory effects of potential new treatments.</div><div>Forty-nine healthy, non-smoking participants were randomised to oral 375 mg EP395 or placebo, daily for 3 weeks. An inhaled LPS challenge (2 μg) was then given, followed 6 h later by bronchoscopy for bronchoalveolar lavage fluid (BALF) collection. Blood samples were collected pre, 6 and 24 h after LPS challenge.</div><div>BALF concentrations of IL-6, TNF-α, MIP-1α, MIP-1β and MCP-1 were lower with EP395 than placebo, while IL-33, IL-8, and IL-1β were higher with EP395 than placebo (not statistically significant). Neutrophil counts were unaffected, but neutrophil elastase and myeloperoxidase were higher with EP395 than placebo (not statistically significant). Serum concentrations of surfactant protein-D significantly increased in the EP395 group in response to LPS at both 6 and 24 h compared with pre-LPS (mean pre-LPS 148.8 ng/mL; mean 24 h post-LPS 183.0 ng/mL) but not in the placebo group (mean pre-LPS 142.4 ng/mL; mean 24 h post-LPS 142.4 ng/mL). The log₂ transformed fold difference in the EP395 group, before and 24 h after LPS challenge was 0.33 (95 % CI 0.52, 0.14; p = 0.0007).</div><div>EP395 treatment increased the host defence response to inhaled LPS, including the epithelial response, whilst reducing inflammatory site pro-inflammatory mediators.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"90 ","pages":"Article 102365"},"PeriodicalIF":3.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel macrolide, EP395, with reduced antibacterial activity and an enhancing effect on respiratory epithelial barrier","authors":"Thorarinn Gudjonsson ,&nbsp;Jon Petur Joelsson ,&nbsp;Ari Jon Arason ,&nbsp;Arni Asbjarnarson ,&nbsp;Fridrik Runar Gardarsson ,&nbsp;Fredrik Lehmann ,&nbsp;Peter Teodorovic ,&nbsp;Saevar Ingthorsson ,&nbsp;Snaevar Sigurdsson ,&nbsp;Bryndis Valdimarsdottir ,&nbsp;Michael John Parnham ,&nbsp;Clive Page ,&nbsp;Jennifer Ann Kricker","doi":"10.1016/j.pupt.2025.102363","DOIUrl":"10.1016/j.pupt.2025.102363","url":null,"abstract":"<div><div>Epithelial barrier failure, a feature of several inflammatory lung diseases, contributes to exacerbations and disease progression. Acute exacerbations are often treated with macrolides, including azithromycin (AZM). In part, this is due to both primary antimicrobial and additional immunomodulatory actions, complemented by recently reported enhanced integrity of respiratory epithelial barriers. However, long-term “off label” use of macrolides is associated with increased bacterial resistance. We now introduce a new class of compounds, “Barriolides” that are analogues of AZM promoting airway epithelial barrier integrity <em>in vitro</em>, with negligible antibacterial activity. The lead compound is EP395 which does not affect cell viability up to 100 μM in VA10 bronchial epithelial cells. Treatment with EP395 for three weeks enhanced epithelial barrier integrity, measured by increased transepithelial electrical resistance, reduced paracellular flux in air-liquid interface culture and increased expression of tight junction proteins. EP395 also induced epidermal differentiation and formation of lamellar bodies, complemented by a relevant genetic footprint. In mice exposed to sulphur dioxide, pre-treatment with EP395 reduced extravasation of human serum albumin into the bronchoalveolar lavage fluid. These data demonstrate epithelial barrier-protecting effects of EP395, a promising candidate for treatment of chronic respiratory diseases without risk of bacterial resistance.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"90 ","pages":"Article 102363"},"PeriodicalIF":3.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitigating systemic corticosteroid risks in COPD: A call for earlier triple therapy initiation","authors":"Luis J. Nannini","doi":"10.1016/j.pupt.2025.102360","DOIUrl":"10.1016/j.pupt.2025.102360","url":null,"abstract":"<div><div>Current GOLD guidelines recommend initial dual therapy with a LABA and LAMA for COPD patients with a high risk of exacerbations (at least two moderate or one severe exacerbation in the previous 12 months), with Inhaled Corticosteroids (ICS) added for specific phenotypes or continued exacerbations. Systemic corticosteroids (SCS) are advised for severe exacerbations, but cumulative SCS exposure is linked to significant adverse outcomes such as endocrine disorders and pneumonia. Studies suggest that after limited exacerbations, COPD patients may exhaust their “SCS credit,” increasing their risk of severe comorbidities. Earlier initiation of triple therapy in high-risk, symptomatic patients shows substantial benefits, including improved quality of life, compared to standard care. Like asthma management, SCS exposure in COPD should be minimised, and precision medicine should guide early triple therapy to preserve SCS use for future exacerbations.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"90 ","pages":"Article 102360"},"PeriodicalIF":3.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The low global warming potential propellant HFA-152a does not induce bronchoconstriction or impair mucociliary clearance","authors":"Michela Salvadori ,&nbsp;Dave Singh ,&nbsp;Kusum Mathews ,&nbsp;Luca Girardello ,&nbsp;Mauro Cortellini ,&nbsp;Aida Emirova ,&nbsp;Ilaria Pacchetti ,&nbsp;Martina Foti ,&nbsp;Veronica Puviani ,&nbsp;Gianluigi Poli ,&nbsp;François Rony","doi":"10.1016/j.pupt.2025.102358","DOIUrl":"10.1016/j.pupt.2025.102358","url":null,"abstract":"<div><h3>Introduction</h3><div>Use of propellants with high global warming potential (e.g., HFA-134a) for pressurised metered-dose inhalers is being phased down. An alternative is reformulation using propellants with low global warming potential (e.g., HFA-152a), which requires evaluation of the propellant's safety, in particular whether it induces bronchoconstriction or impairs mucociliary clearance (MCC). In this manuscript, we describe two studies, the first comparing the bronchoconstriction potential of HFA-152a vs HFA-134a, the second comparing their effect on MCC.</div></div><div><h3>Methods</h3><div>The bronchoconstriction study was single-dose, randomised, double-blind, controlled, crossover, in adults with asthma. The primary endpoint was relative change from baseline in forced expiratory volume in 1 s (FEV₁) at 15 min post-dose.</div><div>The MCC study was multiple-dose (8 days), randomised, open-label, controlled, crossover, in healthy volunteers. The primary endpoint was percent particle retention in the right whole lung at 2 and 4 h after inhalation of radiolabelled particles (PPR₂ and PPR₄).</div></div><div><h3>Results</h3><div>For the bronchoconstriction study (N = 25), the 95 % CI of the adjusted mean FEV₁ difference between HFA-152a vs HFA-134a at 15 min post-dose was within the −10 % to +10 % equivalence limit (1.86 % [95 % CI –0.48 %, 4.20 %]; p = 0.113). Treatment-emergent adverse events were reported by 4.0 % (HFA-152a) and 12.0 % (HFA-134a) patients, all mild or moderate in intensity, and none serious.</div><div>For the MCC study (N = 20), the 95 % CIs for the adjusted mean differences between HFA-152a vs HFA-134a at Day 8 contained 0 for both PPR₂ (1.36 [–2.28, 4.99]%; p = 0.442) and PPR₄ (0.70 [–1.73, 3.12]%; p = 0.553). A similar proportion of subjects had treatment-emergent adverse events (25.0 % vs 35.0 %), all mild in intensity, and none serious.</div></div><div><h3>Conclusions</h3><div>These two studies suggest a switch in propellant from HFA-134a to HFA-152a is unlikely to induce post-dose bronchoconstriction in asthma or impact lung MCC, and is not accompanied by any safety concerns.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"89 ","pages":"Article 102358"},"PeriodicalIF":3.3,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhaled vs. intravenous vasodilators in perioperative pulmonary hypertension during chest surgery using cardiopulmonary bypass: A systematic review and meta-analysis","authors":"Yasuhiro Ogura ,&nbsp;Eriya Imai ,&nbsp;Shunsuke Taito ,&nbsp;Tatsuya Tsuji ,&nbsp;Yuji Kamimura ,&nbsp;Takahiro Tsuge ,&nbsp;Kenichi Amano","doi":"10.1016/j.pupt.2025.102357","DOIUrl":"10.1016/j.pupt.2025.102357","url":null,"abstract":"","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"89 ","pages":"Article 102357"},"PeriodicalIF":3.3,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact on beclometasone dipropionate pharmacokinetics when switching to a low global warming potential propellant in a pressurised metered-dose inhaler","authors":"François Rony ,&nbsp;Maria Gloria Pittelli ,&nbsp;Cristina Contursi ,&nbsp;Ilaria Pacchetti ,&nbsp;Emanuele Rocco Calabrò ,&nbsp;Luca Vittorio Viganò ,&nbsp;Kusum S. Mathews ,&nbsp;Gianluigi Poli ,&nbsp;Katrin Van Leuven ,&nbsp;Matteo Martini","doi":"10.1016/j.pupt.2025.102356","DOIUrl":"10.1016/j.pupt.2025.102356","url":null,"abstract":"<div><h3>Introduction</h3><div>Use of high global warming potential propellants (e.g., HFA-134a) for pressurised metered-dose inhalers (pMDIs) is being phased down. Beclometasone dipropionate (BDP) is approved for the treatment of asthma in several countries via an HFA-134a propellant pMDI. This is being reformulated using the low global warming potential propellant HFA-152a. Two studies compared BDP pharmacokinetics delivered via pMDI using HFA-152a vs HFA-134a.</div></div><div><h3>Methods</h3><div>Both studies (N = 71/study) were single-dose (four inhalations of BDP), randomised, double-blind, crossover (Study 1, four-way; Study 2, two-way), in healthy volunteers. In Study 1, subjects inhaled BDP via HFA-134a pMDI in two periods (200 μg/actuation in one period, 100 μg/actuation in the other) and HFA-152a pMDI in the other two (200 or 100 μg/actuation). In Study 2, subjects inhaled BDP 200 μg/actuation via HFA-134a or HFA-152a pMDI using a spacer device.</div><div>pMDIs containing HFA-152a and HFA-134a were compared in terms of lung availability (BDP comparisons) and total systemic exposure (beclometasone-17-monopropionate comparisons [B17MP; active metabolite of BDP]), with bioequivalence concluded if the 90 % confidence intervals (CIs) of the geometric mean ratios of maximum plasma concentration (C_max) and area under the plasma concentration–time curve between time zero and the last quantifiable timepoint (AUC_0–t) were between 80 and 125 %.</div></div><div><h3>Results</h3><div>BDP C_max and AUC_0-t were equivalent for the two BDP 200 μg formulations, without (Study 1) and with spacer (Study 2). BDP 100 μg AUC_0-t met the bioequivalence criteria, but the C_max lower 90 % CI was marginally below the bioequivalence limit (79.46 %). B17MP C_max and AUC_0-t were bioequivalent with both propellants in all three comparisons.</div></div><div><h3>Conclusions</h3><div>Overall, bioequivalence was confirmed of HFA-152a and HFA-134a for BDP 200 μg/actuation, with and without a spacer. Although bioequivalence of the two formulations cannot be formally concluded for BDP 100 μg, the minimal difference suggests the two formulations can be considered therapeutically equivalent.</div></div>","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"89 ","pages":"Article 102356"},"PeriodicalIF":3.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug repurposing tactics in the USA: Known active pharmaceutical ingredients in new indications","authors":"Thomas P. Dooley","doi":"10.1016/j.pupt.2025.102348","DOIUrl":"10.1016/j.pupt.2025.102348","url":null,"abstract":"","PeriodicalId":20799,"journal":{"name":"Pulmonary pharmacology & therapeutics","volume":"89 ","pages":"Article 102348"},"PeriodicalIF":3.3,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}