Biopharmaceutics & Drug Disposition最新文献

{"title":"Vector-Based Comparison and Average Slope Can Refine Bioequivalence Claims: A Machine and Deep Learning Approach","authors":"Maria Kokkali,&nbsp;Vangelis D. Karalis","doi":"10.1002/bdd.70023","DOIUrl":"10.1002/bdd.70023","url":null,"abstract":"<div>\u0000 \u0000 <p>This study explored the advantages of two innovative concepts: AS and VBC. AS is a pharmacokinetic parameter that measures absorption rates, whereas VBC analyzes clinical endpoints as vectors, breaking them into independent components. Together, these methods aim to improve the accuracy and efficiency of bioequivalence (BE) studies. The performance of AS and VBC was assessed using 14 actual datasets. The study applied both standard statistical methods required by regulatory authorities and advanced techniques, including machine learning and artificial neural networks. The findings showed that combining AS and VBC accurately measures absorption rates while reducing variability. This approach enhances statistical power, addresses multiplicity issues, and supports smaller sample sizes. These improvements simplify BE studies, lower costs, and shorten completion times. The joint use of AS and VBC provides a precise and efficient method for defining absorption rates in BE studies. These methods improve study outcomes while reducing the resources and time required, making them valuable tools for modern BE analysis.</p>\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"47 1","pages":"49-65"},"PeriodicalIF":2.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146176825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nose to Brain Delivery of Curcumin Loaded Therapeutic Nanostructures for Neurodegenerative Diseases","authors":"Rupsikha Kalita,&nbsp;Anupam Sarma,&nbsp;Himakshi Baruah,&nbsp;Asifa Zaman,&nbsp;Deepjyoti Goswami","doi":"10.1002/bdd.70021","DOIUrl":"10.1002/bdd.70021","url":null,"abstract":"<div>\u0000 \u0000 <p>Neurodegenerative diseases are progressive disorders that damage and eventually kill neurons in the central nervous system (CNS). In recent years, various research has been done on reliable and effective treatment methods for the most common neurodegenerative diseases such as Parkinson's, Alzheimer, and Migraine diseases. Different neurodegenerative disorders such as Huntington's disease, Alzheimer's disease, Parkinson's disease, amyotrophic, Lewy body disease can be treated by curcumin, which is a strong antioxidant polyphenol with neuroprotective and anti-amyloid properties. However, Blood-brain barrier (BBB) and blood cerebrospinal fluid barrier restricts the permeation of curcumin to the brain leads poor distribution of the drug in brain tissue. The intranasal pathway holds promise for enhancing the treatment of CNS disorders since it bypasses the BBB and increases the brain bioavailability of drug. As nanotechnology continues to improve, research on the delivery of drug through intranasal route has grown significantly in last 10 years. Several nanocarriers have been developed such as nano-emulsions, microspheres, dendrimers, liposomes, carbon-based nanoformulation, and nanoparticles to deliver curcumin to the brain via intranasal route for the treatment of neurodegenerative diseases. This study provided a thorough analysis of several curcumin nano-formulations used in intranasal pathway as a novel treatment for neurodegenerative diseases.</p>\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"47 1","pages":"12-36"},"PeriodicalIF":2.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145892090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic Studies of a Novel c-Met Targeting PROTAC Drug Candidate Using UPLC-MS/MS Quantification Methods","authors":"Yan Gao,&nbsp;Xinyu Li,&nbsp;Chao Xin,&nbsp;Xiangdong Su,&nbsp;Lianfeng Ai,&nbsp;Jiangmeng Zeng,&nbsp;Shilin Liu,&nbsp;Jinxu Wang","doi":"10.1002/bdd.70022","DOIUrl":"10.1002/bdd.70022","url":null,"abstract":"<div>\u0000 \u0000 <p>TPD354 is a novel Proteolysis Targeting Chimera (PROTAC) drug candidate that targets the degradation of cellular mesenchymal-epithelial transforming factor (c-Met) kinase. It showed significant therapeutic efficacy in vivo gastric cancer models. We have developed a robust and sensitive analytical method for evaluating the pharmacokinetic properties of TPD354, using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) to quantify drug concentrations in diverse biological matrices. The method was validated and applied to pharmacokinetic studies of the compound. The method exhibited excellent specificity in the linear range of 6.995–6995.000 ng/mL. Moreover, the method met or exceeded established criteria for precision, accuracy, recovery, and matrix effects, ensuring its suitability for in vivo analysis. The method was applied to the study of drug pharmacokinetics in rats, stability in different types of liver microsomes, and protein binding in plasma of different species. Our studies have demonstrated that TPD354 exhibits metabolic stability in liver microsomes and is characterized by high plasma protein binding, with a half-life of approximately 16 h in rats. These findings suggest that TPD354 is a promising PROTAC drug candidate, with strong potential for the treatment of c-Met targeted cancer.</p>\u0000 </div>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":"47 1","pages":"37-48"},"PeriodicalIF":2.0,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ointment for Topical Ocular Delivery of Voriconazole: Formulation Development, In-Vitro Characterization & In-Vivo Pharmacokinetic Assessment.","authors":"Amol Chhatrapati Bisen, Ayush Dubey, Sachin Nashik Sanap, Sristi Agrawal, Arpon Biswas, Rabi Sankar Bhatta","doi":"10.1002/bdd.70029","DOIUrl":"https://doi.org/10.1002/bdd.70029","url":null,"abstract":"<p><p>Voriconazole (VCZ) is a broad-spectrum antifungal agent widely used for treating fungal infections caused by Candida, Aspergillus, and Fusarium species, which are commonly associated with fungal keratitis (FK). Topical ophthalmic ointments offer several advantages over conventional eye drops, including prolonged retention on the ocular surface, sustained drug release, and improved bioavailability. In this study, we formulated and optimized a VCZ-loaded ophthalmic ointment intended for effective management of FK. The ointments were prepared using emulsifying wax and varying proportions of liquid paraffins through the fusion method. Among all the formulations, batch F4 demonstrated optimal properties, including a stable, opaque white appearance with drug content of 103.7 ± 2.4%. Microscopic examination showed no drug crystallization, and differential scanning calorimetry (DSC) confirmed the absence of drug-excipient interactions. The in vitro release profile of F4 showed 70% drug release over 24 h, fitting the Higuchi kinetic model, indicative of a sustained release pattern. Ex vivo transcorneal studies revealed that 13.22 ± 0.81% of the drug permeated across the cornea, while 2.51 ± 0.03% remained entrapped in the corneal tissue after 24 h. Ocular irritation studies demonstrated the formulation was non-irritant and safe for ophthalmic use. Furthermore, in vivo pharmacokinetic evaluation in rabbits showed significantly higher corneal drug concentrations for F4 (C_max: 400.76 ± 70.13 μg/mL) compared to a marketed formulation (C_max: 32.60 ± 26.64 μg/mL), indicating approximately 12-fold enhanced retention. These findings suggest that the optimized ointment is a promising option for effective and prolonged ocular delivery of VCZ in the treatment of FK.</p>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corneal Targeted Mucoadhesive Emulsion for Prolonged Delivery of Voriconazole: Formulation Evaluation and Pharmacokinetic Assessment.","authors":"Amol Chhatrapati Bisen, Saurabh Srivastava, Sachin Nashik Sanap, Anjali Mishra, Arpon Biswas, Sristi Agrawal, Rabi Sankar Bhatta","doi":"10.1002/bdd.70028","DOIUrl":"https://doi.org/10.1002/bdd.70028","url":null,"abstract":"<p><p>Voriconazole, a broad-spectrum triazole antifungal, is widely prescribed for fungal keratitis (FK) caused by Candida, Aspergillus, and Fusarium species. Conventional ophthalmic solutions are limited by rapid clearance and low bioavailability. This study describes the development of a voriconazole-loaded ophthalmic emulsion to improve ocular residence and drug disposition. Emulsions were prepared with soybean oil and Tween 80 via high-shear homogenization, with batch VE-3 exhibiting favorable properties, including nanosized globules (95.8 ± 50.2 nm, PDI 0.197), pH 6.94 ± 0.14, high drug content (104.55% ± 7.9%), and physicochemical stability. DSC confirmed the absence of drug-excipient interactions, whereas osmolality (280 ± 4 mOsm/L) and conductance (77.59 ± 1.7 S/m) demonstrated ocular compatibility. To enhance mucoadhesion and prolong corneal residence, chitosan was incorporated into VE-3, yielding CS-VE-3. In vitro release studies showed 81% drug release from VE-3 versus 65% from CS-VE-3, with the latter following Higuchi kinetics, consistent with sustained release. Ex vivo transcorneal studies revealed comparable permeation for VE-3 (43.2% ± 1.14%) and CS-VE-3 (47% ± 1.22%), but distinct drug retention profiles (11.41% ± 0.73% vs. 5.09% ± 0.30%). In vivo pharmacokinetic assessment demonstrated C_max values of 9.66 ± 3.49 μg/mL (marketed), 10.47 ± 6.43 μg/mL (VE-3), and a four-folds higher 41.67 ± 28.48 μg/mL for CS-VE-3, indicating prolonged corneal contact with chitosan incorporation. Ocular irritation studies confirmed safety and tolerability. The optimized mucoadhesive emulsion offers a promising strategy for sustained ocular delivery of voriconazole, potentially improving therapeutic outcomes in FK management.</p>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Novel Slowly Self-Emulsifying Drug Delivery System: Prolonged Systemic Exposure of Tacrolimus With Reduced Risks of Systemic Side Effects.","authors":"Kohei Yamada, Keiya Sonobe, Akihisa Miura, Toshinobu Suzuki, Hiroyuki Uchida, Masataka Katsuma, Hideyuki Sato, Satomi Onoue","doi":"10.1002/bdd.70030","DOIUrl":"https://doi.org/10.1002/bdd.70030","url":null,"abstract":"<p><p>This study aimed to design and characterize a new type of self-emulsifying drug delivery system (SEDDS), slowly SEDDS (SL-SEDDS), for long-lasting systemic exposure of tacrolimus (TAC) with reduced nephrotoxicity. TAC-loaded SL-SEDDS (SL-SEDDS/TAC) was prepared by semi-solidifying TAC-loaded SEDDS (SEDDS/TAC) composed of Capryol 90, Cremophor EL, and polyethylene glycol 400 with Geleol. SEDDS samples were evaluated regarding physicochemical and biopharmaceutical properties. Both SEDDS/TAC and SL-SEDDS/TAC formed fine emulsions in water. The dissolution of SEDDS/TAC reached approximately 100% within the initial 30 min in simulated gastric fluid (SGF), and the SL-SEDDS/TAC samples exhibited slower dissolution than SEDDS/TAC in a Geleol content-dependent manner. SL-SEDDS/TAC with a Geleol content of 17.5 wt% showed 25% dissolution in SGF for 2 h, followed by an additional 31% dissolution in simulated intestinal fluid for 10 h. The sample was selected as a favorable SL-SEDDS/TAC for further studies because of its slow and continuous dissolution. Oral SEDDS/TAC and the selected SL-SEDDS/TAC (10 mg-TAC/kg) offered almost identical bioavailability of 18% and 19%, respectively, in rats. Compared with SEDDS/TAC, SL-SEDDS/TAC achieved a 32% decrease in the maximum plasma concentration, a risk factor of nephrotoxicity, from 383 to 262 ng/mL with significantly prolonged mean residence time. In a rat model of acute kidney injury, SL-SEDDS/TAC (10 mg-TAC/kg/day, 3 days) attenuated the elevation of blood nitrogen urea by 33% compared to SEDDS/TAC, suggesting a reduction in nephrotoxic risks. SL-SEDDS could be a promising dosage form to control oral absorption of TAC for effective and safe medication.</p>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of Data-Driven Techniques in Nanomedicines to Address Diagnosis and Drug Delivery Strategy for Therapy.","authors":"Koyeli Girigoswami, Agnishwar Girigoswami","doi":"10.1002/bdd.70016","DOIUrl":"10.1002/bdd.70016","url":null,"abstract":"<p><p>The progress of drug designing, drug delivery systems (DDS), and disease diagnostic systems has significantly advanced pharmaceutical development, as evidenced by the FDA-approved nanomedicines with enhanced selectivity, controlled release, and synergistic therapeutic effects. However, the design and large-scale development of nanomaterial-based DDS remain challenging due to difficulties in managing and analyzing complex experimental data. The integration of data-driven techniques, high-throughput experimental networks and protocols, automation, artificial intelligence (AI), and machine learning (ML)-a framework known as the fourth paradigm of scientific research that offers a promising solution. This review article highlights milestones in applying these technologies to biomarker-based diagnosis and DDS, including nanomaterial design, and explores their potential to accelerate drug development and clinical translation. It also outlines the future prospects or directions for leveraging these approaches to create highly efficient, customizable nanomedicines and smart materials with defined physicochemical properties, aiming to benefit researchers in materials science, nanotechnology, and biomedical DDS development.</p>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":"183-197"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced Vatiquinone Bioavailability With Fatty Meals and Optimal Dosing Schedule.","authors":"Lucy Lee, Katsuyuki Murase, Martin Thoolen, Peter Giannousis, Diksha Kaushik, Lee Golden, Ronald Kong","doi":"10.1002/bdd.70015","DOIUrl":"10.1002/bdd.70015","url":null,"abstract":"<p><p>Vatiquinone, a 15-lipoxygenase (LO) inhibitor, is an orally bioavailable small molecule being developed for the treatment of Friedreich's ataxia, a disorder characterized by high levels of oxidative stress and dysregulation of energy metabolism. This investigation discusses the results of the food effect and three times a day (TID) dosing schedule studies data. The food effect study showed that absorption is significantly enhanced when vatiquinone was administered with fatty meals, either solid or liquid. Mean vatiquinone area under the concentration-time curve (AUC) values were 22-fold and 3-fold higher in subjects who consumed fatty meals and liquid meals, respectively, compared with subjects who fasted. With fatty meals, the intersubject variabilities appeared lower for AUC. The TID dosing study showed that the typical individual pharmacokinetic concentration profile exhibited 3 peaks on both Day 1 and after multiple dosing on Day 6. Vatiquinone exposures, AUC, and maximum concentration (C_max) appeared to increase from 200 to 400 mg in a dose-proportional manner with moderate variabilities, ranging from approximately 35% to 65%. The mean Day 6 accumulation ratio (AR_AUC) suggested an accumulation ratio of 1.61 and 1.73 for 200 and 400 mg, respectively. The results of both studies support the recommendation of administering vatiquinone TID with fatty meals taken on a convenient dosing regimen.</p>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":"175-182"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12757702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Across-Species Meta-Analysis of Betamethasone Pharmacokinetics Utilizing a Minimal PBPK Model.","authors":"Congyu Zhang, William J Jusko","doi":"10.1002/bdd.70017","DOIUrl":"10.1002/bdd.70017","url":null,"abstract":"<p><p>The pharmacokinetic (PK) profiles and parameters of betamethasone (BET) in seven species were collected and reviewed from the literature along with in-house rat data. The apparent clearance (CL/F) of BET was first evaluated using traditional allometric scaling methods, indicating that CL/F reasonably correlates with body weight (BW) with a power coefficient of 1.0 and R² = 0.93. A minimal physiological-based pharmacokinetic (mPBPK) model containing blood, two lumped tissue compartments, perfusion rate limited distribution, first-order absorption or prodrug conversion when needed, and utilizing the physiological and anatomical sizes of each of five species was implemented. The BET PK profiles were reasonably captured by the mPBPK model in the joint fitting analysis with a conserved partition coefficient (K_p = 0.99) and species-specific CL values. An allometric two-compartment model was also utilized and compared. Overall, the distribution properties of BET were reasonably conserved across species, but species-specific absorption rates and clearances provided best joint fitting of PK data across most species.</p>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":"198-208"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145538999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Physiologically Based Pharmacokinetic (PBPK) Simulation Model for Nicotine.","authors":"Brian Kim, Sung Hun Bae, Mohamed Bashar, Bofang Yi, Mohammad Asikur Rahman, Prince Awuah, Matthew Hartog, Rony Panarsky, Tao Zhang","doi":"10.1002/bdd.70018","DOIUrl":"10.1002/bdd.70018","url":null,"abstract":"<p><p>Tobacco is a major cause of chronic diseases such as lung cancer, cardiovascular disease, and chronic obstructive pulmonary disease worldwide. Nicotine, the primary psychoactive component in tobacco, is highly addictive and while not the primary driver of such tobacco-related diseases, poses various health risks, particularly those affecting the cardiovascular and pulmonary systems. Although nicotine-based therapies, such as nicotine replacement products, are widely utilized in smoking cessation efforts today, the impact of newer, tobacco delivery systems such as electronic nicotine delivery systems, or ENDS, remains uncertain and warrants continued evaluation. This study aims to develop and validate a physiologically based pharmacokinetic (PBPK) simulation model for nicotine using clinical pharmacokinetic data. The PBPK simulation model for nicotine was developed by incorporating drug-specific and system-specific parameters and by considering the systemic absorption, distribution, metabolism, and excretion of nicotine as well as its overall pharmacokinetic behavior on GastroPlus version 9.9. Validation of the developed PBPK model was performed by comparing predicted and observed plasma concentration-time profiles and pharmacokinetic parameters from clinical studies across multiple routes of administration including intravenous infusion, bolus, and pulmonary inhalation. The resulting model accurately captured plasma nicotine concentrations, with predicted pharmacokinetic parameters (C_max, T_max and AUCs) falling within acceptable ranges of observed values and computational average fold error values. The current model provides a practical tool to translate systemic nicotine exposure across delivery systems, support dose optimization against predefined target exposure, and quantify safety margins, thereby informing safer product design and evidence-based decisions in public-health regulatory science.</p>","PeriodicalId":8865,"journal":{"name":"Biopharmaceutics & Drug Disposition","volume":" ","pages":"209-220"},"PeriodicalIF":2.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12757703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145793188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}