Molecular Pharmaceutics最新文献

{"title":"Voices in Molecular Pharmaceutics: Meet Professor Satyavrata Samavedi, Who Spins Polymeric Drug-Carriers to Improve Stability and Tailor Drug Release.","authors":"Satyavrata Samavedi","doi":"10.1021/acs.molpharmaceut.5c01137","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.5c01137","url":null,"abstract":"","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ever-Increasing Role of Computational Tools in Solid-State Pharmaceutics: Advancing Drug Development with Enhanced Molecular Understanding and Risk Assessment","authors":"Abhishek Sharma,&nbsp;Saurabh Shah,&nbsp;Suraj Wagh,&nbsp;Giriraj Pandey,&nbsp;Amit Kumar Pradhan,&nbsp;Shalini Shukla,&nbsp;Sajesh P. Thomas,&nbsp;Amol G. Dikundwar* and Saurabh Srivastava*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00296","DOIUrl":"10.1021/acs.molpharmaceut.5c00296","url":null,"abstract":"<p >The field of solid-state pharmaceutics comprises a broad range of investigations into various structural aspects of pharmaceutical solids, establishing a rational structure–property correlation. These solid systems allow the tunability of the physicochemical properties, such as solubility and dissolution, which in turn influence the pharmacokinetic and pharmacodynamic parameters of the active pharmaceutical ingredient (API). Hence, the study of physical characteristics of an API, e.g., different crystalline vs amorphous forms, molecular complexes such as solvates, cocrystals, coamorphous and polymeric dispersions, etc., along with an understanding of interconversion of one form into the other forms, a basis for successful product development. A product’s time to market is typically prolonged by the time it takes to complete the development aspects of the product compared to the time required for lead optimization, i.e., for identification of the right chemical entity. Recent advancements in computational techniques have revolutionized the field of solid-state pharmaceutics in understanding molecular-level mechanisms while significantly cutting down the time and resources needed for drug development. Over the years, there have been increasing contributions of the computational tools demonstrated by the successful implementation of computationally obtained prediction models validated and benchmarked against conventional experimental results. Examples include application of Density Functional Theory, molecular dynamics, and artificial neural networks to screen coformers, polymers for cocrystallization, and ASD formation; crystal structure prediction to select correct polymorphs with desired characteristics, and also to predict interactions with excipients. It has been proven that computational tools can effectively troubleshoot and address issues associated with the translational output of solid-state pharmaceutics. In this article, we present a series of case studies highlighting the use of modern computational techniques applied to critical stages of API, preformulation, and formulation developments contributing to accelerated drug development, while conserving on chemicals, solvents, and man-hours. Crucially, a concise sequential workflow is presented that explains the benefits of each of the computational methods in the toolbox, with the goal of assisting the readers in the specific application of these techniques, as per their requirements in the solid-state pharmaceutics domain.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5165–5192"},"PeriodicalIF":4.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144843864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D Printing via Melt Extrusion Deposition Facilitates the Use of Extended-Release Profiles in Preclinical Research and Development","authors":"Miao Jin,&nbsp;Xianghao Zuo,&nbsp;Simone M. Blattner,&nbsp;Sandra Frankenreiter,&nbsp;Markus Metzger,&nbsp;Jingyu Lu,&nbsp;Takuya Kikuchi,&nbsp;Katsuyoshi Fujimoto,&nbsp;Atsushi Sakurai,&nbsp;Gang Wang,&nbsp;Achim Grube*,&nbsp;Georg Boeck* and Jun Lu*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00413","DOIUrl":"10.1021/acs.molpharmaceut.5c00413","url":null,"abstract":"<p >Traditional methods for developing modified-release (MR) formulations involve numerous iterations and large quantities of drug substances, which pose considerable challenges in exploration settings. Given the growing necessity for modified-release (MR) formulations in the pharmaceutical industry, particularly during the preclinical research and development phase, modified-release strategies may serve as attractive alternatives to discontinuing clinical development and could mitigate the costs and time associated with identifying new drug candidates. This study specifically explores the application of melt extrusion deposition (MED) 3D printing technology as a rapid prototyping platform for creating extended-release (ER) oral dosage forms tailored for the preclinical phase. Using the model compound BI 894416, the study demonstrated that MED 3D printing enables precise control over drug release profiles through both structural and compositional designs. The physicochemical analysis conducted during the 3D printing process revealed no degradation or compatibility issues. <i>In vivo</i> pharmacokinetic (PK) studies in rats and dogs validated the extended-release (ER) performance of BI 894416, with <i>t</i>_max values of 2–4 h in rats and 5 h in dogs. The ER tablets achieved prolonged plasma exposure and reduced peak-to-trough fluctuations compared to those of immediate-release (IR) formulations (ER: 144 versus IR: 929 in dogs). A Level A <i>in vitro–in vivo</i> correlation (IVIVC) was established, demonstrating strong alignment between <i>in vitro</i> dissolution and <i>in vivo</i> absorption up to 4 h, with a minor lag time observed. These results further confirmed the likely absorption of BI 894416 in the upper gastrointestinal (GI) tract and the potentially ascending colon. These findings highlight the potential of MED 3D printing to streamline the development of MR formulations in preclinical settings, offering a flexible, efficient, and material-sparing alternative to conventional approaches.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5428–5442"},"PeriodicalIF":4.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Developments of RNA Vaccines and Therapeutics: Reagents, Formulations, and Characterization","authors":"Mhd Anas Tomeh*,&nbsp;Rachel K. Smith and Allan Watkinson,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00670","DOIUrl":"10.1021/acs.molpharmaceut.5c00670","url":null,"abstract":"<p >The past few years have shown significant clinical success for RNA vaccines in humans. The spread of SARS-CoV-2 into a global pandemic has boosted the transition of many RNAs to clinical trials and accelerated the development process of various types of RNA-based therapeutics, including vaccines, not only for respiratory illnesses but also for a wide range of diseases. Many studies have designed promising RNAs in various forms (small interfering RNA, mRNA, and self-amplifying RNA) or presented novel nanocarriers to maximize the performance of RNA-based therapeutics. There are several crucial aspects that must be covered during RNA vaccine development, including RNA design and synthesis, formulation optimization, and characterization. This paper aims to shed light on RNA vaccines and therapeutics with various properties and applications and provide a comprehensive review of the recent developments of formulation, analytics, and characterization studies.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5257–5282"},"PeriodicalIF":4.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Preclinical Evaluation of CDH17-Specific ImmunoPET Imaging in Colorectal Cancers","authors":"Xinbing Pan,&nbsp;Qianyun Wu,&nbsp;You Zhang,&nbsp;Dongsheng Xu,&nbsp;Xinyuan Zhou,&nbsp;Lianghua Li,&nbsp;Cheng Wang,&nbsp;Weijun Wei,&nbsp;Shuxian An*,&nbsp;Gang Huang* and Jianjun Liu*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00525","DOIUrl":"10.1021/acs.molpharmaceut.5c00525","url":null,"abstract":"<p >Cadherin 17 (CDH17) is found to be abnormally expressed in colorectal cancer (CRC) and linked to a prognosis. Its consistent presence in both primary and metastatic CRC positions it as a promising biomarker. This study aims to develop CDH17-targeted immuno-positron emission tomography (immunoPET) probes and evaluate their potential for diagnosing CRC. Immunohistochemical (IHC) staining was performed on CRC tissue microarrays to analyze CDH17 expression. The CDH17 expression of CRC cells (LS174T, HCT116, and Caco-2) and pancreatic cancer cells (AsPC-1) was detected by flow cytometry. CDH17-specific nanobodies (i.e., CDH1) were produced and labeled with gallium-68 (⁶⁸Ga) and fluorine-18 (¹⁸F) to generate imaging probes. ImmunoPET imaging was conducted to evaluate the probes’ diagnostic abilities in tumor models. IHC staining of CRC tissue microarrays demonstrated an elevated expression of CDH17 in malignant tissues relative to that in adjacent normal tissues. Flow cytometry showed that CDH17 was expressed on the surface of Caco-2 and AsPC-1 cells but not on the surface of HCT116 or LS174T cells. ImmunoPET imaging with [⁶⁸Ga]Ga-NOTA-CDH1 successfully visualized CDH17 expression in Caco-2 tumors, whereas no significant tracer uptake was observed in HCT116 tumors. [¹⁸F]AlF-RESCA-CDH1 immunoPET imaging demonstrated CDH17 expression in both LS174T and AsPC-1 tumors. IHC confirmed CDH17 expression on the membrane of Caco-2 and AsPC-1 cells with no significant expression on HCT116 cells. CDH17 expression was evident in the LS174T tumor capsule tissue. In this study, we developed three nanobody-based tracers targeting CDH17, of which [⁶⁸Ga]Ga-NOTA-CDH1 and [¹⁸F]AlF-RESCA-CDH1 noninvasively demonstrated CDH17 expression in preclinical models.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5512–5522"},"PeriodicalIF":4.5,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Pectin-Based Delivery Nanoplatform with an Optimized Tradeoff between Active Targeting and Drug Loading for Hepatocellular Carcinoma Treatment","authors":"Yang Qin,&nbsp;Zemin Cao,&nbsp;Jiaqi Wang,&nbsp;Chaoyi Liu,&nbsp;Chonghao Liao,&nbsp;Bo Huang,&nbsp;Qianwen Liu,&nbsp;Bangjun Xia,&nbsp;Qian Ning,&nbsp;Hua Wei* and Cui-Yun Yu*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00594","DOIUrl":"10.1021/acs.molpharmaceut.5c00594","url":null,"abstract":"<p >The presence of multivalent reactive groups in the structure of natural polysaccharides enables diverse modifications toward advanced nanomedicines with integrated functionalities for enhanced cancer therapy; therefore, a polysaccharide-based nanoplatform with an optimized trade-off between multifunctionalities for a maximized therapeutic efficiency has been always a long-term research interest, which, however, remains relatively unexplored. We report herein pectin-based delivery nanoplatforms with an optimized trade-off between active targeting and drug loading for chemo-immunotherapy of hepatocellular carcinoma (HCC). Specifically, the targeting moiety of pectin, galactose, is subjected to partial oxidization to an aldehyde function that enables the simultaneous modulation of active targeting properties and drug conjugation capacity by the degree of oxidation, affording pectin-based polymer prodrugs OP2-DOX, OP6-DOX, and OP10-DOX with three different degrees of oxidation. OP6-DOX nanoprodrugs (NPs) are subsequently screened to be the optimal nanoplatform in terms of the mean hydrodynamic size, colloidal stability, cellular uptake capacity, and in vitro cytotoxicity profiles. Most importantly, OP6-DOX NPs achieve a tumor inhibition rate (TIR) of 86.8%, which induces the efficient polarization of tumor-associated macrophages (TAMs) from M2 to M1 and natural killer (NK) cell recruitment in HCC tissues. Overall, the outcomes of this study could serve as an important theoretical guidance on the active targeting and drug loading trade-off modulation of polysaccharide-based nanoplatforms for cancer chemo-innate immunotherapy.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5555–5566"},"PeriodicalIF":4.5,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Insight on Pillararene-Functionalized Mesoporous Silica Nanoparticles for Targeted Drug Delivery and Theranostics in Cancer","authors":"Amit Kumar,&nbsp;Anchal Karwal and Awesh K Yadav*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00729","DOIUrl":"10.1021/acs.molpharmaceut.5c00729","url":null,"abstract":"<p >Pillararenes, a novel class of pillar-shaped macrocyclic hosts, have expanded from the sole domain of supramolecular chemistry and have attracted immense interest among scientists due to their remarkable characteristics, such as symmetrical structures, electron-rich cavities, tunable functionalization, and unique host–guest interactions. Based on host–guest chemistry, in collaboration with other molecular systems, researchers have focused on the construction and development of pillararene-based mesoporous silica nanoparticles (MSNs). Pillararene-functionalized MSNs have gained considerable attention due to their distinct topological and chemical structures, as well as favorable physicochemical properties. This review discusses the synthesis of pillararene–MSN hybrid systems by integrating pillararenes with MSNs, which offer large surface areas and abundant active sites. Furthermore, recent advancements in their applications are explored, including drug delivery, molecular recognition, biosensing, imaging, and stimuli-responsive cargo release triggered by pH, competitive agents, temperature, near-infrared light, and acetylcholine. We also highlighted current challenges and future perspectives for the clinical translation of pillararene–MSN-based drug delivery systems.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5303–5315"},"PeriodicalIF":4.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hinge Truncation to Improve Aggregation Kinetics and Thermal Stability of an Antibody Fab Fragment","authors":"Cheng Zhang,&nbsp;Kersti Karu and Paul A. Dalby*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00358","DOIUrl":"10.1021/acs.molpharmaceut.5c00358","url":null,"abstract":"<p >The hinge region of antibody fragments plays a crucial role in their stability and aggregation properties. In this study, we investigated the effects of hinge truncations on the thermal stability and aggregation propensity of the A33 Fab antibody fragment. Eight Fab variants were engineered by introducing stop codons to truncate 1–8 residues at the hinge region (heavy chain residues 221–228). These variants were then expressed, purified, and characterized in terms of stability and aggregation propensity using SDS-PAGE, SEC-HPLC, LC–MS, and thermal stability assays. Our findings demonstrate that truncating the hinge region can enhance the thermal stability and reduce the aggregation of Fab fragments, and that progressive truncations identified an optimal hinge length for stability. Notably, the 227TGA variant exhibited a significant 14.5% reduction in aggregation rate compared to the wild type, without compromising thermal stability. By contrast, 221TGA removed all of the hinge and reduced the aggregation rate by 13%, but also decreased the thermal stability. These results suggest that hinge truncation is a promising strategy for improving the developability of therapeutic antibody Fab fragments by mitigating some of the stability issues associated with aggregation.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5389–5399"},"PeriodicalIF":4.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.5c00358","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stimuli-Responsive and Receptor-Targeted Carbon Nanotubes for Multimodal Cancer Therapy and Diagnosis","authors":"Sourabh Tapekar,&nbsp;Anish Dhuri,&nbsp;Priti Paul,&nbsp;Rahul Nair,&nbsp;Tanmoy Kanp,&nbsp;Bharath Manoharan,&nbsp;Anitha Sriram,&nbsp;Khushi Rode,&nbsp;Niveditha Manne and Pankaj Kumar Singh*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00787","DOIUrl":"10.1021/acs.molpharmaceut.5c00787","url":null,"abstract":"<p >Carbon nanotubes (CNTs) are nanoscale tubular structures with significant potential as multifunctional delivery systems in the field of biomedicine, especially regarding cancer diagnosis and treatment. Due to their remarkable physicochemical properties, such as exceptional mechanical strength, high aspect ratio, excellent electrical and thermal conductivity, and lightweight nature, they are considered ideal candidates for incorporation into biomedical applications. The chemically adaptable surfaces of CNTs allow for functionalization with a variety of guest molecules, including drugs, imaging agents, and siRNA, thereby improving their biocompatibility and therapeutic effectiveness. To achieve targeted tumor delivery and retention, CNTs can be further modified with peptides, organic ligands, carbohydrates, or polymers, each tailored to designated biomedical functions. Stimuli-responsive CNT systems, classified as either endogenous or exogenous, have shown significant promise in enhancing therapeutic precision. This review examines the structural characteristics of CNTs and their applications as nanocarriers for targeted anticancer drug delivery. It highlights recent advancements in the development of receptor-targeted and stimuli-responsive CNT-based systems for improved cancer diagnostics and treatments. Additionally, it evaluates a range of CNT-enabled treatment modalities, including chemotherapy, photothermal and photodynamic therapy, radiotherapy, and biosensing, while critically assessing their related cytotoxic effects.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5669–5696"},"PeriodicalIF":4.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Food Additives Inhibit Intestinal Drug Transporters but Have Limited Effect on In Vitro Drug Permeability","authors":"Laura Suominen,&nbsp;Emilia Stenberg,&nbsp;Noora Sjöstedt and Heidi Kidron*,&nbsp;","doi":"10.1021/acs.molpharmaceut.5c00705","DOIUrl":"10.1021/acs.molpharmaceut.5c00705","url":null,"abstract":"<p >Food additives are chemical substances that are added to processed food to improve its flavor, texture, or appearance. Food additives can inhibit intestinal transporters, such as breast cancer resistance protein (BCRP), multidrug resistance associated protein 2 (MRP2), organic anion transporting polypeptide 2B1 (OATP2B1), and P-glycoprotein (P-gp). This inhibition could potentially affect the absorption of their substrate drugs and cause unwanted food–drug interactions. In this study, 22 food additives were evaluated for their impact on BCRP, MRP2, OATP2B1, and P-gp transport. The inhibition potency toward intestinal transporters was first studied using membrane vesicles and HEK293 cells. In these assays, four food additives (beta-carotene, butylated hydroxytoluene, dodecyl gallate, and octyl gallate) were identified as inhibitors. Seven food additives (allura red AC, beta-carotene, brilliant blue FCF, carmoisine, neohesperidin DC, sunset yellow FCF, and tartrazine), which were identified as inhibitors either in the current study or in our previous studies, were selected for Caco-2 permeability studies to further evaluate their possible effect on drug absorption. None of the selected food additives showed any effect on sulfasalazine permeability. These results suggest that the selected food additives are inhibitors of the studied transporters but are unlikely to cause clinically significant intestinal transporter-mediated drug interactions.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":"22 9","pages":"5627–5637"},"PeriodicalIF":4.5,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.molpharmaceut.5c00705","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}