AAPS Journal最新文献

{"title":"Updated Recommendations for the Bioanalysis of Antibody-Drug Conjugates (ADC) from the ADC working group of the AAPS Bioanalytical Community.","authors":"Jim X Shen, Robert Dodge, Shoshana Oberstein, Jennifer Cunliffe, Varun Ramani, Soumya Mohana Sundaram, Ines C Santos, Chongwoo Yu, Sanjay L Dholakiya, Seema Kumar, Xiaohui Sophia Xu, Sasha Fraser, Zeinab Mokhtari, Feng Yin, David G Rizzo, Omar S Barnaby, Honglue Shen, Dominic E Warrino, Shivangi Awasthi, Krista Burke, Stephanie Schaffer, Alok Rathi","doi":"10.1208/s12248-026-01268-1","DOIUrl":"10.1208/s12248-026-01268-1","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) represent a rapidly evolving therapeutic modality, combining the selective targeting of monoclonal antibodies with highly potent small molecule payloads. Their inherent structural complexity demands a sophisticated and multi-faceted bioanalytical approach spanning preclinical discovery through late-stage clinical development. This white paper, developed by the ADC Working Group of the AAPS bioanalytical community, comprising over 100 members from industry, contract research organizations (CROs), and regulatory agencies, provides updated recommendations for ADC bioanalysis. Building upon the foundational 2013 AAPS position paper and recent publications governing regulatory frameworks on PK considerations, this work addresses advances in bioanalytical quantitation strategies for total antibody (tAb), conjugated ADC, free (unconjugated) payload, and drug-to antibody ratio (DAR); novel immunogenicity assessment considerations; soluble target interference; critical reagent lifecycle management; payload-specific stability requirements; cross-validation strategies; and regulatory considerations. The recommendations presented herein reflect over a decade of scientific progress and are designed to serve as a comprehensive, empirically validated, and industry aligned bioanalytical framework for contemporary ADC drug development.</p>","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"28 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148370466","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 vivo Predictive Dissolution Test Using Biorelevant Bicarbonate Buffer for High-dose Free Acid Drug.","authors":"Yuki Tarumi, Kiyohiko Sugano","doi":"10.1208/s12248-026-01274-3","DOIUrl":"10.1208/s12248-026-01274-3","url":null,"abstract":"<p><p>The purpose of the present study was to evaluate whether dissolution testing in biorelevant bicarbonate buffer (BCB) can predict the solubility-limited oral absorption of high-dose free acid drugs. Valsartan and naproxen were selected as model compounds exhibiting solubility-limited absorption at high doses. A biorelevant BCB solution (concentration: 10 mM, initial pH (pH_ini) = 6.5, buffer capacity (β) = 4.4 mM/pH) (BCB), a phosphate buffer solution with the same pH and β (PPB), and a USP phosphate buffer solution (β = 27 mM/pH, modified to pH_ini 6.5) were employed for dissolution tests. The dose-to-fluid volume ratio (Dose/FV) was set to reflect the clinical or compendial conditions. The fraction of a dose absorbed in humans (Fa) predicted using a simple theoretical framework was compared with the clinical Fa calculated from pharmacokinetic data in the literature. When using BCB or PPB with the same β and the clinical Dose/FV, the bulk-phase pH after 4 h (pH_bulk, _4 h) was markedly lower than pH_ini (< pH 6.0 for naproxen, < pH 5.0 for valsartan). Consequently, the dissolved drug concentration at 4 h (C_{dissolv, 4 h}) was markedly lower than the solubility at pH 6.5. Using C_{dissolv, 4 h}, the dose dependency of Fa was appropriately predicted. In contrast, when using USP or the compendial Dose/FV, the pH_bulk, _4 h and C_{dissolv, 4 h} were less reduced, leading to an overestimation of Fa. Overall, the use of BCB or PPB and a clinical Dose/FV improved the in vivo predictability for high-dose free acid drugs.</p>","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"28 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148363623","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":"Whole-Body Pharmacokinetics of Ionizable Lipid, mRNA, and the Expressed Antibody following Intravenous Administration of mRNA-Loaded Lipid Nanoparticles.","authors":"Shrusti Tiwari, Mokshada Kumar, Shengjia Wu, Rutuja Kulkarni, Dhaval K Shah","doi":"10.1208/s12248-026-01273-4","DOIUrl":"10.1208/s12248-026-01273-4","url":null,"abstract":"<p><p>Lipid nanoparticles (LNPs) containing mRNA that encodes therapeutic proteins have emerged as a promising therapeutic modality for a myriad of diseases. However, the pharmacokinetic (PK) relationships between the nanoparticle carrier, its mRNA payload, and the expressed protein remain poorly understood. Here we have investigated whole-body PK of these components in mice following intravenous administration of an mRNA-LNP that expresses a non-cross-reactive monoclonal antibody. LNPs encapsulating mRNA were prepared via microfluidic mixing and characterized for physicochemical properties and encapsulation efficiency. Following a single intravenous administration of mRNA-LNP, blood, plasma, and tissues were collected for PK measurement over 2 weeks. Ionizable lipid (i.e., ALC-0315) concentrations were determined using LC-MS, mRNA concentrations were measured using qPCR, and the expressed antibody concentrations were determined using ELISA. It was found that each component exhibited a distinct PK profile. For example, lipid exposure was highest in liver and spleen, while mRNA accumulation peaked in spleen and heart. Strikingly, the expressed antibody demonstrated a distribution pattern that did not mirror mRNA exposure, with the lung showing the greatest antibody levels despite only modest mRNA delivery. Tissue-to-plasma ratios for the expressed antibody exceeded values reported for intravenously administered antibodies, suggesting localized production or enhanced retention following in situ translation. These findings highlight that functional protein exposure is governed by tissue-specific translational efficiency and protein properties, rather than just nanoparticle delivery. The comprehensive PK data presented here also provides a foundation for the development of systems-based PK models for antibody expressing mRNA-LNPs.</p>","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"28 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148354628","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":"Simple Hydrodynamic Molecular Weight Model for Rapid Assessment of Therapeutic Protein Oligomerization States in Formulation.","authors":"Jiaqi Lu, Kang Chen","doi":"10.1208/s12248-026-01270-7","DOIUrl":"10.1208/s12248-026-01270-7","url":null,"abstract":"<p><p>Therapeutic peptides and proteins form higher-order structures (HOS) including oligomeric forms in formulation, critical for drug efficacy, safety, and stability. To quickly assess protein oligomerization, dynamic light scattering (DLS) was applied to measure a series of protein standards with molecular weight (MW) range of 1.3-660 kDa, yielding translational diffusion coefficients (D_dls), which were corrected to D_corr using water diffusion data. A correlation between D_corr and protein monomeric MW, representing their hydrodynamic MW (MW_hd), was established as <math><mrow><mi>l</mi> <mi>o</mi> <mi>g</mi> <mrow><mo>(</mo> <msub><mrow><mi>D</mi></mrow> <mrow><mi>c</mi> <mi>o</mi> <mi>r</mi> <mi>r</mi></mrow> </msub> <mo>)</mo></mrow> <mo>=</mo> <mo>-</mo> <mn>0.428</mn> <mi>l</mi> <mi>o</mi> <mi>g</mi> <mfenced> <msub><mrow><mi>M</mi> <mi>W</mi></mrow> <mrow><mi>h</mi> <mi>d</mi></mrow> </msub> </mfenced> <mo>-</mo> <mn>5.412</mn></mrow> </math> . This DLS/MW_hd model was subsequently applied to therapeutic protein formulations with monomeric MW ranging from 3.8 to 149 kDa. The resulting MW_hd values were several-fold greater than the corresponding monomeric MW of the glucagon-like peptide-1/2 (GLP-1/2) analogs, insulin analogs, and the monoclonal antibodies (mAbs) infliximab and bevacizumab, indicating varying degrees of oligomerization. The observed oligomerization states were largely consistent with those reported in literature. For insulin and mAb oligomers, pseudo-spherical diffusion coefficients (D_s) back calculated from the oligomer MW agreed within 6% of experimental D_corr values, except for the insulin dimer. Incorporation of Perrin's anisotropic correction reduced insulin dimer discrepancy from 9 to 5%. Overall, the established MW_hd model, incorporating a larger exponent of 0.428 that accounts for protein anisotropy, provides a rapid, non-invasive method to factually assess protein oligomerization in as-is formulations, aiding drug development and quality control. Minor discrepancies relative to size exclusion chromatograph (SEC) or prior biophysical studies may arise from experimental differences in protein concentration, oligomeric equilibrium, pH, excipients or modeling assumptions, warranting further investigation.</p>","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"28 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148354635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Guiding the Molnupiravir Tablet Formulation Using Physiologically Based Biopharmaceutics Modeling and Successfully Establishing Dissolution Safe Space.","authors":"Thomas Morrow, Nicole Jarvi, Madeline Halota, Cheng Sun, Prapti Kafle, Rachel King, Grace Okoh, Sanjaykumar Patel, Tycho Heimbach","doi":"10.1208/s12248-026-01249-4","DOIUrl":"10.1208/s12248-026-01249-4","url":null,"abstract":"<p><p>Physiologically Based Biopharmaceutics Models (PBBMs) are evolving tools which can be used to aid in drug product quality specifications. PBBMs have gained increased regulatory interest and acceptance over the past 5 years. For molnupiravir, PBBM has been used for: a) calculation of a bioequivalence safe space for capsule formulation and tablets, b) informing of the definitive bioequivalence study (P011) with a target tablet formulation selection designed to be bioequivalent to the capsule formulation, c) selection of a deliberately slower release tablet formulation (beyond f₂ similarity criteria) designed to widen the dissolution knowledge space, d) help select the clinically relevant specification and the dissolution bioequivalence safe space. PBBM data inputs, model development, validation, and application using data from several independent clinical studies are described. Predictive errors for Cmax and AUC were < 25%. The z-factor for dissolution data modeling is described for QC (Quality Control) method(s). The molnupiravir bioequivalence safe space or knowledge space widening is described. The value of the wider dissolution space includes increased potential flexibility with scale-up and post approval changes (SUPAC), including adding or changing a site for a high-volume drug product such as molnupiravir. PBBM is not only important in the development of drug products aiding formulation selection, but can also be a key component toward regulatory flexibility and approval of clinically relevant specifications, such as when the clinical knowledge space has been widened through inclusion of a slow-release variant, as was done for the relative bioavailability study for molnupiravir.</p>","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"28 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148206861","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":"Correction: Nanotechnology-enhanced Natural Products for Cancer Chemoprevention: Molecular Mechanisms and Clinical Translation.","authors":"Rajat Nath, Sibashish Kityania, Deepa Nath, Jayanta Kumar Patra, Emran Habibi, Satyajit D Sarker, Anupam Das Talukdar, Lutfun Nahar","doi":"10.1208/s12248-026-01266-3","DOIUrl":"10.1208/s12248-026-01266-3","url":null,"abstract":"","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"28 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148206811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative Estimation of Clinical Intrasubject Variability of a Pharmacokinetic Parameter.","authors":"Hao-Jui Hsu, Katrina Casteel, Samuel Yang, Vivek Purohit, Vu Le, Kazuko Sagawa","doi":"10.1208/s12248-026-01264-5","DOIUrl":"10.1208/s12248-026-01264-5","url":null,"abstract":"<p><p>The virtual bioequivalence (VBE) approach, which employs physiologically based pharmacokinetic (PBPK) modeling in lieu of clinical bioequivalence (BE) studies, provides a valuable alternative for the pharmaceutical industry. The VBE has the potential to substantially reduce both the time and costs associated with traditional clinical BE studies. Furthermore, this approach supports ethical principles by eliminating the need to expose healthy volunteers to investigational compounds without medical benefit. Intrasubject variability (intrasubject coefficient of variation, ICV) is a main factor for balanced cross-over design BE studies in calculating the confidence intervals for the geometric mean ratio of AUC and C_max, which determines if bioequivalence criteria are met. Thus, it is essential to employ realistic and accurate ICV values for BE assessment through PBPK modeling. Published literature indicates that the drug properties that affect oral bioavailability exhibit a good correlation with ICV. The aim of this research is to expand drug databases to reevaluate the correlation between drug properties and clinically observed ICV for C_max (ICV_{_Cmax}). The results demonstrated that the dose number (dose to solubility ratio), permeability and elimination half-life are three main factors influencing ICV_{_Cmax}. Permeability becomes a dominating factor when the value is relatively low (P_app < 0.8 × 10^-6 cm/sec). In addition, PBPK modeling tools, Gastroplus and Simcyp were evaluated for their ability to predict ICV_{_Cmax} based on drug properties and their built-in physiological variations. Both simulation tools estimated intersubject variability and ICV_{_Cmax} similarly and underestimated ICV_{_Cmax} compared with clinically observed ICV_{_Cmax}.</p>","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"28 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148177143","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":"Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies.","authors":"Jiaxing Wang, Wenyu Zhang, Nana Shen, Pan Li, Wentao Xie, Shuya Wang, Ye Cheng, Lin Zhao, Yang Yang, Huadong Zhao","doi":"10.1208/s12248-026-01261-8","DOIUrl":"10.1208/s12248-026-01261-8","url":null,"abstract":"<p><p>The pathogenesis of cancer represents a multifaceted, progressive process driven by an intricate interplay of physical, chemical, biological, and other etiological factors. Recent advancements in clinical oncology, including targeted therapy, surgical resection, radiation therapy, chemotherapy, and immunotherapy, have substantially improved patient outcomes. Targeted therapy has emerged as a promising approach due to its precision and minimal adverse effects. Pyruvate kinase M2 (PKM2) is a metabolic enzyme with protein kinase function that has been extensively studied for its critical role in inflammation and metabolic diseases. By interacting with key oncogenic signaling pathways, PKM2 exerts a critical influence on cancer progression, thereby establishing its status as a potential therapeutic target for cancer. Notably, the role of PKM2 in cancer is not determined solely by expression level but also depends on post-translational modifications, conformational plasticity, nuclear localization, and tumor microenvironment. Extensive preclinical studies have demonstrated that various natural products and compounds exert antitumor effects by modulating PKM2 activity and expression, conformation, or nuclear localization. However, these strategies have not yet entered the clinical trial phase, and the path to clinical application remains fraught with challenges, including the biological complexity of PKM2, tumor resistance, and drug specificity. In summary, this article summarizes the regulatory network between PKM2 and oncogenic signaling pathways, highlights the importance of PKM2 in current clinical strategies for cancer treatment, and discusses the challenges facing therapies targeting PKM2 as well as future research directions.</p>","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"28 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148152245","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":"Context-of-use-Guided Development and Validation of a Transthyretin Immunoassay: A Framework for Biomarker Assay Design.","authors":"Tanya Watanabe, John Canfield, Erin Anderson, Leighla Tayefeh, John L Allinson, Nicholas J Viney, Joel A Mathews","doi":"10.1208/s12248-026-01262-7","DOIUrl":"10.1208/s12248-026-01262-7","url":null,"abstract":"<p><p>Transthyretin (TTR) is a circulating protein biomarker central to the evaluation of therapies for transthyretin amyloidosis. Clinical trials with Eplontersen, a TTR-targeting antisense oligonucleotide, required an assay with a context of use differing from existing assay, requiring a more sensitive method. This study describes the development, optimization, and validation of a quantitative immunoassay for TTR, guided by a context-of-use framework. Method development focused on calibration curve modeling, weighting, parallelism, and determination of the minimal required dilution. Antibody selection and calibrator characterization followed established best practices. Pre-validation experiments optimized antibody concentrations and curve-fitting (five-parameter logistic with 1/y² weighting). Assay performance was then evaluated through validation, including assessments of accuracy, precision, parallelism, specificity, stability, interference of endogenous binding partners, and comparison against other commercially available assays. The assay demonstrated a functional lower limit of quantitation of approximately 0.07 mg/dL, which would enable measurement of > 95% reductions in TTR after treatment. Parallelism improved at higher dilutions. The assay showed robust performance across endogenous samples, recombinant TTR variants and in the presence of potential interferents. Total analytical variability was shown to be 29.4%. Comparisons with commercial assays showed strong correlation, though absolute values varied by platform. This work establishes a robust, context-driven assay for quantifying TTR in clinical studies. The development process highlights generalizable principles in biomarker assay design, including matrix considerations, variability analysis, and curve optimization. These insights provide a transferable framework for biomarker method development in regulated environments.</p>","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"28 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148145432","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":"New Frontiers of Drug Development Through the Use of New Approach Methodologies.","authors":"M N Martinez, J P Mochel, K Allenspach, C Zdyrski, S Krishna, I Rusyn","doi":"10.1208/s12248-026-01263-6","DOIUrl":"10.1208/s12248-026-01263-6","url":null,"abstract":"<p><p>On November 2025, AAPS PharmSci 360 convened a symposium that included experts in the application of various types of New Approach Methodologies (NAMs). They shared their experiences and insights on topics that included microphysiological systems (MPS), the use of 3D organoids, and in silico tools. MPS systems were explored from the perspective of their testing and qualification through an academia-industry-government tissue chip testing consortium whose mission is to perform context-of-use-based testing of MPS and conduct comparative evaluations to support the use of MPS systems in safety assessments. 3D organoids were described and insights shared on how and when they may provide an appropriate tool for evaluating drug safety and effectiveness, and their use in supporting personalized medicine. Regarding in silico tools, examples were provided to describe their growing utility in predicting drug toxicity, population variability, and its potential benefits over traditional evidence-based toxicology. These tools include in silico models (e.g., physiologically based pharmacokinetic models), Artificial Intelligence (AI), and Machine Learning (ML) which, unlike other aspects of model informed drug development, reduce reliance on predefined models and allows for the integration of diverse sources of data. Computationally, these tools can generate predictions in hours where it would otherwise have taken weeks or months (and extensive experimentation). Within this meeting report, we highlight the key issues discussed during that symposium and share additional aspects to consider when developing a NAMs-based roadmap for specific contexts of use.</p>","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":"28 4","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13334498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148058201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}