Progress in Retinal and Eye Research最新文献

{"title":"Alzheimer's disease pathophysiology in the Retina","authors":"Bhakta Prasad Gaire ,&nbsp;Yosef Koronyo ,&nbsp;Dieu-Trang Fuchs ,&nbsp;Haoshen Shi ,&nbsp;Altan Rentsendorj ,&nbsp;Ron Danziger ,&nbsp;Jean-Philippe Vit ,&nbsp;Nazanin Mirzaei ,&nbsp;Jonah Doustar ,&nbsp;Julia Sheyn ,&nbsp;Harald Hampel ,&nbsp;Andrea Vergallo ,&nbsp;Miyah R. Davis ,&nbsp;Ousman Jallow ,&nbsp;Filippo Baldacci ,&nbsp;Steven R. Verdooner ,&nbsp;Ernesto Barron ,&nbsp;Mehdi Mirzaei ,&nbsp;Vivek K. Gupta ,&nbsp;Stuart L. Graham ,&nbsp;Maya Koronyo-Hamaoui","doi":"10.1016/j.preteyeres.2024.101273","DOIUrl":"10.1016/j.preteyeres.2024.101273","url":null,"abstract":"<div><p>The retina is an emerging CNS target for potential noninvasive diagnosis and tracking of Alzheimer's disease (AD). Studies have identified the pathological hallmarks of AD, including amyloid β-protein (Aβ) deposits and abnormal tau protein isoforms, in the retinas of AD patients and animal models. Moreover, structural and functional vascular abnormalities such as reduced blood flow, vascular Aβ deposition, and blood-retinal barrier damage, along with inflammation and neurodegeneration, have been described in retinas of patients with mild cognitive impairment and AD dementia. Histological, biochemical, and clinical studies have demonstrated that the nature and severity of AD pathologies in the retina and brain correspond. Proteomics analysis revealed a similar pattern of dysregulated proteins and biological pathways in the retina and brain of AD patients, with enhanced inflammatory and neurodegenerative processes, impaired oxidative-phosphorylation, and mitochondrial dysfunction. Notably, investigational imaging technologies can now detect AD-specific amyloid deposits, as well as vasculopathy and neurodegeneration in the retina of living AD patients, suggesting alterations at different disease stages and links to brain pathology. Current and exploratory ophthalmic imaging modalities, such as optical coherence tomography (OCT), OCT-angiography, confocal scanning laser ophthalmoscopy, and hyperspectral imaging, may offer promise in the clinical assessment of AD. However, further research is needed to deepen our understanding of AD's impact on the retina and its progression. To advance this field, future studies require replication in larger and diverse cohorts with confirmed AD biomarkers and standardized retinal imaging techniques. This will validate potential retinal biomarkers for AD, aiding in early screening and monitoring.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"101 ","pages":"Article 101273"},"PeriodicalIF":17.8,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141052146","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}

{"title":"Resilience to diabetic retinopathy","authors":"Anara Serikbaeva ,&nbsp;Yanliang Li ,&nbsp;Simon Ma ,&nbsp;Darvin Yi ,&nbsp;Andrius Kazlauskas","doi":"10.1016/j.preteyeres.2024.101271","DOIUrl":"10.1016/j.preteyeres.2024.101271","url":null,"abstract":"<div><p>Chronic elevation of blood glucose at first causes relatively minor changes to the neural and vascular components of the retina. As the duration of hyperglycemia persists, the nature and extent of damage increases and becomes readily detectable. While this second, overt manifestation of diabetic retinopathy (DR) has been studied extensively, what prevents maximal damage from the very start of hyperglycemia remains largely unexplored. Recent studies indicate that diabetes (DM) engages mitochondria-based defense during the retinopathy-resistant phase, and thereby enables the retina to remain healthy in the face of hyperglycemia. Such resilience is transient, and its deterioration results in progressive accumulation of retinal damage. The concepts that co-emerge with these discoveries set the stage for novel intellectual and therapeutic opportunities within the DR field. Identification of biomarkers and mediators of protection from DM-mediated damage will enable development of resilience-based therapies that will indefinitely delay the onset of DR.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"101 ","pages":"Article 101271"},"PeriodicalIF":17.8,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1350946224000363/pdfft?md5=48ec3fcd40a3434c60c8e0b9ae84898d&pid=1-s2.0-S1350946224000363-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916789","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}

{"title":"Mitochondrial retinopathies and optic neuropathies: The impact of retinal imaging on modern understanding of pathogenesis, diagnosis, and management","authors":"Enrico Borrelli ,&nbsp;Francesco Bandello ,&nbsp;Camiel J.F. Boon ,&nbsp;Valerio Carelli ,&nbsp;Guy Lenaers ,&nbsp;Michele Reibaldi ,&nbsp;Srinivas R. Sadda ,&nbsp;Alfredo A. Sadun ,&nbsp;David Sarraf ,&nbsp;Patrick Yu-Wai-Man ,&nbsp;Piero Barboni","doi":"10.1016/j.preteyeres.2024.101264","DOIUrl":"https://doi.org/10.1016/j.preteyeres.2024.101264","url":null,"abstract":"<div><p>Advancements in ocular imaging have significantly broadened our comprehension of mitochondrial retinopathies and optic neuropathies by examining the structural and pathological aspects of the retina and optic nerve in these conditions. This article aims to review the prominent imaging characteristics associated with mitochondrial retinopathies and optic neuropathies, aiming to deepen our insight into their pathogenesis and clinical features. Preceding this exploration, the article provides a detailed overview of the crucial genetic and clinical features, which is essential for the proper interpretation of <em>in vivo</em> imaging. More importantly, we will provide a critical analysis on how these imaging modalities could serve as biomarkers for characterization and monitoring, as well as in guiding treatment decisions. However, these imaging methods have limitations, which will be discussed along with potential strategies to mitigate them. Lastly, the article will emphasize the potential advantages and future integration of imaging techniques in evaluating patients with mitochondrial eye disorders, considering the prospects of emerging gene therapies.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"101 ","pages":"Article 101264"},"PeriodicalIF":17.8,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140842987","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}

{"title":"Targeting inflammasomes and pyroptosis in retinal diseases—molecular mechanisms and future perspectives","authors":"Yimeng Sun ,&nbsp;Fan Li ,&nbsp;Yunfei Liu ,&nbsp;Dijie Qiao ,&nbsp;Xinyu Yao ,&nbsp;Guei-Sheung Liu ,&nbsp;Dequan Li ,&nbsp;Chuanle Xiao ,&nbsp;Tao Wang ,&nbsp;Wei Chi","doi":"10.1016/j.preteyeres.2024.101263","DOIUrl":"10.1016/j.preteyeres.2024.101263","url":null,"abstract":"<div><p>Retinal diseases encompass various conditions associated with sight-threatening immune responses and are leading causes of blindness worldwide. These diseases include age-related macular degeneration, diabetic retinopathy, glaucoma and uveitis. Emerging evidence underscores the vital role of the innate immune response in retinal diseases, beyond the previously emphasized T-cell-driven processes of the adaptive immune system. In particular, pyroptosis, a newly discovered programmed cell death process involving inflammasome formation, has been implicated in the loss of membrane integrity and the release of inflammatory cytokines. Several disease-relevant animal models have provided evidence that the formation of inflammasomes and the induction of pyroptosis in innate immune cells contribute to inflammation in various retinal diseases. In this review article, we summarize current knowledge about the innate immune system and pyroptosis in retinal diseases. We also provide insights into translational targeting approaches, including novel drugs countering pyroptosis, to improve the diagnosis and treatment of retinal diseases.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"101 ","pages":"Article 101263"},"PeriodicalIF":17.8,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1350946224000284/pdfft?md5=30481d259a17070859035f5d2b0f8ac5&pid=1-s2.0-S1350946224000284-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852626","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}

{"title":"Toward an internationally accepted standard for reading charts","authors":"Wolfgang Radner","doi":"10.1016/j.preteyeres.2024.101262","DOIUrl":"https://doi.org/10.1016/j.preteyeres.2024.101262","url":null,"abstract":"<div><p>Patients who suffer from sight-threatening eye diseases share a desire to regain a comfortable reading ability. In light of the modern advances achieved in ophthalmic diagnosis and therapy, and because a significant lack of comparability between reading charts still exists, there is an increasing need for a worldwide standard in the form of a norm for diagnostic reading charts. Already, applied advancements such as digital print, which allow a calibration of the print sizes of reading charts in correctly progressing geometric proportions by using the actual height of a lower case “x” in millimeters (x-height), and psychophysically standardizing reading charts and their test items by applying modern statistical methods have significantly contributed to establishing a norm for reading charts. In 2020, a proposal of the British delegation was accepted by the International Organization for Standardization (ISO) group “Visual Optics and Optical Instruments,” and a working group was established. Bearing in mind the efforts of the ISO with regard to an international norm, this review article is intended to (a) give an overview of the historical background and related normative approaches for diagnostic reading tests used in ophthalmology and optometry, (b) explain psychophysical and technical concerns, and (c) discuss the possibilities and limits of concepts that seem relevant to developing a modern standard for reading charts.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"101 ","pages":"Article 101262"},"PeriodicalIF":17.8,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1350946224000272/pdfft?md5=8ed70bd26536e3c135f3f9d27c671125&pid=1-s2.0-S1350946224000272-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140554664","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}

{"title":"Addressing neurodegeneration in glaucoma: Mechanisms, challenges, and treatments","authors":"Ghazi O. Bou Ghanem,&nbsp;Lauren K. Wareham,&nbsp;David J. Calkins","doi":"10.1016/j.preteyeres.2024.101261","DOIUrl":"10.1016/j.preteyeres.2024.101261","url":null,"abstract":"<div><p>Glaucoma is the leading cause of irreversible blindness globally. The disease causes vision loss due to neurodegeneration of the retinal ganglion cell (RGC) projection to the brain through the optic nerve. Glaucoma is associated with sensitivity to intraocular pressure (IOP). Thus, mainstay treatments seek to manage IOP, though many patients continue to lose vision. To address neurodegeneration directly, numerous preclinical studies seek to develop protective or reparative therapies that act independently of IOP. These include growth factors, compounds targeting metabolism, anti-inflammatory and antioxidant agents, and neuromodulators. Despite success in experimental models, many of these approaches fail to translate into clinical benefits. Several factors contribute to this challenge. Firstly, the anatomic structure of the optic nerve head differs between rodents, nonhuman primates, and humans. Additionally, animal models do not replicate the complex glaucoma pathophysiology in humans. Therefore, to enhance the success of translating these findings, we propose two approaches. First, thorough evaluation of experimental targets in multiple animal models, including nonhuman primates, should precede clinical trials. Second, we advocate for combination therapy, which involves using multiple agents simultaneously, especially in the early and potentially reversible stages of the disease. These strategies aim to increase the chances of successful neuroprotective treatment for glaucoma.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"100 ","pages":"Article 101261"},"PeriodicalIF":17.8,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140288866","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}

{"title":"Glycative stress as a cause of macular degeneration","authors":"Eloy Bejarano ,&nbsp;Alicia Domenech-Bendaña ,&nbsp;Norma Avila-Portillo ,&nbsp;Sheldon Rowan ,&nbsp;Sachini Edirisinghe ,&nbsp;Allen Taylor","doi":"10.1016/j.preteyeres.2024.101260","DOIUrl":"10.1016/j.preteyeres.2024.101260","url":null,"abstract":"<div><p>People are living longer and rates of age-related diseases such as age-related macular degeneration (AMD) are accelerating, placing enormous burdens on patients and health care systems. The quality of carbohydrate foods consumed by an individual impacts health<em>.</em> The glycemic index (GI) is a kinetic measure of the rate at which glucose arrives in the blood stream after consuming various carbohydrates. Consuming diets that favor slowly digested carbohydrates releases sugar into the bloodstream gradually after consuming a meal (low glycemic index). This is associated with reduced risk for major age-related diseases including AMD, cardiovascular disease, and diabetes<em>.</em> In comparison, consuming the same amounts of different carbohydrates in higher GI diets, releases glucose into the blood rapidly, causing glycative stress as well as accumulation of advanced glycation end products (AGEs). Such AGEs are cytotoxic by virtue of their forming abnormal proteins and protein aggregates, as well as inhibiting proteolytic and other protective pathways that might otherwise selectively recognize and remove toxic species. Using <em>in vitro</em> and animal models of glycative stress, we observed that consuming higher GI diets perturbs metabolism and the microbiome, resulting in a shift to more lipid-rich metabolomic profiles. Interactions between aging, diet, eye phenotypes and physiology were observed. A large body of laboratory animal and human clinical epidemiologic data indicates that consuming lower GI diets, or lower glycemia diets, is protective against features of early AMD (AMDf) in mice and AMD prevalence or AMD progression in humans. Drugs may be optimized to diminish the ravages of higher glycemic diets. Human trials are indicated to determine if AMD progression can be retarded using lower GI diets. Here we summarized the current knowledge regarding the pathological role of glycative stress in retinal dysfunction and how dietary strategies might diminish retinal disease.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"101 ","pages":"Article 101260"},"PeriodicalIF":17.8,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140194485","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}

{"title":"How gut microbiota may impact ocular surface homeostasis and related disorders","authors":"Marc Labetoulle ,&nbsp;Christophe Baudouin ,&nbsp;Jose M. Benitez del Castillo ,&nbsp;Maurizio Rolando ,&nbsp;Maria Rescigno ,&nbsp;Elisabeth M. Messmer ,&nbsp;Pasquale Aragona","doi":"10.1016/j.preteyeres.2024.101250","DOIUrl":"10.1016/j.preteyeres.2024.101250","url":null,"abstract":"<div><p>Changes in the bacterial flora in the gut, also described as gut microbiota, are readily acknowledged to be associated with several systemic diseases, especially those with an inflammatory, neuronal, psychological or hormonal factor involved in the pathogenesis and/or the perception of the disease. Maintaining ocular surface homeostasis is also based on all these four factors, and there is accumulating evidence in the literature on the relationship between gut microbiota and ocular surface diseases. The mechanisms involved are mostly interconnected due to the interaction of central and peripheral neuronal networks, inflammatory effectors and the hormonal system. A better understanding of the influence of the gut microbiota on the maintenance of ocular surface homeostasis, and on the onset or persistence of ocular surface disorders could bring new insights and help elucidate the epidemiology and pathology of ocular surface dynamics in health and disease. Revealing the exact nature of these associations could be of paramount importance for developing a holistic approach using highly promising new therapeutic strategies targeting ocular surface diseases.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"100 ","pages":"Article 101250"},"PeriodicalIF":17.8,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1350946224000156/pdfft?md5=b67c068d00faa8fa767a90eb51da509c&pid=1-s2.0-S1350946224000156-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140068669","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}

{"title":"Translocator protein (18 kDa) (Tspo) in the retina and implications for ocular diseases","authors":"Mandy Hector ,&nbsp;Thomas Langmann ,&nbsp;Anne Wolf","doi":"10.1016/j.preteyeres.2024.101249","DOIUrl":"10.1016/j.preteyeres.2024.101249","url":null,"abstract":"<div><p>Translocator protein (18 kDa) (Tspo), formerly known as peripheral benzodiazepine receptor is a highly conserved transmembrane protein primarily located in the outer mitochondrial membrane. In the central nervous system (CNS), especially in glia cells, Tspo is upregulated upon inflammation. Consequently, Tspo was used as a tool for diagnostic <em>in vivo</em> imaging of neuroinflammation in the brain and as a potential therapeutic target. Several synthetic Tspo ligands have been explored as immunomodulatory and neuroprotective therapy approaches. Although the function of Tspo and how its ligands exert these beneficial effects is not fully clear, it became a research topic of interest, especially in ocular diseases in the past few years. This review summarizes state-of-the-art knowledge of Tspo expression and its proposed functions in different cells of the retina including microglia, retinal pigment epithelium and Müller cells. Tspo is involved in cytokine signaling, oxidative stress and reactive oxygen species production, calcium signaling, neurosteroid synthesis, energy metabolism, and cholesterol efflux. We also highlight recent developments in preclinical models targeting Tspo and summarize the relevance of Tspo biology for ocular and retinal diseases. We conclude that glial upregulation of Tspo in different ocular pathologies and the use of Tspo ligands as promising therapeutic approaches in preclinical studies underline the importance of Tspo as a potential disease-modifying protein.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"100 ","pages":"Article 101249"},"PeriodicalIF":17.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140023947","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}

{"title":"Pluripotent stem cell-derived models of retinal disease: Elucidating pathogenesis, evaluating novel treatments, and estimating toxicity","authors":"Marzena Kurzawa-Akanbi ,&nbsp;Nikolaos Tzoumas ,&nbsp;Julio C. Corral-Serrano ,&nbsp;Rosellina Guarascio ,&nbsp;David H. Steel ,&nbsp;Michael E. Cheetham ,&nbsp;Lyle Armstrong ,&nbsp;Majlinda Lako","doi":"10.1016/j.preteyeres.2024.101248","DOIUrl":"10.1016/j.preteyeres.2024.101248","url":null,"abstract":"<div><p>Blindness poses a growing global challenge, with approximately 26% of cases attributed to degenerative retinal diseases. While gene therapy, optogenetic tools, photosensitive switches, and retinal prostheses offer hope for vision restoration, these high-cost therapies will benefit few patients. Understanding retinal diseases is therefore key to advance effective treatments, requiring <em>in vitro</em> models replicating pathology and allowing quantitative assessments for drug discovery. Pluripotent stem cells (PSCs) provide a unique solution given their limitless supply and ability to differentiate into light-responsive retinal tissues encompassing all cell types. This review focuses on the history and current state of photoreceptor and retinal pigment epithelium (RPE) cell generation from PSCs. We explore the applications of this technology in disease modelling, experimental therapy testing, biomarker identification, and toxicity studies. We consider challenges in scalability, standardisation, and reproducibility, and stress the importance of incorporating vasculature and immune cells into retinal organoids. We advocate for high-throughput automation in data acquisition and analyses and underscore the value of advanced micro-physiological systems that fully capture the interactions between the neural retina, RPE, and choriocapillaris.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"100 ","pages":"Article 101248"},"PeriodicalIF":17.8,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1350946224000132/pdfft?md5=bcd3eac64c7f370b88be13ead82062f1&pid=1-s2.0-S1350946224000132-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139773988","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}