Yang Liu , Mengmeng Wang , Fengju Zhang , Jingyao Tang , Xinyue Han , Yiqing He
{"title":"Effect of 0.05% cyclosporine A eye drops on the healing process of corneal epithelial defects in rats","authors":"Yang Liu , Mengmeng Wang , Fengju Zhang , Jingyao Tang , Xinyue Han , Yiqing He","doi":"10.1016/j.exer.2024.110198","DOIUrl":"10.1016/j.exer.2024.110198","url":null,"abstract":"<div><div>0.05% cyclosporine A eye drops is a kind of new medication for dry eye after corneal refractive surgeries. However, it is still unclear how this eye drops affect the healing process of corneal epithelial defects caused by operative procedures. In this vivo study, the effect of 0.05% cyclosporine A eye drops on the healing process of the corneal epithelium was assessed in a rat model featuring mechanically induced central corneal epithelial defects. These Sprague-Dawley rats were randomly divided into three groups, the 0.05% cyclosporine A eye drops group (CsA group), the 0.1% sodium hyaluronate eye drops group (HA group), and the model control group (MC group). The epithelial healing, tear secretion, epithelial microvilli, expression of apoptosis markers (TUNEL, p53, and bcl-2 proteins), inflammatory factors (IL-1β, TNF-α, and IL-6), and epidermal growth factor (EGF) were detected in the current study using corneal fluorescein sodium staining, phenol red thread test, transmission electron microscopy (TEM), immunofluorescence, and enzyme-linked immunosorbent assay (ELISA), respectively. Compared to the other two groups, lower expression of apoptosis markers and inflammatory factors were exhibited in the CsA group, along with its faster and better epithelial healing and higher tear secretion (<em>P</em> < 0.05). In conclusion, 0.05% cyclosporine A eye drops effectively promote the healing process for corneal epithelial defects in rats, potentially offering advantages for rapid corneal recovery after refractive surgical procedures.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110198"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785064","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}
Yongzhen Yu , Mengyi Zhang , Wenjie Zhou , Yangyang Yu , Liulian Jian , Yuping Zou , Long Pang , Xiulan Zou
{"title":"miR-151a-5p predicts severity of diabetic retinopathy and protects from retinal cell injury by inactivating MAPK signaling via DKK3","authors":"Yongzhen Yu , Mengyi Zhang , Wenjie Zhou , Yangyang Yu , Liulian Jian , Yuping Zou , Long Pang , Xiulan Zou","doi":"10.1016/j.exer.2024.110212","DOIUrl":"10.1016/j.exer.2024.110212","url":null,"abstract":"<div><div>Diabetes mellitus (DM) is always accompanied by various complications, where diabetic retinopathy was a serious microvascular complications threatening the visual function of patients.</div><div>This study evaluated the significance of miR-151a-5p and its effect on DR progression aiming to explore a novel biomarker for disease screening and monitoring. Study enrolled 137 patients with DM and 103 diabetes patients with DR. Serum miR-151a-5p was compared with PCR, and its clinical significance was evaluated from the perspectives of diagnosis and severity prediction. High-glucose-treated human retinal cell model was established, the effect of miR-151a-5p on high-glucose-induced cell injury was assessed based on cell growth, inflammation, oxidative stress, and endoplasmic reticulum stress. In mechanism, the downstream targets of miR-151a-5p were predicted, based on the function enrichment, the involvement of DKK3 and the MAPK signaling was estimated. Increasing miR-151a-5p was identified as a risk factor for DR in DM patients diagnosing DR patients and was positively correlated with disease severity predicting severe development of DR. Silencing miR-151a-5p alleviated high-glucose-induced reducing proliferation, activated inflammation, oxidative stress, and endoplasmic reticulum stress in human retinal cells. Negative regulation of DKK3 by miR-151a-5p was observed, and the knockdown of DKK3 could reversed the protective effect of miR-151a-5p. High-glucose activate the MAPK signaling, which was suppressed by the miR-151a-5p/DKK3 axis, and MAPK signaling was demonstrated to mediate the functional role of the miR-151a-5p/DKK3 axis.</div><div>miR-151a-5p can be considered as a biomarker for the onset and progression of DR. miR-151a-5p potentially modulates the progression of DR through regulating inflammation, oxidative stress, and endoplasmic reticulum stress via the MAPK signaling.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110212"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863868","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":"Emerging treatment strategies in dry eye disease: Potential of blood-derived approaches and natural plant-based products","authors":"Lingli Kong , Jiali Sun , Razzagh Abedi-Firouzjah","doi":"10.1016/j.exer.2024.110217","DOIUrl":"10.1016/j.exer.2024.110217","url":null,"abstract":"<div><div>Dry eye disease (DED) is a common ocular condition characterized by chronic inflammation and tear film disruption. It affects millions of people worldwide, causing significant eye discomfort and vision disturbances. Despite its prevalence, DED remains a complex condition that is not yet fully understood. It can arise from various ocular pathologies, including endocrinological disorders such as diabetes and Graves' orbitopathy. Natural products, including plant- and blood-based therapies, have shown promise in alleviating DED symptoms and may represent effective therapeutic approaches. In this study, we review recent research on natural product treatments for DED, focusing on blood-derived therapies (e.g., autologous serum, albumin serum, and allogeneic serum) and plant-based compounds such as omega-3 fatty acids (O3FA), omega-6 fatty acids (O6FA), antioxidants, polyphenols, and flavonoids. Additionally, we examine the efficacy, mechanisms of action, and delivery systems of these treatments, highlighting the potential of blood-derived therapies, polyphenols, and flavonoids to improve or treat DED through multiple mechanisms. However, the use of these natural products as instilled drugs is limited by challenges such as solubility, stability, and biological barriers. Finally, we discuss drug delivery systems and structural modifications designed to enhance the therapeutic effects of these treatments, emphasizing their potential in managing DED.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110217"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871862","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}
Timothy T. Lee, Brent A. Bell, Ying Song, Joshua L. Dunaief
{"title":"Testosterone promotes photoreceptor degeneration in the sodium iodate model","authors":"Timothy T. Lee, Brent A. Bell, Ying Song, Joshua L. Dunaief","doi":"10.1016/j.exer.2024.110221","DOIUrl":"10.1016/j.exer.2024.110221","url":null,"abstract":"<div><div>Previously, we found that retinas of young male mice were more damaged than those of young female mice in the sodium iodate (NaIO<sub>3</sub>) model. The purpose of this study was to test whether reducing testosterone levels would be retina-protective. Male C57Bl/6J mice underwent surgical castration or sham surgery, then were given an intraperitoneal injection of NaIO<sub>3</sub> at 25 mg/kg. The mice were imaged a week later using optical coherence tomography (OCT). ImageJ with a custom macro was utilized to measure retinal thicknesses in OCT images. Electroretinography (ERG) was used to measure retinal function one week post-injection. After euthanasia, quantitative real-time PCR (qRT-PCR) was performed. Surgical castration partially protected photoreceptors, which was indicated by less photoreceptor layer thinning exhibited in OCT images compared to the sham surgery group. Consistent with this, qRT-PCR of castration group neural retinas revealed less reduction of rhodopsin mRNAs, and less upregulation of antioxidant as well as glucose transporter 1 mRNAs. ERG results also demonstrated partial preservation of both cone and rod function. These results indicate that surgical castration provided structural and functional protection to photoreceptors against NaIO<sub>3</sub>. These neuroprotective effects suggest that testosterone may be harmful to the stressed retina. Further investigation of this pathway could lead to a better understanding of the mechanisms involved in retinal degeneration.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110221"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876618","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}
Chen Chu , Luyao Ye , Qingqing Chi , Jiangnan He , Jianfeng Zhu
{"title":"Proteomic analysis of effects of 1% atropine in myopia therapy in Guinea pigs","authors":"Chen Chu , Luyao Ye , Qingqing Chi , Jiangnan He , Jianfeng Zhu","doi":"10.1016/j.exer.2024.110224","DOIUrl":"10.1016/j.exer.2024.110224","url":null,"abstract":"<div><div>Myopia is a significant global public health issue. Key interventions for managing myopia include atropine treatment, optical correction, and surgical methods. This study focused on evaluating alterations in retinal protein expression after atropine therapy for myopia. Guinea pigs were randomly divided into four groups: control (CON), monocular form-deprivation myopia (FDM), FDM with 2-week atropine treatment (FDM + ATR), and atropine-only treatment (ATR). After two weeks of FDM induction, the FDM group showed significant differences in refractive error and increased axial lengths. In comparing the retinas of myopic and normal eyes, 30 proteins were found to have increased expression, while 8 proteins showed decreased expression. Atropine-treated retinas exhibited 73 proteins with increased expression and 29 proteins with decreased expression compared to the normal eyes. A total of 11 regulated proteins overlapped between the FDM + ATR vs FDM and FDM vs CON groups. IPA analysis indicates significant alterations in amino acid metabolism, energy production, post-translational modification, small molecule biochemistry, and free radical scavenging. Our study identifies retinal protein changes in myopic guinea pigs and in guinea pigs treated with atropine after myopia. These proteins could serve as potential targets for atropine treatment of myopia.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110224"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893276","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":"miRNAs, piRNAs, and lncRNAs: A triad of non-coding RNAs regulating the neurovascular unit in diabetic retinopathy and their therapeutic potentials","authors":"Muthuramalingam Karpagavalli , Manavi D. Sindal , Jayamuruga Pandian Arunachalam , Subbulakshmi Chidambaram","doi":"10.1016/j.exer.2025.110236","DOIUrl":"10.1016/j.exer.2025.110236","url":null,"abstract":"<div><div>Diabetic Retinopathy (DR), a leading complication of diabetes mellitus, has long been considered as a microvascular disease of the retina. However, recent evidence suggests that DR is a neurovascular disease, characterized by the degeneration of retinal neural tissue and microvascular abnormalities encompassing ischemia, neovascularization, and blood-retinal barrier breakdown, ultimately leading to blindness. The intricate relationship between the retina and vascular cells constitutes a neurovascular unit, a multi-cellular framework of retinal neurons, glial cells, immune cells, and vascular cells, which facilitates neurovascular coupling, linking neuronal activity to blood flow. These interconnections between the neurovascular components get compromised due to hyperglycemia and are further associated with the progression of DR early on in the disease. As a result, therapeutic approaches are needed to avert the advancement of DR by acting at its initial stage to delay or prevent the pathogenesis. Non-coding RNAs (ncRNAs) such as microRNAs, piwi-interacting RNAs, and long non-coding RNAs regulate various cellular components in the neurovascular unit. These ncRNAs are key regulators of neurodegeneration, apoptosis, inflammation, and oxidative stress in DR. In this review, research related to alterations in the expression of ncRNAs and, correspondingly, their effect on the disintegration of the neurovascular coupling will be discussed briefly to understand the potential of ncRNAs as therapeutic targets for treating this debilitating disease.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110236"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970314","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}
Sharmila Rajendran , Angayarkanni Narayansamy , Radha Annamalai , Lawrence D. Cruze , Purushothaman Kathiresan , Kaviarasan Kuppan
{"title":"Proteome of pericytes from retinal vasculature of diabetic donor eyes","authors":"Sharmila Rajendran , Angayarkanni Narayansamy , Radha Annamalai , Lawrence D. Cruze , Purushothaman Kathiresan , Kaviarasan Kuppan","doi":"10.1016/j.exer.2024.110178","DOIUrl":"10.1016/j.exer.2024.110178","url":null,"abstract":"<div><div>Retinal pericytes (PCs) are contractile microvascular smooth muscle cells that wrap around the endothelial cells (ECs) maintaining intact retinal vasculature (RV) with a 1:1 ratio. Microvascular complications like diabetic retinopathy (DR) due to chronic diabetes causes apoptotic loss of PCs followed by diminished vessel stability, EC apoptosis, and ischemia, leading to retinal angiogenesis, and eventually severe vision loss. This study aimed to analyze the proteins in PCs isolated from the RV of diabetic human donor eyes and compare them with remaining mixed population (MP) of retinal vascular cells. PCs and MP proteomes were analyzed using semi-quantitative proteomics. Proteins were extracted, quantified, and analyzed in duplicate using LC-MS/MS on a Tandem mass spectrometer. Overall, 42 PC and 27 MP proteins, with 19 shared proteins, were identified. Functional enrichment analysis indicated that PC proteins share common biological processes, such as negative regulation of fibrinolysis and vLDL particle remodeling, nitric oxide transport, phospholipid efflux, positive control over the clearance of apoptotic cells, chondrocyte proliferation, lipoprotein lipase activity, and oxidative stress-induced intrinsic atrophic signaling pathways. In the fold enrichment analysis, the PC proteins were associated with cholesterol metabolism, Complement and coagulant, ECM-receptor interaction, longevity regulating pathway, Peroxisome proliferator-activated receptors (PPAR), focal adhesion and PI3 Akt signaling pathways. Among the PC proteins, vitronectin, gelsolin, hornerin, apolipoprotein A1, C3, H, and complement Factors C3, C4, and C9 were identified as the most highly ranked proteins in diabetes. The identified unique proteins of retinal PC could prove beneficial as a therapeutic target in the management of DR.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110178"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695322","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":"Metabolomic and transcriptomic analysis reveals metabolic-immune interactions in choroid neovascularization","authors":"Yihan Zhang , Siyi Qi , Weiai Shen , Ying Guo , Yu Liang , Qiao Zhuo , Hongyu Kong , Shujie Zhang , Chen Zhao","doi":"10.1016/j.exer.2024.110227","DOIUrl":"10.1016/j.exer.2024.110227","url":null,"abstract":"<div><div>Choroid neovascularization (CNV) is a distinct type of age-related macular degeneration (AMD) with a poor prognosis and responsible for the majority of vision loss in the elderly population. The laser-induced CNV model is a well-established animal model frequently used to study CNV. In this study, we performed an integrated analysis of metabolomic and transcriptomic data from CNV samples, utilizing multiple approaches including single-sample gene set enrichment analysis (ssGSEA), correlation analysis, and weighted gene co-expression network analysis (WGCNA), alongside various bioinformatics platforms, to identify key metabolic and immune signatures and to investigate their interplay during angiogenesis. Dominant infiltration of macrophages and monocytes was detected and a positive correlation between dysregulated riboflavin metabolism and angiogenesis pathways was characterized. Hub genes such as ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) and acid phosphatase 5, tartrate resistant (ACP5) emerged as potential central regulators of immune-metabolic crosstalk in CNV. The classification of the immune and metabolic landscape and their critical interactions in CNV models will enhance the understanding of the pathogenesis of neovascular AMD and other neovascular eye diseases, contributing to the development of multi-targeted therapeutic strategies with better efficacy.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110227"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893272","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}
Lynn J.A. Ebner , Duygu Karademir , Sarah Nötzli , Gabriele M. Wögenstein , Marijana Samardzija , Christian Grimm
{"title":"Oxygen-dependent alternative mRNA splicing and a cone-specific motor protein revealed by single-cell RNA sequencing in hypoxic retinas","authors":"Lynn J.A. Ebner , Duygu Karademir , Sarah Nötzli , Gabriele M. Wögenstein , Marijana Samardzija , Christian Grimm","doi":"10.1016/j.exer.2024.110190","DOIUrl":"10.1016/j.exer.2024.110190","url":null,"abstract":"<div><div>Restricted oxygen supply in the aging eye may lead to hypoxic conditions in the outer retina and contribute not only to physiological aging but also to nonhereditary degenerative retinal diseases. To understand the hypoxic response of specific retinal cell types, we performed single-cell RNA sequencing of retinas isolated from mice exposed to hypoxia. Significantly upregulated expression of marker genes in hypoxic clusters confirmed a general transcriptional response to hypoxia. By focusing on the hypoxic response in photoreceptors, we identified and confirmed a kinesin motor protein (<em>Kif4</em>) that was specifically and strongly induced in hypoxic cones. In contrast, RNA-binding proteins <em>Rbm3</em> and <em>Cirbp</em> were differentially expressed across clusters but demonstrated isoform switching in hypoxia. The resulting short variants of these gene transcripts are connected to epitranscriptomic regulation, a notion supported by the differential expression of writers, readers and erasers of m<sup>6</sup>A RNA methylations in the hypoxic retina. Our data indicate that retinal cells adapt to hypoxic conditions by adjusting their transcriptome at various levels including gene expression, alternative splicing and the epitranscriptome. Adaptational processes may be cell-type specific as exemplified by the cone-specific upregulation of <em>Kif4</em> or general like alternative splicing of RNA binding proteins.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110190"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785065","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":"A combined experimental-computational approach for retinal characterization","authors":"Beatrice Belgio, Francesca Berti, Riccardo Tripputi, Federica Potere, Sara Mantero, Federica Boschetti","doi":"10.1016/j.exer.2025.110242","DOIUrl":"10.1016/j.exer.2025.110242","url":null,"abstract":"<div><div>Subretinal injection of gene products is the only treatment option for inherited retinal diseases. However, this procedure induces localized high multiaxial deformations, potentially causing irreversible tissue damage due to retinal overstretching and tearing. Comprehensive characterization of retinal mechanical behavior is essential for performing safe injections. Although uniaxial tensile test has been used in the literature, it has many limitations for retinal characterization. To date, retinal mechanical properties are poorly understood due to the lack of standardized testing protocol. This study aimed to introduce a combined experimental-computational approach using small punch testing and finite element simulations to investigate retina elastic behavior under biaxial deformations. To develop a suitable testing protocol for retinal samples, we evaluated the impact of environmental conditions on retinal elasticity by performing uniaxial tensile tests on porcine retinal strips in air, in a saline bath, and at different temperatures. The results showed that conditions did not significantly affect the elastic modulus. We then developed an easy and reproducible small punch test protocol, allowing to measure for the first time the load-displacement response of the retina under biaxial deformations. Computational simulations enabled the analysis of retinal deformations and the identification of its elastic modulus (5.5 kPa). The outcomes of this study highlight the great potential of the combined approach as a viable alternative to uniaxial tensile test to advance the understanding of retinal biomechanics. This is essential not only for minimizing sight-threatening surgical complications during injections, but also for building predictive in silico models, and developing biomimetic scaffolds.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110242"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002439","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}