Purpose:Diabetic retinopathy (DR) remains a leading cause of vision loss, with macrophages and glycosylation dysregulation implicated in DR pathogenesis. However, the potential as diagnostic biomarkers has been rarely investigated. Methods:We integrated single-cell RNA sequencing (scRNA-seq) datasets to profile DR cell landscapes. The immune cell heterogeneity was dissected, and glycosylation-related transcriptional programs were delineated in DR. Machine learning-based diagnostic modeling was also conducted to identify macrophage differentiation-related glycosylation genes (MDRGGs). Results:Macrophages exhibited elevated abundance in proliferative DR and showed intense interactions with other monocytes. Endothelial cells were subdivided into four subtypes, with Endo_KCNQ3 representing a dominant proliferative and highly glycosylated phenotype. Monocytes were clustered into three subtypes; Mono_RGS1 emerged as a transitional phenotype in the monocyte-to-macrophage trajectory. Macro_MIR181A1HG was identified as a proliferative and glycosylation-active macrophage subset. A total of 100 MDRGGs were identified. Among them, seven hub genes (AKAP13, SRGAP2, AFF1, ARHGAP24, RNF149, PTK2B, ATP1B3) were incorporated into a diagnostic model. The model achieved high predictive accuracy in both training and external validation cohorts (AUC > 0.85) and was further validated via nomogram and decision curve analyses. Conclusion:Glycosylation is closely associated with macrophage heterogeneity in DR. A seven-gene MDRGG-based diagnostic model demonstrated robust diagnostic performance in DR.

The aim of the present study was to investigate the efficacy and safety of posterior chamber Ejinn Phakic Refractive Lens (EPRL) for patients with ultra-high myopia. A total of 51 eyes from 26 patients with ultra-high myopia underwent EPRL implantation at Zhongshan Ophthalmic Center (Guangzhou, China) between July 2021 and November 2022, were enrolled in this retrospective study. Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), refractive errors, anterior chamber depth (ACD), and corneal endothelial cell density were measured before and after surgery. The efficacy index (postoperative UDVA/ preoperative CDVA), safety index (postoperative CDVA/preoperative CDVA), and factors influencing postoperative vault, and EPRL position through anterior segment optical coherence tomography were analyzed. Inter-eye correlation was addressed using generalized estimating equation (GEE) models. Multiple linear regression analysis adjusted for age, gender, EPRL model, EPRL diopter, lens thickness, postoperative ACD, and anterior chamber width was used to evaluate factors associated with postoperative vault, decentration, and tilt of EPRL. The mean age of these 26 patients (five male and 21 female) who underwent EPRL implantation was 30.27 +/- 7.76 years. The mean preoperative and postoperative UDVA was 0.04 +/- 0.03 (0.01-0.12), and 0.50 +/- 0.23 (0.10-1.00). The mean preoperative and postoperative CDVA was 0.55 +/- 0.29 (0.15-1.00), and 0.70 +/- 0.26 (0.30-1.00). UDVA and CDVA were higher than those before surgery (p < 0.05). The efficacy index was 1.00 +/- 0.51 and the safety index was 1.44 +/- 0.45. The endothelial cell density was 2976.82 +/- 306.38 preoperationly, and 2854.43 +/- 335.693 postoperationly. The rate of endothelial cell loss was 3.98% (p = 0.057). The mean vault was 313.75 +/- 217.29 mu m. Vault was related to gender (male, beta = 0.51; 95% confidence interval [CI], 0.16 to 0.84; p = 0.014), larger diameter EPRL model (BK113, beta = 0.56; 95% CI, 0.18 to 0.87; p = 0.014), and EPRL diopter (beta = 0.39, 95% CI, 0.04 to 0.71; p = 0.032), and lens thickness (beta = -0.40, 95% CI, -0.72 to -0.08; p = 0.023). EPRL horizontal decentration was related to gender (male, beta = 0.42; 95% CI, 0.12 to 0.72; p = 0.036), smaller diameter EPRL model (BK108, beta = -0.35; 95% CI, -0.61 to -0.09; p = 0.036), anterior chamber width (beta = 0.52; 95% CI, 0.16 to 0.89; p = 0.036), and postoperative ACD (beta = -0.79; 95% CI, -1.41 to -0.17; p = 0.039). Severe complications were not detected at a mean follow-up period of 9.75 +/- 6.88 months. EPRL demonstrated effective correction of ultra-high myopia with relative safety in the short term. The postoperative position of EPRL exhibited a significant correlation with gender, EPRL model, and anterior chamber parameters.

PURPOSE:To investigate the characteristics of the vortex vein (VV) in healthy adults and patients with different fundus diseases using montaged ultra-widefield swept-source optical coherence tomography angiography (UWF SS-OCTA) images. METHODS:En face UWF SS-OCTA mosaic choroidal images in five fixation directions and macular scan were acquired in healthy adults, patients with normal choroidal thickness (retinal vein occlusion, diabetic retinopathy), patients with thick choroidal thickness (central serous chorioretinopathy and polypoidal choroidal vasculopathy), and patients with thin choroidal thickness (retinitis pigmentosa, and high myopia). The frequency, morphology, anastomoses, asymmetry and vascularity index (CVI) of VVs were assessed. RESULTS:The totality of VVs and macular CVI presented a gradual decline in the elderly (all P < 0.05). Anastomoses and asymmetric VVs appeared in normal eyes. The quantitation and morphology of VV in retinal vein occlusion, diabetic retinopathy, retinitis pigmentosa, and high myopia were not significantly different from those of controls. Macular CVI was reduced in retinitis pigmentosa and high myopia. There was an increased proportion of type I VV and a decrease in type IV VV in central serous chorioretinopathy and polypoidal choroidal vasculopathy groups (both P < 0.05). CVI in central serous chorioretinopathy was elevated, while it remained unchanged in polypoidal choroidal vasculopathy. The anastomoses and asymmetry in both groups were higher than those of controls (all P < 0.05). CONCLUSIONS:The distribution patterns of VVs exhibited similarity among healthy adults, patients with fundus diseases and normal choroidal thickness or thin choroidal thickness, with frequent observations of anastomoses and asymmetry. Notedly, pachychoroid diseases demonstrated a higher prevalence of high-resistance VVs (type IV), anastomoses, and asymmetry, which might drive pathogenesis of pachychoroid diseases.

The evolution of surgical techniques aims to augment surgeons' capabilities through digital guidance and robotization for higher precision and consistency. Currently, surgeries heavily rely on surgeon's experience and visual judgment, causing operation variations. Artificial intelligence (AI) offers a solution by extracting and digitizing surgical trajectories and features from videos to provide digital guidance. In this study, we collected 17,538 videos of capsulorhexis, a crucial step in cataract surgery, to create an AI-driven system named Meta Surgery (MetaS). MetaS evaluates and identifies ideal cases, extracts their digital characteristics, and fits an optimal capsulorhexis path in real-time during surgery. Surgeons performed capsulorhexis benefited from MetaS's guidance and a lens caliper, which increased the rate of ideal capsulorhexis by ~40%. Additionally, these digital features enabled a surgical robot to perform precise capsulorhexis autonomously in porcine eyes. This approach augments surgeons' surgical skills and paves the way for the autonomous operation of surgical robots.

PURPOSE:Retinal non-perfusion areas (NPAs) are a crucial biomarker for assessing the degree of retinal ischaemia of patients with retinal vascular diseases. Accurate identification of NPA is useful for assessing therapeutic approaches, guiding laser treatments and predicting prognosis. The ultra-widefield swept-source optical coherence tomography angiography (UWF-SS-OCTA) has emerged as a superior non-invasive imaging modality with an outstanding ability to detect NPA. This study aimed to establish an efficient NP-Unet model to accurately segment and quantify NPA in the UWF-SS-OCTA image of branch retinal vein occlusion (BRVO), central RVO (CRVO) and diabetic retinopathy (DR). METHODS:The 29×24 mm retinal images from the posterior pole of patients with retinal vascular diseases (BRVO, CRVO and DR) were acquired by the UWF-SS-OCTA. The enhanced inner retinal OCTA images datasets were constructed for model training. An efficient NP-Unet model was developed to precisely segment and quantify NPA with ischaemic index (ISI). The performance of the NP-Unet model was compared against different typical segmentation models. RESULTS:The NP-Unet model demonstrated its superior capability in segmenting and quantifying NPAs t0 the other models, achieving an accuracy of 93.4%, with an area under the curve of 0.986 and a dice similarity coefficient of 0.904. CONCLUSION:The NP-Unet model can efficiently and accurately segment and quantify NPAs with the ISI in the UWF-SS-OCTA image of BRVO, CRVO and DR, offering a non-invasive, valuable tool for clinical evaluation and treatment guidance.

PURPOSE:This study aimed to evaluate the feasibility of ultra-widefield swept-source optical coherence tomography angiography (UWF SS-OCTA) in guiding laser photocoagulation for retinal vascular diseases. METHODS:A total of 285 eyes from 195 patients with retinal vein occlusion and diabetic retinopathy were retrospectively evaluated at the Medical Retina Department of Zhongshan Ophthalmic Center, Sun Yat-sen University, from July 24 to October 27, 2023. All patients underwent UWF SS-OCTA (VG200, Intalight Imaging, Ltd, Luoyang, China) examination with a single scan using the widefield AngioMosaic protocol. A subset of patients also underwent fluorescein fundus angiography and fundus photography based on clinical discretion. Retinal nonperfusion area, a key biomarker for guiding laser photocoagulation, along with other findings such as existing laser spots were analyzed to guide treatment. RESULTS:The UWF SS-OCTA produced a 29 × 24-mm single-scan angiographic image and generated a 220° field-of-view montage. Images of the retinal superficial vascular complex could distinctly depict nonperfusion area, retinal neovascularization, and intraretinal microvascular abnormalities, while enhanced angio mode images of the choroidal capillary layer effectively demonstrated the location of existing laser spots. Using the UWF SS-OCTA findings, initial photocoagulation therapy was performed in 34.3% of patients with retinal vein occlusion and 15.8% of patients with diabetic retinopathy, and supplementary photocoagulation was applied in 13.9% of patients with retinal vein occlusion and 13.6% of patients with diabetic retinopathy. CONCLUSION:UWF SS-OCTA images of the retinal superficial vascular complex and the choroidal capillary layer with the enhanced angio mode provide a noninvasive, efficient, and precise method for guiding retinal photocoagulation, representing a viable alternative to conventional invasive techniques.

With the development of astronomical observation equipment and the expansion of astronomical education in China, how to conduct practical teaching in astronomy has become a challenge for astronomy departments and physics departments with astronomy majors in colleges and universities, To adapt students to the rapid development of national major scientific installations, the School of Physics and Astronomy at Sun Yat-sen University (SYSU) completed the construction of a 3. 2-meter teaching radio telescope in 2021. Through three years of exploration in the course of u201CAstronomical Observation Practiceu201D, the goal of helping students understand the structure and principles of radio telescopes, as well as the basic processes of astronomical observation, has been achieved, At the same time, we realize that this experimental platform can help students learn basic physical concepts such as spectral line broadening, error analysis and control, and time-frequency analysis of signals in practice. Students need to apply multidisciplinary knowledge to complete experiments, making it suit.able to open to general physics and engineering majors. This special topic is prepared in two parts to introduce the experiments on SYSU 3. 2-meter radio telescope, including telescope pointing control, generation of standard astronomical data, and specific time-domain and frequency-domain astronomical observation experiments, that is, experiment of solar radio flux intensity time-domain variation and the observation experiment of neutral hydrogen spectral lines. They are noted as a reference for us and other schools to carry out practical astronomy teaching, and for the radio telescope to serve as a platform for elective experiments in university physics. This is the first part of the special topic, in which the basic parameters of the telescope as well as the design of student's experiments are introduced, It also has specific contents of two experiments that make the telescope functional for astronomical observations, i.e., astronomical source tracking and data file generation, The sun is an astronomical source with strong radio emission, Based on an example, we introduce the experiment of temporal variations of solar radio emissions.

Background: Retinal microvascular abnormalities (RMA) reflect cumulative microvascular damage from systemic diseases and aging. However, little is known about the association between RMA and long-term survival outcomes. This study aimed to examine the relationships between RMA and the risk of all-cause and specific-cause mortality among U.S. adults. Methods: Individuals aged > 40 years were included from the U.S. National Health and Nutrition Examination Survey, 2005-2008. RMA and its subtypes, including retinopathy, arteriovenous nicking (AVN), focal arteriolar narrowing (FAN) and Hollenhorst plaque (HP), were manually graded from retinal photographs. Associations between RMA and the risk of all-cause and cause-specific mortality were examined with Cox regression analysis. Results: This cohort study of 5775 adults included 2881 women (weighted proportion, 52.6%) and 2894 men (weighted, 47.4%), with a weighted mean (SE) age of 56.6 (0.4) years. RMA were present in 1251 participants (weighted, 17.9%), of whom 710 (weighted, 9.8%) had retinopathy, 635 (weighted, 9.3%) had AVN, 64 (weighted, 1.0%) had FAN, and 21 (weighted, 0.3%) had HP. During a median of 12.2 years (range, 0.1-15.0 years) of follow-up, 1488 deaths occurred, including 452 associated with cardiovascular disease (CVD), 341 associated with cancer, and 695 associated with other causes. After adjusting confounding factors, the presence of any RMA and retinopathy at baseline was associated with higher risk of all-cause mortality (HR, 1.26; 95%CI, 1.07-1.47; HR, 1.36; 95%CI, 1.09-1.71, respectively), CVD mortality (HR, 1.36; 95%CI, 1.06-1.73; HR, 1.53; 95%CI, 1.04-2.26, respectively) and other-cause mortality (HR, 1.33; 95%CI, 1.06-1.67; HR, 1.55; 95%CI, 1.20-2.01, respectively). Additionally, FAN was significantly associated with an increased risk of other-cause mortality (HR, 2.06; 95%CI, 1.16-3.65). Although AVN was not associated with mortality in the whole population, it was significantly related to higher risks of all-cause and CVD death in those with obesity (HR, 1.68; 95%CI, 1.12-2.52; HR, 1.96; 95%CI, 1.23-3.13, respectively). Conclusions: This study revealed that the presence of RMA is independently associated with greater risks of all-cause, CVD and other-cause mortality in adults aged 40 years or older.

Background: Copper and zinc are involved in the development of multiple malignancies; yet, epidemiological evidence on hepatocellular carcinoma (HCC) is limited. This study aimed to investigate the association between dietary intake and serum levels of copper and zinc with the risk of HCC. Methods: A total of 434 case-control pairs matched for sex and age (±1 year) were included in this study. Cases with newly diagnosed HCC were from the Guangdong Liver Cancer Cohort (GLCC) study, and healthy controls were from the Guangzhou Nutrition and Health Study (GNHS). A semi-quantitative 79-item food frequency questionnaire (FFQ) was used to assess habitual dietary intakes of copper and zinc. Serum levels of copper and zinc were measured by using inductively coupled plasma mass spectrometry. The copper (Cu)/ zinc (Zn) ratio was computed by dividing copper levels by zinc levels. Conditional logistic regression models were performed to calculate the odds ratio (OR) and 95% confidence intervals (CI) for per 1 standard deviation increase (per-SD increase) in copper and zinc levels. Results: Higher dietary intake (OR per-SD increase = 0.65, 95% CI: 0.44, 0.96, P trend = 0.029) and serum levels of zinc (OR per-SD increase = 0.11, 95% CI: 0.04, 0.30, P trend <0.001) were both associated with a lower risk of HCC. Subgroup analyses showed that the inverse association was only pronounced in men but not in women ( P interaction = 0.041 for dietary zinc intake and 0.010 for serum zinc levels). Serum copper levels (OR per-SD increase = 2.05, 95% CI: 1.39, 3.03, P trend = 0.020) and serum Cu/Zn ratio (OR per-SD increase = 6.53, 95% CI: 2.52, 16.92, P trend <0.001) were positively associated with HCC risk, while dietary copper intake and dietary Cu/Zn ratio were not associated with HCC risk. Conclusion: Zinc may be a protective factor for HCC, especially among men, but the effects of copper on HCC risk are not clear.

Purpose:To determine the topographic relationships and geographic distribution of prevascular vitreous fissures (PVFs) and cisterns across the entire posterior vitreous membrane in healthy subjects, using ultrawidefield en face and cross-sectional swept-source OCT (SS-OCT) images. Design:Observational cross-sectional study. Participants:Ninety-six eyes of 96 healthy participants (age range, 20-49 years) without posterior vitreous detachment. Methods:For each eye, a 29 × 24-mm SS-OCT volume scan was obtained, along with standardized horizontal and vertical scans through the fovea. Main Outcome Measures:Ultrawidefield en face and cross-sectional images were analyzed to assess the topographic relationships and geographic distribution of PVFs and cisterns in the posterior vitreous. Results:En face imaging readily distinguished various preretinal liquefaction spaces throughout the posterior vitreous, extending to near the equator. Aside from the posterior precortical vitreous pocket (PPVP) and the area of Martegiani, all preretinal liquefied fissures and cisterns were distributed along superficial retinal vessels, suggesting they originated from prevascular vitreous liquefaction. In 96 eyes of healthy young and middle-aged adults, PVFs were identified in all participants, presenting a continuous course. Cisterns were detected in 79 eyes (82.3%) and were distributed as follows: superotemporal (91.1%), infratemporal (63.3%), supranasal (41.8%), and inferonasal (22.8%), respectively. The superotemporal cistern was most frequently observed (P < 0.001), and cisterns were more likely to involve multiple quadrants with age (P = 0.005). Additionally, all preretinal liquefaction spaces, including the PPVP, PVFs, and cisterns, were consistently located overlying the vitreoretinal tightly adhered regions. Conclusions:Ultrawidefield en face vitreous imaging in healthy young and middle-aged adults revealed that (1) PVFs distributed along superficial retinal vessels with continuous course; (2) cisterns may develop from PVFs and are more common in the superotemporal quadrant; (3) cisterns appear early in life and become more widespread with age; (4) preretinal vitreous liquefaction follows a stereotypic pattern, aligning along regions of firm vitreoretinal adhesion. Financial Disclosures:Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Background Adenylyl cyclase (AC) isoforms played a key role in the multiple cancer pathology, However, the expression, prognostic value and function of ADCY5 in Glioblastoma (GBM) have not been reported yet. This research intends to discover the expression, epigenetic alteration and biological function of ADCY5 in GBM and its value on patients' prognosis. Methods ① Transcriptional level, epigenetic alteration, prognostic value and molecular network of ADCY5 were analyzed by using of public online datasets. ② The mRNA expression profile of ADCY5 was explored by using GEPIA database and protein expression levels were detected by HPA Database. ③ The prognostic value of ADCY5 was determined by Kaplan-Meier Plotter, GEPIA and CGGA database. ④ The epigenetic characteristics of ADCY5 were determined by DiseaseMeth database. ⑤ Identification of genes co-expressed with ADCY5 and potential mechanism analyses were performed by using DAVID cBioPorta and STRING. ⑥ Reverse transcription-polymerase chain reaction (RT-PCR), cell counting kit-8 (CCK-8), colony formation, wound-healing scratch and transwell assay were applied to detect relative mRNA expression and biological function of ADCY5 in GMB cells. Results ADCY5 mRNA and protein were downregulated in GBM compared with normal tissues. Analysis of the genetics and epigenetics of ADCY5 suggested that its expression was negatively correlated with DNA methylation. High expression of ADCY5 was significantly associated with age, grade, IDH mutation, 1p19q_codeletion, radiotherapy and chemotherapy and acted as an independent prognostic factor in GBM. ADCY5 mRNA also down-expressed in GBM cell lines and re-expressed of ADCY5 could inhibit cell proliferation, viability, migration/invasion and epithelial-mesenchymal transition (EMT) in vitro. In the analysis of genes co-expressed with ADCY5, we found that cAMP/AKT pathway, cGMP-PKG pathway, Wnts pathway were dissimilarly enriched. Conclusion Our study indicated that ADCY5 could act as an epigenetic biomarker in GBM, as well as a prognosis target in patients with GBM.

Introduction: This study aimed to investigate the characteristics of retinal vascular degeneration and the expression of vessel-related Claudin (CLD) proteins in retinal degeneration mouse ( Pde6βrd1/rd1 rd1 mouse). Methods: Retinas from wild-type (WT) mice and rd1 mice at postnatal day 3 (P3), P5, P8, P11, P13, P15, P18, and P21 were collected. Immunofluorescence staining was used to assess the retinal vascular plexus, cell proliferation, CLD expression, and retinal ganglion cells (RGCs). The distribution of retinal superficial and deep vessels was determined by Isolectin B4 fluorescence staining of retinal flat mounts and frozen sections. Hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dNTP nick end labeling were used to investigate retinal histological degeneration and apoptosis in rd1 mice respectively. Quantitative real-time PCR and western blot were used to measure the expression of vessel-related CLD-1, 2, 3 and CLD-5, vascular endothelial growth factor A (VEGFA), and vascular endothelial growth factor receptor 2 (VEGFR2) in the retinas. Results: Compared to the WT mice, the rd1 mice displayed delayed but completed progressive development in the retinal superficial vascular plexuses (SVP) and deep vascular plexuses (DVP). In the rd1 mice, the thickness of retinal layers gradually decreased and the retinas underwent progressive atrophy and degeneration. The deterioration got worse at the late developmental stage. The declined vessel density of SVP and DVP correlated with the decreased thickness of the full and inner parts of the retina and the reduced number of RGCs. DVP degeneration and the thinning of the outer nuclear layer occurred an obvious reduction at P15. The expression levels of CLD-1, CLD-2, CLD-3, CLD-5, VEGFA, and VEGFR2 decreased and were consistently lower in the rd1 mice than in WT mice since P15. Conclusion: Rd1 mice exhibited progressive vascular degeneration of retinal SVP and DVP, the thinning and atrophy of retinal ONL and RGC, and the downregulation of vessel-related CLD proteins during the late developmental period. Thus, the rd1 mouse is a useful model of not only retinal neuro-degeneration but also retinal vascular degeneration.

We present a novel natural language processing (NLP) approach to deriving plain English descriptors for science cases otherwise restricted by obfuscating technical terminology. We address the limitations of common radio galaxy morphology classifications by applying this approach. We experimentally derive a set of semantic tags for the Radio Galaxy Zoo EMU (Evolutionary Map of the Universe) project and the wider astronomical community. We collect 8,486 plain English annotations of radio galaxy morphology, from which we derive a taxonomy of tags. The tags are plain English. The result is an extensible framework which is more flexible, more easily communicated, and more sensitive to rare feature combinations which are indescribable using the current framework of radio astronomy classifications.

To test the hypothesis that daily supplementation with low-dose B vitamins plus betaine could significantly reduce plasma homocysteine concentrations in Chinese adults with hyperhomocysteinemia and free from background mandatory folic acid fortification. One hundred apparently healthy adults aged 18–65 years with hyperhomocysteinemia were recruited in South China from July 2019 to June 2021. They were randomly assigned to either the supplement group (daily supplementation: 400 μg folic acid, 8 mg vitamin B6, 6.4 μg vitamin B12 and 1 g betaine) or the placebo group for 12 weeks. Fasting venous blood was collected at baseline, week 4 and week 12 to determine the concentrations of homocysteine, folate, vitamin B12 and betaine. Generalized estimation equations were used for statistical analysis. Statistically significant increments in blood concentrations of folate, vitamin B12 and betaine after the intervention in the supplement group indicated good participant compliance. At baseline, there were no significant differences in plasma homocysteine concentration between the two groups (P = 0.265). After 12-week supplementation, compared with the placebo group, there was a significant reduction in plasma homocysteine concentrations in the supplement group (mean group difference − 3.87; covariate-adjusted P = 0.012; reduction rate 10.1 https://clinicaltrials.gov/ct2/show/NCT03720249 .

The study aimed to investigate the role of microRNA (miR)-124-3p in retinal angiogenesis in a mouse model. An intravitreal injection of miR-124-3p antagomir was used to knockdown the expression of miR-124-3p in the mouse retina at postnatal day (P)3. Immunofluorescent staining of both retinal frozen sections and whole retina were used to observe retinal vascular development in the P6, P9 and P12 mice, as well as the changes in retinal ganglion cells, astrocytes, Müller cells and microglia. Whole retinal RNA extracted from P9 mice was used for transcriptome sequencing. Following gene set enrichment analysis, the enriched genes caused by miR-124-3p inhibition were analyzed by immunofluorescent staining and western blot. Results indicated that deep vascular development was significantly inhibited by the activation of M1 phenotype microglia. Moreover, there were no notable effects on superficial retinal vascular development, the retinal ganglion cells, astrocytes, and Müller cells. The expression of the Stat1/Irf9/Eif2ak2/Ripk1 axis in the miR-124-3p knockdown group was significantly increased. The microglia penetrated deep into the retina and the activation of Ripk1(+) microglia significantly increased, which was accompanied by an increased level of apoptosis to inhibit the deep vascular sprout. Downregulation of miR-124-3p during the early retinal development can suppress the development of the deep retinal blood vessels by enhancing the expression level of the Stat1/Irf9/Eif2ak2/Ripk1 axis and inducing the cell apoptosis of the activation of Ripk1(+) microglia.

INTRODUCTION Vascular endothelial cell injury and angiogenesis induced by hyperglycemia are the main pathological basis of vascular complications in diabetes mellitus. The purpose of our study was to investigate the role and mechanism of miR-210-3p on high glucose-induced angiogenesis. METHODS Human umbilical vein endothelial cells (HUVECs) were treated with high glucose (HG) to mimic the pathological process of hyperglycemia. HUVECs were divided into the Control group, HG group, HG+inhibitor-NC group, and HG+miR-210-3p inhibitor group. Proliferation and migration were tested by wound healing assay, tube formation, and Transwell assay. Quantitation real-time PCR and Western blots were performed to determine the expression of miR-210-3p and relative proteins, respectively. RESULTS The level of miR-210-3p significantly increased in HUVECs treated by HG. The knockdown of miR-210-3p attenuated the tube formation, proliferation, and migration of cultured HUVECs in vitro to inhibit angiogenesis by increasing the expression of fibroblast growth factor receptor-like 1 (FGFRL1) and then attenuating the phosphorylation of STAT3, ERK, and ATK. CONCLUSION Our study revealed that miR-210-3p might be a promising target for the treatment of diabetic-associated vascular injury.

Objective. To explore a centralized approach to build test sets and assess the performance of an artificial intelligence medical device (AIMD) which is intended for computer-aided diagnosis of diabetic retinopathy (DR). Method. A framework was proposed to conduct data collection, data curation, and annotation. Deidentified colour fundus photographs were collected from 11 partner hospitals with raw labels. Photographs with sensitive information or authenticity issues were excluded during vetting. A team of annotators was recruited through qualification examinations and trained. The annotation process included three steps: initial annotation, review, and arbitration. The annotated data then composed a standardized test set, which was further imported to algorithms under test (AUT) from different developers. The algorithm outputs were compared with the final annotation results (reference standard). Result. The test set consists of 6327 digital colour fundus photographs. The final labels include 5 stages of DR and non-DR, as well as other ocular diseases and photographs with unacceptable quality. The Fleiss Kappa was 0.75 among the annotators. The Cohen’s kappa between raw labels and final labels is 0.5. Using this test set, five AUTs were tested and compared quantitatively. The metrics include accuracy, sensitivity, and specificity. The AUTs showed inhomogeneous capabilities to classify different types of fundus photographs. Conclusions. This article demonstrated a workflow to build standardized test sets and conduct algorithm testing of the AIMD for computer-aided diagnosis of diabetic retinopathy. It may provide a reference to develop technical standards that promote product verification and quality control, improving the comparability of products.