Pharmaceutical Research最新文献

{"title":"A Cell-Based Reporter Gene Assay for TNF-α Neutralization: Analytical Qualification and Application to Adalimumab and Its Biosimilars.","authors":"Christelle Anne F Ancajas, Shen Luo, Baolin Zhang","doi":"10.1007/s11095-026-04093-5","DOIUrl":"https://doi.org/10.1007/s11095-026-04093-5","url":null,"abstract":"<p><strong>Purpose: </strong>To qualify a mechanism-of-action (MoA)-reflective reporter gene assay (RGA) for measuring the biological activity of adalimumab (Humira) and its biosimilars, supporting assessment of product quality, comparability, and functional consistency across the product lifecycle.</p><p><strong>Methods: </strong>The assay evaluates TNF-α neutralization by monitoring inhibition of NF-κB signaling in a reporter system. Qualification focused on key performance attributes, including system suitability, working range, reproducibility, and intermediate precision, to confirm fitness for routine use.</p><p><strong>Results: </strong>The RGA yielded MoA-relevant readouts of NF-κB pathway inhibition in the presence of adalimumab, demonstrating strong system suitability, a broad working range, high reproducibility, and consistent intermediate precision across repeated measures. These characteristics support reliable measurement of functional activity among adalimumab products and biosimilars.</p><p><strong>Conclusions: </strong>The qualified, MoA-reflective RGA provides a robust tool for lifecycle management of adalimumab products, enabling quality assessment, comparability exercises, and monitoring of functional consistency across indications in which adalimumab is broadly used (e.g., rheumatoid arthritis, Crohn's disease, psoriasis).</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841442","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":"Thermally Stressed Solid-State Stability of Semaglutide: Understanding the Influence of Temperature on Protein Content, Secondary Structure, Phase Transition, and Chemical Degradation.","authors":"Sideequl Akbar, Adarsh Malgave, Anumol Joseph, Ankit Kumar, Rajkumar Malayandi","doi":"10.1007/s11095-026-04094-4","DOIUrl":"https://doi.org/10.1007/s11095-026-04094-4","url":null,"abstract":"<p><strong>Objective: </strong>Semaglutide (SMG), a clinically relevant peptide-based therapeutic whose physical and chemical stability are critical concerns during manufacturing and storage. Although the stability of SMG in solution has been extensively studied, its solid-state behaviour remains unclear. This study aimed to systematically evaluate the impact of thermal stress on the solid-state physicochemical stability of SMG.</p><p><strong>Methods: </strong>The solid-state stability of SMG was assessed using complementary analytical techniques, including Fourier transform-infrared (FT-IR) spectroscopy, circular dichroism (CD), differential scanning calorimetry (DSC), hot-stage microscopy (HSM), reverse-phase high-performance liquid chromatography (RP-HPLC), and liquid chromatography-high-resolution mass spectrometry (LC-HRMS).</p><p><strong>Results: </strong>FT-IR and CD analyses demonstrated that SMG retains its native α-helical conformation up to 60°C. However, the α-helical content decreased from 49.07% to 43.75% at 60°C and further to 0.2% at 80°C, indicating extensive conformational transitions at elevated temperatures that compromise receptor binding and in vivo performance. DSC and HSM confirmed that SMG remains amorphous under all tested conditions and revealed three major thermal events: residual water loss, enthalpy recovery associated with physical ageing, and thermal decomposition. The overlap of enthalpy recovery with the glass transition phase limited the determination of Tg by conventional DSC; however, modulated DSC enabled the separation of these events, establishing a Tg of 169°C. RP-HPLC and LC-HRMS analyses showed a temperature-dependent degradation and impurity formation.</p><p><strong>Conclusion: </strong>The solid-state stability study identified temperature as a critical factor influencing SMG stability and emphasises the importance of stringent process control in the development of SMG-based formulations.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841497","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":"Trichomonas vaginalis Drug Targets and Their Role in Drug Discovery and Development.","authors":"Mirna Samara Dié Alves, Ângela Sena-Lopes, Luiza Domingues Moron, Bárbara da Rocha Fonseca, Sibele Borsuk","doi":"10.1007/s11095-026-04098-0","DOIUrl":"https://doi.org/10.1007/s11095-026-04098-0","url":null,"abstract":"<p><p>Trichomonas vaginalis is the causative agent of trichomoniasis, the most common and prevalent sexually transmitted infection (STI) globally, with about 156 million cases annually. Trichomoniasis is a critical public health problem, and it is aggravated due to its association with a higher risk of HIV-1 acquisition and transmission and complications such as preterm delivery and pelvic inflammatory disease. This STI is treated mainly through the 5-nitroimidazole class, specifically metronidazole and tinidazole. However, drug resistance, which can represent between 5 and 20% of clinical cases, and hypersensitivity reactions are a general concern. In this context, drug development for trichomoniasis is an ever-growing research field. Therefore, considering how important drug targets and the mechanism of action of compounds can be to drug discovery, there is a growing interest in better understanding how some molecules can be used as targets. This article offers an overview of T. vaginalis drug targets, their significance in metabolism, pathogenesis, or survival, and their contribution to drug development for trichomoniasis.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841545","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":"PK-PD Modeling Suggests Tumor Heterogeneity Limits Preclinical to Clinical Translation of Enzalutamide in Prostate Cancer.","authors":"Se Jin Kim, Robert Bies, Donald E Mager","doi":"10.1007/s11095-026-04091-7","DOIUrl":"https://doi.org/10.1007/s11095-026-04091-7","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the translational performance of preclinical models to anticipate enzalutamide clinical efficacy in prostate cancer using a cross-species physiologically-based pharmacokinetic (PBPK)-pharmacodynamic (PD) model and published enzalutamide preclinical and clinical PK-PD data.</p><p><strong>Methods: </strong>A mouse PBPK model was developed and linked to a tumor growth inhibition (TGI) model to describe tumor volume profiles in 5 cell line-derived and 3 patient-derived xenografts. Estimated preclinical PD model parameters were fixed to simulate clinical progression free survival (PFS) using a scaled-up human PBPK model and a calculated prostate cancer tumor growth rate. Tumor static concentrations (TSCs) were calculated and assessed relative to predicted steady-state concentrations from a standard dosing regimen.</p><p><strong>Results: </strong>Estimated mouse model parameters were precise (CV% < 15% and 45% for most PK and PD parameters), and the estimated hepatic intrinsic clearance was comparable to conventional allometry (allometric exponent = 0.722). The 8 TSC values were near or below the simulated steady-state plasma drug concentration (18,000 ng/mL) achieved with a standard enzalutamide regimen (TSC range 203-20,740 ng/mL). The TGI model failed to predict clinical PFS unless a tumor heterogeneity model with sensitive and resistant tumor cell populations and individually calibrated growth rates were explicitly incorporated.</p><p><strong>Conclusions: </strong>The potential and the limitations of using preclinical PD parameters for clinical translation were assessed, and more biologically accurate TGI models are needed to enhance the use of translational modeling in oncology.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841483","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":"Raman Imaging-based Analysis of Drug Powder Dissolution on Calu-3 Cell Monolayers as a Mechanistic Predictor of Nasal Absorption.","authors":"Tomoyuki Furubayashi, Akiko Tanaka, Ryosuke Tatsuta, Maako Fujiwara, Nana Izumi, Mamiko Kiyohara, Kei Moriyama","doi":"10.1007/s11095-026-04104-5","DOIUrl":"https://doi.org/10.1007/s11095-026-04104-5","url":null,"abstract":"<p><strong>Background: </strong>Intranasal powder formulations offer advantages in terms of stability and portability; however, their absorption is critically dependent on dissolution within the limited fluid volume of the nasal cavity. Conventional dissolution tests, originally developed for oral medicines, fail to adequately capture dissolution dynamics under nasal conditions, making the prediction of bioavailability after intranasal powder administration (BAp) particularly challenging.</p><p><strong>Methods: </strong>A Raman spectroscopy-based approach was established to directly monitor the time-dependent dissolution of drug particles in Calu-3 cell layers. Dissolution rate constants derived from particle size reduction were integrated with the nasal mean residence time (MRT) and bioavailability after intranasal solution administration (BAs) to define a predictive metric, the dissolution-MRT-BAs (DTB) parameter.</p><p><strong>Results: </strong>Model drugs exhibited distinct dissolution profiles: rapid (antipyrine and atenolol), intermediate (acyclovir and levofloxacin), and limited (norfloxacin and griseofulvin). The DTB parameter was strongly correlated with BAp (R = 0.983, p < 0.001), and the enhancement of norfloxacin dissolution by lactose was also captured by this metric.</p><p><strong>Conclusion: </strong>The DTB parameter, which integrates dissolution kinetics, nasal residence time, and bioavailability, serves as a rational tool for predicting the absorption behavior of nasal powder formulations. This study highlights the potential of Raman spectroscopy as a quantitative method to support formulation design and establish in vitro-in vivo correlations in nasal drug delivery.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841457","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 a Water-soluble Form of Umifenovir Through the Synergistic Action of a Surfactant and a Hydrotropic Agent: A Multifactorial Study.","authors":"Tatyana V Volkova, Olga R Simonova, German L Perlovich","doi":"10.1007/s11095-026-04106-3","DOIUrl":"https://doi.org/10.1007/s11095-026-04106-3","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to develop a water-soluble form of umifenovir (UMF) through the synergistic action of the non-ionic surfactant Brij35 and choline bitartrate (ChB), and to investigate the solubility, aggregation and diffusion.</p><p><strong>Methods: </strong>UMF solubilization was assessed using the saturation shake-flask method. The hydrodynamic radii and aggregation behavior of Brij35 micelles were characterized by light scattering. UMF diffusion rate was investigated using a Franz diffusion cell and an artificial membrane.</p><p><strong>Result: </strong>Introduction of ChB into the UMF/Brij35 system reduced the degree of association with Brij35 micelles and the micelle/water partition coefficient, increased the solubilizing capacity, and modulated the aggregation behavior of Brij35 and permeability. The increase in total (micelle-associated and freely dissolved) drug solubility of UMF in buffer рН 7.4 in the system with the minimal Brij35 concentration (0.45%) was 18.4%, whereas upon addition of ChB (1.0%) - 35.2%. However, calculation of the molecularly dissolved fractions (f_free) of the compound showed that the increase in solubility of the freely dissolved drug in the system with ChB was only 10.6%. This finding is of fundamental importance because only the molecularly dissolved form of a drug can cross biological membranes. Optimization of membrane permeability in the UMF/Brij35 (0.45%)/ChB (1.0%) system was achieved by increasing the fraction of molecularly dissolved UMF molecules in the presence of ChB.</p><p><strong>Conclusion: </strong>This study highlights the advantage of simultaneously using low concentrations of Brij35 and ChB to achieve a synergistic action for maximal improvement in UMF solubility with a minimal reduction in permeability.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841526","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":"Cutaneous Bioavailability of Corticosteroids from Topical Formulations: a Retrospective Analysis of Data from In Vitro Permeation Testing (IVPT) and In Vivo Assessments.","authors":"Paul A Lehman, Thomas J Franz","doi":"10.1007/s11095-026-04089-1","DOIUrl":"https://doi.org/10.1007/s11095-026-04089-1","url":null,"abstract":"<p><strong>Background: </strong>The In Vitro Permeation Test (IVPT) is a valuable tool for the study of topical pharmacokinetics of dermatologic formulations. A 45 year retrospective analysis was performed on archived percutaneous absorption data from various corticosteroids found in the author's files.</p><p><strong>Objective: </strong>The objective was to collate archived data on the relative bioavailability of topical corticosteroids from 15 steroids found in 62 formulations using the in vitro permeation test (IVPT) and the finite dose human cadaver skin model. Studies were conducted with and without occlusion, at different active ingredient concentrations and dose durations. Select steroids also had evaluations with vasoconstriction, and stratum corneum content by tape stripping.</p><p><strong>Results: </strong>The percutaneous absorption of topical corticosteroids is highly dependent on formulation, but less so on steroid concentration within the formulation, and whether the applied dose is occluded or not occluded. In addition vasoconstriction does not necessarily correlate with steroid permeation.</p><p><strong>Conclusions: </strong>The IVPT method demonstrates that it can characterize the topical pharmacokinetics of topical corticosteroids. Overall, this retrospective analysis of data supports the value of the IVPT method for evaluating percutaneous absorption pharmacokinetics for topical therapeutic agents.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841514","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":"CFD Modeling of Airflow and Aerosol Transport in the Human Respiratory System: A Comprehensive Review.","authors":"Dogan Ciloglu, Hacer Ucuncu","doi":"10.1007/s11095-026-04080-w","DOIUrl":"10.1007/s11095-026-04080-w","url":null,"abstract":"<p><strong>Background: </strong>Accurate modelling of airflow and aerosol/particle dynamics within the human respiratory system is essential for improving inhalation-based drug delivery strategies and for evaluating the health risks associated with hazardous particulates. Owing to the complex geometry of the human airways, inter-individual anatomical variations, and variable breathing patterns, this process constitutes a highly complex multiphase flow problem. To address the constraints associated with in vivo and in vitro techniques, in silico approaches based on computational fluid dynamics (CFD) have been extensively utilized to examine respiratory airflow and aerosol dynamics at microscopic scales.</p><p><strong>Objectives: </strong>The aim of this study is to review recent CFD-based approaches for modeling airflow and aerosol behavior in the human respiratory system, summarize key modeling strategies and influential parameters, and identify future research directions.</p><p><strong>Results: </strong>Recent studies indicate a transition of respiratory tract models toward more physiologically realistic and whole-lung representations. These studies demonstrate that coupling CFD with particle models enables reliable prediction of aerosol transport and deposition by accounting for the effects of geometric variations, breathing conditions, turbulence characteristics, and particle physical and chemical properties.</p><p><strong>Conclusion: </strong>CFD-based modeling, particularly when integrated with particle dynamics, provides a powerful and reliable framework for investigating airflow and aerosol behavior in the human respiratory system. Continued advancements toward realistic whole-lung models and improved representation of physiological and particle-related parameters are expected to further enhance predictive accuracy and support both clinical and environmental health applications.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147841349","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":"Microdermabrasion with Calcium Hydrogen Phosphate for Enhancing Skin Permeation of Lidocaine-tetracaine Eutectic Microemulsion Gel.","authors":"Ying Chen, Yuye Yang, Jin Su, Yuanxin Ji, Bingning Liu, Yan Chen, Yihan Peng, Xinghuang Cai, Huixian Zhang, Mei Dong, Qingsong Wang, Chunmeng Sun, Zhigui Su","doi":"10.1007/s11095-026-04064-w","DOIUrl":"https://doi.org/10.1007/s11095-026-04064-w","url":null,"abstract":"<p><strong>Background: </strong>Transdermal drug delivery (TDD) offers a convenient administration for treating local or systemic diseases. However, the dense \"brick-mortar\" structure of the stratum corneum hinders the skin permeation of most of bioactive molecules, which highly constrained the application of TDD.</p><p><strong>Methods: </strong>This study analyzed stratum corneum disruption and enhanced permeation by gently rubbing calcium hydrogen phosphate (Chp) particles of varying sizes on skin. Enhanced anesthetic efficacy of Chp-containing microemulsion gel (MG) loaded with lidocaine-tetracaine eutectic was evaluated in guinea pigs using a needle-prick model.</p><p><strong>Results: </strong>Using Chp as dermabrasion particle could effectively disrupt the barrier of stratum corneum after applying gently rubbing on the skin, which resulted in increasing skin permeation of both FITC, FITC-Dextran4000 and MG loaded with lidocaine-tetracaine eutectic. The enhanced skin permeation depended not only on the increase of particle size and amount of Chp in the MG, but also on the increase of rubbing pressure and duration after being applied to the skin, finally shortening the onset time and improving the efficacy of local anesthetics.</p><p><strong>Conclusions: </strong>The incorporation of Chp into the topical formulation, followed by rubbing them on the skin with appropriate pressure and a certain duration, can significantly disrupt the stratum corneum, enhance drug permeation through the skin, and shorten the onset time of local anesthetics. This study provided a potential strategy for improving the skin permeation with well tolerance, which could be further used to expand the range of bioactive molecules for TDD.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147778409","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":"Mucolytic Core-Shell Particles to Boost Levofloxacin Penetration Through the Mucus Barrier in Cystic Fibrosis.","authors":"Valentina Ruggiero, Francesca Mariano, Domenico Larobina, Gaetano D'Avino, Marco Trofa, Consiglia Tedesco, Pasquale Del Gaudio, Paola Russo","doi":"10.1007/s11095-026-04103-6","DOIUrl":"https://doi.org/10.1007/s11095-026-04103-6","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate multi-fluid spray drying as a formulation strategy to engineer inhalable microparticles containing levofloxacin and mucolytic agents, and to evaluate how formulation and process parameters influence particle properties, aerosol performance, and drug release under mucus-relevant conditions.</p><p><strong>Methods: </strong>Microparticles containing levofloxacin in combination with mucolytic agents were produced using a mini spray dryer equipped with a triple-fluid nozzle. Different compositions and particle architectures were obtained by varying formulation and excipient allocation. The resulting powders were characterized in terms of morphology, bulk, tapped and true density, aerodynamic performance, and in vitro drug release evaluated both in the absence and presence of a mucus layer.</p><p><strong>Results: </strong>Ambroxol showed greater suitability for spray drying than N-acetylcysteine, resulting in markedly higher process yields (up to 74%). The incorporation of L-leucine as a functional excipient reduced particle agglomeration and improved powder handling and aerosolization, with fine particle fractions exceeding 38% for leucine containing formulations. Drug release experiments demonstrated that spray drying altered release behaviour under diffusion limiting conditions imposed by a mucus layer compared to dissolution under sink conditions.</p><p><strong>Conclusions: </strong>Overall, the results indicate that multi-fluid spray drying enables effective modulation of the physicochemical and aerodynamic properties of inhalable microparticles. This study provides mechanistic insight into how formulation composition and process design influence particle behaviour in mucus-relevant environments, supporting the use of this approach as a flexible platform for the development of inhalable formulations.</p>","PeriodicalId":20027,"journal":{"name":"Pharmaceutical Research","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777688","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}