Pub Date : 2024-10-29DOI: 10.1016/j.addr.2024.115471
María J. Blanco-Prieto, Elisa Garbayo
No Abstract
无摘要
{"title":"Preface: RNA delivery technologies: From concept toward the clinic","authors":"María J. Blanco-Prieto, Elisa Garbayo","doi":"10.1016/j.addr.2024.115471","DOIUrl":"https://doi.org/10.1016/j.addr.2024.115471","url":null,"abstract":"No Abstract","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":null,"pages":null},"PeriodicalIF":16.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-29DOI: 10.1016/j.addr.2024.115470
Tingting Yu, Xiang Zhong, Dongyu Li, Jingtan Zhu, Valery V. Tuchin, Dan Zhu
Advanced optical imaging provides a powerful tool for the structural and functional analysis of tissues with high resolution and contrast, but the imaging performance decreases as light propagates deeper into the tissue. Tissue optical clearing technique demonstrates an innovative way to realize deep-tissue imaging and have emerged substantially in the last two decades. Here, we briefly reviewed the basic principles of tissue optical clearing techniques in the view of delivery strategies via either free diffusion or external forces-driven advection, and the commonly-used optical techniques for monitoring kinetics of clearing agents in tissue, as well as their ex vivo to in vivo applications in multiple biomedical research fields. With future efforts on the even distribution of both clearing agents and probes, excavation of more effective clearing agents, and automation of tissue clearing processes, tissue optical clearing should provide more insights into the fundamental questions in biological events clinical diagnostics.
{"title":"Delivery and kinetics of immersion optical clearing agents in tissues: Optical imaging from ex vivo to in vivo","authors":"Tingting Yu, Xiang Zhong, Dongyu Li, Jingtan Zhu, Valery V. Tuchin, Dan Zhu","doi":"10.1016/j.addr.2024.115470","DOIUrl":"https://doi.org/10.1016/j.addr.2024.115470","url":null,"abstract":"Advanced optical imaging provides a powerful tool for the structural and functional analysis of tissues with high resolution and contrast, but the imaging performance decreases as light propagates deeper into the tissue. Tissue optical clearing technique demonstrates an innovative way to realize deep-tissue imaging and have emerged substantially in the last two decades. Here, we briefly reviewed the basic principles of tissue optical clearing techniques in the view of delivery strategies via either free diffusion or external forces-driven advection, and the commonly-used optical techniques for monitoring kinetics of clearing agents in tissue, as well as their <em>ex vivo</em> to <em>in vivo</em> applications in multiple biomedical research fields. With future efforts on the even distribution of both clearing agents and probes, excavation of more effective clearing agents, and automation of tissue clearing processes, tissue optical clearing should provide more insights into the fundamental questions in biological events clinical diagnostics.","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":null,"pages":null},"PeriodicalIF":16.1,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142541488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1016/j.addr.2024.115461
Johannes Bader, Finn Brigger, Jean-Christophe Leroux
Extracellular vesicles (EVs) are increasingly investigated for delivering nucleic acid (NA) therapeutics, leveraging their natural role in transporting NA and protein-based cargo in cell-to-cell signaling. Their synthetic counterparts, lipid nanoparticles (LNPs), have been developed over the past decades as NA carriers, culminating in the approval of several marketed formulations such as patisiran/Onpattro® and the mRNA-1273/BNT162 COVID-19 vaccines. The success of LNPs has sparked efforts to develop innovative technologies to target extrahepatic organs, and to deliver novel therapeutic modalities, such as tools for in vivo gene editing. Fueled by the recent advancements in both fields, this review aims to provide a comprehensive overview of the basic characteristics of EV and LNP-based NA delivery systems, from EV biogenesis to structural properties of LNPs. It addresses the primary challenges encountered in utilizing these nanocarriers from a drug formulation and delivery perspective. Additionally, biodistribution profiles, in vitro and in vivo transfection outcomes, as well as their status in clinical trials are compared. Overall, this review provides insights into promising research avenues and potential dead ends for EV and LNP-based NA delivery systems.
细胞外囊泡（EVs）在细胞间信号转导中运输核酸（NA）和基于蛋白质的货物方面发挥着天然作用，因此越来越多的研究将其用于递送核酸（NA）治疗药物。在过去的几十年里，人们开发了脂质纳米颗粒（LNPs）作为核酸载体，并最终批准了几种上市配方，如 patisiran/Onpattro® 和 mRNA-1273/BNT162 COVID-19 疫苗。LNPs 的成功促使人们努力开发针对肝外器官的创新技术，并提供新的治疗方式，如体内基因编辑工具。随着这两个领域的最新进展，本综述旨在从EV的生物发生到LNP的结构特性，全面概述EV和基于LNP的NA递送系统的基本特征。它从药物配制和递送的角度探讨了利用这些纳米载体所遇到的主要挑战。此外，还比较了生物分布特征、体外和体内转染结果以及它们在临床试验中的状况。总之，本综述为基于 EV 和 LNP 的 NA 给药系统提供了有前途的研究途径和潜在的死胡同。
{"title":"Extracellular vesicles versus lipid nanoparticles for the delivery of nucleic acids","authors":"Johannes Bader, Finn Brigger, Jean-Christophe Leroux","doi":"10.1016/j.addr.2024.115461","DOIUrl":"https://doi.org/10.1016/j.addr.2024.115461","url":null,"abstract":"Extracellular vesicles (EVs) are increasingly investigated for delivering nucleic acid (NA) therapeutics, leveraging their natural role in transporting NA and protein-based cargo in cell-to-cell signaling. Their synthetic counterparts, lipid nanoparticles (LNPs), have been developed over the past decades as NA carriers, culminating in the approval of several marketed formulations such as patisiran/Onpattro® and the mRNA-1273/BNT162 COVID-19 vaccines. The success of LNPs has sparked efforts to develop innovative technologies to target extrahepatic organs, and to deliver novel therapeutic modalities, such as tools for <em>in vivo</em> gene editing. Fueled by the recent advancements in both fields, this review aims to provide a comprehensive overview of the basic characteristics of EV and LNP-based NA delivery systems, from EV biogenesis to structural properties of LNPs. It addresses the primary challenges encountered in utilizing these nanocarriers from a drug formulation and delivery perspective. Additionally, biodistribution profiles, <em>in vitro</em> and <em>in vivo</em> transfection outcomes, as well as their status in clinical trials are compared. Overall, this review provides insights into promising research avenues and potential dead ends for EV and LNP-based NA delivery systems.","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":null,"pages":null},"PeriodicalIF":16.1,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-22DOI: 10.1016/j.addr.2024.115457
Márcia T. Rodrigues, Manuela E. Gomes
The editors regret the unintentional omission of two additional manuscripts from the original editorial note for this special issue. These review articles complement the existing research and add valuable perspectives, further enriching the ongoing discussions in the field, and enhancing the overall impact of the special issue. Thus, we have included a brief paragraph emphasizing the relevance of these works.
{"title":"Corrigendum to “Editorial: Advanced strategies to bridge the gap between inflammation and tissue regeneration” [Adv. Drug Deliv. Rev. 209 (2024) 115328]","authors":"Márcia T. Rodrigues, Manuela E. Gomes","doi":"10.1016/j.addr.2024.115457","DOIUrl":"https://doi.org/10.1016/j.addr.2024.115457","url":null,"abstract":"The editors regret the unintentional omission of two additional manuscripts from the original editorial note for this special issue. These review articles complement the existing research and add valuable perspectives, further enriching the ongoing discussions in the field, and enhancing the overall impact of the special issue. Thus, we have included a brief paragraph emphasizing the relevance of these works.","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":null,"pages":null},"PeriodicalIF":16.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1016/j.addr.2024.115460
Yu Seok Youn, Koen Raemdonck
Section snippets
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
{"title":"Editorial: Subcellular organelle-targeting of nanomaterials for enhancing therapeutic effectiveness","authors":"Yu Seok Youn, Koen Raemdonck","doi":"10.1016/j.addr.2024.115460","DOIUrl":"https://doi.org/10.1016/j.addr.2024.115460","url":null,"abstract":"<h2>Section snippets</h2><section><section><h2>Declaration of competing interest</h2>The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.</section></section>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":null,"pages":null},"PeriodicalIF":16.1,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1016/j.addr.2024.115458
Emerging studies have disclosed the pivotal role of cancer-associated microbiota in supporting cancer development, progression and dissemination, with the in-depth comprehending of tumor microenvironment. In particular, certain invasive bacteria that hide in various cells within the tumor tissues can render assistance to tumor growth and invasion through intricate mechanisms implicated in multiple branches of cancer biology. Thus, tumor-resident intracellular microbes are anticipated as next-generation targets for oncotherapy. This review is intended to delve into these internalized bacteria-driven cancer-promoting mechanisms and explore diversified antimicrobial therapeutic strategies to counteract the detrimental impact caused by these intruders, thereby improving therapeutic benefit of antineoplastic therapy.
{"title":"Progress of tumor-resident intracellular bacteria for cancer therapy","authors":"","doi":"10.1016/j.addr.2024.115458","DOIUrl":"10.1016/j.addr.2024.115458","url":null,"abstract":"<div><div>Emerging studies have disclosed the pivotal role of cancer-associated microbiota in supporting cancer development, progression and dissemination, with the in-depth comprehending of tumor microenvironment. In particular, certain invasive bacteria that hide in various cells within the tumor tissues can render assistance to tumor growth and invasion through intricate mechanisms implicated in multiple branches of cancer biology. Thus, tumor-resident intracellular microbes are anticipated as next-generation targets for oncotherapy. This review is intended to delve into these internalized bacteria-driven cancer-promoting mechanisms and explore diversified antimicrobial therapeutic strategies to counteract the detrimental impact caused by these intruders, thereby improving therapeutic benefit of antineoplastic therapy.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":null,"pages":null},"PeriodicalIF":15.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1016/j.addr.2024.115459
In the past decade, biopharmaceutical research and development in China has been notably boosted by government policies, regulatory initiatives and increasing investments in life sciences. With regulatory agency acting as a strong driver, model-informed drug development (MIDD) is transitioning rapidly from an academic pursuit to a critical component of innovative drug discovery and development within the country. In this article, we provided a cross-sectional summary on the current status of MIDD implementations across early and late-stage drug development in China, illustrated by case examples. We also shared insights into regulatory policy development and decision-making. Various modeling and simulation approaches were presented across a range of applications. Furthermore, the challenges and opportunities of MIDD in China were discussed and compared with other regions where these practices have a more established history. Through this analysis, we highlighted the potential of MIDD to enhance drug development efficiency and effectiveness in China’s evolving pharmaceutical landscape.
{"title":"Current status and challenges of model-informed drug discovery and development in China","authors":"","doi":"10.1016/j.addr.2024.115459","DOIUrl":"10.1016/j.addr.2024.115459","url":null,"abstract":"<div><div>In the past decade, biopharmaceutical research and development in China has been notably boosted by government policies, regulatory initiatives and increasing investments in life sciences. With regulatory agency acting as a strong driver, model-informed drug development (MIDD) is transitioning rapidly from an academic pursuit to a critical component of innovative drug discovery and development within the country. In this article, we provided a cross-sectional summary on the current status of MIDD implementations across early and late-stage drug development in China, illustrated by case examples. We also shared insights into regulatory policy development and decision-making. Various modeling and simulation approaches were presented across a range of applications. Furthermore, the challenges and opportunities of MIDD in China were discussed and compared with other regions where these practices have a more established history. Through this analysis, we highlighted the potential of MIDD to enhance drug development efficiency and effectiveness in China’s evolving pharmaceutical landscape.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":null,"pages":null},"PeriodicalIF":15.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.addr.2024.115456
The ability of three-dimensional (3D) bioprinting to fabricate biomimetic organ and disease models has been recognised to be promising for drug discovery and development as 3D bioprinted models can better mimic human physiology compared to two-dimensional (2D) cultures and animal models. This is useful for target selection where disease models can be studied to understand disease pathophysiology and identify disease-linked compounds. Lead identification and preclinical studies also benefit from 3D bioprinting as 3D bioprinted models can be utilised in high-throughput screening (HTS) systems and to produce efficacy and safety data that closely resembles clinical observations. Although no published applications of 3D bioprinting in clinical trials were found, there are two clinical trials planning to evaluate the predictive ability of 3D bioprinted models by comparing human and model responses to the same chemotherapy. Overall, this review provides a comprehensive summary of the latest applications of 3D bioprinting in drug discovery and development.
{"title":"Recent applications of three-dimensional bioprinting in drug discovery and development","authors":"","doi":"10.1016/j.addr.2024.115456","DOIUrl":"10.1016/j.addr.2024.115456","url":null,"abstract":"<div><div>The ability of three-dimensional (3D) bioprinting to fabricate biomimetic organ and disease models has been recognised to be promising for drug discovery and development as 3D bioprinted models can better mimic human physiology compared to two-dimensional (2D) cultures and animal models. This is useful for target selection where disease models can be studied to understand disease pathophysiology and identify disease-linked compounds. Lead identification and preclinical studies also benefit from 3D bioprinting as 3D bioprinted models can be utilised in high-throughput screening (HTS) systems and to produce efficacy and safety data that closely resembles clinical observations. Although no published applications of 3D bioprinting in clinical trials were found, there are two clinical trials planning to evaluate the predictive ability of 3D bioprinted models by comparing human and model responses to the same chemotherapy. Overall, this review provides a comprehensive summary of the latest applications of 3D bioprinting in drug discovery and development.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":null,"pages":null},"PeriodicalIF":15.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18DOI: 10.1016/j.addr.2024.115448
Hematological cancers encompass a diverse group of malignancies affecting the blood, bone marrow, lymph nodes, and spleen. These disorders present unique challenges due to their complex etiology and varied clinical manifestations. Despite significant advancements in understanding and treating hematological malignancies, innovative therapeutic approaches are continually sought to enhance patient outcomes.
This review highlights the application of RNA nanoparticles (RNA-NPs) in the treatment of hematological cancers. We delve into detailed discussions on in vitro and preclinical studies involving RNA-NPs for adult patients, as well as the application of RNA-NPs in pediatric hematological cancer. The review also addresses ongoing clinical trials involving RNA-NPs and explores the emerging field of CAR-T therapy engineered by RNA-NPs. Finally, we discuss the challenges still faced in translating RNA-NP research to clinics.
{"title":"RNA-loaded nanoparticles for the treatment of hematological cancers","authors":"","doi":"10.1016/j.addr.2024.115448","DOIUrl":"10.1016/j.addr.2024.115448","url":null,"abstract":"<div><p>Hematological cancers encompass a diverse group of malignancies affecting the blood, bone marrow, lymph nodes, and spleen. These disorders present unique challenges due to their complex etiology and varied clinical manifestations. Despite significant advancements in understanding and treating hematological malignancies, innovative therapeutic approaches are continually sought to enhance patient outcomes.</p><p>This review highlights the application of RNA nanoparticles (RNA-NPs) in the treatment of hematological cancers. We delve into detailed discussions on <em>in vitro</em> and preclinical studies involving RNA-NPs for adult patients, as well as the application of RNA-NPs in pediatric hematological cancer. The review also addresses ongoing clinical trials involving RNA-NPs and explores the emerging field of CAR-T therapy engineered by RNA-NPs. Finally, we discuss the challenges still faced in translating RNA-NP research to clinics.</p></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":null,"pages":null},"PeriodicalIF":15.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0169409X24002709/pdfft?md5=394e09e402e81b0f66099b1b06ffb9f2&pid=1-s2.0-S0169409X24002709-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142271869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1016/j.addr.2024.115446
In the past decade, nucleic acid therapies have seen a boon in development and clinical translation largely due to advances in nanotechnology that have enabled their safe and targeted delivery. Nanoparticles can protect nucleic acids from degradation by serum enzymes and can facilitate entry into cells. Still, achieving endosomal escape to allow nucleic acids to enter the cytoplasm has remained a significant barrier, where less than 5% of nanoparticles within the endo-lysosomal pathway are able to transfer their cargo to the cytosol. Lipid-based drug delivery vehicles, particularly lipid nanoparticles (LNPs), have been optimized to achieve potent endosomal escape, and thus have been the vector of choice in the clinic as demonstrated by their utilization in the COVID-19 mRNA vaccines. The success of LNPs is in large part due to the rational design of lipids that can specifically overcome endosomal barriers. In this review, we chart the evolution of lipid structure from cationic lipids to ionizable lipids, focusing on structure–function relationships, with a focus on how they relate to endosomal escape. Additionally, we examine recent advancements in ionizable lipid structure as well as discuss the future of lipid design.
{"title":"Breaking the final barrier: Evolution of cationic and ionizable lipid structure in lipid nanoparticles to escape the endosome","authors":"","doi":"10.1016/j.addr.2024.115446","DOIUrl":"10.1016/j.addr.2024.115446","url":null,"abstract":"<div><div>In the past decade, nucleic acid therapies have seen a boon in development and clinical translation largely due to advances in nanotechnology that have enabled their safe and targeted delivery. Nanoparticles can protect nucleic acids from degradation by serum enzymes and can facilitate entry into cells. Still, achieving endosomal escape to allow nucleic acids to enter the cytoplasm has remained a significant barrier, where less than 5% of nanoparticles within the <em>endo</em>-lysosomal pathway are able to transfer their cargo to the cytosol. Lipid-based drug delivery vehicles, particularly lipid nanoparticles (LNPs), have been optimized to achieve potent endosomal escape, and thus have been the vector of choice in the clinic as demonstrated by their utilization in the COVID-19 mRNA vaccines. The success of LNPs is in large part due to the rational design of lipids that can specifically overcome endosomal barriers. In this review, we chart the evolution of lipid structure from cationic lipids to ionizable lipids, focusing on structure–function relationships, with a focus on how they relate to endosomal escape. Additionally, we examine recent advancements in ionizable lipid structure as well as discuss the future of lipid design.</div></div>","PeriodicalId":7254,"journal":{"name":"Advanced drug delivery reviews","volume":null,"pages":null},"PeriodicalIF":15.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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