Journal of Aerosol Medicine and Pulmonary Drug Delivery最新文献

{"title":"Abstracts from The Aerosol Society Drug Delivery to the Lungs 33.","authors":"","doi":"10.1089/jamp.2023.ab01.abstracts","DOIUrl":"https://doi.org/10.1089/jamp.2023.ab01.abstracts","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 3","pages":"A1-A39"},"PeriodicalIF":3.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9630158","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}

{"title":"Nanoparticle Diffusion in Respiratory Mucus Influenced by Mucociliary Clearance: A Review of Mathematical Modeling.","authors":"Mohammad Hadi Sedaghat,&nbsp;Mehrdad Behnia,&nbsp;Omid Abouali","doi":"10.1089/jamp.2022.0049","DOIUrl":"https://doi.org/10.1089/jamp.2022.0049","url":null,"abstract":"<p><p><b><i>Background:</i></b> Inhalation and deposition of particles in human airways have attracted considerable attention due to importance of particulate pollutants, transmission of infectious diseases, and therapeutic delivery of drugs at targeted areas. We summarize current state-of-the art research in particle deposition on airway surface liquid (ASL) influenced by mucociliary clearance (MCC) by identifying areas that need further investigation. <b><i>Methodology:</i></b> We aim to review focus on governing and constitutive equations describing MCC geometry followed by description of mathematical modeling of ciliary forces, mucus rheology properties, and numerical approaches to solve modified time-dependent Navier-Stokes equations. We also review mathematical modeling of particle deposition in ASL influenced by MCC, particle transport in ASL in terms of Eulerian and Lagrangian approaches, and discuss the corresponding mass transport issues in this layer. Whenever required, numerical predictions are contrasted with the pertinent experimental data. <b><i>Results:</i></b> Results indicate that mean mucus and periciliary liquid velocities are strongly influenced by mucus rheological characteristics as well as ciliary abnormalities. However, most of the currently available literature on mucus fiber spacing, ciliary beat frequency, and particle surface chemistry is based on particle deposition on ASL by considering a fixed value of ASL velocity. The effects of real ASL flow regimes on particle deposition in this layer are limited. In addition, no other study is available on modeling nonhomogeneous and viscoelastic characteristics of mucus layer on ASL drug delivery. <b><i>Conclusion:</i></b> Simplification of assumptions on governing equations of drug delivery in ASL influenced by MCC leads to imposing some limitations on numerical results.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 3","pages":"127-143"},"PeriodicalIF":3.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9627742","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}

{"title":"Inhaled Nitric Oxide in Acute Respiratory Distress Syndrome Subsets: Rationale and Clinical Applications.","authors":"Simone Redaelli, Matteo Pozzi, Marco Giani, Aurora Magliocca, Roberto Fumagalli, Giuseppe Foti, Lorenzo Berra, Emanuele Rezoagli","doi":"10.1089/jamp.2022.0058","DOIUrl":"10.1089/jamp.2022.0058","url":null,"abstract":"<p><p>Acute respiratory distress syndrome (ARDS) is a life-threatening condition, characterized by diffuse inflammatory lung injury. Since the coronavirus disease 2019 (COVID-19) pandemic spread worldwide, the most common cause of ARDS has been the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Both the COVID-19-associated ARDS and the ARDS related to other causes-also defined as classical ARDS-are burdened by high mortality and morbidity. For these reasons, effective therapeutic interventions are urgently needed. Among them, inhaled nitric oxide (iNO) has been studied in patients with ARDS since 1993 and it is currently under investigation. In this review, we aim at describing the biological and pharmacological rationale of iNO treatment in ARDS by elucidating similarities and differences between classical and COVID-19 ARDS. Thereafter, we present the available evidence on the use of iNO in clinical practice in both types of respiratory failure. Overall, iNO seems a promising agent as it could improve the ventilation/perfusion mismatch, gas exchange impairment, and right ventricular failure, which are reported in ARDS. In addition, iNO may act as a viricidal agent and prevent lung hyperinflammation and thrombosis of the pulmonary vasculature in the specific setting of COVID-19 ARDS. However, the current evidence on the effects of iNO on outcomes is limited and clinical studies are yet to demonstrate any survival benefit by administering iNO in ARDS.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 3","pages":"112-126"},"PeriodicalIF":3.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10402704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9945943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract Author Index <i>by abstract number</i>.","authors":"","doi":"10.1089/jamp.2023.ab01.index.abstracts","DOIUrl":"https://doi.org/10.1089/jamp.2023.ab01.index.abstracts","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 3","pages":"A40-A43"},"PeriodicalIF":3.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9630152","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}

{"title":"Minimizing Aerosol Leakage from Facemasks in the COVID-19 Pandemic.","authors":"Mylene G H Frankfort,&nbsp;Iris Lauwers,&nbsp;Emerentia M C Pruijn,&nbsp;Sjoerd F Dijkstra,&nbsp;Liza H G Boormans,&nbsp;Nicolaas A Schouten,&nbsp;Corrinus C van Donkelaar,&nbsp;Hettie M Janssens","doi":"10.1089/jamp.2022.0036","DOIUrl":"https://doi.org/10.1089/jamp.2022.0036","url":null,"abstract":"<p><p><b><i>Background:</i></b> Aerosol therapies with vented facemasks are considered a risk for nosocomial transmission of viruses such as severe acute respiratory syndrome coronavirus 2. The transmission risk can be decreased by minimizing aerosol leakage and filtering the exhaled air. <b><i>Objective:</i></b> In this study, we determined which closed facemask designs show the least leakage. <b><i>Methods:</i></b> Smoke leakage was quantified during in- and exhalation in a closed system with expiration filter for three infant, six child, and six adult facemasks (three times each mask), using age-appropriate anatomical face models and breathing patterns. To assess leakage, smoke release was recorded and cumulative average pixel intensity (cAPI) was calculated. <b><i>Results:</i></b> In the adult group, aircushion edges resulted in less leakage than soft edges (cAPI: 407 ± 250 vs. 774 ± 152) (<i>p</i> = 0.004). The Intersurgical^® Economy 5 mask (cAPI: 146 ± 87) also released less smoke than the Intersurgical^® Clearlite 5 (cAPI: 748 ± 68) mask with the same size, but different geometry and edge type (<i>p</i>-value <0.05). Moreover, mask size had an effect, as there was a difference between Intersurgical^® Economy 4 (cAPI: 708 ± 346) and 5, which have the same geometry but a different size (<i>p</i>-value <0.05). Finally, repositioning masks increased the standard deviations. Mask leakage was not dependent on breathing patterns within the child group. <b><i>Conclusions:</i></b> Mask leakage can be minimized by using a closed system with a well-fitting mask that is appropriately positioned. To decrease leakage, and therewith minimize potential viral transmission, selecting a well-fitting mask with an aircushion edge is to be recommended.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 3","pages":"101-111"},"PeriodicalIF":3.4,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9629614","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}

{"title":"Flow Resistance of the Micro-Orifice Collector in the Next Generation Impactor.","authors":"Daryl L Roberts","doi":"10.1089/jamp.2023.0012","DOIUrl":"https://doi.org/10.1089/jamp.2023.0012","url":null,"abstract":"","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2023-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9406829","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}

{"title":"Pressure Drop Characteristics of the Reduced NGI Configuration with Several Common Glass Fiber Filters.","authors":"Daryl L Roberts","doi":"10.1089/jamp.2022.0070","DOIUrl":"https://doi.org/10.1089/jamp.2022.0070","url":null,"abstract":"<p><p><b><i>Background:</i></b> Measurement of aerodynamic particle size distribution, a clinically relevant <i>in vitro</i> attribute of inhalable drug products, involves multistage cascade impactors and is tedious and expensive. A leading candidate for a quicker method is the reduced NGI™ (rNGI). This method involves placing glass fiber filters on top of the nozzles of a chosen NGI stage, selected often to collect all particles with an aerodynamic diameter smaller than approximately five microns. These filters contribute additional flow resistance that can alter the flow rate start-up curve, potentially affecting the size distribution and mass of the drug product dispensed by passive dry powder inhalers (DPIs). The magnitude of these additional flow resistance measurements is currently unreported in the literature. <b><i>Materials and Methods:</i></b> We placed glass fiber filters on top of the stage 3 nozzles of an NGI, along with the necessary support screen and hold-down ring. We measured the pressure drop across NGI stage 3 with the assistance of a delta P lid and a high-precision pressure transducer. With each filter material type and multiple individual filters, we gathered eight replicates at flow rates of 30, 45, and 60 L/min. <b><i>Results:</i></b> The filters typically doubled the total pressure drop through the NGI. For example, at a flow rate of 60 L/min, the Whatman 934-AH filters introduced a pressure drop of about 9800 Pa at stage 3, reducing the absolute pressure exiting the NGI to about 23 kPa below ambient, compared with a typical value of 10 kPa for the NGI alone at this flow rate. <b><i>Conclusions:</i></b> The pressure drop across typical filters is approximately equal to that through the NGI alone and therefore will affect the flow start-up rate intrinsic to compendial testing of passive DPIs. This change in start-up rate could cause differences between results of the rNGI configuration and those of the full NGI and will increase the required vacuum pump capacity.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 2","pages":"82-88"},"PeriodicalIF":3.4,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9473277","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}

{"title":"Safety, Tolerability, and Pharmacokinetics of Nebulized Hydroxychloroquine: A Pilot Study in Healthy Volunteers.","authors":"Feras Hawari,&nbsp;Yasmeen Dodin,&nbsp;Rabab Tayyem,&nbsp;Samer Najjar,&nbsp;Hanan Kakish,&nbsp;Mohammed Abu Fara,&nbsp;Abdullah Al Zou'bi,&nbsp;Nasir Idkaidek","doi":"10.1089/jamp.2022.0062","DOIUrl":"https://doi.org/10.1089/jamp.2022.0062","url":null,"abstract":"<p><p><b><i>Background:</i></b> Early in the coronavirus disease 2019 (COVID-19) pandemic, hydroxychloroquine (HCQ) drew substantial attention as a potential COVID-19 treatment based on its antiviral and immunomodulatory effects <i>in vitro</i>. However, HCQ showed a lack of efficacy <i>in vivo</i>, and different groups of researchers attributed this failure to the insufficient drug concentration in the lung following oral administration (HCQ is only available in the market in the tablet form). Delivering HCQ by inhalation represents a more efficient route of administration to increase HCQ exposure in the lungs while minimizing systemic toxicity. In this pilot study, the safety, tolerability, and pharmacokinetics of HCQ nebulizer solution were evaluated in healthy volunteers. <b><i>Methods:</i></b> Twelve healthy participants were included in this study and were administered 2 mL of HCQ01 solution (equivalent to 25 mg of HCQ sulfate) through Aerogen^® Solo, a vibrating mesh nebulizer. Local tolerability and systemic safety were assessed by forced expiratory volume in the first and second electrocardiograms, clinical laboratory results (e.g., hematology, biochemistry, and urinalysis), vital signs, and physical examinations. Thirteen blood samples were collected to determine HCQ01 systemic exposure before and until 6 hours after inhalation. <b><i>Results:</i></b> The inhalation of HCQ01 was well tolerated in all participants. The mean value of <i>C</i>_max for the 12 participants was 9.66 ng/mL. <i>T</i>_max occurred at around 4.8 minutes after inhalation and rapidly decreased thereafter. The reported systemic exposure was very low with a mean value of 5.28 (0.6-15.6) ng·h/mL. <b><i>Conclusion:</i></b> The low systemic concentrations of HCQ01 of 9.66 ng/mL reported by our study compared with 1 μg/mL previously predicted after 200 mg BID oral administration, and the safety and tolerability of HCQ01 administered as a single dose through nebulization, support the assessment of its efficacy, safety, and tolerability in further studies for the treatment of COVID-19.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 2","pages":"76-81"},"PeriodicalIF":3.4,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9825557","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}

{"title":"Pharmacokinetic and Pharmacodynamic Comparison of Fluticasone Propionate/Formoterol Fumarate Administered via a Pressurized Metered-Dose Inhaler and a Novel Breath-Actuated Inhaler in Healthy Volunteers.","authors":"Sanjeeva Dissanayake,&nbsp;Gill Mundin,&nbsp;Jo Woodward,&nbsp;Mark Lomax,&nbsp;Prashant Dalvi","doi":"10.1089/jamp.2022.0064","DOIUrl":"https://doi.org/10.1089/jamp.2022.0064","url":null,"abstract":"<p><p><b><i>Introduction:</i></b> Fluticasone propionate/formoterol fumarate (fluticasone/formoterol) exposures, following administration of Flutiform^® K-haler^®, a breath-actuated inhaler (BAI), were compared with the Flutiform pressurized metered-dose inhaler (pMDI) with/without spacer in two healthy volunteer studies. In addition, formoterol-induced systemic pharmacodynamic (PD) effects were examined in the second study. <b><i>Methods:</i></b> Study 1: single-dose, three-period, crossover pharmacokinetic (PK) study with oral charcoal administration. Fluticasone/formoterol 250/10 μg was administered via BAI, pMDI, or pMDI with spacer (pMDI+S). Pulmonary exposure for BAI was deemed no less than for pMDI (primary comparator) if the lower limit of 94.12% confidence intervals (CIs) for BAI:pMDI maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUCt) ratios was ≥80%. Study 2: two-stage adaptive design, both stages being single-dose, crossover without charcoal administration. The PK stage compared fluticasone/formoterol 250/10 μg via BAI, pMDI, or pMDI+S. The primary comparisons were as follows: BAI versus pMDI+S for fluticasone and BAI versus pMDI for formoterol. Systemic safety with BAI was deemed no worse than primary comparator if the upper limit of 94.12% CIs for Cmax and AUCt ratios was ≤125%. PD assessment was to be conducted if BAI safety was not confirmed in the PK stage. Based on PK results, only formoterol PD effects were evaluated. The PD stage compared fluticasone/formoterol 1500/60 μg via BAI, pMDI, or pMDI+S; fluticasone/formoterol 500/20 μg pMDI; and formoterol 60 μg pMDI. The primary endpoint was maximum reduction in serum potassium within 4 hours postdose. Equivalence was defined as 95% CIs for BAI versus pMDI+S and pMDI ratios within 0.5-2.0. <b><i>Results:</i></b> Study 1: lower limit of 94.12% CIs for BAI:pMDI ratios >80%. Study 2, PK stage: upper limit of 94.12% CIs for fluticasone (BAI:pMDI+S) ratios <125%; upper limit of 94.12% CIs for formoterol (BAI:pMDI) ratios >125% (for Cmax, not AUCt). Study 2, PD stage: 95% CIs for serum potassium ratios 0.7-1.3 (BAI:pMDI+S) and 0.4-1.5 (BAI:pMDI). <b><i>Conclusions:</i></b> Fluticasone/formoterol BAI performance was within the range observed for the pMDI with/without a spacer. Sponsor: Mundipharma Research Ltd. EudraCT 2012-003728-19 (Study 1) and 2013-000045-39 (Study 2).</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 2","pages":"65-75"},"PeriodicalIF":3.4,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9465958","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}

{"title":"Stability and Activity of Interferon Beta to Treat Idiopathic Pulmonary Fibrosis with Different Nebulizer Technologies.","authors":"Edgar Hernan Cuevas Brun,&nbsp;Zuo-Yi Hong,&nbsp;Yuan-Ming Hsu,&nbsp;Ciou-Ting Wang,&nbsp;Dai-Jung Chung,&nbsp;Shang-Kok Ng,&nbsp;Yau-Hsuan Lee,&nbsp;Tzu-Tang Wei","doi":"10.1089/jamp.2022.0020","DOIUrl":"https://doi.org/10.1089/jamp.2022.0020","url":null,"abstract":"<p><p><b><i>Background:</i></b> Idiopathic pulmonary fibrosis (IPF) is a serious lung disease characterized by lung scarring, which results in breathing difficulty. Currently, patients with IPF exhibit a poor survival rate and have access to very limited therapeutic options. Interferon beta (IFN-β) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of relapsing forms of multiple sclerosis, and it has also been shown to exhibit therapeutic potential in IPF. However, clinical use of IFN-β did not lead to improved overall survival in IPF patients in existing studies. One possibility is the limited efficiency of IFN-β delivery through intravenous or subcutaneous injection. <b><i>Materials and Methods:</i></b> The aerosol particle size distribution was determined with a laser diffraction particle size analyzer to characterize the droplet size and fine particle fraction generated by three types of nebulizers: jet, ultrasonic, and mesh. A breathing simulator was used to assess the delivery efficiency of IFN-β, and the temperature in the medication reservoirs was monitored with a thermocouple during nebulization. To further evaluate the antifibrotic activity of IFN-β pre- and postnebulization, bleomycin (BLM)- or transforming growth factor-beta (TGF-β)-treated human lung fibroblast (HLF) cells were used. Cell viability was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Transwell migration assay and Q-PCR analysis were used to evaluate cell migration and the myofibroblast differentiation ability, respectively. IFN-β protein samples were prepared using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) sample loading buffer, and the expression of IFN-β was assessed by western blotting. <b><i>Results:</i></b> Among the current drug delivery systems, aerosolized medication has shown increased efficacy of drug delivery for treating respiratory diseases when compared with parenteral drugs. It was found that neither the structural integrity nor the biological function of nebulized IFN-β was compromised by the nebulization process of the mesh nebulizer. In addition, in BLM dose-response or TGF-β-induced lung fibroblast proliferation assays, these effects could be reversed by both parenteral and inhaled IFN-β nebulized with the mesh nebulizer. Nebulized IFN-β with the mesh nebulizer also significantly inhibited the migration and myofibroblast differentiation ability of TGF-β-treated HLF cells. <b><i>Conclusions:</i></b> The investigations revealed the potential efficacy of IFN-β in the treatment of IPF with the mesh nebulizer, demonstrating the higher efficiency of IFN-β delivered through the mesh nebulizer.</p>","PeriodicalId":14940,"journal":{"name":"Journal of Aerosol Medicine and Pulmonary Drug Delivery","volume":"36 2","pages":"55-64"},"PeriodicalIF":3.4,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9471839","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}