Journal of pharmaceutical sciences最新文献

{"title":"Fast-dissolving electrospun cellulose fiber-based matrices as modular oral dosage forms.","authors":"Mario A Cano-Vega, Héctor Lozano-Perez, Rodolfo Pinal, Meng Deng","doi":"10.1016/j.xphs.2025.103908","DOIUrl":"10.1016/j.xphs.2025.103908","url":null,"abstract":"<p><p>Fast-dissolving oral dosage forms are attractive systems for controlled delivery of poorly water-soluble drugs. This study introduces a novel modular oral dosage platform composed of fast-dissolving drug-loaded electrospun hydroxypropyl methylcellulose (HPMC)/ polyethylene oxide (PEO) fibers. Electrospun fibers were fabricated and optimized using two solvent systems, namely dichloromethane/ethanol and water/ethanol, and loaded with model compounds exhibiting different solubility profiles. Characterization by scanning electron microscopy, differential scanning calorimetry, and X-ray diffraction confirmed the formation of drug-loaded HPMC/PEO-based fibers with drug amorphization. Dissolution studies of as-fabricated fibers demonstrated rapid disintegration and efficient drug release from the fibers. An optimized fabrication process was further developed to form a proof-of-concept integrated bilayer module by enabling the precise deposition of drug-loaded electrospun fibers onto a solvent-cast non-drug-loaded HPMC-based film. The fibrous layer maintained its bead-free morphology, reduced crystallinity, and fast dissolution properties post-integration. Our findings highlight the potential of drug-loaded electrospun HPMC/PEO fibers as an advanced drug delivery system, supporting the development of next-generation modular oral dosage forms for controlled and customizable drug delivery.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"103908"},"PeriodicalIF":3.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675041","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":"Taking Backgrounded Membrane Imaging (BMI) for particle analysis in biopharmaceutics to the next level - Statistical variability, detection limits and novel metrics","authors":"Thorben Höltkemeier ,&nbsp;Hugo Aragao ,&nbsp;Ingo Fischer ,&nbsp;Wolfgang Friess","doi":"10.1016/j.xphs.2025.103905","DOIUrl":"10.1016/j.xphs.2025.103905","url":null,"abstract":"<div><div>The aggregation of proteins is a major threat to the integrity of biopharmaceutical products. Typically the state of aggregation at a specific timepoint is evaluated via particle analysis and counting or turbidity. Backgrounded Membrane Imaging (BMI) is a recently introduced methodology that provides a low-volume, high-throughput alternative to be used in biopharmaceutical development. Recent work has successfully evaluated BMI as an orthogonal method regarding its counting and sizing accuracy for subvisible particle analysis. The work at hand shows that apart from background noise, stochastic variations need to be considered to define the lower limit of detection. A systematic evaluation of particle identification robustness shows that particles at the lower and upper size limit of the technique are not reliably detected. To overcome potential biases due to particle crowding and overlapping, novel evaluation parameters are introduced: the Total Area, the Total Intensity and the BMI-Z-Average to be reported alongside the particle count. Overall, we were able to refine root causes for loss in data quality in BMI and to showcase the use of additional reporting parameters to shift focus to more robustly-identified and quantified larger particles.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 9","pages":"Article 103905"},"PeriodicalIF":3.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659499","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":"Development of an inhaled spray-freeze-dried powder composed of methyl cellulose and a dispersion enhancer for prolonged pulmonary drug retention and high aerosol performance","authors":"Motoki Sugiura,&nbsp;Tomoyuki Okuda,&nbsp;Hirokazu Okamoto","doi":"10.1016/j.xphs.2025.103907","DOIUrl":"10.1016/j.xphs.2025.103907","url":null,"abstract":"<div><div>The application of mucoadhesive agents in inhalation powders is expected to increase pulmonary drug retention through inhibited mucociliary clearance, leading to improved inhalation therapy. In the present study, we combined methyl cellulose as a mucoadhesive agent and <span>l</span>-leucine or dileucine as a dispersion enhancer to produce an inhalation powder with both prolonged pulmonary drug retention and high aerosol performance using the spray freeze drying technique. The spray-freeze-dried (SFD) powder consisting solely of methyl cellulose had a smooth surface structure, showing high cohesiveness, high hygroscopicity, and poor aerosol performance. The addition of dispersion enhancers resulted in a rougher surface structure in the SFD powder, which improved both dispersibility in air and aerosol performance and reduced hygroscopicity. <span>l</span>-Leucine provided lower hygroscopicity and higher aerosol performance in the SFD powder than dileucine. Biodistribution and toxicity studies <em>in vivo</em> demonstrated that the intratracheal administration to mice of SFD powders containing methyl cellulose and dispersion enhancers achieved prolonged pulmonary drug retention with minimal toxicity regardless of the type of dispersion enhancers used. These results suggest that SFD powders containing methyl cellulose and dispersion enhancers will contribute to more effective inhalation therapy through prolonged pulmonary drug retention and high aerosol performance.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 9","pages":"Article 103907"},"PeriodicalIF":3.7,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659498","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":"Quantitative characterization of drug metabolism and transport alterations in obesity with metabolic fatty liver disease: A physiologically based pharmacokinetic modelling approach","authors":"Yuewu Xie ,&nbsp;Xiaoqin Bai ,&nbsp;Chaozhuang Shen ,&nbsp;Chaoran Xu ,&nbsp;Chi Cui ,&nbsp;Yujie Yang","doi":"10.1016/j.xphs.2025.103906","DOIUrl":"10.1016/j.xphs.2025.103906","url":null,"abstract":"<div><h3>Background</h3><div>Metabolic fatty liver disease (MAFLD), a condition characterized by impaired hepatic and intestinal metabolic function, predominantly affects the in vivo drug process of obese individuals. Despite its clinical significance, the impact of MAFLD on drug metabolism enzymes and transporters throughout disease progression remains poorly understood. This study aimed to quantitatively characterize alterations during MAFLD progression and develop a comprehensive physiologically based pharmacokinetic (PBPK) model incorporating both intra- and extrahepatic drug transport and metabolic changes to predict drug disposition.</div></div><div><h3>Methods</h3><div>We established high fat diet (HFD)- fed mice across five progressive stages (8, 16, 24, 32, and 40 weeks). Hepatic and intestinal expression profiles of metabolic enzymes and transporters were analyzed using RNA-sequencing (RNA-Seq). Differential gene expression analysis was performed, with subsequent validation through quantitative real-time PCR (qPCR). A novel MAFLD population profile was developed in PK-Sim by integrating preclinical data with PBPK modeling parameters based on metabolic enzyme and transporter alterations.</div></div><div><h3>Results</h3><div>RNA-Seq and qPCR analyses revealed that Abcc2, Cyp2b9, Cyp2c38 and Cyp17a1 were upregulated by MAFLD in liver, whereas Slco1a1, Cyp2c29, Cyp3a11 and Cyp3a25 were downregulated. Intestinal expression changes were most pronounced for Slco10a2, Cyp3a11, and Ugt1a1. Cross-species analysis revealed strong correlations in drug transport and metabolism genes between murine and human tissues. PBPK modeling simulations predicted increased systemic exposure in MAFLD patients for drugs primarily metabolized by CYP2B6, CYP3A4, and CYP2C19. Interestingly, intestinal BCRP expression alterations in MAFLD showed minimal impact on drug exposure.</div></div><div><h3>Conclusions</h3><div>Closer monitoring of MAFLD patients receiving medications predominantly cleared by CYP 2B6, 3A4, and CYP2C19 is warranted to minimise toxicity risk. Further clinical investigations directly evaluating drug disposition in MAFLD patients are needed to confirm the modelling findings.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 9","pages":"Article 103906"},"PeriodicalIF":3.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626603","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":"Physiologically based pharmacokinetic model of IgG to predict mother-to-fetus transfer of ustekinumab in pregnant patients with inflammatory bowel disease","authors":"Xiaoxi Cai ,&nbsp;Wanhong Wu ,&nbsp;Jianwen Xu ,&nbsp;WeiWei Lin ,&nbsp;Pinfang Huang ,&nbsp;Cuihong Lin ,&nbsp;Rongfang Lin","doi":"10.1016/j.xphs.2025.103904","DOIUrl":"10.1016/j.xphs.2025.103904","url":null,"abstract":"<div><div>The placenta serves as a critical interface for maternal-fetal substance exchange, including the active transport of immunoglobulin G (IgG), which is essential for neonatal immune protection. While mechanisms of IgG transfer are well-studied, the impact of therapeutic monoclonal antibodies (mAbs) on placental IgG dynamics during pregnancy remains unclear. This study aimed to predict maternal and fetal drug concentrations of ustekinumab (UST), an IgG1 monoclonal antibody used for treating inflammatory bowel disease (IBD), using a physiologically based pharmacokinetic (PBPK) model. The study utilized an established PBPK framework, incorporating pregnancy-specific physiological changes to construct and validate an endogenous IgG placental transfer model using clinical data. This model was subsequently extended to simulate maternal-fetal drug transfer in IBD pregnancies treated with UST. This model was extended to simulate maternal-fetal drug transfer in IBD pregnancies treated with UST, incorporating gestational age-specific parameters and the neonatal Fc receptor (FcRn) - mediated IgG transport. Competitive dynamics between endogenous IgG and UST were evaluated. Key findings included accurate predictions of endogenous IgG and UST plasma concentrations in both maternal and neonatal compartments. Results indicated that UST had minimal impact on endogenous IgG transfer kinetics, though scenarios such as mid-pregnancy UST discontinuation significantly reduced fetal UST exposure and potentially slowed IgG placental transfer due to decreased maternal IgG levels. The use of UST during pregnancy does not significantly affect the dynamics of endogenous IgG maternal-fetal transfer. This model provides a robust tool for assessing the safety and dosing strategies of monoclonal antibodies during pregnancy.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 9","pages":"Article 103904"},"PeriodicalIF":3.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608634","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":"Semi-solid extrusion 3D printing of pediatric acetazolamide formulation: Impact of the spatial arrangement of extruded material on quality attributes","authors":"Javier Suárez-González ,&nbsp;Alba Marsella-Aldegheri ,&nbsp;Mabel Soriano ,&nbsp;Alexis Oliva ,&nbsp;Ana Santoveña-Estévez ,&nbsp;José B Fariña","doi":"10.1016/j.xphs.2025.103892","DOIUrl":"10.1016/j.xphs.2025.103892","url":null,"abstract":"<div><div>Three-dimensional printing has emerged as a transformative technology in pharmaceutical manufacturing, enabling the production of individualized dosage forms. Considering all 3DP techniques, semi-solid extrusion (SSE) stands out in comparison to others. However, the influence of spatial material arrangement on the critical quality attributes (CQAs) of printed dosage forms remains poorly understood. This study aims to quantify the impact of the spatial arrangement of extruded material, infill density and area-to-volume ratio on the CQAs of SSE 3D-printed formulations. Acetazolamide (AZM) printlets were manufactured using a M3DIMAKER 3D printing platform, varying important structural parameters to assess their effect on product performance. A generalized linear model with a Quasi-poisson link function was applied to quantify the contribution of each factor to the final dosage form characteristics. Statistical analysis revealed that infill density had the most significant impact on CQAs, with higher densities improving mechanical strength but prolonging disintegration time. The solid bottom shell increased variability, leading to inconsistencies in weight distribution and dissolution profiles, whereas the shell wall had a minor effect on disintegration and release but contributed to structural integrity. Drug release was significantly influenced by infill density, while the surface area-to-volume ratio showed no strong correlation with dissolution behaviour. This study provides a quantitative assessment of how spatial material distribution in SSE 3D printing affects the CQAs of printed dosage forms. The findings highlight the need to optimize structural parameters to balance mechanical stability and dissolution characteristics, ensuring pharmaceutical compliance.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 9","pages":"Article 103892"},"PeriodicalIF":3.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144605658","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":"Synthesis and characterization of modified nanodiamonds for use as a potential vaccine adjuvant delivery platform for a candidate ricin toxin vaccine","authors":"Mark Francis Seán Craven ,&nbsp;Allison Jo Brachtenbach Mitchell ,&nbsp;Kenneth Ryan Moulder ,&nbsp;Greta Van Slyke ,&nbsp;Nicholas R. Larson ,&nbsp;Nicholas J. Mantis ,&nbsp;C. Russell Middaugh ,&nbsp;M. Laird Forrest","doi":"10.1016/j.xphs.2025.103900","DOIUrl":"10.1016/j.xphs.2025.103900","url":null,"abstract":"<div><div>Adjuvants are a necessary excipient in most vaccine formulations to promote efficient antigen uptake and sampling by professional antigen presenting cells (APCs) in local tissues and regional lymph nodes. Nanoparticles have the unique capacity to serve as both antigen carriers and adjuvants by virtue of their size, shape, and modifiable surface properties. Nanodiamonds represent a novel type of diamond-based nanoparticle because they have easily modified surface chemistry and high binding capacity for surface display of protein antigens. Nanodiamonds are also non-toxic but still capable of stimulating a limited inflammatory response. In this study, we modified nanodiamonds with different surface chemistries and investigated in a murine model their ability to act as an adjuvant delivery platform for a ricin subunit vaccine, RiVax. The nanodiamonds were compared to RiVax adjuvanted with aluminum salts, liposomes, and gold nanoparticles. Vaccine efficacy was assessed based on an immunity to lethal challenge model. Our studies found that although the nanodiamonds could be coated with RiVax, the resulting formulation did not improve the protective capabilities of RiVax in a murine model. However, modified nanodiamonds were also investigated and characterized and may be investigated in the future as an improvement over their unmodified counterparts.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 9","pages":"Article 103900"},"PeriodicalIF":3.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608635","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 of droplet size and surface charge on oral bioavailability of Norcantharidin-loaded SEDDS: Mechanistic insights into lymphatic transport and intestinal permeability","authors":"Wenyou Fang ,&nbsp;Yulian Sun ,&nbsp;Wenjie Lu ,&nbsp;Lujun Wang ,&nbsp;Jihui Tang ,&nbsp;Shenqi Chen ,&nbsp;Rongfeng Hu","doi":"10.1016/j.xphs.2025.103898","DOIUrl":"10.1016/j.xphs.2025.103898","url":null,"abstract":"<div><div>Norcantharidin (NCTD), a promising anti-tumor agent, is limited by poor water solubility and low oral bioavailability. This study aimed to formulate NCTD into a self-emulsifying drug delivery system (SEDDS) to enhance its oral bioavailability and elucidate the underlying mechanisms. Six NCTD-loaded SEDDS formulations with droplet sizes ranging from 50 nm to 200 nm and different surface charges were prepared. These formulations were characterized, and the impact of digestion on drug solubility was evaluated through in vitro lipolysis. The effects of droplet size and surface charge on cellular uptake were investigated using in vitro cell experiments. Intestinal permeability was evaluated using a Caco-2 cell monolayer model, with apparent permeability coefficients and trans-epithelial electrical resistance (TEER) changes monitored. The oral bioavailability of different SEDDS formulations was clarified by in vivo pharmacokinetics and the influence of surface charge on lymphatic absorption was examined through in vivo distribution studies. Results showed that reducing droplet size and modifying droplets to carry a positive charge significantly enhanced NCTD’s oral bioavailability by improving cellular uptake, intestinal permeability, and modulating lymphatic absorption. These findings provide valuable insights for the design of effective oral nanoformulations of NCTD.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 9","pages":"Article 103898"},"PeriodicalIF":3.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608631","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":"Nasal versus sublingual routes for emergency drug administration","authors":"Manar Samir Debe ,&nbsp;Saeed Ahmad Khan ,&nbsp;Iman Saad Ahmed ,&nbsp;Zahid Hussain ,&nbsp;Mohammad Nasir Uddin ,&nbsp;Mutasem Rawas-Qalaji","doi":"10.1016/j.xphs.2025.103903","DOIUrl":"10.1016/j.xphs.2025.103903","url":null,"abstract":"<div><div>Rapid drug absorption is essential for achieving immediate or life-saving therapeutic effects in medical emergencies. While intravenous and intramuscular routes are ideal due to their rapid onset of action, they are invasive and require administration by a healthcare professional. Scientists are therefore actively seeking alternatives that reduce invasiveness, enable self-administration, and enhance patient acceptance without compromising efficacy. Both nasal and sublingual routes offer rapid and direct access into the bloodstream. They offer attractive alternatives to invasive routes by reducing the need for needles and improving medicine delivery in emergency situations. This review delves into the comparative analysis of emergency drug administration via nasal and sublingual routes. It aims to comprehensively compare these non-invasive routes by considering factors such as onset of action, bioavailability, and administration practicality. Additionally, this review comprehensively examines marketed products and ongoing potential research to evaluate the applicability of these routes in emergency situations.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 9","pages":"Article 103903"},"PeriodicalIF":3.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608633","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 of electrostatics on the aggregation, genome release, and self-interactions of AAV9 capsids","authors":"Lily Motabar ,&nbsp;Veerabhadraiah Palakollu ,&nbsp;Hassan Shahfar ,&nbsp;Justin Thomas ,&nbsp;Garrett Daniels ,&nbsp;Adnan Arnaout ,&nbsp;Jorge Haller ,&nbsp;Christopher J. Roberts","doi":"10.1016/j.xphs.2025.103899","DOIUrl":"10.1016/j.xphs.2025.103899","url":null,"abstract":"<div><div>Understanding solution conditions that enable favorable biophysical characteristics is important for formulation development of biologics and is a relatively new area for adeno-associated virus (AAV) products compared to more traditional therapeutic proteins. Solution pH and ionic strength have a considerable impact on electrostatic interactions and thus capsid-capsid interactions, which can potentially influence aggregation propensity. We have examined the impact of electrostatic interactions on the aggregation, genome release, and self-interaction behavior of AAV9 capsids. Aggregation at pH 4.5 after temperature stress was potentially exacerbated by a large population of empty/partial capsids, while at pH 7.4 degradation via genome loss was more likely. Additionally, decreasing the ionic strength from 150 mM to 5 mM caused reversible aggregate formation, though pH significantly impacted the salt concentration required for aggregate reversal. Static light scattering revealed capsid-capsid self-interactions are driven by strong electrostatic attractions at 150 mM for both pH 4.5 and 7.4, with stronger capsid-capsid interactions at pH 4.5. We employed a coarse-grained molecular model which predicted that capsid self-interactions are more sensitive to the change of ionic strength in the low/medium regime at pH 4.5 compared to pH 7.4. Overall, our data supports that electrostatic interactions play a key role in the stability of AAV9 capsids.</div></div>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":"114 9","pages":"Article 103899"},"PeriodicalIF":3.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608632","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}