Journal of pharmaceutical sciences最新文献

{"title":"Impact of oxidative degradation on the bioavailability of subcutaneously administered adalimumab.","authors":"Moustafa M Abdelaziz, Chad Groer, Yilue Zhang, David S Richards, Maribel Espinoza Ballesteros, Ishini Ranatunga, Huan Gong, Xiaoqing Wu, Liang Xu, Thomas Dimke, Stephan Koepke, Gerard Bruin, Karoline Bechtold-Peters, Christian Schöneich, M Laird Forrest","doi":"10.1016/j.xphs.2026.104550","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104550","url":null,"abstract":"<p><p>Subcutaneous (SC) administration of therapeutic antibodies enhances patient convenience and healthcare resource efficiency compared to intravenous (IV) delivery, but therapy can be limited by incomplete bioavailability (BA) of SC biotherapeutics. This limitation may be attributed to processes inherent to the unique composition of SC tissue, including the potential presence of reactive oxygen species (ROS) within the SC microenvironment, which can induce chemical and structural instability and functional impairment. This study investigated the impact of oxidation on the SC BA of adalimumab (Humira® biosimilar) as a representative IgG1 therapeutic protein. Two models of oxidation, mimicking some of those ROS encountered in the SC tissue, were applied to adalimumab, then the resulting oxidized variants were characterized and subsequently administered SC to rats to evaluate changes in SC BA. HPLC-MS/MS analysis identified methionine residues within CH2-CH3 interface as the primary sites of oxidation. Oxidation at these sites correlated with reduced conformational stability, alterations in the charge variant profile, and diminished binding affinity to the neonatal Fc receptor (FcRn). SC administration of oxidized species at 18% (w/w), diluted with excess unstressed IgG, to rats resulted in a slight decrease in SC BA, although not statistically significant. Additionally, oxidized AdmAb showed prolonged retention at the SC injection site, which may be associated with reduced conformational stability and higher propensity to aggregation and precipitation, although the underlaying mechanism requires further studies. Collectively, these findings demonstrate that oxidation can substantially alter the biophysical stability and FcRn binding affinity, while administering a moderate proportion of those oxidized species 18% (w/w) results in minimal changes in PK profile and overall SC BA.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104550"},"PeriodicalIF":3.9,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216414","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":"Hydrodynamic approximation of particle anisometry in solid lipid nanoparticles: Influence of lipid and emulsifier.","authors":"Anas Bagonaid, Pauline Breunig, Sherif Okeil, Georg Garnweitner, Heike Bunjes","doi":"10.1016/j.xphs.2026.104548","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104548","url":null,"abstract":"<p><p>Solid lipid nanoparticles (SLNPs) may be used as carriers for lipophilic drugs but also offer potential for the formulation of hydrophilic biomacromolecules via surface adsorption. Regarding the latter, specific surface area and particle anisometry are key parameters, yet quantitative methods to assess them for non-spherical particles remain limited. In this study, a hydrodynamic approach based on Perrin's theory for oblate ellipsoids was applied to approximate particle anisometry from dynamic light scattering data. Using this approach, the influence of matrix lipid type, particle size, emulsifier type, and emulsifier concentration on the shape of SLNPs was systematically investigated. Along the triglyceride series trilaurin to tristearin, particle anisometry increased with chain length, consistent with the formation of thinner, more platelet-like particles. Smaller SLNPs exhibited lower anisometry than larger particles. Interfacial effects were pronounced: post-modification with different emulsifiers resulted in marked differences in hydrodynamically approximated anisometry, with sucrose monolaurate-treated systems showing the highest and poloxamer 407-treated systems the lowest apparent anisometry. Increasing the concentration of poloxamer 188 reduced anisometry, whereas increasing the concentration of sucrose monolaurate increased it. Electron microscopic imaging qualitatively confirmed the calculated trends in particle shape. Overall, the presented method provides a practical screening tool for comparing relative changes in SLNP anisometry. It also enables the assessment of formulation-dependent differences in particle shape characteristics, which may be highly relevant for optimizing the adsorption of hydrophilic macromolecules to nanoparticle surfaces.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104548"},"PeriodicalIF":3.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149207055","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":"Of mice and little humans: A comparison of the issues facing drug delivery to wildlife and pediatric patients.","authors":"Arlene McDowell, Ben J Boyd","doi":"10.1016/j.xphs.2026.104549","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104549","url":null,"abstract":"<p><p>Despite them being two very different patient populations, wildlife and pediatrics share many of the same challenges when it comes to drug development, delivery and the regulatory and clinical factors that impact on development of effective medicines. Drug delivery to wildlife species for prevention and treatment of disease, for conservation or pest control, is an emerging field of research. The current global H5N1 avian flu outbreaks has highlighted zoonotic disease and made us acutely aware of the important link between human health and wildlife health, however effective treatment of wildlife faces significant practical challenges and a paucity of quantitative data. Pediatric patients are also disadvantaged under current development paradigms, in part through ethical hurdles, but also through biopharmaceutical and clinical practice complications. Here, we provide a comparison of the challenges faced with the development of oral formulations for pediatric and wildlife patients and identify areas of translation from one field to the other that can benefit both of these populations. More broadly, realisation of the nexus between prevention of zoonotic diseases and healthy aging from child through to late adulthood is important for the health of humanity in the framework of One Health.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104549"},"PeriodicalIF":3.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206922","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":"Are we selecting the right model compounds for advanced formulation research?","authors":"Tamás Solymosi, Dalip Kumar, Jesús Alberto Afonso Urich, Theresa Hörmann-Kincses, Martin Spoerk, Johannes Khinast","doi":"10.1016/j.xphs.2026.104537","DOIUrl":"10.1016/j.xphs.2026.104537","url":null,"abstract":"<p><p>Numerous advanced-formulation papers begin with the same problem statement: \"30-40% of marketed drugs, 70-75% of clinical candidates and 90% of new chemical entities are poorly soluble in water\". However, these figures are not fully supported by data and citations. We traced these numbers back to their original sources and reassessed them against the current API landscape. The 30-40% value was derived from a 2006 analysis of top selling drugs. Reassessing the top selling drugs in 2025 reveals a marked increase: about 55% of the orally administered small molecules now fall into the practically insoluble category. The 70-75% and 90% claims could only be traced to conference presentations and a review abstract with no underlying data. We further argue that the Biopharmaceutics Classification System categorization is not an intrinsic property of an API since it shifts depending on dose, particle size and formulation, i.e., no compound can be classified without considering the formulation and dose. A Scopus analysis showed that the APIs most frequently used as poorly soluble model compounds are the NSAIDs, antifungals and compounds, such as carbamazepine, carvedilol and simvastatin. The majority of these \"poorly solubles\" are in fact completely absorbed in vivo with no solubility issues at all. As more relevant alternatives to the above-mentioned compounds, we propose and briefly review ten marketed non-oncology APIs with unresolved dissolution and solubility limitations that would make better model compounds for advanced formulation research.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104537"},"PeriodicalIF":3.9,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167129","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 physiologically relevant fed gastric pH profile improves the prediction of food effects.","authors":"Lisa Cheng, Po-Chang Chiang, Matthew R Wright, Cornelis E C A Hop, Harvey Wong","doi":"10.1016/j.xphs.2026.104539","DOIUrl":"10.1016/j.xphs.2026.104539","url":null,"abstract":"<p><p>Food intake may significantly influence oral drug pharmacokinetics, primarily through changes in gastric pH, increased gastric emptying time, and the presence of fats and bile salts in the small intestine. Physiologically-based pharmacokinetic (PBPK) models can be leveraged to evaluate potential food effects by comparing simulated exposure parameters in the fed and fasted states. The incorporation of a more physiologically relevant, dynamic fed gastric pH profile into a PBPK model was evaluated for its impact on the performance of food effect predictions. Two models that capture changes in fed gastric pH over time were proposed: the multi-compartment stomach (MCS) and the dynamic one-compartment stomach (DOCS) models. Using the MCS and DOCS models, the predicted food effect of three compounds with pH-dependent solubility were compared to those obtained using the conventional approach of setting the fed gastric pH at a static pH 5 (termed the static one-compartment [SOCS] model). The MCS and DOCS PBPK models were successful in predicting the observed food effect of ibuprofen sodium, itraconazole, and posaconazole. In contrast, the SOCS model could predict the correct observed effect of food for ibuprofen sodium and posaconazole but misassigned the food effect for itraconazole. In general, the MCS and DOCS models offered better performance when predicting food effects when compared to the conventional approach. These results indicate that a dynamic fed gastric pH profile in PBPK models can improve model performance when investigating food effects of ionizable compounds.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104539"},"PeriodicalIF":3.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148629","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":"Preclinical intraperitoneal delivery: Modulating dilution-induced precipitation from aqueous cosolvent formulations.","authors":"Jack Terry, Josephine Banks, Josephine Herrold, Indeewara Munasinghe, Sara Thomas, Michael Hageman","doi":"10.1016/j.xphs.2026.104530","DOIUrl":"https://doi.org/10.1016/j.xphs.2026.104530","url":null,"abstract":"<p><p>Aqueous-cosolvent formulations of celecoxib containing solubilizers or precipitation inhibitors sulfobutyl ether β-cyclodextrin (SBEβCD) and polyvinylpyrrolidone (PVPK30) were evaluated using in vitro and in vivo methods. Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2) which exhibits adequate permeability but poor aqueous solubility (BCS class II). In vitro methods were used to quantify (UV probe monitoring turbidity, UPLC monitoring solution concentration) and characterize (polarized light microscopy) precipitation following dilution of an aqueous-cosolvent solution. Subsequently, in vivo drug plasma concentrations following intraperitoneal administration were quantified using UPLC-MS/MS methods. Both in vitro and in vivo evaluations indicated that PVPK30 performed significantly better as a precipitation inhibitor than SBEβCD as a solubilizer/precipitation inhibitor, providing a metastable supersaturated state following the dilution-induced precipitation. This difference was reflected in an enhanced bioavailability which was almost 3 times higher in the first 24 hours following administration. Additionally, varying the volume but maintaining the mass of drug dosed did not provide a significant difference in drug exposure based on a subsequent administration of PVPK30 containing formulations with varying concentrations. The rank order of in vitro results was reflected by in vivo IP dosing displaying potential for utility in development of precipitation resistant formulations of poorly soluble compounds. Development of precipitation-resistant formulations of poorly soluble compounds is valuable for the achievement of adequate in vivo blood levels for preclinical and toxicological studies during early stages of drug development.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104530"},"PeriodicalIF":3.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149430","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":"In-line laser triangulation-based 3D profiling for real-time tablet monitoring in a rotary tablet press.","authors":"Jona Sandström, Mariano Patrizio Del Rio Reinoso, Leonie-Lara Dorothea Uth, Stefan Klinken-Uth","doi":"10.1016/j.xphs.2026.104529","DOIUrl":"10.1016/j.xphs.2026.104529","url":null,"abstract":"<p><p>Direct in-line measurement of tablet geometry provides product-related information that complements indirect, force-based control strategies in rotary tablet presses. Here, a laser line triangulation profiling sensor was integrated at the ejection position of a rotary press to acquire 3D surface profiles of tablets. A semi-automated Python workflow was developed for signal filtering, coordinate correction, height calibration, tablet detection, and extraction of tablet height and surface topography. Sensor mode, exposure time, and acquisition frequency were optimized to enable simultaneous detection of the rotor and tablet surfaces. Verification against caliper measurements yielded a mean difference of 1 µm with 95 % limits of agreement from -34 to +36 µm and a mean absolute error of 15 µm. In a 30-run Latin hypercube study, in-line tablet heights closely agreed with offline values measured after 24 h, indicating that rapid elastic recovery was largely complete at the measurement position. Adding laser-derived height to machine data reduced the cross-validated mean absolute error of tablet mass prediction from 1.71 to 1.20 mg, whereas tensile strength prediction improved only marginally. Imprints on biconvex oblong tablets remained clearly resolved at turret speeds of up to 50 rpm. Laser triangulation therefore offers a robust, chemometric-model-free PAT approach for simultaneous dimensional monitoring and surface inspection, with potential for 100 % inspection at industrial production speeds.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104529"},"PeriodicalIF":3.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149829","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":"Particle engineering enables laser powder bed fusion of highly loaded metoprolol tablets at room temperature.","authors":"Florian Engelsing, Wessel Kooijman, Teemu Tomberg, Clare Strachan, Lukas Vaartjes, Jochen Thies, Annette Grave, Robbert Jan Kok, Julian Quodbach","doi":"10.1016/j.xphs.2026.104531","DOIUrl":"10.1016/j.xphs.2026.104531","url":null,"abstract":"<p><p>Laser powder bed fusion (LPBF) is a promising additive manufacturing technology for producing personalized pharmaceutical dosage forms at industrial scale. In this process, a laser fuses thin layers of powder composed of an active pharmaceutical ingredient (API) and a binder to build three-dimensional objects layer-by-layer. A key limitation for pharmaceutical application of LPBF is the poor flowability and spreadability of fine and cohesive API powders, especially at high API loadings, which can cause spreading defects and poor process reproducibility. The purpose of this study was to enable LPBF manufacturing of highly loaded metoprolol (MTP) tablets by tailoring powder properties through particle engineering. Tangential spray fluidized bed processing was employed to produce MTP-polymer composite particles with API loadings between 75-90% (w/w). The engineered particles exhibited narrow particle size distributions, good flowability, and favorable spreadability, as determined by the roughness index of the spread powder layers. Tablets were manufactured without preheating the powder, using the laser as the sole energy source. Stimulated Raman scattering microscopy allowed visualization of the fine distribution of MTP and polymer within the tablets across the different API loadings. This particle engineering approach overcomes key material barriers to LPBF of highly loaded drug products and demonstrates that room-temperature manufacturing of metoprolol tablets is feasible. This strategy provides a foundation for extending LPBF to highly dosed APIs, supporting future development of personalized medicines.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104531"},"PeriodicalIF":3.9,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147906","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":"Influence of drug loading and lipid dose on the in vivo performance of fenofibrate in medium- and long-chain triglyceride solutions.","authors":"René Holm, Anja Kusic, Erling B Jørgensen, Huiling Mu","doi":"10.1016/j.xphs.2026.104536","DOIUrl":"10.1016/j.xphs.2026.104536","url":null,"abstract":"<p><p>The influence of drug loading relative to the saturation solubility of a lipid vehicle and the administered lipid dose on the in vivo performance of lipid-based formulations remains incompletely understood. The present study investigated these formulation variables using fenofibrate dissolved in medium-chain triglyceride (MCT) and long-chain triglyceride (LCT) vehicles. The saturated solubility of fenofibrate in MCT and LCT at 37 °C was assessed to determine suitable concentrations for in vivo studies. Fenofibrate showed higher solubility in MCT (185.8 mg/mL) compared to LCT (70.8 mg/mL), consistent with previous findings indicating lipid chain length affects solubilization. In vivo studies using rats involved administering a fixed lipid dose (2 mL/kg), with fenofibrate solubilized in the lipid solution at 25 %, 50 %, and 90 % of its saturation solubility. In a separate dose-escalation study, the relative drug loading was maintained at 90 % of its saturation solubility while the administered lipid volume, and consequently the fenofibrate dose, was increased. Pharmacokinetic analysis revealed that fenofibrate in MCT achieved higher plasma concentrations before dose correction, whereas fenofibrate in LCT led to higher plasma concentrations after dose correction. In the dose-escalation study, systemic exposure increased with increasing fenofibrate dose in both vehicles; however, less-than-dose-proportional increases in AUC_0-30 _h and C_max were observed over the dose ranges investigated. The deviation from proportionality in AUC_0-30 _h was greater for MCT than for LCT, while decreasing dose-normalized exposure was observed for the higher doses of both vehicles. These findings demonstrate that drug loading relative to saturation solubility, lipid type, and administered lipid dose can all influence the in vivo performance of lipid-based formulations and should be considered when designing and comparing such formulations.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104536"},"PeriodicalIF":3.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137343","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":"Integrated gastric to intestinal pH-shift dissolution and permeation testing can predict the marked oral absorption enhancement of an itraconazole-carboxymethyl ethylcellulose amorphous solid dispersion.","authors":"Hironori Tanaka, Tatsuya Fukuta, Rikuto Ihara, Haruka Mogami, Yuna Shimazaki, Mayumi Ikeda-Imafuku, Kazunori Kadota, Hiroshi Ueda","doi":"10.1016/j.xphs.2026.104528","DOIUrl":"10.1016/j.xphs.2026.104528","url":null,"abstract":"<p><p>In this study, we aimed to investigate correlation of oral absorption and dissolution-permeation behaviors carboxymethyl ethylcellulose (CMEC)-based amorphous solid dispersion (ASD) for itraconazole (ITZ). Amorphization of ITZ and formation of the ASDs through ball milling were confirmed by powder X-ray diffraction, thermal and spectroscopic analyses, using hydroxypropyl methylcellulose acetate succinate (HPMCAS) as an additional carrier. ITZ rapidly dissolved in pH 1.2 medium; however, this was suppressed by ASD formation. The dissolution of ITZ in pH 6.8 medium was <0.2 μg/mL, which was improved by ASD formation. The ASD of ITZ-CMEC (3:7) especially enhanced dissolution to >15-fold that of HPMCAS-based ASDs. The drug-rich colloids generated and grew in the supersaturated solution, but they were effectively inhibited by CMEC. In the oral administration of the ASDs to rat, CMEC resulted in 2-fold higher area under the plasma concentration curve than HPMCAS. Additional dissolution studies combined with gastric, intestinal, and permeated compartments were performed. Both ASDs showed similar dissolution profiles in the simulated gastric fluid followed by reduction and re-dissolution in the fasted state gastrointestinal fluid. Approximately 2- and 1.5-fold higher dissolution and permeation by CMEC compared to HPMCAS was confirmed, respectively, reflecting oral absorption. Therefore, we conclude that CMEC is one of the best ASD carriers, and the oral absorption performances could be understood from the dissolution-permeation performances through both the gastric and intestinal phases.</p>","PeriodicalId":16741,"journal":{"name":"Journal of pharmaceutical sciences","volume":" ","pages":"104528"},"PeriodicalIF":3.9,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127753","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}