{"title":"CpG ODNs: Precision Immunotherapy and Recent Trends in Nano-Enabled Nucleotide Delivery.","authors":"Anamika Verma, Nitisha Beniwal, Chandra Lekha Putta, Sasvat Sayee Ram Ramesh, Sajmina Khatun, Soumitra Pathak, Tomohiko Yamazaki, Aravind Kumar Rengan","doi":"10.1615/CritRevTherDrugCarrierSyst.2025057385","DOIUrl":"https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2025057385","url":null,"abstract":"<p><p>Synthetic ODNs (oligodeoxynucleotides) with immunostimulatory CpG (cytosine-phosphate-guanine) motifs induce an immune-mediated response, activating B cells, T cells, natural killer cells, and competent antigen-presenting cells (APCs). This activation stimulates T helper 1 (TH1) cell activity and induces the release of pro-inflammatory cytokines, making CpG ODNs effective as immunoprotectants, vaccination adjuvants, and antiallergens. The findings that toll-like receptors (TLRs) integrating both adaptive and innate immunity prompted greater interest in TLRs' immunostimulatory capabilities, activators, and effects. Potent adjuvants such as TLR agonists are crucial for effective vaccine formulations because they stimulate dendritic cells (DCs) to activate specific T-cells. Non-methylated cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) have proven to be successful adjuvants central to TLR9 receptor activation, facilitating the necessary innate immune signaling cascade. Artificially synthesized CpG ODNs are durable, cost-effective, and easy to produce, making them promising candidates for advanced studies on innate immunity and immunoprotection mechanisms. This review discusses CpG ODN-mediated immunomodulatory interventions, their potential as biomedical tools for specific diseases, recent advances in their applications, and related clinical trials from the past decade.</p>","PeriodicalId":50614,"journal":{"name":"Critical Reviews in Therapeutic Drug Carrier Systems","volume":"43 1","pages":"57-95"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195580","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":"Plant-Based Exosomes: Insights and Therapeutic Applications.","authors":"Chandrika Kumari Bodala, Aliya Parveen, Bhagya Lakshmi Gogireddy, S Priya, Lankalapalli Srinivas","doi":"10.1615/CritRevTherDrugCarrierSyst.2025057676","DOIUrl":"https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2025057676","url":null,"abstract":"<p><p>Exosomes, a type of extracellular vesicle (EV), have received much attention in recent years for their potential in drug delivery systems and therapeutic applications. These nano-sized vesicles, secreted by various plant and animal species, serve as natural carriers of bioactive compounds, including proteins, lipids, and RNA, facilitating intercellular communication between tissue and cells and influencing physiological processes. Stahl and group discovered exosomes from maturing mammalian reticulocytes (immature red blood cells) in 1983, followed by Johnstone and colleagues in 1987, who named them exosomes. Animal-derived exosomes are a popular choice for small-molecule drug delivery due to their biocompatibility and homing properties in various domains, including biology and medicine. After animal-derived exosomes, researchers focused on plant-based exosomes and found several good sources of exosomes from different fruits, vegetables, leaves, and other parts of plants that have different effects like anticancer, anti-inflammatory, antioxidants, and so on. Plant-derived exosomes are also used as carriers for different drugs to treat disease. This review examines the biological component, biogenesis of plant exosomes, their sources, and the methodologies employed for their isolation and purification. We also explore the evaluation techniques for characterizing their biological components, such as proteins and lipids. Furthermore, we discuss the applications of plant-derived exosomes in drug delivery, highlighting their application in different disorders with some research references, including biocompatibility, stability, and targeted delivery. Additionally, this review also addresses the challenges associated with plant-based exosomes in different stages of research including isolation and purification, standardization, optimization, drug loading, and so on. The goal of this in-depth review is to provide insight into the current status of research on exosomes derived from plants and the ways that they could advance in drug delivery systems.</p>","PeriodicalId":50614,"journal":{"name":"Critical Reviews in Therapeutic Drug Carrier Systems","volume":"43 1","pages":"1-55"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195782","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}
Sunil Bharti, Gajanand Sharma, Amita Sarwal, Om Parkash Katare
{"title":"Nano Lipid Carriers (NLCs): Potential and Promises in Drug Delivery.","authors":"Sunil Bharti, Gajanand Sharma, Amita Sarwal, Om Parkash Katare","doi":"10.1615/CritRevTherDrugCarrierSyst.2025056948","DOIUrl":"https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2025056948","url":null,"abstract":"<p><p>Transdermal drug delivery offers several benefits compared with oral delivery, including the bypassing of first-pass metabolism, the ability to target active ingredients for localized effects, and improved patient compliance. Nevertheless, achieving transdermal delivery requires addressing the challenges of permeation through the skin barrier at various levels, including the skin surface, epidermis, dermis, and hypodermis. Nanostructured lipid carriers (NLCs) were invented in the early 1990s as a second generation of lipidic nano carriers. The NLCs are favored over SLNs because they offer greater stability, allowing for higher drug loading, maintaining a consistent drug release profile over time, and preventing gelation during storage. This article aims to offer brief summary of nano system, including the various types of NLCs, their composition, production methods, physiochemical evaluation techniques, mechanistic pathways, recent advancements in transdermal applications, and the use of these carriers for both local and systemic effects. Additionally, it will cover updates on patents and the scalability of NLCs in industrial settings. We also examine important factors for standardization, significant scale-up challenges, and the future prospective of NLCs. Over the past 10 years, the extensive work on NLCs is evident in numerous research reports, consisting patents related to their development, providing a deeper understanding of this growing area of innovation. NLCs serve as an excellent \"safe\" nano-carrier because of their biodegradable nature and hold significant potential to address the challenges associated with transdermal delivery.</p>","PeriodicalId":50614,"journal":{"name":"Critical Reviews in Therapeutic Drug Carrier Systems","volume":"43 1","pages":"97-142"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195558","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":"Nanomedicine-Mediated Therapies to Target Cancer Stem Cells: An Emerging Technology.","authors":"Sana Kauser, Irzam Haroon, Saima Wajid","doi":"10.1615/CritRevTherDrugCarrierSyst.2025047123","DOIUrl":"https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2025047123","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) are a category of cancer cells endowed with the ability to renew themselves, undergo unregulated growth, and exhibit a differentiation capacity akin to that of normal stem cells. CSCs have been linked with tumor metastasis and cancer recurrence due to their ability to elude immune monitoring. As a result, targeting CSCs specifically may improve the efficacy of cancer therapy. Recently, the use of nanotechnology has gained substantial attention in cancer treatment. Cancer nanotechnology is an interdisciplinary field of research where nano-biotechnology fosters the combination of diagnostics and treatments, which is an important part of a personalized approach to cancer treatment. Thus, using nanoparticles against cancer cells and CSCs simultaneously may lead to the development of a better therapeutic intervention to eradicate cancer. In this review, we describe recent achievements in cancer therapy targeting CSCs of various malignancies, such as lung cancer, breast cancer, colorectal cancer, and prostate cancer, by using nanotechnology.</p>","PeriodicalId":50614,"journal":{"name":"Critical Reviews in Therapeutic Drug Carrier Systems","volume":"42 6","pages":"1-44"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024707","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}
D Santhakumar, R Prasanna, M Sivakumar, S Aswath, P S Arthy, R Rajesh Kanna
{"title":"Enhanced Early Brain Tumor Detection Crossing Blood-Brain Barrier through MRI Images Using Berkeley Wavelet-Transformation-Based Segmentation.","authors":"D Santhakumar, R Prasanna, M Sivakumar, S Aswath, P S Arthy, R Rajesh Kanna","doi":"10.1615/CritRevTherDrugCarrierSyst.2025055526","DOIUrl":"https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2025055526","url":null,"abstract":"<p><p>Brain tumor is one of the reasons for several mortality cases in hospitals. Early detection and diagnosis of brain tumors are necessary to cure the disease early. The extraction of the tumor from the brain's magnetic resonance image (MRI) is considered to be a difficult task when done by clinical experts, and it is also pretty time-consuming. These drawbacks can be overcome by using computer vision-based technologies. The proposed method detects brain tumor crossing the blood-brain barrier (BBB) through MRI images by using Berkeley wavelet transformation (BWT) for segmenting the affected areas. Support vector machine (SVM) is used for classification purpose by which the classification process is divided into two different categories namely, the tumor affected and tumor non-affected parts. Initially, the acquired image is converted to a greyscale from RGB. Then, image segmentation is done. During the image segmentation, morphological operations are carried out. Two morphological operations have been used in the proposed system. They are erosion and dilation. Both these techniques are used for edge detection. In erosion, the pixels are removed from the edges of the tumor image. In dilation, pixels are added at the edges of the tumor images. After the morphological operation, feature extraction is carried out. The features like homogeneity, contrast of the image and the energy might be determined. Then, the image is classified using the SVM classification algorithm. The experimental results have been tabulated and depicted using graphical representations. Comparing to the existing approaches the proposed method is proved to be better in accuracy and efficiency.</p>","PeriodicalId":50614,"journal":{"name":"Critical Reviews in Therapeutic Drug Carrier Systems","volume":"42 4","pages":"93-125"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217451","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":"Drug Delivery Approaches for Rheumatoid Arthritis: Recent Advances and Clinical Translation Aspects.","authors":"Madhumithra Thangadurai, Swaminathan Sethuraman, Anuradha Subramanian","doi":"10.1615/CritRevTherDrugCarrierSyst.v42.i3.10","DOIUrl":"10.1615/CritRevTherDrugCarrierSyst.v42.i3.10","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a multifactorial autoimmune disease characterized with symmetrical progression of joint deformity that is often diagnosed at a chronic condition with other associated pathological conditions such as pericarditis, keratitis, pulmonary granuloma. Despite the understanding of RA pathophysiology in disease progression, current clinical treatment options such as disease-modifying anti-rheumatic drugs (DMARDs), biologics, steroids, and non-steroidal anti-inflammatory drugs (NSAIDs) provide only palliative therapy while causing adverse side effects such as off-target multi-organ toxicity and risk of infections. Further, available drug delivery strategies to treat RA pathogenicity does not successfully reach the site of action due to various barriers such as phagocytosis and first pass effect in addition to the disease complexity and unknown etiology, thereby leading to the development of irreversible joint dysfunction. Therefore, novel and effective strategies remain an unmet need to control the disease progression and to maintain the balance between pro- and anti-inflammatory cytokines. This review provides a comprehensive outlook on the RA pathophysiology and its corresponding disease progression. Contributions of synoviocytes such as macrophages, fibroblast-like cells in increasing invasiveness to exacerbate joint damage is also outlined in this review, which could be a potential future therapeutic target to complement the existing treatment regimens in controlling RA pathogenesis. Further, various smart drug delivery approaches under research to achieve maximum therapeutic efficacy with minimal adverse side effects have been discussed, which in turn emphasize the unmet challenges and future perspectives in addressing RA complications.</p>","PeriodicalId":50614,"journal":{"name":"Critical Reviews in Therapeutic Drug Carrier Systems","volume":"42 3","pages":"1-54"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626744","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":"Polymeric Nanoparticles Revolutionizing Brain Cancer Therapy: A Comprehensive Review of Strategies and Advances.","authors":"Gilchrist Singh Wahengbam, Sakshi Nirmal, Jai Nandwana, Swatileena Kar, Vandana Kumari, Rajeev Mishra, Abhijeet Singh","doi":"10.1615/CritRevTherDrugCarrierSyst.2024051822","DOIUrl":"10.1615/CritRevTherDrugCarrierSyst.2024051822","url":null,"abstract":"<p><p>Brain cancer continues to be one of the most formidable malignancies to manage, mainly attributable to the presence of the blood-brain barrier (BBB) limiting the permeability of drugs and the diverse characteristics of brain tumors complicating treatment. The management of brain tumors has been hampered by many different factors, including the impermeability of the BBB, which restricts the delivery of chemotherapeutic agents to the tumor site, as well as intertumoral heterogeneity and the influence of brain tumor stem cells. In addition, small molecular weight drugs cannot specifically accumulate in malignant cells and have a limited circulation half-life. Nanoparticles (NPs) can be engineered to traverse the BBB and transport therapeutic medications directly into the brain, enhancing their efficacy compared with the conventional delivery of unbound drugs. Surface modifications of NPs can boost their efficiency by increasing their selectivity towards tumor receptors. This review covers treatment methods for malignant gliomas, associated risk factors, and improvements in brain drug administration, emphasizing the future potential of polymeric NPs and their mechanism for crossing the BBB. To surmount these obstacles, the newly formulated drug-delivery approach utilizing NPs, particularly those coated with cell membranes, has demonstrated potential in treating brain cancer. These NPs provide targeted tumor specificity, biocompatibility, extended circulation, enhanced BBB penetration, and immune evasion. This review focuses on coating strategies for PLGA NPs, particularly dual-targeting methods, to enhance BBB permeability and tumor-targeted delivery of drugs in brain cancer.</p>","PeriodicalId":50614,"journal":{"name":"Critical Reviews in Therapeutic Drug Carrier Systems","volume":"42 2","pages":"73-106"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015672","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":"Next-Generation Nanoparticle-Enabled mRNA Vaccines in the Treatment of COVID-19.","authors":"Eknath Kole, Krishna Jadhav, Raghuraj Singh, Rahul K Verma, Aniruddha Chatterjee, Jitendra Naik","doi":"10.1615/CritRevTherDrugCarrierSyst.2025053265","DOIUrl":"https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2025053265","url":null,"abstract":"<p><p>The emergence of messenger ribonucleic acid (mRNA) vaccines as an alternative platform to traditional vaccines has been accompanied by advances in nanobiotechnology, which have improved the stability and delivery of these vaccines through novel nanoparticles (NPs). Specifically, the development of NPs for mRNA delivery has facilitated the loading, protection and release of mRNA in the biological microenvironment, leading to the stimulation of mRNA translation for effective intervention strategies. Intriguingly, two mRNA vaccines, BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna), have been permitted for emergency usage authorization to prevent COVID-19 infection by USFDA. Both mRNA vaccines utilized lipidic NPs (LNPs) as a delivery platform and demonstrated superior efficacy and safety profiles compared to traditional vaccines. This review article gives insight into ongoing pre-clinical and clinical developments of mRNA vaccine candidates, their efficacy against coronavirus variants, and analysis of NP-based approaches to recognize their potential for forthcoming growth. This review article highlights recent advances in delivery strategies, including LNPs, polymeric NPs, and exosomes, for effective immunization against COVID-19. The key challenges associated with mRNA NPs have been identified, and potential strategies to overcome these difficulties have been proposed. Production of nanomaterials for specific mRNA applications can offer new insights into next-generation nanomaterials, revolutionizing mRNA technology.</p>","PeriodicalId":50614,"journal":{"name":"Critical Reviews in Therapeutic Drug Carrier Systems","volume":"42 6","pages":"83-123"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024684","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}
S M Simi, R Pruthvi, K S Nagashree, Bhavya Malgur Vishweshwaraiah, Riyaz Ali M Osmani
{"title":"Microneedle-Mediated Delivery for Targeted Cancer Therapy: A Comprehensive Review.","authors":"S M Simi, R Pruthvi, K S Nagashree, Bhavya Malgur Vishweshwaraiah, Riyaz Ali M Osmani","doi":"10.1615/CritRevTherDrugCarrierSyst.2025053964","DOIUrl":"https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2025053964","url":null,"abstract":"<p><p>Microneedle-based delivery systems have emerged as a groundbreaking technology in the realm of targeted cancer therapy. By facilitating the transdermal administration of therapeutic agents, microneedles offer a minimally invasive method to overcome the limitations posed by conventional drug delivery systems. This review comprehensively examines the potential of microneedles to enhance drug bioavailability, improve therapeutic outcomes, and reduce systemic toxicity. We explore the diverse applications of MNs in cancer treatment, including their use in chemotherapy, where MNs enable direct delivery of chemotherapeutic agents to tumor sites, thus maximizing drug efficacy and minimizing adverse effects. Additionally, we discuss the role of MNs in immunotherapy, highlighting how they can be used to deliver immune-modulating agents that activate localized immune responses against cancer cells. Furthermore, the potential of microneedles in gene therapy is addressed, emphasizing their ability to deliver genetic material directly to tumor cells, thereby offering a novel approach to cancer treatment. The review also delves into the challenges associated with MN-based therapies, such as ensuring consistent and controlled drug delivery, addressing patient variability, and overcoming manufacturing and scalability issues. Despite these challenges, the advancements in microneedle technology and the promising results from preclinical and clinical studies underscore their transformative potential in cancer therapy. We emphasize the need for further research and clinical trials to validate the efficacy and safety of microneedles.</p>","PeriodicalId":50614,"journal":{"name":"Critical Reviews in Therapeutic Drug Carrier Systems","volume":"42 5","pages":"101-120"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144762175","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":"Advancements in Protein-Based Therapeutic Delivery Approaches Targeting the Blood-Brain Barrier and Insights on Computational Strategies.","authors":"Radhakrishnan Nithya, Muthiah Ramanathan","doi":"10.1615/CritRevTherDrugCarrierSyst.2025054214","DOIUrl":"https://doi.org/10.1615/CritRevTherDrugCarrierSyst.2025054214","url":null,"abstract":"<p><p>Treating neurological disorders is challenging due to the blood-brain barrier (BBB), which limits therapeutic agents, including proteins and peptides, from entering the central nervous system. Despite their potential, the BBB's selective permeability is a significant obstacle. This review explores recent advancements in protein therapeutics for BBB-targeted delivery and highlights computational tools. Strategies such as nanoparticulate-mediated delivery, nose-to-brain delivery, lipid-based approaches, exosomes, cell-penetrating peptides (CPPs), and BBB shuttle peptides have been developed to overcome this barrier. Nanoparticulate systems deliver protein therapeutics across the BBB and can be surface-functionalized to target therapeutic agents into the brain parenchyma. Nose-to-brain delivery is a minimally invasive approach to bypass the BBB. Lipid-based strategies like liposomal systems and nanostructured lipid carriers enhance protein therapies by overcoming BBB restrictions. Exosomes, with unique lipid and surface protein compositions, and CPPs provide versatile drug delivery across the BBB. BBB shuttle peptides, designed for targeted brain delivery, show enhanced stability, efficiency, and cargo transport. Computational tools, notably molecular dynamics simulations, are essential in optimizing protein therapeutics for BBB penetration. These tools offer insights into molecular interactions, guiding the design and optimization of protein therapeutics for better brain penetration. Despite accuracy, limitations due to the BBB's complexity, integrating realistic models and experimental data can improve predictions.</p>","PeriodicalId":50614,"journal":{"name":"Critical Reviews in Therapeutic Drug Carrier Systems","volume":"42 6","pages":"45-81"},"PeriodicalIF":2.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024618","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}