Tumor necrosis factor ligand-related molecule 1A maintains blood-retinal barrier via modulating SHP-1-Src-VE-cadherin signaling in diabetic retinopathy.

An impaired blood-retinal barrier (BRB) leads to diabetic macular edema (DME), which is a major complication of Diabetic retinopathy (DR). Mediators such as inflammation cause BRB breakdown. However, the explicit mechanism of its disruption is largely unknown. In this study, we identified tumor necrosis factor ligand-related molecule 1A (TL1A) as a crucial factor which protect retinal endothelial cells integrity in DR. By providing both human and mouse data, we show that TL1A is significantly decreased in the retinas of DME patients and diabetic rodents. We further demonstrate that the loss of TL1A accelerated diabetes-induced retinal barrier breakdown. TL1A supplementation protects the diabetic retina against BRB breakdown. Mechanistically, TL1A stabilize intracellular junctions and protect vascular integrity by blocking SHP1-Src-regulated VE-cadherin phosphorylation. Collectively, our findings reveal that loss of TL1A in the retina leads to increased vascular permeability in DR, and that TL1A treatment is of potential therapeutic interest for the treatment of DME.

Coaxial double-hole PEDOT: PSS electrodes achieving tunable terahertz zoomable convergence.

The local wavefront modulation technique in the terahertz band is an important basis for the development of terahertz modulation technology. Here, an electrically controlled convergent tunable device based on patterned transparent electrode poly (3, 4-ethylenedioxythiophene): poly (styrene sulfonate) (PEDOT: PSS) is realized to locally tune the terahertz wavefront. The device consists of two substrates with circular-hole electrodes and liquid crystal sandwiched between them. The refractive index gradient of liquid crystal in the device can be generated by the coaxial double-hole electrodes, which realize continuous control of significant focusing of the terahertz wave. The test results show that the focal length can be modulated in the range of 3-12 cm with varied external voltage; when it varies from 3 to 8 V, the 1/e2 radius of the spot decreases to 1.3 mm, 0.27 times the initial state, and the spot central intensity magnification increases gradually with the change, up to 3.31 times. The acquisition of the large tunable focal length range of the continuous terahertz zoom device shows that the construction of the gradient refractive index is an important method to regulate the terahertz wavefront by optical means, which greatly promotes the research of terahertz imaging devices.

Photovoltaic properties in an orthorhombic Fe doped KTN single crystal.

Since the domain wall photovoltaic effect (DW-PVE) is reported in BiFeO3 film, the investigations on photovoltaic properties in ferroelectrics have appealed more and more attention. In this work, we employed two Fe doped KTa1-xNbxO3 (Fe:KTN) single crystals in tetragonal phase and orthorhombic phase, respectively, possessing similar net polarization along [001]C direction, to quantize the contribution on photovoltaic properties from bulk photovoltaic effect (BPVE) and DW-PVE in Fe:KTN. The results show that there are significant enhancements of open-circuit voltages (VOC = -6.0 V, increases over 440%) and short-circuit current density (JSC = 18.5 nA cm-2, increases over 1580%) in orthorhombic Fe:KTN with engineer-domain structure after poled, corresponding to 14.2 mV and 2.2 mV for the single domain wall and bulk region under illumination of 405 nm light (100 mW). It reveals that DW-PVE plays a major role in KTN-based ferroelectrics, indicating an orthorhombic Fe:KTN single crystal is one of the potential photovoltaic materials.

Characteristics and outcomes of vitrectomy for proliferative diabetic retinopathy in young versus senior patients.

BACKGROUND: Proliferative diabetic retinopathy (PDR) is one of the most common cause of vision loss in diabetic patients, and the incidence age of PDR patients gradually gets younger. This study aims to compare the characteristics of PDR and outcomes following vitrectomy in young and senior patients. METHODS: This is a retrospective case series study. Data of 116 eyes of 92 patients who underwent vitrectomy for PDR from February 2012 to February 2017 were reviewed, which were divided into young and senior patient groups. All patients were followed up for 24 months at least. RESULTS: There were 62.1% of eyes with tractional retinal detachment secondary to PDR in the young patient group, while only 12.1% of eyes in the senior patient group with this surgery indication. (P < 0.001) The best corrected visual acuity increased in 41 eyes (70.7%), stable in 9 eyes (15.5%), and decreased in 8 eyes (13.8%) in young patients at the final follow-up. And it increased in 47 eyes (81.0%), stable in 2 eyes (3.4%), and decreased in 9 eyes (15.5%) in senior patients.(P = 0.085) Postoperative complications mainly included recurrent vitreous hemorrhage (24.1%), retinal detachment (3.4%), neovascular glaucoma (NVG) (27.6%) and nuclear sclerosis (53.4%) in young patients, and it was 19.0, 0.0, 1.7 and 3.4% in senior patients respectively. CONCLUSION: PDR of young patients is more severe than that of senior patients, and vitrectomy is an effective and safe method for PDR treatment. NVG is a main and severe complication besides nuclear sclerosis in young patients, and the incidence of NVG is higher compared to that in senior patients.

Is it necessary to use tobramycin-dexamethasone eye ointment prophylactically in eyes at the end of intraocular surgery?

BACKGROUND: There are no data available regarding the complications associated with using antibiotic ointment at the end of intraocular surgery. This study aimed to explore the necessity of using ocular tobramycin-dexamethasone prophylactically at the end of intraocular surgery. METHODS: This was a retrospective cohort study of patients who received intraocular surgery at Tianjin Medical University General Hospital from January 2015 to December 2017. The patients were grouped according to whether they received tobramycin-dexamethasone eye ointment or not after surgery. The Tobramycin dexamethasone eye ointment was sampled to observe bacterial contamination pathogens at 0.5, 1, 1.5, 2, 2.5, 3, 6, 8, 24, 36, 48, 72, and 168 h after being opened. RESULTS: A total of 3811 eyes in 3811 patients (mean age of 63 ± 12 years) were included: 2397 eyes that received prophylactic tobramycin-dexamethasone eye ointment and 1414 eyes that did not. The overall rate of endophthalmitis was 0.08% (3/3811) in our study, all in the eye ointment group (0.12%, 3/2397); no patients developed endophthalmitis in the non-ointment group (0%, 0/1414)(P = 0.184). The anterior chamber reactions 1 day after surgery were more serious in the eye ointment group compared with the non-ointment group (all P < 0.05), but there were no statistically significant differences at 1 month postoperatively (all P > 0.05). The contamination rate was 0% at all time points over 7 days. CONCLUSION: We did not observe a statistically significant difference in the incidence of endophthalmitis in patients with or without prophylactic tobramycin-dexamethasone eye ointment. And tobramycin-dexamethasone eye ointment seemed to increase some side effects such as eye secretions increasing and foreign body feeling.

Impact of dipolar clusters on electro-optic effects in KTa1- xNbxO3 crystal.

Dipolar clusters are crucial structure factors in electro-optic (EO) effects. Here, the impacts of dipolar clusters on EO effects are investigated in KTa1-xNbxO3 using electric-field-dependent EO characteristics. The results indicate that the field-driven reorientation of dipolar clusters determines the orientational electric susceptibility, deeply contributing to the excellent quadratic EO effects. The controlled average size of correlated local dipoles and uniform orientation of ferroelectric domains efficiently suppress light scattering, being beneficial for the modulation of incident light. The understanding of dipolar cluster-triggered EO responses is valuable for exploring origins of large EO effects and optimizing EO properties of materials.

Transplantation of IL-10-transfected endothelial progenitor cells improves retinal vascular repair via suppressing inflammation in diabetic rats.

PURPOSE: We aimed to evaluate the effect of IL-10 gene transfection on endothelial progenitor cells (EPCs) under inflammatory conditions, and explore the therapeutic potential of IL-10-transfected EPC transplantation on nonproliferative diabetic retinopathy (NPDR). METHODS: Lentivirus vectors encoding IL-10 were constructed and introduced into EPCs isolated from rat bone marrow. After exposure to recombinant rat TNF-α, abilities of nontransfected EPCs (non-EPCs) and EPCs transfected with normal control lentivirus (EPCs-GFP) or IL-10 expressing lentivirus (EPCs-IL-10-GFP) were assessed, including migration, adhesion, and tube formation. IL-10 production by EPCs-IL-10-GFP was determined by ELISA. Following 12 weeks after establishment of diabetes, diabetic rats were randomly injected with non-EPCs, EPCs-GFP, or EPCs-IL-10-GFP via tail vein. Expression of inflammatory factors and factors associated with nuclear factor-kappa B (NF-kB) signal pathway, retinal histological analysis, and retinal vascular permeability were assessed 2 weeks after transplantation. RESULTS: The detrimental effects of TNF-ɑ on the abilities of EPCs were significantly attenuated in EPCs-IL-10-GFP compared with non-EPCs and EPCs-GFP. The concentration of IL-10 in the EPCs-IL-10-GFP group was significantly higher than the non-EPCs and EPCs-GFP groups. Additionally, transplantation of EPCs-IL-10-GFP significantly inhibited inflammatory factors expression and activation of NF-kB signal pathway, improved retinal histological changes, and attenuated retinal vascular permeability. CONCLUSION: In conclusion, transplantation of IL-10-transfected EPCs significantly improved EPCs-mediated retinal vascular repair and subsequently suppressed NPDR progression. This was associated with inflammation suppression, at least partly via inhibiting the NF-kB signal pathway. Transplantation of IL-10-transfected EPCs may be a new strategy for treatment of NPDR.

TNFSF15 Inhibits Blood Retinal Barrier Breakdown Induced by Diabetes.

Tumor necrosis factor superfamily 15 (TNFSF15) is an endogenous neovascularization inhibitor and an important negative regulator of vascular homeostasis. This study aimed to explore the potential role of TNFSF15 in diabetic retinopathy. Vitreous TNFSF15 and VEGF levels in proliferative diabetic retinopathy (PDR) patients were detected by ELISA. Retinal expression of TNFSF15 and the content of tight junction proteins (TJPs) in rats were detected by immunohistochemistry and Western blot, respectively. The blood retinal barrier (BRB) permeability was evaluated using Evans Blue (EB) dye. The TNFSF15/VEGF ratio was decreased in the vitreous fluid of patients with PDR relative to the controls, even though the expression levels of TNFSF15 were higher. TNFSF15 was dramatically decreased one month later after diabetes induction (p < 0.001), and then increased three months later and thereafter. TNFSF15 treatment significantly protected the BRB in the diabetic animals. Diabetes decreased TJPs levels in the retina, and these changes were inhibited by TNFSF15 treatment. Moreover, TNFSF15 decreased activation of VEGF both in mRNA and protein levels caused by diabetes. These results indicate that TNFSF15 is an important inhibitor in the progression of DR and suggest that the regulation of TNFSF15 shows promise for the development of diabetic retinopathy treatment strategies.

Therapeutic efficacy of methylprednisolone sodium succinate via diverse administration routes for mid- to high-frequency sudden sensorineural hearing loss.

BACKGROUND: Sudden sensorineural hearing loss (SSNHL), characterized by a rapid and unexplained loss of hearing, particularly at moderate to high frequencies, presents a significant clinical challenge. The therapeutic use of methylprednisolone sodium succinate (MPSS) via different administration routes, in combination with conventional medications, remains a topic of interest. AIM: To compare the therapeutic efficacy of MPSS administered via different routes in combination with conventional drugs for the treatment of mid- to high-frequency SSNHL. METHODS: The medical records of 109 patients with mid- to high-frequency SSNHL were analyzed. The patients were divided into three groups based on the route of administration: Group A [intratympanic (IT) injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection], Group B (intravenous injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection), and Group C (single IT injection of MPSS). The intervention effects were compared and analyzed. RESULTS: The posttreatment auditory thresholds in Group A (21.23 ± 3 .34) were significantly lower than those in Groups B (28.52 ± 3.36) and C (30.23 ± 4.21; P < 0.05). Group A also exhibited a significantly greater speech recognition rate (92.23 ± 5.34) than Groups B and C. The disappearance time of tinnitus, time to hearing recovery, and disappearance time of vertigo in Group A were significantly shorter than those in Groups B and C (P < 0.05). The total effective rate in Group A (97.56%) was significantly greater than that in Groups B and C (77.14% and 78.79%, χ 2 = 7.898, P = 0.019). Moreover, the incidence of adverse reactions in Groups A and C was significantly lower than that in Group B (4.88%, 3.03% vs 2.57%, χ 2 = 11.443, P = 0.003), and the recurrence rate in Group A was significantly lower than that in Groups B and C (2.44% vs 20.00% vs 21.21%, χ 2 = 7.120, P = 0.028). CONCLUSION: IT injection of MPSS combined with conventional treatment demonstrates superior efficacy and safety compared to systemic administration via intravenous infusion and a single IT injection of MPSS. This approach effectively improves patients' hearing and reduces the risk of disease recurrence.

Interaction between parental myopia and children lifestyle on the incidence of myopia among children aged 6-18 years: a cross-sectional study in Tianjin, China.

OBJECTIVES: This study aimed to explore the influence of the interaction between parental myopia and lifestyle on myopia among school-age children. DESIGN: Cross-sectional study. SETTING: This study used data from the Tianjin Child and Adolescent Research of Eye between August and October 2022. PARTICIPANTS: A total of 49 035 participants between 6 and 18 years of age were eligible for this study. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the interaction between eye-healthy lifestyle and parental myopia on myopia. Parental myopia and eye-healthy lifestyle were ascertained by a Child and Adolescent Behavior Questionnaire. The lifestyle risk score (LRS) of eye health was calculated based on beta-coefficient in the backward regression model. The interaction between LRS and parental myopia was analysed by multivariate logistic regression. The predictive value of different predicted models was estimated using receiver operating characteristic curves. Multiple linear regression was used to evaluate the associations of lifestyle risk factors and parental myopia with spherical equivalent refraction, which were defined as the secondary outcomes. RESULTS: A total of 31 839 participants aged 6-18 years were included, and the myopia prevalence was 55.46%. Eye-healthy lifestyle and parental myopia were significantly associated with myopia, as was interaction. The predictive value for LRS & parental myopia was 0.714 (95% CI: 0.709 to 0.720), which was higher than LRS (0.693, 95% CI: 0.687 to 0.699) and parental myopia (0.710, 95% CI: 0.704 to 0.716) separately. CONCLUSIONS: High-risk lifestyles of myopia and parental myopia were significantly associated with a higher risk of myopia, and the combination had the strongest effect. For children, lifestyle adjustment should be prioritised in preventing myopia, especially for those with parental myopia.

The Myopia Prevalence and Association With Physical Activity Among Primary School Students Aged 6-12 Years: A Cross-Sectional Study in Tianjin, China.

Purpose: This study aimed to investigate the prevalence of myopia and determine the association between physical activity and risk of myopia among primary school students in Tianjin, China. Methods: A cross-sectional study was conducted among subjects from nine primary schools. All of the subjects underwent visual acuity and spherical equivalent (SE) with noncycloplegic autorefraction measurement. Myopia was defined as an SE refraction ≤-0.50D and an uncorrected visual acuity <5.0 in either eye. Physical activity was measured via the Physical Activity Questionnaire for Children. Data were analyzed using the Pearson χ2 test and binary logistic regression. Stratification analysis by sex was also performed. Results: A total of 2976 participants (1408 boys and 1568 girls) aged six to 12 years (mean age 8.82 years) were included in this study. The overall prevalence of myopia was 52.92%. When stratified according to physical activity, myopia prevalence significantly decreased with increasing physical activity levels (χ2 trend test = 127.63, P < 0.001). In the binary logistic regression analysis, after adjusting for age, sex, and school region, the odds ratio for the association between physical activity and myopia was 0.762 (95% confidence interval, 0.675-0.862, P < 0.001). When stratified by sex, the significant statistical association between physical activity and myopia both can be found in two groups (P < 0.05). Conclusions: Higher levels of physical activity were independently associated with decreased risk of myopia. The significant reverse statistical association between physical activity and myopia can be found in male or female groups. Translational Relevance: Taking part in physical activities may be an effective way to reduce the prevalence of myopia.

An interpretable model predicts visual outcomes of no light perception eyes after open globe injury.

BACKGROUND: The visual outcome of open globe injury (OGI)-no light perception (NLP) eyes is unpredictable traditionally. This study aimed to develop a model to predict the visual outcomes of vitrectomy surgery in OGI-NLP eyes using a machine learning algorithm and to provide an interpretable system for the prediction results. METHODS: Clinical data of 459 OGI-NLP eyes were retrospectively collected from 19 medical centres across China to establish a training data set for developing a model, called 'VisionGo', which can predict the visual outcome of the patients involved and compare with the Ocular Trauma Score (OTS). Another 72 cases were retrospectively collected and used for human-machine comparison, and an additional 27 cases were prospectively collected for real-world validation of the model. The SHapley Additive exPlanations method was applied to analyse feature contribution to the model. An online platform was built for real-world application. RESULTS: The area under the receiver operating characteristic curve (AUC) of VisionGo was 0.75 and 0.90 in previtrectomy and intravitrectomy application scenarios, which was much higher than the OTS (AUC=0.49). VisionGo showed better performance than ophthalmologists in both previtrectomy and intravitrectomy application scenarios (AUC=0.73 vs 0.57 and 0.87 vs 0.64). In real-world validation, VisionGo achieved an AUC of 0.60 and 0.91 in previtrectomy and intravitrectomy application scenarios. Feature contribution analysis indicated that wound length-related indicators, vitreous status and retina-related indicators contributed highly to visual outcomes. CONCLUSIONS: VisionGo has achieved an accurate and reliable prediction in visual outcome after vitrectomy for OGI-NLP eyes.

Long-term outcomes of administration of intravitreal triamcinolone acetonide after posterior vitreous detachment during pars plana vitrectomy for proliferative diabetic retinopathy.

AIM: To evaluate the long-term outcomes of intravitreal triamcinolone acetonide (TA) administration after posterior vitreous detachment (PVD) during pars plana vitrectomy (PPV) for patients with proliferative diabetic retinopathy (PDR). METHODS: A total of 189 eyes (152 patients) who underwent PPV for severe PDR were reviewed. Intravitreal injection of TA (IVTA) was administered during PPV in 118 eyes (PPV+IVTA group), and 71 eyes did not receive IVTA (PPV group). Immediately after PVD, when most of the vitreous and proliferative membranes were removed, 0.1 mL TA (40 mg/mL) was injected into the vitreous cavity in the PPV+IVTA group. All patients were followed-up for least 12 months. Visual outcomes and postoperative complications were recorded and compared between the two groups. RESULTS: IVTA was helpful for proliferative membrane peeling and haemostasis during PPV. In the PPV+IVTA group, best-corrected visual acuity had significantly improved and the intraocular pressure was controlled well during the follow-up. The incidence of early recurrent vitreous haemorrhage after PPV was significantly lower in the PPV+IVTA group (1.7%) than in the PPV group (9.9%) (p=0.028). CONCLUSION: The administration of IVTA after PVD during PPV can effectively improve the final visual outcomes and prevent postoperative complications in patients with severe PDR.

Global Trends of Gastrointestinal Endoscopy Anesthesia/Sedation: A Bibliometric Study (from 2001 to 2022).

Background: Gastrointestinal (GI) endoscopy becomes more and more common now in order to diagnose and treat GI diseases, and anesthesia/sedation plays an important role. We aim to discuss the developmental trends and evaluate the research hotspots using bibliometric methods for GI endoscopy anesthesia/sedation in the past two decades. Methods: The original and review articles published from 2001 to December 2022 related to GI endoscopy anesthesia/sedation were extracted from the Web of Science database. Four different softwares (CiteSpace, VOSviewer, and Bibliometrix, Online Analysis Platform of Literature Metrology (Bibliometric)) were used for this comprehensive analysis. Results: According to our retrieval strategy, we found a total of 3154 related literatures. Original research articles were 2855, and reviews were 299. There has been a substantial increase in the research on GI endoscopy anesthesia/sedation in recent 22 years. These publications have been cited 66,418 times, with a mean of 21.04 citations per publication. The US maintained a leading position in global research, with the largest number of publications (29.94%), and China ranked second (19.92%). Keyword burst and concurrence showed that conscious sedation, colonoscopy and midazolam were the most frequently occurring keywords. Conclusion: Our research found that GI endoscopy anesthesia/sedation was in a period of rapid development and demonstrated the improvement of medical instruments and surgical options that had significantly contributed to the field of GI endoscopy anesthesia/sedation. The US dominates this field, and the selection and dosage of sedative regimens have always been the foci of disease research to improve comfort and safety, while adverse events and risks arouse attention gradually. In the past 20 years, hotspots mainly focus on upper gastrointestinal endoscopy, gastroscopy, and esophagogastroduodenoscopy. These data would provide future directions for clinicians and researchers regarding GI endoscopy anesthesia/sedation.

Prevalence of myopia among children and adolescents aged 6-16 during COVID-19 pandemic: a large-scale cross-sectional study in Tianjin, China.

PURPOSE: This study aimed to determine the prevalence of myopia among children and adolescents aged 6-16 years during COVID-19 pandemic in Tianjin, China. METHODS: This was a cross-sectional study using data from the Tianjin Child and Adolescent Research of Eye between March and June in 2021. A total of 909 835 children and adolescents aged 6-16 years from 1348 primary and secondary schools in Tianjin, China were recruited. Prevalence of myopia with 95% CIs was described in different regions, sexes and ages. The regions-standardised prevalence rate and chain growth rate of myopia in different ages were described the characteristics of myopia. RESULTS: A total of 864 828 participants (95.05% participation rate) were included in the analysis. The age range was 6-16 with a mean age of 11.50±2.79 years. The overall prevalence of myopia was 54.71% (95% CI 54.60% to 54.81%). The prevalence of myopia was 57.58% (95% CI 57.43% to 57.73%) for girls and 52.05% (95% CI 51.91% to 52.20%) for boys. Students living in the six central districts had the highest prevalence of moderate myopia (19.09% (95% CI 19.01% to 19.17%)) and high myopia (5.43% (95% CI 5.39% to 5.48%)). The regions-standardised prevalence of myopia was increased by age and the highest chain growth rate of myopia was up to 47.99% at 8 years. CONCLUSIONS: The prevalence of myopia in Tianjin is high during COVID-19 pandemic. The progression of myopia started to increase dramatically at 8 years, and the increasing slowed down at 14 years. For policy-makers, intervention in the lower age groups may be important to control myopia progression.

EE-Explorer: A Multimodal Artificial Intelligence System for Eye Emergency Triage and Primary Diagnosis.

PURPOSE: To develop a multimodal artificial intelligence (AI) system, EE-Explorer, to triage eye emergencies and assist in primary diagnosis using metadata and ocular images. DESIGN: A diagnostic, cross-sectional, validity and reliability study. METHODS: EE-Explorer consists of 2 models. The triage model was developed from metadata (events, symptoms, and medical history) and ocular surface images via smartphones from 2038 patients presenting to Zhongshan Ophthalmic Center (ZOC) to output 3 classifications: urgent, semiurgent, and nonurgent. The primary diagnostic model was developed from the paired metadata and slitlamp images of 2405 patients from ZOC. Both models were externally tested on 103 participants from 4 other hospitals. A pilot test was conducted in Guangzhou to evaluate the hierarchical referral service pattern assisted by EE-Explorer for unspecialized health care facilities. RESULTS: A high overall accuracy, as indicated by an area under the receiver operating characteristic curve (AUC) of 0.982 (95% CI, 0.966-0.998), was obtained using the triage model, which outperformed the triage nurses (P < .001). In the primary diagnostic model, the diagnostic classification accuracy (CA) and Hamming loss (HL) in the internal testing were 0.808 (95% CI 0.776-0.840) and 0.016 (95% CI 0.006-0.026), respectively. In the external testing, model performance was robust for both triage (average AUC, 0.988, 95% CI 0.967-1.000) and primary diagnosis (CA, 0.718, 95% CI 0.644-0.792; and HL, 0.023, 95% CI 0.000-0.048). In the pilot test in the hierarchical referral settings, EE-explorer demonstrated consistently robust performance and broad participant acceptance. CONCLUSION: The EE-Explorer system showed robust performance in both triage and primary diagnosis for ophthalmic emergency patients. EE-Explorer can provide patients with acute ophthalmic symptoms access to remote self-triage and assist in primary diagnosis in unspecialized health care facilities to achieve rapid and effective treatment strategies.

DeepFundus: A flow-cytometry-like image quality classifier for boosting the whole life cycle of medical artificial intelligence.

Medical artificial intelligence (AI) has been moving from the research phase to clinical implementation. However, most AI-based models are mainly built using high-quality images preprocessed in the laboratory, which is not representative of real-world settings. This dataset bias proves a major driver of AI system dysfunction. Inspired by the design of flow cytometry, DeepFundus, a deep-learning-based fundus image classifier, is developed to provide automated and multidimensional image sorting to address this data quality gap. DeepFundus achieves areas under the receiver operating characteristic curves (AUCs) over 0.9 in image classification concerning overall quality, clinical quality factors, and structural quality analysis on both the internal test and national validation datasets. Additionally, DeepFundus can be integrated into both model development and clinical application of AI diagnostics to significantly enhance model performance for detecting multiple retinopathies. DeepFundus can be used to construct a data-driven paradigm for improving the entire life cycle of medical AI practice.

Prognostic value of preoperative inflammatory markers among different molecular subtypes of lower-grade glioma.

BACKGROUND: The inflammatory response is closely related to cancer progression and prognosis. The aim of this study was to determine the prognostic value of preoperative inflammatory markers among different molecular subtypes of lower-grade glioma (LGG). METHODS: We performed a retrospective analysis of 214 patients with LGG from 2001 to 2013, evaluating the effect of the neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR) and derived NLR (dNLR) on prognosis among different molecular subtypes. Isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase (TERT) promotor mutations were detected by gene sequencing, and Chromosome arms 1p and 19q (1p/19q) codeletion was estimated via fluorescence in situ hybridization. RESULTS: Survival analysis showed that a high NLR, low LMR, and high dNLR were associated with poor prognosis, while the PLR had no prognostic significance. The subsequent molecular subtype analysis indicated that a high NLR and dNLR predicted worse survival in the IDH mutation only group, a high NLR and PLR predicted worse survival in the IDH and TERT promoter mutation group, and a high PLR was associated with shorter survival in the triple-positive group. Furthermore, univariate and multivariate Cox regression analysis suggested that the dNLR was an independent prognostic factor for LGG. Finally, the prognostic nomogram was developed by integrating the inflammatory marker dNLR and independent clinical risk factors. CONCLUSION: The results of this study indicated that a high dNLR was an independent risk factor for overall survival rates in patients with LGG, which may increase prognostic accuracy and improve patient outcomes.

Timely vitrectomy without intraocular lens removal for acute endophthalmitis after cataract surgery.

AIM: To investigate the clinical features, causative organisms and effects of timely vitrectomy and silicone oil tamponade without intraocular lens (IOL) removal in the treatment of acute-onset endophthalmitis after cataract surgery (APCE). METHODS: We retrospectively analyzed the clinical features and microbiological factors in 10 eyes of 10 patients with APCE at Tianjin Medical University General Hospital from January 2010 to December 2018. Data on the clinical features, causative organisms, visual acuity, intraocular pressure (IOP) and complications were collected. The mean follow-up period was 25.5mo. RESULTS: The mean age of the patients was 71.4y. The mean time between cataract surgery and the onset of endophthalmitis was 2.0d. Preoperative visual acuity ranged from no light perception to hand motion. After vitrectomy, the visual acuity increased in nine eyes (90%), and was unchanged in one eye (10%). A significant difference was observed between the mean preoperative (36.3±7.1 mm Hg) and postoperative IOP (14.9±4.3 mm Hg, P<0.05). Staphylococcus epidermidis was isolated in 5 eyes, S. aureus in 2 eyes, and Enterococcus in 1 eye. Postoperative complications mainly included fibrin exudates in the anterior chamber at the early stages in all eyes and temporary IOP elevation in one eye. No retinal detachment or ocular atrophy was observed during the follow-up period. CONCLUSION: Under systemic antibiotic treatment and timely diagnosis, vitrectomy and silicone oil tamponade without IOL removal is a safe and effective method for APCE.

Inhibition of ferroptosis promotes retina ganglion cell survival in experimental optic neuropathies.

Retinal ganglion cell (RGC) death is a hallmark of traumatic optic neuropathy, glaucoma, and other optic neuropathies that result in irreversible vision loss. However, therapeutic strategies for rescuing RGC loss still remain challenging, and the molecular mechanism underlying RGC loss has not been fully elucidated. Here, we highlight the role of ferroptosis, a non-apoptotic form of programmed cell death characterized by iron-dependent lethal lipid peroxides accumulation, in RGC death using an experimental model of glaucoma and optic nerve crush (ONC). ONC treatment resulted in significant downregulation of glutathione peroxidase 4 (GPx4) and system xc(-) cystine/glutamate antiporter (xCT) in the rat retina, accompanied by increased lipid peroxide and iron levels. The reduction of GPx4 expression in RGCs after ONC was confirmed by laser-capture microdissection and PCR. Transmission electron microscopy (TEM) revealed alterations in mitochondrial morphology, including increased membrane density and reduced mitochondrial cristae in RGCs after ONC. Notably, the ferroptosis inhibitor ferrostatin-1 (Fer-1) significantly promoted RGC survival and preserved retinal function in ONC and microbead-induced glaucoma mouse models. In addition, compared to the apoptosis inhibitor Z-VAD-FMK, Fer-1 showed better effect in rescuing RGCs death in ONC retinas. Mechanistically, we found the downregulation of GPx4 mainly occurred in the mitochondrial compartment, accompanied by increased mitochondrial reactive oxygen species (ROS) and lipid peroxides. The mitochondria-selective antioxidant MitoTEMPO attenuated RGC loss after ONC, implicating mitochondrial ROS and lipid peroxides as major mechanisms in ferroptosis-induced RGC death in ONC retinas. Notably, administering Fer-1 effectively prevented the production of mitochondrial lipid peroxides, the impairment of mitochondrial adenosine 5'-triphosphate (ATP) production, and the downregulation of mitochondrial genes, such as mt-Cytb and MT-ATP6, in ONC retinas. Our findings suggest that ferroptosis is a major form of regulated cell death for RGCs in experimental glaucoma and ONC models and suggesting targeting mitochondria-dependent ferroptosis as a protective strategy for RGC injuries in optic neuropathies.