Journal of pharmaceutical sciences最新文献

{"title":"Non-viral in vivo cell and gene therapies: A change journey for CMC science and scientists.","authors":"Annette Bak, Marianne Ashford","doi":"10.1016/j.xphs.2026.104312","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104312","url":null,"abstract":"<p><p>The CMC (Chemistry Manufacturing and Controls) landscape is rapidly evolving as pharmaceutical science shifts from traditional small molecules and peptides towards non-viral in vivo cell and gene therapies. The article highlights the skills required including hybrid scientific roles spanning chemistry, biology, drug delivery, formulation and analytical development. They are essential to deliver clinical non-viral in vivo cell and gene therapy products. In addition, organizational structures that are best suited for these new therapies are discussed. To frame the discussion on skills, we briefly start out by summarizing the increased modality complexity in terms of multicomponent LNPs (lipid nanoparticles), including novel excipients, new product manufacturing methods, complex analytical requirements, and a regulatory framework that is still developing. Finally, it is highlighted how non-viral in vivo cell and gene therapies will have clinical and patient access advantages. We hope to provide inspiration for scientists on a similar journey and demonstrate that expanding your skills, knowledge and science is a worthwhile undertaking to aid in developing the differentiated medicines of the future.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104312"},"PeriodicalIF":3.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816529","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":"Mechanism-informed evaluation of particle formation in high-concentration monoclonal antibodies during fill-finish: Impact of pump materials, surface interactions, and system architecture.","authors":"Adam Hartman, Deep Bhattacharya, Mingyue Li, Vicky Lin, Eda Fenercioglu, Patrice Anleitner, Advait Badkar, Parag Kolhe","doi":"10.1016/j.xphs.2026.104309","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104309","url":null,"abstract":"<p><p>Particle formation during fill-finish operations poses a critical risk to the quality and manufacturability of high-concentration monoclonal antibody drug products. This study systematically evaluates the influence of pump material, clearance tolerance, and flow-path architecture on subvisible and visible particle generation using a model IgG formulation. Controlled simulations compared peristaltic pumping with ceramic and stainless-steel rotary piston pumps under standstill and recirculation conditions, including a configuration incorporating a three-way valve and deliberate metal particulate spiking. Subvisible particle analysis revealed that particulate generation was dominated by surface-mediated mechanisms: stainless-steel components, tighter (5 µm) pump clearances, and increased flow-path complexity produced the highest particle levels, while ceramic RPPs with moderate clearance generated substantially fewer particulates and avoided pump seizure. Visible particles were observed only in the stainless-steel RPP system containing the three-way valve and metal spiking. Orthogonal characterization (FTIR, Raman, SEM-EDX) confirmed that particulates were primarily proteinaceous and frequently contained embedded metallic inclusions, in the deliberate particulate challenge configuration, consistent with heterogeneous nucleation at high-energy interfaces In contrast, DSC, DSF, MM-IR, DLS-derived kD, and wNMR analyses demonstrated unchanged thermal stability, secondary structure, and protein-protein interaction behavior across all conditions, with no measurable changes in bulk stability metrics across conditions. Mechanistically, the standstill-restart design and orthogonal particle characterization support a surface-mediated pathway in which proteins accumulate at high-energy interfaces during static holds and are subsequently detached under flow, with metal inclusions providing heterogeneous nucleation sites, while bulk IgG stability remains unchanged across conditions. The data support process-development strategies that underscore pump material of contact evaluations, avoid overly tight clearances, reduce recirculation, and simplify valve geometry. This mechanistic-informed framework provides practical guidance for designing robust, patient-centric fill-finish processes aligned with quality-by-design principles. While the study uses a single model IgG1, the observed surface-mediated trends align with broader literature on adsorption-induced particle formation at solid-liquid interfaces.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104309"},"PeriodicalIF":3.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816443","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 transcript length, temperature, and lyophilization on mRNA-lipid nanoparticle stability.","authors":"Manasa Chillara, Weibo Zhao, Jonathan S Dordick, Todd Przybycien","doi":"10.1016/j.xphs.2026.104308","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104308","url":null,"abstract":"<p><p>Lyophilization enhances the long-term stability of mRNA-lipid nanoparticles (LNPs), yet the full extent of the physicochemical and functional implications of freeze-drying remains underexplored. In the current work, the influence of key variables, such as mRNA length, formulation conditions, and lyophilization status, on the stability of mRNA-LNPs was investigated. mRNA constructs were synthesized encoding monomeric (egfp)₁, dimeric (egfp)₂, and tetrameric (egfp)₄ sequences to vary mRNA length systematically. A suitable LNP composition and lyophilization conditions were identified to generate lyophilized mRNA-LNPs for a long-term stability study. The physicochemical properties of mRNA-LNPs changed initially after lyophilization but were stable during storage for both lyophilized and aqueous samples. However, these properties did not reliably predict functional stability. Aqueous (egfp)₁-LNPs stored at room temperature showed a rapid 50-fold decrease in enhanced green fluorescent protein (EGFP) expression within 28 days. In contrast, lyophilized mRNA-LNPs underwent only a 6-fold loss in EGFP expression at 28 days, followed by a gradual decline to a 9-fold loss at 84 days. Lyophilization appears to result in two or more LNP subpopulations, leading to functional heterogeneity. Furthermore, inactivation rate constants were calculated using a first-order rate model as a function of temperature and mRNA length, which can serve as a basis for future mRNA-LNP stability modeling.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104308"},"PeriodicalIF":3.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816499","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":"Zeolitic imidazolate frameworks for delivery of repurposed drugs with anti-chikungunya activity.","authors":"Rutuja Jagtap, Kalichamy Alagarasu, Poonam Patil, Shakil Ahmed Polash, M B Kakade, Atharva Manoj Deshpande, Sarah Cherian, Ravi Shukla, Deepti Parashar","doi":"10.1016/j.xphs.2026.104311","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104311","url":null,"abstract":"<p><p>Chikungunya virus (CHIKV) is a major global concern due to its emergence and re-emergence and the lack of effective antiviral treatments. Conventional antiviral drugs struggle with poor bioavailability, rapid degradation, and cytotoxicity, limiting their effectiveness. Nanoparticle-based drug delivery systems, particularly Zeolitic Imidazolate Frameworks (ZIF-C), have shown potential in improving the therapeutic outcomes of antiviral drugs. We encapsulate four repurposed drugs - Enalaprilat, Lomibuvir, Metyrapone, and Resveratrol within ZIF-C. Cytotoxicity assay of the formulations (ZIF-C(E), ZIF-C(L), ZIF-C(M), and ZIF-C(R)) show that free Enalaprilat, Lomibuvir, Metyrapone, and Resveratrol are toxic above 1.56 µM, 6.25 µM, 200 µM, and 12.5 µM, respectively, while their ZIF-C counterparts maintain >90% cell viability even at 50-100 µM. Antiviral studies further show that ZIF-C(E), ZIF-C(L), ZIF-C(M), and ZIF-C(R) reduce CHIKV viral titers by 3.8, 3.8, 2.9, and 3.9 logs, respectively with reference to virus control (VC), while the free drugs Enalaprilat, Lomibuvir, Metyrapone, and Resveratrol show 0.7, 0.7, 0.01, and 0.8 log reduction, respectively. Empty ZIF-C nanoparticles exhibit negligible antiviral effects. The results suggest that encapsulation within ZIF-C nanoparticles can help improve the stability, delivery, and effectiveness of antiviral drugs. This could be a promising strategy for treating CHIKV and other viral infections.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104311"},"PeriodicalIF":3.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816550","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":"Divergent host cell protein profiles during special purification of biologics from prokaryotic versus eukaryotic systems dictate the need for tailored ELISA assay development.","authors":"Ran Zhang, Yue Yu, Zuxia Zhou, Zou Bing, Chuanlei Liu, Zhenhao Yin, Feng Zhang, Hongyan Ye, Xi Hu, Qingmin Wang, Daoyuan Li, Zhenming An","doi":"10.1016/j.xphs.2026.104302","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104302","url":null,"abstract":"<p><p>Therapeutic antibodies are expressed via host systems, such as Chinese hamster ovary (CHO) cells and Escherichia coli (strain B / BL21-DE3, E.coli BL21), followed by purification to remove host cell proteins (HCPs), thereby averting risks including immunogenicity, antibody degradation, and protein aggregation. During regulatory filing, drug-specific HCP ELISA kits custom-developed using null-transfected harvest cell culture fluid (HCCF) are typically required to ensure accurate HCP quantification. In a case involving an E.coli-expressed antibody, initial HCP ELISA kits derived solely from HCCF significantly underestimated HCP levels in the purification intermediate (cation-exchange chromatography fraction, CEX1). Supplementing anti-CEX1 HCP antibodies significantly improved detection capability. Subsequent high-resolution mass spectrometry (HRMS) characterization revealed substantial shifts in HCP composition and abundance between HCCF and CEX1. Conversely, for CHO cell-derived antibodies (eukaryotic system), no significant alteration in HCP profiles was observed between HCCF and the analogous purification intermediate. This divergence provides critical insights for optimizing HCP analytical strategies of special purification antibody therapeutics.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104302"},"PeriodicalIF":3.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816463","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 predictive model for paracellular solute transport across vascular endothelia: Quantitative insight into factors affecting subcutaneous absorption.","authors":"Krishnaveni Thota, Anitha Mogilicharla, Vasanthakumar Sekar, Vijay Joguparthi","doi":"10.1016/j.xphs.2026.104305","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104305","url":null,"abstract":"<p><p>This study presents a predictive computational model that simulates drug absorption across vascular endothelia after subcutaneous (SC) injection of small hydrophilic drugs (<20 kDa). A three-dimensional finite element model was constructed using COMSOL Multiphysics 6.3, treating SC tissue as a poroelastic medium. The model integrates interstitial fluid flow, SC tissue deformation, and both diffusive and convective drug transport via paracellular capillary uptake. Human plasma concentration-time data for various hydrophilic drugs, obtained from published literature, were used to estimate observed absorption rate constants. These were compared with predicted absorption rate constants from simulations and used to evaluate the model's accuracy. The model demonstrates that absorption rate decreases with increasing solute size and formulation viscosity. The absorption rate increases as tissue capillary density and capillary hydraulic conductivity increases at the site of injection. Incorporating solute aggregation into the numerical simulations improves the accuracy of the predicted absorption rate constant. Integrating a tissue-level vascular transport in silico model with human pharmacokinetics allows formulators to systematically evaluate variables that enhance the optimization of subcutaneous absorption.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104305"},"PeriodicalIF":3.8,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816414","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":"Resolving drug release mechanisms of amorphous solid dispersions using optical coherence tomography.","authors":"Daniel Powell, Ecaterina Bordos, John Robertson, Jukka Rantanen, Daniel Markl","doi":"10.1016/j.xphs.2026.104300","DOIUrl":"10.1016/j.xphs.2026.104300","url":null,"abstract":"<p><p>This study presents an integrated approach utilising optical coherence tomography (OCT) to investigate the drug release mechanisms of hot-melt extruded (HME) amorphous solid dispersions (ASDs) of ritonavir and Soluplus®. Ritonavir-Soluplus® extrudates were prepared via HME using a twin-screw extruder and characterized during dissolution using a custom-designed 3D-printed flow cell, which enabled in-situ OCT imaging and continuous UV-vis monitoring of drug release. OCT provided high-resolution, time resolved visualization of structural transformations within the dissolving extrudates, while UV-vis spectroscopy quantified active pharmaceutical ingredient (API) release kinetics. Results revealed a multiphase dissolution mechanism involving sequential surface film formation, polymer swelling, delamination, and erosion. Increasing drug loading (10-30% w/w) produced marked effects on dissolution behaviour: formulations above 14% exhibited delayed release onset, extended swelling phases, and reduced overall release efficiency. OCT data showed that drug loadings above 14% led to slower erosion rates, greater swelling, and prolonged structural integrity, correlating with delayed UV-vis release profiles. Image processing using a machine learning segmentation model enabled quantitative extraction of sample cross-sectional area, confirming load-dependent swelling and erosion dynamics. Together, these findings establish a mechanistic link between structural evolution and release kinetics in HME ASDs and demonstrate the capability of OCT to provide real-time, non-destructive insight into solid dosage form dissolution. This methodology offers a powerful framework for optimizing ASD formulations and enhancing the predictive understanding of drug release mechanisms.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104300"},"PeriodicalIF":3.8,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816602","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":"Chemoenzymatic synthesis of a CD19/CD20 bispecific nanobody-rhamnose conjugate with reconstituted Fc effector functions for immunotherapy of B-cell malignancies^✰.","authors":"Yu Zhu, Wenxian Cao, Zhouyi Shi, Shaojie Xu, Lu Cheng, Haofei Hong, Zhimeng Wu","doi":"10.1016/j.xphs.2026.104303","DOIUrl":"10.1016/j.xphs.2026.104303","url":null,"abstract":"<p><p>Recent advances in bispecific agents targeting both CD19 and CD20 highlight their potential as an effective strategy for improving clinical outcomes in B-cell malignancies. Herein, we developed a CD19/CD20 bispecific nanobody, 19Nb1-20Nb2, by fusing the anti-CD19 nanobody 19Nb1 to the N-terminus of the anti-CD20 nanobody 20Nb2. To reconstitute missing Fc effector functions, 19Nb1-20Nb2 was site-specifically conjugated with a tetravalent rhamnose (Rha) derivative via sortase A-mediated ligation. The resulting conjugate, 19Nb1-20Nb2-(Rha)₄, exhibited good affinity for CD19/CD20 dual-positive cancer cells, and was capable of triggering potent antibody-dependent cell-mediated phagocytosis and complement-dependent cytotoxicity for B cell killing through recruiting high level of anti-Rha antibodies. Furthermore, the bispecific conjugate 19Nb1-20Nb2-(Rha)₄ demonstrated higher anti-tumor activity in vitro compared to monospecific therapeutics. This study provides a novel perspective for the development of CD19/CD20 dual-targeting therapeutic strategies.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104303"},"PeriodicalIF":3.8,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816466","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":"Probing surfactant protein B fragments as endogenous RNA carriers for pulmonary delivery.","authors":"Michael Y T Chow, Paulina Goldbaum, Cheng Ma, Siti Aisy, Giorgia Cipollone, Jenny K W Lam","doi":"10.1016/j.xphs.2026.104301","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104301","url":null,"abstract":"<p><p>Pulmonary delivery of gene therapy holds significant clinical potential. While pulmonary administration of naked RNA could induce modest transfection in lung tissues, the underlying transfection mechanisms remain unclear. A hypothesis suggests that the positively charged surfactant protein B (SP-B) may play a significant role in mediating cellular uptake of RNA. Leveraging the advantage of employing an endogenous protein as potential RNA carrier for enhanced biocompatibility and safety, this study aimed to explore the transfection capacity of SP-B by identifying the active regions responsible. The siRNA transfection potential of four peptide fragments strategically derived from SP-B were investigated. SPB-L, the peptide fragment derived from the first 25 amino acids in the N-terminal region, demonstrated significant transfection capacity in A549 human alveolar epithelial cells. Unlike many other reported peptide vectors, transfection efficiency with SPB-L was primarily dependent on peptide concentration with limited correlation to RNA dose. The dependence of peptide concentration on cellular uptake of SPB-L/siRNA complexes was also illustrated in flow cytometry. Overall, these findings support the hypothesis that SP-B can act as an endogenous RNA transfection agent, and that SPB-L represents a promising lead candidate for further optimization.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104301"},"PeriodicalIF":3.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147816557","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":"Pharmacokinetics and safety study of methylphenidate hydrochloride sustained-release tablets in Chinese healthy participants.","authors":"Di Zhou, Yinxia Li, Lijuan Ning, Yue Wang, Huijuan Qu, Jie He, Yuanyuan Li, Jun Chen, Aizong Shen, Zhaoyi Yang","doi":"10.1016/j.xphs.2026.104299","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104299","url":null,"abstract":"<p><p>This study aims to investigate the pharmacokinetic (PK) properties and safety of generic versus brand-name methylphenidate hydrochloride (MPH) sustained-release tablets (Concert®) under fasting and fed conditions, and to evaluate bioequivalence between the two formulations, thereby providing sufficient evidence for an abbreviated new drug application. A randomized, open-label, single-dose, four-period, fully replicated crossover bioequivalence study was conducted on healthy Chinese volunteers under fasting and fed conditions (n=36). Eligible Participants received 18 mg test (T) or reference (R) MPH sustained-release tablets, followed by a 7-day washout interval for each period. Blood samples were collected predose through 72 hours postdose. The plasma concentration of methylphenidate was analyzed by validated LC-MS/MS. Bioequivalence evaluation included C_max, AUC_0-∞. Furthermore, owing to the biphase distribution profile of this formulation attributed to the osmotic release oral system (OROS) technology, a partial AUCs (AUC_0-4h,AUC_4-8h ,AUC_8-12h,AUC_0-24h for fed and AUC_0-3h,AUC_3-7h,AUC_7-12h,AUC_0-24h for fasting condition) analysis is necessary. Under both conditions, the T and R formulations showed comparable pharmacokinetics. The geometric mean ratios with 90% confidence interval (CI) were as follows: under fasting conditions, C_max was 91.57-101.48%, AUC_0-∞ was 99.85-106.45%; under fed conditions, these values were 89.88-98.22% and 97.87-103.03%, respectively. Additionally, the partial AUCs results for both fasting and fed trials were consistent. All confidence intervals fell within the 80-125% bioequivalence range. Both formulations demonstrated good tolerability, with no serious adverse events observed. Under both fasting and fed conditions, the test formulation demonstrated bioequivalence to the reference formulation in healthy Chinese Participants. Both preparations were safe and well-tolerated.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104299"},"PeriodicalIF":3.8,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774694","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}