{"title":"Accumulation of autophagosomes in aging human photoreceptor cell synapses","authors":"Tapas C. Nag","doi":"10.1016/j.exer.2025.110240","DOIUrl":"10.1016/j.exer.2025.110240","url":null,"abstract":"<div><div>Autophagy is common in the aging retinal pigment epithelium (RPE). A dysfunctional autophagy in aged RPE is implicated in the pathogenesis of age-related macular degeneration. Aging human retina accompanies degenerative changes in photoreceptor mitochondria. It is not known how the damaged mitochondria are handled by photoreceptor cells with aging. This study examined donor human retinas (age: 56–94 years; N = 12) by transmission electron microscopy to find mitochondrial dynamics and status of autophagy in macular photoreceptor cells. Observations were compared between the relatively lower age (56–78 years) and aged retinas (80–94 years). Mitochondrial fusion was predominant in photoreceptor inner segments (ellipsoids), but rarely seen in the synaptic terminals. Also, fusion became widespread with progressive aging in ellipsoids (12% and 21% between rods and cones at tenth decade, respectively). More importantly, it was found that the photoreceptor synaptic mitochondria altered significantly with aging (swelling and loss of cristae), compared to those in ellipsoids that became dark and condensed. The damaged synaptic mitochondria were sequestered inside autophagosomes, whose frequency was higher in aged photoreceptors, being 34% in cone and 24% in rod terminals, at tenth decade. However, autolysosomes/residual bodies were rare, and thus the aged photoreceptor synaptic terminals harboured many autophagosomes, the possible reasons for which are discussed. Such age-related altered mitochondrial population and defective autophagy in synaptic terminals may influence photoreceptor survival in late aging.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110240"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970311","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}
John C. Morrison, William Cepurna, Eliesa Ing, Elaine Johnson, Aryana Abtin, Susan Wentzien, Elizabeth White, Diana C. Lozano
{"title":"A system for producing controlled elevation of intraocular pressure in awake Brown Norway rats","authors":"John C. Morrison, William Cepurna, Eliesa Ing, Elaine Johnson, Aryana Abtin, Susan Wentzien, Elizabeth White, Diana C. Lozano","doi":"10.1016/j.exer.2025.110237","DOIUrl":"10.1016/j.exer.2025.110237","url":null,"abstract":"<div><div>Animal models that help us understand how elevated intraocular pressure (IOP) causes axonal injury will lead to new glaucoma therapies. Because reliable measurements are difficult to obtain in chronic models, we developed the controlled elevation of IOP (CEI) approach. Here, a cannula connected to an elevated balanced salt solution (BSS) reservoir is inserted into the anterior chamber of anesthetized Brown Norway rats. The extent and duration of IOP exposure is controlled by adjusting the reservoir height. We now describe a method for creating CEI in awake animals. A Pinport, which has a silicone plug that can be penetrated repeatedly, is modified, attached to the skull, and connected to a microcannula that is implanted in the posterior chamber. To elevate IOP, BSS from a reservoir is allowed to flow through a pressure transducer to a swivel-mounted tether and injector. The injector is placed on the Pinport, bypassing the need for anterior chamber cannulation and general anesthesia during CEI. The surgical technique and equipment required for implantation are described, as well as the equipment and methods for performing awake CEI in several animals at a time. The ability of this system to control the level of IOP is demonstrated by TonoLab measurement, and by comparing reservoir (Pinport) pressures to direct measurement using an independent anterior chamber cannula and transducer. We also demonstrate that IOP elevation can be maintained over several hours. Specific pitfalls during and after surgical implantation are highlighted to help other researchers adopt these techniques.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110237"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978083","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}
Cong Han , Yuting Li , Xingxing Zheng , Jianping Zhang , Xin Zhao , Keke Ge , Guonian Li , Yi Yang , Wenfang Zhang
{"title":"Choroidal thickening and retinal dopamine increase in mice at high altitude","authors":"Cong Han , Yuting Li , Xingxing Zheng , Jianping Zhang , Xin Zhao , Keke Ge , Guonian Li , Yi Yang , Wenfang Zhang","doi":"10.1016/j.exer.2025.110241","DOIUrl":"10.1016/j.exer.2025.110241","url":null,"abstract":"<div><div>The mechanisms underlying the low incidence of myopia at high altitudes remain unclear. Choroidal thickness and the dopaminergic system have been shown to be closely associated with myopia development. This study aimed to investigate the effects of high altitude exposure on choroidal thickness and the dopaminergic system. Mice were subjected to acute hypobaric hypoxia at an altitude of 5000 m for durations ranging from 2 to 72 h, as well as chronic exposure at an altitude of 3670 m for a period of 3 months. Choroidal thickness was assessed using hematoxylin and eosin (H&E) staining of ocular tissues. The retinal dopamine (DA) levels and its primary metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), were quantified via high-performance liquid chromatography (HPLC). The expression levels of dopamine D1 receptor (D1R) and dopamine D2 receptor (D2R) were evaluated using immunofluorescence techniques. Study results indicated that choroidal thickness significantly increased after 6 h of high altitude exposure. Retinal dopamine levels showed significant increases in both the 2–10 h and 3 months high altitude groups. Conversely, retinal DOPAC levels decreased in the 2 h and 4 h groups but increased significantly at 72 h. Following high altitude exposure, D1R expression correlated positively with DA levels, while D2R expression exhibited a negative correlation. In conclusion, high-altitude exposure is associated with significant increases in choroidal thickness and retinal DA levels, with D1R and D2R expression patterns varying in response to changes in retinal DA. These findings may represent a key molecular mechanism contributing to the lower incidence of myopia observed at high altitudes.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110241"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002147","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}
Rachel L. Fehrman , Kristina J. Chern , Kyle P. Stoltz , Daniel M. Lipinski
{"title":"The vectors went in two-by-two: Transduction efficiency and tolerability of dual and triple rAAV vector delivery following intravitreal injection for genome-editing applications","authors":"Rachel L. Fehrman , Kristina J. Chern , Kyle P. Stoltz , Daniel M. Lipinski","doi":"10.1016/j.exer.2024.110223","DOIUrl":"10.1016/j.exer.2024.110223","url":null,"abstract":"<div><div>Genome or prime editing has become a promising tool for the treatment of hereditary disorders affecting the inner retina, such as dominant optic neuropathies. <em>In vivo</em> delivery of gene editors, such as Cas9, is typically achieved using recombinant adeno-associated virus (rAAV) vectors, which have a broad range of cellular tropisms and are well tolerated following intravitreal administration. Owing to the large size of gene editing constructs and the limited carrying capacity of rAAV (<5.1 kb) it is unfortunately usually necessary to split therapeutic transgene cassettes across multiple co-administered vector genomes. While the efficiency with which multiple vector genomes recombine following cellular entry has been studied extensively, another potentially limiting factor is the likelihood of target cells (e.g. retinal ganglion cells) receiving two or more vectors containing genomes that correspond to the full-length expression cassette when recombined. In this study we examine the efficiency with which two or more vector genomes transduce various retinal cell types following intravitreal administration. rAAV2/2[MAX] vectors expressing individual fluorescent reporters (GFP, BFP or mCherry) were co-injected intravitreally singly or in combination (dual or triple), allowing the extent of co-transduction to be assessed through multimodal <em>in vivo</em> imaging, electroretinography, flow cytometry and post-mortem histology. We find that intravitreal co-administration of vectors containing multiple genomes is well tolerated – with no observed alterations in retinal thickness or ERG amplitudes – but that co-transduction efficiency decreases significantly with increasing genome number. As such co-transduction of multiple vectors may be a major bottleneck limiting gene editing of inherited disorders affecting the inner retina.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110223"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876619","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}
Sabrina Nau da Silva Piazza , Paula Bortoluzzi Canteiro , Natalia dos Santos Tramontin , Giulia Strapazzon , Vanessa de Moraes Andrade , Alexandre Pastoris Muller
{"title":"Protective effects of different exercise modalities on oxidative stress in animal models of high intraocular pressure and diabetes","authors":"Sabrina Nau da Silva Piazza , Paula Bortoluzzi Canteiro , Natalia dos Santos Tramontin , Giulia Strapazzon , Vanessa de Moraes Andrade , Alexandre Pastoris Muller","doi":"10.1016/j.exer.2024.110216","DOIUrl":"10.1016/j.exer.2024.110216","url":null,"abstract":"<div><div>High intraocular pressure (HIOP) and high glucose levels are associated with oxidative stress. Although physical exercise protects against oxidative damage, its specific impact on eye health remains unclear. Thus, this study aimed to assess the impact of physical exercise on the oxidative status of whole eyes in male Swiss mice subjected to HIOP model and cafeteria diet (CD). In experiment one, mice were divided into sedentary, aerobic, and strength (four-week physical exercise) groups and subjected to an HIOP/ischemia model. In experiment two, mice were submitted to CD and voluntary physical exercise for 18 weeks, according to the following groups: sedentary control, sedentary CD, exercise control, and exercise CD. Experiment one revealed elevated 2′,7′-dichlorodihydrofluorescein (DCFH) levels in aerobic group, which decreased in all groups after ischemia. Nitrite levels were decreased on strength than in sedentary group. The superoxide dismutase (SOD) activity did not change in all treatments. Although catalase (CAT) activity increased in aerobic and strength groups, and after ischemia in all groups. In experiment two, the sedentary CD group presented higher body weight than the other groups. DCFH levels were increased in the exercise control and reduced in the exercise CD compared with the other groups. CAT activity and sulfhydryl groups were decreased, while protein carbonylation was increased in the sedentary CD group compared with the other groups. Thus, these results suggested that physical exercise promoted antioxidant effects on eyes exposed to an HIOP model and CD.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110216"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876695","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}
Jingyan Ge , Yinan Zhang , Ling Han , Liangliang Zhao , Hongwei Zhao , Dan Qiao , Yan Cheng
{"title":"Photobiomodulation inhibits retinal degeneration in diabetic mice through modulation of stem cell mobilization and gene expression","authors":"Jingyan Ge , Yinan Zhang , Ling Han , Liangliang Zhao , Hongwei Zhao , Dan Qiao , Yan Cheng","doi":"10.1016/j.exer.2024.110218","DOIUrl":"10.1016/j.exer.2024.110218","url":null,"abstract":"<div><div>The number of people suffering from type 2 diabetes (DM2) is increasing and over 30 percent of DM2 patients will develop diabetic retinopathy (DR). Available therapeutic approaches for DR have their limitations. It is of great significance to search for other effective alternate therapeutic approaches. The present study aimed to explore the beneficial effects of photobiomodulation (PBM) on the diabetic retinopathy and underlying mechanisms. Streptozotocin was administered to male mice to establish diabetic model. The mice in the diabetic group (DM) received no treatment, and the mice in DM + PBM group received LED illumination (wavelength 670 nm) once a day for 20 consecutive weeks. Retinal vessel degenerate changes, the expression levels of E-Cadherin, N-Cadherin and the mRNA levels of c-kit, CXCR4, MYPT1, SCF, SDF1-α in retina, the levels of SDF-1α and SCF in the peripheral blood and the number of LSK cells expressing c-kit and sca-1 were determined. PBM could significantly inhibit the degenerative change of diabetic retinal vessels, decrease the expression levels of E-Cadherin and N-Cadherin and the mRNA levels of c-kit, CXCR4, MYPT1, SCF, SDF1-α and increase VEGF mRNA levels in retina. PBM could also increase the levels of SDF-1α and SCF in the peripheral blood and the number of LSK cells expressing c-kit and sca-1 in diabetic mice. PBM at 4 min/day for 20 consecutive weeks significantly inhibit the degenerative change of diabetic retinal vessels, and PBM is likely to produce its beneficial effects on the retina through promoting the migration of bone marrow stem cells to circulation and diabetic retinal tissue. The present study provides a new therapeutic direction and experimental foundation for the treatment of diabetic retinopathy.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110218"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881676","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":"In Memoriam: David S. Papermaster (1937–2024)","authors":"Dean Bok, Steven J. Fliesler","doi":"10.1016/j.exer.2024.110184","DOIUrl":"10.1016/j.exer.2024.110184","url":null,"abstract":"","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110184"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143155413","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}
LingQiao Li , Han Bao , ErChi Zhang , ShuTing Wu , XiaoYang Jiang , YuJia Xiao , ShiJing Fan , YiXin Luo , YunYun Huang , Pei Zhang , Michael Swain , Ahmed Elsheikh , ShiHao Chen , XiaoBo Zheng
{"title":"Effect of corneal cross-linking on biomechanical properties of swollen rabbit corneas","authors":"LingQiao Li , Han Bao , ErChi Zhang , ShuTing Wu , XiaoYang Jiang , YuJia Xiao , ShiJing Fan , YiXin Luo , YunYun Huang , Pei Zhang , Michael Swain , Ahmed Elsheikh , ShiHao Chen , XiaoBo Zheng","doi":"10.1016/j.exer.2024.110191","DOIUrl":"10.1016/j.exer.2024.110191","url":null,"abstract":"<div><div>Corneal cross-linking (CXL) is an effective method to prevent the progression of keratoconus. CXL combined with hypotonic riboflavin solution is a modified treatment for thin corneas, which are deemed to be below the safe thickness threshold. In this study, rabbit corneas were subjected to different hydration levels using different osmolarity of riboflavin dextran solutions before CXL. Inflation testing was performed to evaluate the corneal biomechanical stiffening effect of hypotonic riboflavin solutions crosslinking. One-month post-CXL, the stromal demarcation line depth (DLD) and the biomechanical property parameter – tangent modulus (Et) – were measured. All CXL groups showed higher Et than the corresponding Ctrl groups (all P < 0.001), however, the Et values showed no statistical differences between the CXL-ed groups with different hydration levels (all P > 0.05). The relative depth ratio of DLD to total corneal thickness (TCT) did not show significant differences (P > 0.05), while the DLD was statistically different in three CXL groups (P < 0.001). The research suggested that riboflavin solutions with different osmolarities are suitable for preoperative swelling of corneas with different thickness ranges. Furthermore, crosslinking with hypotonic riboflavin solutions has no significant effect on corneal biomechanical improvement under a certain degree of hydration.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110191"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767658","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}
Lei Lin , Lili Liang , Liming Xu , Yu Zheng , Hanwen Guo , Bei Zhang , Yun-e Zhao
{"title":"Heat stress regulates the migration and proliferation of lens epithelial cells through ferroptosis and NCOA4-FTH1 interaction","authors":"Lei Lin , Lili Liang , Liming Xu , Yu Zheng , Hanwen Guo , Bei Zhang , Yun-e Zhao","doi":"10.1016/j.exer.2024.110182","DOIUrl":"10.1016/j.exer.2024.110182","url":null,"abstract":"<div><div>Posterior capsule opacification (PCO) due to the proliferation and migration of lens epithelial cells (LECs) is the main complication after surgery. Heat stress has demonstrated impressive results in halting cell proliferation and migration, while also facilitating cell death. This study aimed to investigate the role and mechanism of ferroptosis in the proliferation and migration of LECs under heat stress. CCK-8 assays, scratch assays, and transcriptome analysis were used to evaluate the impact of temperature on human lens epithelial cells (HLECs) and explore the potential mechanisms. The role of ferroptosis in the proliferation of HLECs induced by heat was investigated using the ferroptosis inhibitor Fer-1 and siRNA-mediated NCOA4 protein interference. Fluorescence staining and Western blot experiments were used to detect the expression of Fe<sup>2+</sup>, reactive oxygen species (ROS), and ferroptosis-related proteins NCOA4, FTH1, and SLC3A2. The results of CCK-8 assays, scratch assays, and transcriptome analysis demonstrated significant thermal effects on HLEC behavior. After heat treatment, there were significant changes in the fluorescence expression of Fe<sup>2+</sup> and ROS in the HLECs and lens explant. In addition, the expression of NCOA4, FTH1, and SLC3A2 also changed significantly. Using Fer-1 or NCOA4 siRNA-mediated interference restored cell viability decreased by thermal stress. Furthermore, interference with NCOA4 protein effectively restored the expression of Fe<sup>2+</sup>, ROS, and FTH1. In conclusion, heat stress has a significant effect on LECs by regulating ferroptosis and the interaction between NCOA4 and FTH1 proteins play an important role.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110182"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715800","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}
Mohammad Soleimani , Seyed Mahbod Baharnoori , Hamed Massoumi , Kasra Cheraqpour , Hassan Asadigandomani , Arash Mirzaei , Mohammad Javad Ashraf , Raghuram Koganti , Madhurima Chaudhuri , Mahmood Ghassemi , Elmira Jalilian , Ali R. Djalilian
{"title":"A deep dive into radiation keratopathy; Going beyond the current frontierss","authors":"Mohammad Soleimani , Seyed Mahbod Baharnoori , Hamed Massoumi , Kasra Cheraqpour , Hassan Asadigandomani , Arash Mirzaei , Mohammad Javad Ashraf , Raghuram Koganti , Madhurima Chaudhuri , Mahmood Ghassemi , Elmira Jalilian , Ali R. Djalilian","doi":"10.1016/j.exer.2025.110234","DOIUrl":"10.1016/j.exer.2025.110234","url":null,"abstract":"<div><div>Radiotherapy is one of the conventional treatments for head and neck malignancies. Despite the implementation of protective measures to minimize the detrimental impact on healthy tissues surrounding the radiation site, radiation keratopathy remains a prevalent complication. We aimed to establish a mouse model of radiation keratopathy to characterize the pathophysiology of the disease and enable future identification of potential treatments. Thirty-six mice were divided equally into six groups. One eye of each mouse was irradiated with 5, 10, 15, 20, 25, and 30 Gy and the other eye used as a control. The mice were clinically monitored for one year, at which time eyes were tested using anterior segment optical coherence tomography, then the mice were euthanized, and the corneas dissected. Corneal sections were stained with hematoxylin and eosin, β-galactosidase, and CK12. The results indicated that animals experiencing increased doses of radiation had increased corneal vascularization, fibrosis, and opacity and conjuctivalization and a higher number of positive results of beta-galactosidase staining, which indicates an increase in the tendency of senescence. The results of β-III tubulin staining indicated that the density of corneal stromal nerves and the subepithelial nerve plexus decreases as the dose increases. Also, as the irradiation dose increases, the central corneal thickness decreases as well.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110234"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947127","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}