Diabetic retinopathy (DR) is a microvascular complication of diabetes with its exact underlying mechanisms have not been fully elucidated. This study aimed to investigate the effects of key proteins and metabolites on the development of DR. Undiluted vitreous fluid samples were collected from eight patients with proliferative diabetic retinopathy (PDR) and six non-diabetic idiopathic macular hole (iMH) controls. Integration of TMT-tagged quantitative proteomics and untargeted metabolomics analyses was combined with bioinformatics approaches (PCA, differential expression, PPI network, OPLS-DA, pathway enrichment). Key results were validated by ELISA, immunohistochemistry, and cell proliferation and migration assays. Seven key proteins with six key metabolites were identified to be significantly dysregulated in the PDR. In the vitreous body and retinal nerve fiber layer of the DR group, CD5L expression was upregulated, while CLU was downregulated with SERPINF1 (PEDF). CD5L markedly promotes the proliferation and migration of endothelial cells.These molecules were co-enriched in pathways such as the “complement and coagulation cascade” and “prion disease,” suggesting a common mechanism of abnormal vascular permeability, inflammatory response, and microthrombosis. Disturbances in creatine metabolism suggested AMPK-related energy dysregulation, and the interaction between CD5L and microglia emphasized its neuroinflammatory regulatory function. This study revealing biomarkers and therapeutic targets, which provide new ideas for diagnosis and precise intervention.

To address the difficulty in comprehensive screening of fundus diseases, we develop three deep learning algorithms (DLAs) based on different algorithms (Swin Transformer and cross-domain collaborative learning [CdCL]) and imaging modalities (ultra-wide-field [UWF] images and the cropped posterior-pole-region [PPR] images) to identify 25 fundus conditions and provide referral suggestions: WARM (CdCL + UWF images), BASE (Swin Transformer + UWF images), and WARM-PPR (CdCL + PPR images). 59,475 UWF images are included to establish internal and external datasets. WARM shows the best performance on the internal test (area under the receiver operating characteristic curve [AUC] for screening = 0.915; AUC for referral = 0.911) and the external multi-center test (AUC for screening = 0.912; AUC for referral = 0.902). UWF images and the CdCL approach significantly enhance the DLA's ability to detect abnormalities in the peripheral retina. The WARM model shows promise as a reliable and accurate tool for comprehensive fundus screening on a large scale.

Ocular trauma is a leading cause of vision impairment and blindness worldwide,significantly affecting quality of life[1].Each year,an estimated 55 million ocular injuries occur worldwide,with nearly 19 million resulting in vision loss or blindness and approx-imately 750,000 requiring hospitalization[2,3].Understanding the causes and trends of ocular trauma is essential for developing effective prevention strategies.However,most existing studies on the epidemiology and risk factors of ocular trauma have been con-ducted in Western countries,with limited population-based stud-ies available from China[1,4-6].To date,the United States is the only country to report national-level ocular trauma data,though this information is outdated,with data only available up to 2018.

Subretinal fibrosis is a main cause of visual loss in patients with neovascular age-related macular degeneration (nAMD), for whom there has been a lack of effective medication. Metformin can improve inflammation and angiogenesis in eye diseases. This study aimed to investigate the mechanism by which metformin inhibits subretinal fibrosis. A subretinal fibrosis cell model was induced by treating human retinal pigment epithelial cells (ARPE-19) with TGF-β1, a subretinal fibrosis mouse model was induced by a laser, and both cells and mice were treated with metformin. Cell proliferation, migration, and invasion were detected by CCK-8, scratch, and Transwell assays. Western blotting and immunofluorescence were used to evaluate protein expression levels, and RT‒qPCR was used to detect gene expression levels. HE and Masson staining were used to observe the morphological changes in retinal and choroidal tissues. Metformin treatment inhibited the TGF-β1-induced proliferation, migration, invasion and epithelial‒mesenchymal transition (EMT) of ARPE-19 cells and effectively ameliorated laser-induced subretinal fibrosis in mice. Mechanistically, metformin inhibits the expression of miR-126-5p, promotes Klotho synthesis, slows the progression of subretinal fibrosis, and miR-126-5p targets and negatively regulates Klotho. Metformin activates Klotho by inhibiting miR-126-5p, thereby reversing TGF-β1-induced ARPE-19 cell EMT and improving laser-induced subretinal fibrosis in mice.

The aim of this study was to compare the therapeutic efficacy of pars plana vitrectomy (PPV) combined with anti-vascular endothelial growth factor (VEGF) therapy, and anti-VEGF treatment alone in proliferative diabetic retinopathy (PDR) complicated by diabetic macular edema (DME), thereby providing clinical evidence to support the use of combined therapy in this population. This retrospective study analyzed 51 eyes from patients treated at the First Affiliated Hospital of Kunming Medical University between May 2020 and Feb 2024. Participants were stratified into two groups: the multimodal treatment group (n = 27 eyes) receiving PPV combined with anti-VEGF therapy, and the standalone treatment (n = 24 eyes) group receiving anti-VEGF monotherapy. Paired t-tests were performed to analyze intragroup changes in outcome measures, including best-corrected visual acuity (BCVA), central macular thickness (CMT), presence of disorganization of retinal inner layers (DRIL), density of hyperreflective foci (HF) < 30 mu m in diameter located between the outer nuclear layer and RPE, anti-VEGF injection frequency during the 24-month follow-up period. The multimodal treatment showed lower BCVA at 1 month (1.023 +/- 0.639 vs 0.497 +/- 0.440; p = 0.009), and 2 months (0.774 +/- 0.411 vs 0.542 +/- 0.430; p = 0.024) follow-up intervals, but demonstrated superior visual outcomes at 18 and 24 months compared to standalone treatment (p = 0.045 and p = 0.007, respectively). CMT measurements revealed greater thickness in the multimodal treatment group at 3 and 9 months (317.125 +/- 40.851 vs 295.667 +/- 34.236 mu m, p = 0.047; 325.500 +/- 40.729 vs 301.444 +/- 36.833 mu m, p = 0.019), ultimately achieving significantly greater reduction by 24-month follow-up (293.917 +/- 14.943 vs 309.296 +/- 26.025 mu m, p = 0.014). The multimodal approach demonstrated markedly superior resolution in improving DRIL (p < 0.001), while both groups exhibited comparable reductions in HF (p < 0.05). For patients with PDR complicated by DME, multimodal treatment demonstrates significant long-term advantages over anti-VEGF monotherapy, including better BCVA, greater CMT reduction, and more substantial resolution of DRIL.

PurposeTo assess the differences in the measurement of central foveal thickness (CFT) in patients with macular edema (ME) between two display modes (1:1 pixel and 1:1 micron) on optical coherence tomography (OCT).DesignThis is a retrospective, cross-sectional study.MethodsGroup A consisted of participants with well-horizontal OCT B-scan images and group B consisted of participants with tilted OCT B-scan. We manually measured the CFT under the two display modes, and the values were compared statistically using the paired t-test. Spearman’s test was used to assess the correlations between the OCT image tilting angle (OCT ITA) and the differences in CFT measurement. The area under the curve (AUC) was calculated to define the OCT ITA cutoff for a defined CFT difference.ResultsIn group A, the mean CFT in the 1:1 pixel display mode was 420.21 ± 130.61 µm, similar to the mean CFT of 415.27 ± 129.85 µm in the 1:1 micron display mode. In group B, the median CFT in the 1:1 pixel display mode is 409.00 μm (IQR: 171.75 μm) and 368.00 μm (IQR: 149.00 μm) in the 1:1 micron display mode. There were significant differences between the two display modes with the median (IQR) absolute difference and median (IQR) relative difference of 38.00 μm (75.00 μm) and 10.19% (21.91%) (all p = 0.01). The differences in CFT measurement between the two display modes were correlated with the OCT ITA (absolute differences, r = 0.88, p < 0.01; relative differences, r = 0.87, p < 0.01). The AUC for a predefined CFT difference was 0.878 (10 μm), 0.933 (20 μm), 0.938 (30 μm), 0.961 (40 μm), 0.962 (50 μm), and 0.970 (60 μm).ConclusionIn patients with DM, when the OCT B-scan images were well-horizontal, manual CFT measurements under the two display modes were similar, but when the B-scan images were tilted, the CFT measurements were different under the two display modes, and the differences were correlated to the OCT ITA.

To address challenges in screening for chronic kidney disease (CKD), we devised a deep learning-based CKD screening model named UWF-CKDS. It utilizes ultra-wide-field (UWF) fundus images to predict the presence of CKD. We validated the model with data from 23 tertiary hospitals across China. Retinal vessels and retinal microvascular parameters (RMPs) were extracted to enhance model interpretability, which revealed a significant correlation between renal function and RMPs. UWF-CKDS, utilizing UWF images, RMPs, and relevant medical history, can accurately determine CKD status. Importantly, UWF-CKDS exhibited superior performance compared to CTR-CKDS, a model developed using the central region (CTR) cropped from UWF images, underscoring the contribution of the peripheral retina in predicting renal function. The study presents UWF-CKDS as a highly implementable method for large-scale and accurate CKD screening at the population level.

OBJECTIVE:Diabetic macular edema (DME) is the leading cause of visual impairment in patients with diabetes mellitus (DM). The goal of early detection has not yet achieved due to a lack of fast and convenient methods. Therefore, we aim to develop and validate a prediction model to identify DME in patients with type 2 diabetes mellitus (T2DM) using easily accessible systemic variables, which can be applied to an ophthalmologist-independent scenario. METHODS:In this four-center, observational study, a total of 1994 T2DM patients who underwent routine diabetic retinopathy screening were enrolled, and their information on ophthalmic and systemic conditions was collected. Forward stepwise multivariable logistic regression was performed to identify risk factors of DME. Machine learning and MLR (multivariable logistic regression) were both used to establish prediction models. The prediction models were trained with 1300 patients and prospectively validated with 104 patients from Guangdong Provincial People's Hospital (GDPH). A total of 175 patients from Zhujiang Hospital (ZJH), 115 patients from the First Affiliated Hospital of Kunming Medical University (FAHKMU), and 100 patients from People's Hospital of JiangMen (PHJM) were used as external validation sets. Area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity, and specificity were used to evaluate the performance in DME prediction. RESULTS:The risk of DME was significantly associated with duration of DM, diastolic blood pressure, hematocrit, glycosylated hemoglobin, and urine albumin-to-creatinine ratio stage. The MLR model using these five risk factors was selected as the final prediction model due to its better performance than the machine learning models using all variables. The AUC, ACC, sensitivity, and specificity were 0.80, 0.69, 0.80, and 0.67 in the internal validation, and 0.82, 0.54, 1.00, and 0.48 in prospective validation, respectively. In external validation, the AUC, ACC, sensitivity and specificity were 0.84, 0.68, 0.90 and 0.60 in ZJH, 0.89, 0.77, 1.00 and 0.72 in FAHKMU, and 0.80, 0.67, 0.75, and 0.65 in PHJM, respectively. CONCLUSION:The MLR model is a simple, rapid, and reliable tool for early detection of DME in individuals with T2DM without the needs of specialized ophthalmologic examinations.

PurposeThis study aimed to assess the effectiveness and safety of intravitreal injection of conbercept (IVC) in treating moderate to severe nonproliferative diabetic retinopathy (NPDR), with or without accompanying diabetic macular edema.MethodsIn this longitudinal retrospective study, 35 patients (50 eyes) with moderate to severe NPDR and Diabetic Retinopathy Severity Scale (DRSS) scores between 43 and 53 were treated at the Department of Ophthalmology, First Affiliated Hospital of Kunming Medical University, from October 2018 to January 2023. Treatment protocol included three monthly IVC injections followed by a pro re nata (PRN) regimen over a two-year follow-up period. Outcome measures were best-corrected visual acuity (BCVA), intraocular pressure, central macular thickness (CMT), extent of hard exudate (HE), and changes in DRSS scores. DRSS scores before and after treatment were analyzed using the Wilcoxon rank-sum test. Both systemic and ocular adverse events were meticulously documented to ascertain safety.ResultsFrom baseline to the final follow-up, the mean BCVA improved from 0.41 ± 0.39 to 0.23 ± 0.20 logMAR (p<0.05). The mean CMT decreased from 306.22 ± 77.40 to 297.97 ± 88.15 μm (p = 0.385). At 24 months, DRSS scores improved by ≥1 stage in 40 eyes (80%), ≥ 2 stages in 28 eyes (56%), ≥3 stages in 10 eyes (20%), and remained stable in 6 eyes (12%). The DRSS scores at each follow-up interval demonstrated statistically significant improvement from baseline (p<0.05). In 15 of 27 eyes (55.56%) with diabetic macular edema (DME), there was a significant reduction in the mean area of HE from baseline (p<0.05). No serious systemic adverse events were observed.ConclusionIVC is an effective and safe treatment for moderate to severe NPDR, demonstrating significant improvements in DRSS scores.

目的:探讨基于团队学习(TBL)教学法的肾内科知识与技能培训对护理实习生综合能力提升的效果.方法:选取2022年1—12月昆明医科大学第二附属医院接收的护理实习生60名为观察对象,按照随机数字表法分为对照组和观察组,各30名.两组进行肾内科知识与技能培训,对照组采取传统教学模式,观察组采取TBL教学.比较两组护理实习生测试得分、对教学方法评价情况、理论与实践考试成绩.结果:观察组客观题、简答题、应用分析题得分均高于对照组,差异有统计学意义(P=0.001);观察组优良率高于对照组,差异有统计学意义(P=0

荜茇是一味经典的中草药,味辛,性热,具有温中散寒、下气止痛的功效.通过查阅历代本草、现代文献,从荜茇出处、名称、植物形态、产地、性味归经、炮制、功效、主治用量及禁忌等多方面进行梳理考证,以便为现代临床医师和研究者提供理论依据和研究方向.

Subretinal fibrosis (SF) is an important cause of submacular neovascularization that leads to permanent vision loss, but has no effective clinical treatment. The present study examined the influence of metformin on SF, and investigated whether the mechanism involves the microRNA (miR)-140-3p/LIN28B/JNK/STAT3-mediated regulation of oxidative stress, angiogenesis and fibrosis-associated indicators. A mouse model of laser-induced SF was established. In addition, an ARPE-19 fibrotic cell model was established using TGF-β1. A Cell Counting Kit-8 assay was used to examine cell viability. Flow cytometry was used to measure reactive oxygen species levels, and western blotting was used to detect the levels of proteins associated with epithelial-mesenchymal transition (EMT), signaling and fibrosis. The levels of superoxide dismutase, malondialdehyde, glutathione-peroxidase and catalase were measured using kits. Scratch assays and Transwell assays were used to assess cell migration and invasion, respectively, and reverse transcription-quantitative PCR was used to determine the levels of miR-140-3p and LIN28B. Dual-luciferase assays were used to verify the targeting relationship between miR-140-3p and LIN28B, and coimmunoprecipitation was used to confirm the interaction between LIN28B and JNK. Masson staining and hematoxylin and eosin staining were used to examine collagenous fibers and the histopathology of eye tissue. In ARPE-19 cells induced by TGF-β1, metformin promoted miR-140-3p expression and inhibited LIN28B expression and JNK/STAT3 pathway activation, thereby inhibiting oxidative stress, EMT and fibrosis in ARPE-19 cells. The overexpression of LIN28B or treatment with the JNK/STAT3 agonist anisomycin partially reversed the inhibitory effect of metformin on oxidative stress and fibrosis in ARPE-19 cells. The dual-luciferase reporter assay and coimmunoprecipitation assay showed that miR-140-3p targeted the 3' untranslated region of LIN28B mRNA and inhibited LIN28B expression. LIN28B targeted and bound to JNK and regulated the JNK/STAT3 pathway. Therefore, it may be concluded that metformin can promote miR-140-3p expression, inhibit LIN28B and then inhibit the JNK/STAT3 pathway to alleviate SF.

目的 利用网络药理学及分子对接技术分析千金藤素(cepharanthine,CEP)治疗新型冠状病毒感染的作用机制.方法 通过PubChem及SwissTargetPrediction网站检索CEP的作用靶点;在GeneCards数据库获取COVID-19的疾病靶点;将Venny 2.1.0中得到的"药物-疾病"交集靶点导入STRING 11.5网站和Cy-toscape 3.9.0软件中构建蛋白互作网络(protein-protein interaction network,PPI)分析其网络拓扑结构;通过DIVAD数据库进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclo-pedia of genes and genomes,KEGG)通路富集分析,预测其作用机制;利用AutoDock软件将CEP与核心靶点以及COVID-19的明星靶点血管紧张素转化酶2(angiotensin converting enzyme 2,ACE2)和SARS-CoV-2产生的主要蛋白酶(3-chymotrypsin-likeprotease,3CLpro)进行分子对接.结果 CEP与COVID-19共有40个交集靶点,关键靶点涉及Src、AKT1、EGFR、mTOR等;潜在靶点多富集在PI3K-AKT信号通路、coronavirus dis-ease-COVID-19等信号通路.分子对接结果显示CEP与ACE2和3CLpro均能紧密结合,且结合能力比指南推荐药物更佳.结论 CEP作用于COVID-19时主要通过PI3K-AKT信号通路、coronavirus disease-COVID-19信号通路调控炎性反应,大量靶标蛋白参与细胞增殖、凋亡与自噬,抑制病毒复制、肺组织重构从而改善呼吸系统环境,提示了新冠病毒感染的关键机制和途径;CEP可较好地作用于COVID-19的两大主要受体ACE2和3CLpro,有利于CEP抗病毒活性的研发.

AIMS:To develop a deep learning (DL) model for automatic classification of macular hole (MH) aetiology (idiopathic or secondary), and a multimodal deep fusion network (MDFN) model for reliable prediction of MH status (closed or open) at 1 month after vitrectomy and internal limiting membrane peeling (VILMP).METHODS:In this multicentre retrospective cohort study, a total of 330 MH eyes with 1082 optical coherence tomography (OCT) images and 3300 clinical data enrolled from four ophthalmic centres were used to train, validate and externally test the DL and MDFN models. 266 eyes from three centres were randomly split by eye-level into a training set (80%) and a validation set (20%). In the external testing dataset, 64 eyes were included from the remaining centre. All eyes underwent macular OCT scanning at baseline and 1 month after VILMP. The area under the receiver operated characteristic curve (AUC), accuracy, specificity and sensitivity were used to evaluate the performance of the models.RESULTS:In the external testing set, the AUC, accuracy, specificity and sensitivity of the MH aetiology classification model were 0.965, 0.950, 0.870 and 0.938, respectively; the AUC, accuracy, specificity and sensitivity of the postoperative MH status prediction model were 0.904, 0.825, 0.977 and 0.766, respectively; the AUC, accuracy, specificity and sensitivity of the postoperative idiopathic MH status prediction model were 0.947, 0.875, 0.815 and 0.979, respectively.CONCLUSION:Our DL-based models can accurately classify the MH aetiology and predict the MH status after VILMP. These models would help ophthalmologists in diagnosis and surgical planning of MH.

目的:研究甘松饮含药血清对高糖作用下小鼠肾小管上皮细胞(TCMK-1)的作用及相关分子机制.方法:体外培养TCMK-1细胞,加入葡萄糖液模拟高血糖环境,以甘松饮含药血清作为干预药物.实验设计空白对照组、模型组及甘松饮高、中、低剂量含药血清组.经高浓度葡萄糖液和甘松饮干预后,用流式细胞仪检测细胞凋亡、活性氧(ROS)、线粒体膜电位(JC-1);MDC法检测自噬体的形成;Western Blot法检测凋亡相关蛋白Bcl-2、Bax、Caspase-7、Caspase-9及自噬相关蛋白LC3、P62、SGLT2、SIRT1的表达.结果:与模型组比较,甘松饮各组细胞凋亡率、ROS水平及线粒体膜电位下降百分比显著降低,细胞内荧光自噬体形成显著增多,Bcl-2、LC3、SIRT1蛋白表达显著升高,Bax、Caspase-7、Caspase-9、SGLT2、P62蛋白表达显著降低(P＜0.05或P＜0.01).结论:甘松饮既能通过降低细胞内ROS及升高JC-1,减少细胞凋亡,对高糖作用下的TCMK-1细胞发挥保护作用;还能通过下调SGLT2、上调SIRT1激活SGLT2-SIRT1信号通路,促进TCMK-1细胞内的自噬,减轻肾脏损伤.

目的:基于数据挖掘技术研究中华医典治疗消渴的用药规律.方法:选取中华医典5.0系统中治疗消渴的处方,利用Excel 2010软件建立消渴处方数据库,并使用古今医案云平台集成的数据挖掘功能对数据进行中药频次统计、中药属性统计、聚类分析、关联分析、社团分析、复杂网络分析.结果:共纳入治疗消渴的处方452首,涉及中药270味;排名前十的高频药物是麦冬、天花粉、甘草、人参、茯苓、黄连、知母、地黄、五味子、黄芪;药性以寒、微寒、平性为主,药味以甘味为主,归经排名前三的分别是肺经、肾经、胃经;前20味高频中药生成3个聚类分析结果;设置置信度＞0.50,支持度＞0.10得到关联规则22条;复杂网络分析得到治疗消渴的新方为:麦冬、天花粉、人参、甘草、黄连、茯苓、知母、地黄、五味子、黄芪、石膏、熟地黄、当归、黄芩、葛根、茯神、地骨皮、肉桂、牡蛎、泽泻、白术、白芍、升麻.结论:通过对中华医典的挖掘,客观呈现了中华医典治疗消渴的组方用药规律,能为现代临床合理、有效用药提供理论借鉴.

目的:芦荟应用有数千年的历史,是一种常用的中药,而且品种繁多,但应用到临床中的品种较少,为了正本清源,理清芦荟品种,为其进一步探索提供本草参考,遂通过查阅历代本草和现代文献,对芦荟的名称、基源、功效主治、性味归经和产地进行考证.发现芦荟起初记载为卢会,亦称为奴会、讷会、象胆、劳伟;芦荟最初为单基源植物,现代多部药典记载为多基源植物;芦荟的功效主治首见于《药性论》,后世本草有所补充;芦荟苦寒、无毒,归经以入心、肝、脾经为主;芦荟源于伊朗,当时由我国广州进口,现国内亦有种植.芦荟入药品种目前是以斑纹芦荟、好望角芦荟、库拉索芦荟为主,其前景应用广泛,应该加强芦荟研究.

通过查阅古代本草文献中大黄的记载,梳理大黄的性味归经与功效,归纳大黄的用药特点.大黄味苦性寒,主归胃、大肠经,具有攻积滞,行土郁,清火热,解热毒,凉血热,下瘀血,通经脉,祛痰湿,利水道,退黄疸,外用解毒消肿止痛之功效;主治脏腑积滞、痰热腑实、癥瘕积聚、痞满燥实、热结便秘、瘟疫发斑、阳狂谵语、痢下赤白、里急腹痛、口舌生疮、齿龈肿痛、湿热黄疸、小便淋漓、热毒疮痈、水火烫伤、瘀血诸证及血热妄行之各种出血证.从现代药理学角度分析,大黄具有泻下与止泻双向调节、保护胃及十二指肠黏膜、护肝利胆、保护胰腺细胞及功能、活血、止血、调节血脂、保护心脑血管、保护肾脏功能、抗炎抑菌、抗病毒、抗肿瘤、免疫调节等作用.

Background To develop a deep learning (DL) model for prediction of idiopathic macular hole (MH) status after vitrectomy and internal limiting membrane peeling (VILMP) based on optical coherence tomography (OCT) images from four ophthalmic centers. Methods Eyes followed up at 1 month after VILMP for full-thickness MH were included. In the internal training set, 920 preoperative macular OCT images (as the input) and post-operative status of MH (closed or open, as the output) of 256 eyes from two ophthalmic centers were used to train the DL model using VGG16 algorithm. In the external validation set, 72 preoperative macular OCT images of 36 MH eyes treated by VILMP from another two ophthalmic centers were used to validate the prediction accuracy of the DL model. Results In internal training, the mean of overall accuracy for prediction of MH status after VILMP was 84.6% with a mean area under the receiver operating characteristic (ROC) curve (AUC) of 91.04% (sensitivity 85.37% and specificity 81.99%). In external validation, the overall accuracy of predicting MH status after VILMP was 84.7% with an AUC of 89.32% (sensitivity 83.33% and specificity 87.50%). The heatmaps showed that the area critical for prediction was at the central macula, mainly at the MH and its adjacent retina. Conclusions The DL model trained by preoperative macular OCT images can be used to predict postoperative MH status after VILMP. The prediction accuracy of our DL model has been validated by multiple ophthalmic centers.