AIM: To investigate the role of pyruvate kinase M2 (PKM2) in high glucose (HG)-stimulated retinal endothelial cells and its underlying molecular mechanisms and signaling pathways in retinal angiogenesis. METHODS: Human retinal microvascular endothelial cells (HRMECs) were cultured and divided into the following groups: normal glucose (NG, 5.5 mmol/L), HG (30 mmol/L), HG with PKM2 knockdown (HG+shPKM2), and HG treated with the pharmacological activator TEPP-46 (HG+TEPP-46). Cellular viability, proliferation, migration, and tube-forming ability were assessed using CCK-8, EdU, wound healing/Transwell, and Matrigel assays, respectively. The expression levels of PKM2, phosphorylated PKM2 (p-PKM2, Y105), hypoxia-inducible factor-1α (HIF-1α), and vascular endothelial growth factor A (VEGFA) were detected by Western blotting. The oligomerization status of PKM2 was analyzed via native gel electrophoresis. The subcellular localization of PKM2 was examined by immunofluorescence and nuclear-cytoplasmic fractionation. RESULTS: Under HG stimulation, the expression level of PKM2 was significantly increased (P<0.05). Knockdown of PKM2 was found to markedly suppress cell viability, proliferation, migration, and tube formation in HRMECs (P<0.05). Mechanistic studies revealed that phosphorylation of PKM2 at the Y105 site was promoted by HG treatment, which induced its dissociation from a tetramer to a dimer, thereby driving its nuclear translocation. Upon entering the nucleus, PKM2 was shown to exert critical non-metabolic functions; it was physically bound to HIF-1α and acted as its co-activator, leading to significant upregulation of VEGFA expression (P<0.05). In contrast, the PKM2 activator TEPP-46 effectively prevented dimerization and nuclear translocation of PKM2 by promoting its tetramerization. Consequently, the PKM2/HIF-1α axis-mediated upregulation of VEGFA was blocked, ultimately resulting in the reversal of HG-induced angiogenesis. CONCLUSION: HG influences retinal endothelial cell function by inducing PKM2 phosphorylation, dimerization, and nuclear translocation. The shift in PKM2 phosphorylation and oligomerization status represents a key mechanism through which TEPP-46 reverses HG-induced angiogenesis.

Diffuse large B-cell lymphoma (DLBCL), the most common type of lymphoma, arises from various pathogenic mechanisms including gene translocations and fusions. Detection of gene rearrangements using fluorescence in situ hybridization (FISH) is a standard practice for DLBCL diagnosis and guides treatment decisions. High-throughput chromosome conformation capture (Hi-C) DNA sequencing is a next-generation sequencing-based technology to identify genome-wide rearrangements using a single assay. In this study, Hi-C sequencing was performed using FFPE tissues from 159 patients with DLBCL, and identified 746 cancer genes at or proximal to the rearrangement breakpoints with a total of 1903 occurrences. Focusing on clinically important rearrangements, Hi-C detected 102 rearrangements of MYC, BCL2, and/or BCL6 in 92 patients and revealed the fusion partners, including 25 rearrangements missed by FISH. Causes of FISH negative results included FISH-cryptic breakpoints, complex or faint FISH signals, low percentage of FISH positivity, and issues related to tissue fixation. Moreover, in 20 patients (12.6%), Hi-C sequencing detected 22 rearrangements characteristic of other lymphoma types, including CCND1 rearrangements that could lead to reclassification as mantle cell lymphoma. Survival analysis for genome-wide rearrangements using machine learning models identified MYC, PD-L1, CCND1, BCL2, NTRK1/PRCC, RRAS, and FANCE rearrangements with significant prognostic effects in the DLBCL cohort. In conclusion, Hi-C sequencing detects gene rearrangements crucial for diagnosis in an unbiased and molecular manner and showed high sensitivity and specificity in our study. These advantages of Hi-C sequencing offer help to improve the workflow of clinical pathology laboratories, diagnostic precision, and treatment of large B-cell lymphoma.

IntroductionDiabetic retinopathy (DR) represents a prevalent and severe eye complication in diabetic patients. With DR progresses, destruction of tight junctions (TJs) in RPE cells leads to irreversible visual impairment. Gypenoside XLIX (Gyp XLIX) is a dammarane-type glycoside, which can suppress inflammation and oxidative stress. This study sought to investigate and verify the mechanism underlying the regulatory effects of Gyp XLIX in the early protection of junctional integrity of DR.MethodsWe combined bioinformatics and network pharmacology to pinpoint the core therapeutic targets of Gyp XLIX for DR. Mice with diabetes mellitus (DM) and high glucose (HG)-stimulated ARPE-19 cells were treated with Gyp XLIX. Its impact on TJ integrity in RPE cells and ferroptosis was evaluated via Western blotting, immunofluorescence staining, and assays for iron content, lipid peroxidation, and glutathione (GSH) levels. Prostaglandin-endoperoxide synthase 2 (PTGS2) was overexpressed to elucidate the mechanism of action of Gyp XLIX in the early protection of junctional integrity of DR.ResultsAmong the shared targets between Gyp XLIX and DR, ALB, VEGFA, JUN, ESR1, PTGS2, STAT3, MMP9, HSP90AA1, BCL2L1 and AR were identified. Western blotting and immunofluorescence staining revealed that Gyp XLIX preserved TJ integrity in RPE cells. In addition, iron, lipid peroxidation and GSH assays revealed that Gyp XLIX inhibited ferroptosis in both mice with DM and HG-stimulated ARPE-19 cells. Overexpression of PTGS2 partially reversed the protective impacts induced by Gyp XLIX.DiscussionThis study demonstrated that Gyp XLIX suppressed ferroptosis and preserved TJ integrity in RPE cells, with these effects being closely associated with the downregulation of PTGS2, thereby exerting early protective effects on junctional integrity of DR.

Ocular neovascular diseases (ONDs) are a leading cause of global blindness. While current anti-vascular endothelial growth factor (VEGF) treatments have revolutionized management, their efficacy is constrained by issues such as non-response, resistance development, and the burden of repeated intravitreal injections. Recent studies have highlighted the growing importance of transfer RNA-derived small RNAs (tsRNAs) in regulating pathological angiogenesis. This review provides a systematic analysis of tsRNAs, encompassing their origins, classification, and mechanisms of action, followed by an exploration of their implications in OND. Targeting tsRNAs may offer a novel multi-level regulatory strategy to overcome the limitations of current anti-VEGF therapies.

AIM To investigate the role of pyruvate kinase M2 (PKM2) in high glucose (HG)-stimulated retinal endothelial cells and its underlying molecular mechanisms and signaling pathways in retinal angiogenesis. METHODS Human retinal microvascular endothelial cells (HRMECs) were cultured and divided into the following groups: normal glucose (NG, 5.5 mmol/L), HG (30 mmol/L), HG with PKM2 knockdown (HG+shPKM2), and HG treated with the pharmacological activator TEPPu201146 (HG+TEPPu201146). Cellular viability, proliferation, migration, and tubeu2011forming ability were assessed using CCKu20118, EdU, wound healing/Transwell, and Matrigel assays, respectively. The expression levels of PKM2, phosphorylated PKM2 (pu2011PKM2, Y105), hypoxia-inducible factor-1u03B1 (HIFu20111u03B1), and vascular endothelial growth factor A (VEGFA) were detected by Western blotting. The oligomerization status of PKM2 was analyzed via native gel electrophoresis. The subcellular localization of PKM2 was examined by immunofluorescence and nuclearu2011cytoplasmic fractionation. RESULTS Under HG stimulation, the expression level of PKM2 was significantly increased (Pu0026lt;0.05). Knockdown of PKM2 was found to markedly suppress cell viability, proliferation, migration, and tube formation in HRMECs (Pu0026lt;0.05). Mechanistic studies revealed that phosphorylation of PKM2 at the Y105 site was promoted by HG treatment, which induced its dissociation from a tetramer to a dimer, thereby driving its nuclear translocation. Upon entering the nucleus, PKM2 was shown to exert critical nonu2011metabolic functions; it was physically bound to HIFu20111u03B1 and acted as its cou2011activator, leading to significant upregulation of VEGFA expression (Pu0026lt;0.05). In contrast, the PKM2 activator TEPPu201146 effectively prevented dimerization and nuclear translocation of PKM2 by promoting its tetramerization. Consequently, the PKM2/HIFu20111u03B1 axisu2011mediated upregulation of VEGFA was blocked, ultimately resulting in the reversal of HGu2011induced angiogenesis. CONCLUSION HG influences retinal endothelial cell function by inducing PKM2 phosphorylation, dimerization, and nuclear translocation. The shift in PKM2 phosphorylation and oligomerization status represents a key mechanism through which TEPP-46 reverses HG-induced angiogenesis.

Collision tumors composed of colorectal adenocarcinoma and mantle cell lymphoma are exceptionally rare, and component-resolved molecular characterization is largely lacking. We report a 65-year-old woman who initially presented with rectal adenocarcinoma and underwent radical resection followed by adjuvant capecitabine. Seven months later, she developed generalized lymphadenopathy, and excisional cervical lymph node biopsy confirmed mantle cell lymphoma with Cyclin D1 and SOX11 positivity, t(11;14)(q13;q32) rearrangement, and a Ki-67 proliferation index of approximately 40%. Retrospective review of the original rectal resection specimen identified an occult mantle cell lymphoma component at the tumor margin and within the submucosa, leading to reclassification as a synchronous rectal collision tumor composed of adenocarcinoma and mantle cell lymphoma. Targeted sequencing across four specimens revealed a shared TP53 exon 7 frameshift in the archival composite rectal specimen, the rectal lymphoma component, and the adenocarcinoma component, whereas the nodal lymphoma specimen showed a dominant NOTCH2-truncating profile without a reported pathogenic TP53 alteration. The adenocarcinoma component additionally harbored a truncating APC alteration consistent with colorectal tumorigenesis. These findings support partial molecular overlap together with compartment- and site-specific divergence, while not establishing a common clonal origin. The patient received bendamustine plus rituximab followed by zanubrutinib maintenance and remained in remission at the last follow-up. This case highlights a clinically important diagnostic pitfall, shows how retrospective pathologic review can uncover occult gastrointestinal mantle cell lymphoma in a colorectal resection specimen, and provides multi-specimen molecular evidence of spatial heterogeneity across synchronous bowel and nodal disease.

AIM:This study aims to evaluate the impact of a pay-for-performance (P4P) program on health outcomes for patients with type 2 diabetes mellitus in Chinese primary care settings. METHODS:Conducted from February to March 2019, this trial involved 1,085 participants from 19 rural villages in China. Family physicians in the intervention group received P4P incentives. We collected clinical health outcomes, including fasting blood glucose, blood pressure, and lipid levels, at baseline and after one year. A differences-in-differences model was employed to assess the P4P program's effects on these health outcomes. Additionally, a multiple regression analysis was performed to evaluate the influence of P4P on patients' health behaviors, such as self-management, doctor-patient trust, and self-rated health. RESULTS:Following the intervention, the intervention group showed significant reductions in fasting plasma glucose (0.88 mmol/L), systolic blood pressure (11.10 mmHg), and total cholesterol (0.50 mmol/L) compared to the control group. The P4P program also improved control rates for fasting glucose (OR = 2.34, 95 % CI:1.57-3.48), blood pressure (OR = 7.57, 95 % CI: 4.98-11.50), and total cholesterol (OR = 2.47, 95 % CI:1.61-3.79), while enhancing self-management behaviors (OR = 0.21, 95 % CI: 0.08-0.34) and doctor-patient trust (OR = 0.75, 95 % CI: 0.39-1.11). CONCLUSIONS:The P4P incentive effectively improved glycemic control and diabetes management in rural China.

To determine the impact of sodium butyrate on the activation of the reactive oxygen species (ROS)/nuclear factor kappa B (NF-κB)/NLR family pyrin domain containing 3 (NLRP3) signaling pathway and angiogenesis in human retinal microvascular endothelial cells (HRMECs) caused by high glucose (HG). HRMECs were grown for 24 h or 72 h in HG solution (30 mmol/L D-glucose) with 5 mM NaB. Using Cell Counting Kit-8, the effects of HG and NaB levels on the viability of HRMECs were examined. Using various kits, intracellular ROS levels, lactate dehydrogenase (LDH), and Malondialdehyde (MDA) in cell supernatants were measured. Western blot, Immunofluorescence, and Real-time quantitative polymerase chain reaction were employed to quantify protein and messenger RNA expression. Using wound-healing and tube formation tests, the migratory proficiency and angiogenesis of HRMECs were evaluated. NaB demonstrated a reduction in ROS production, as well as the release of LDH and MDA in HG-induced HRMECs. Additionally, NaB led to a decrease in protein expression of phosphorylation of NF-κB, NLRP3, Caspase 1, interleukin, vascular cell adhesion molecule-1 and intercellular adhesion molecule-1. The impact of HG on zonula occluden-1, a tight junction protein, was attenuated by NaB. Furthermore, NaB inhibited the migration and tube formation of HRMECs partly by ROS/NF-κB/NLRP3 pathway. NaB suppresses the activation of ROS/NF-κB/NLRP3 signaling pathway and angiogenesis in HRMECs induced by HG.

BACKGROUND:Social anxiety has been shown to affect college students' academic performance. However, the role of social media addiction and academic engagement in this association is unclear.METHODS:A total 2661 college students completed a self-report questionnaire including Liebowitz Social Anxiety Scale, the Bergen Social Media Addiction Scale, the Utrecht Student Work Engagement Scale for Students, and the grade point average. Hayes' PROCESS macro for SPSS was employed to test the serial mediation effect.RESULTS:Results indicated that social anxiety was negatively related to academic performance, only academic engagement played a single mediating role in the relationship between social anxiety and academic performance, meanwhile social media addiction and academic engagement acted as serial mediators between social anxiety on academic performance.CONCLUSIONS:Social media addiction and academic engagement can explain the potential mechanisms of the association between social anxiety and academic performance, which have implications for devising intervention strategies to enhance the mental health and academic outcomes of college students.

Background As stroke has become the leading cause of death and disability in China, it has induced a heavy disease burden on society, families, and patients. Despite much attention within the literature, the effect of multiple risk factors on length of stay (LOS) and inpatient costs in China is still not fully understood. Aim To analyse the association between the number of risk factors combined and inpatient costs among adults with stroke and explore the mediating effect of LOS on inpatient costs. Methods A retrospective cross-sectional study was conducted among stroke patients in a tertiary hospital in Nantong City from January 2018 to December 2019. Lifestyle factors (smoking status, exercise), personal disease history (overweight, hypertension, dyslipidemia, diabetes mellitus, atrial fibrillation), family history of stroke, and demographic characteristics were interviewed by trained nurses. Inpatient costs and LOS were extracted from electronic medical records. Hierarchical multiple linear regression models and mediation analysis were used to examine the direct and indirect effects of the number of risk factors combined for stroke on inpatient costs. Results A total of 620 individuals were included, comprising 391 ischaemic stroke patients and 229 haemorrhagic stroke patients, and the mean age was 63.2 years, with 60.32% being male. The overall mean cost for stroke inpatients was 30730.78 CNY ($ 4444.91), and the average length of stay (LOS) was 12.50 days. Mediation analysis indicated that the greater number of risk factors was not only directly related to higher inpatient costs (direct effect = 0.16, 95%CI:[0.11,0.22]), but also indirectly associated with inpatient cost through longer LOS (indirect effect = 0.08, 95% CI: [0.04,0.11]). Furthermore, patients with high risk of stroke had longer LOS than those in low-risk patients, which in turn led to heavier hospitalization expenses. Conclusions Both the greater number of risk factors and high-risk rating among stroke patients increased the length of stay and inpatient costs. Preventing and controlling risk behaviors of stroke should be strengthened.

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.

Composite lymphoma is an uncommon type of lymphoid malignancy, and those consisting of concurrent diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) in the same organ are rare. Here, we report a case of a 75-year-old male patient admitted to our emergency department with intestinal obstruction presenting with abdominal pain and vomiting. He underwent partial resection of the small intestine under general anesthesia, and subsequent histopathology confirmed the mass to be composite DLBCL and PTCL-NOS. The patient received chemotherapy with a rituximab-based regimen and achieved complete remission (CR). However, the recurrent disease presented with obstruction again ten months after treatment. He refused a second surgery, but salvage treatment was not effective. The patient survived for 20 months after diagnosis. In addition, we did a literature review to understand the clinical features, pathology, treatment, and prognosis of this type of composite lymphoma.

AIM:To compare the expression of apoptosis-related factors and Nlrp3-related proteins in the lens epithelial cells (LECs) of patients with diabetes and cataract and patients with age-related cataract (ARC) alone.METHODS:All patients were divided into four groups according to the presence or absence of diabetes mellitus (DM) and the degree of diabetic retinopathy (DR). LECs were obtained during cataract surgery. The expression levels of cleaved caspase-3, caspase-7, ASC, caspase-1and Nlrp3 in LECs were determined. And analyzed by age, course of DM, and HbA1c levels.RESULTS:The incidence of LEC apoptosis and positive rates of cleaved caspase-3 and caspase-7 expression were significantly higher in the groups with DM (P<0.05).The positive expression rates of ASC, caspase-1, and Nlrp3 increased with longer duration of DM, increased HbA1c level, or advanced DR (P<0.05).CONCLUSION:In cataract patients with DM, the expression of apoptosis-related factors in LECs increased. Nlrp3-related protein expression levels, diabetes duration, HbA1c levels, and extent of DR may be potential risk factors for diabetic cataract formation.

目的 观察钙敏感受体(CaSR)在高糖(HG)诱导的人视网膜血管内皮细胞(HRCECs)内皮间质转化(EndMT)中的作用和机制.方法 将HRCECs分为3组:对照组(NG组,培养基中加入5.5 mmol·L-1 D-葡萄糖)、高糖组(HG组,培养基中加入25.0 mmol·L-1D-葡萄糖)及HG+Calhex231组(培养基中加入25.0 mmol·L-1 D-葡萄糖和3μmol·L-1 Calhex231).CCK-8法检测各组HRCECs的细胞活力,Transwell实验检测各组HRCECs的迁移能力,利用细胞管腔形成实验检测各组HRCECs的管腔形成能力,Western blot 检测 CaSR、VE-cadherin、CD31、α-SMA 及 Nuclear β-catenin 蛋白的表达.结果 HG 组CaSR的表达较NG组增加.与NG组相比,HG组HRCECs的细胞活力、迁移能力和成管能力均增强,细胞中CaSR、α-SMA和Nuclear β-catenin蛋白表达均明显增加,VE-cadherin和CD31蛋白表达均明显降低(均为P＜0.05).与HG组相比,HG+Calhex231组HRCECs的上述指标均明显逆转(均为P＜0.05).结论 CaSR表达参与HG诱导的EndMT进展,其机制可能与促进β-catenin核易位有关.

Background:During the COVID-19 pandemic, the frontline medical staff faced more workload and heavier physical and mental stress, which increased their job burnout and negative emotions. However, little is known about the potential factors mediating and moderating these relations. This study investigates the association between long working hours and depressive symptoms among frontline medical staff in China, and explores the potential mediating effect of job burnout, and moderating effect of family and organizational support on these associations. Methods:Data of 992 frontline medical staff who participated in the prevention and control of COVID-19 was obtained from the online survey conducted in November to December 2021 in China. Depressive symptoms were evaluated using the Patient Health Questionaire-9 (PHQ-9). Moderated mediating model was employed to understand the relationship between long working hours (X), depressive symptoms (Y) mediated through job burnout (M), moderated by family support (W1) and organizational support (W2), while controlling all possible covariates. Results:56.96% of participants worked more than 8 h per day. 49.8% of them had depressive symptoms (PHQ-9 ≥ 5) and 65.8% experienced job-related burnout. Long working hours was positively associated with depressive symptoms score (β = 0.26, 95% CI:0.13 ~ 0.40). Mediation analyses revealed that job burnout significantly mediated this relationship (indirect effect = 0.17, 95% CI: 0.08 ~ 0.26). Moderated mediation further indicated that both two interactions of social support (family support W1, organizational support W2) and job burnout were negatively related to depressive symptoms among frontline medical staff, indicating that higher social support being less job burnout with lower depressive symptoms. Conclusion:Longer working hours and higher job burnout may contribute to worse mental health among frontline medical staff. Social support could buffer the detrimental effects by reducing their job burnout. Contribution:The main contribution of this study was to estimate the negative effect of long working hours on depressive symptoms among frontline medical staff and explore the potential mediating role of job burnout and moderating role of social support on these associations.

Choroidal neovascularization (CNV), is a major cause of irreversible blindness among the elderly population in developed countries, which is resulted from subretinal fibrosis without effective therapeutic strategies. Endothelial-to-mesenchymal transition (EndMT) of choroidal vascular endothelial cells (CVECs) contributes to subretinal fibrosis. Lycopene (LYC), a non-pro-vitamin A carotenoid, plays an anti-fibrotic role. Herein, we explored the effect and mechanism of LYC on the EndMT of CVECs during CNV. Firstly, LYC inhibited EndMT in hypoxic human choroidal endothelial cells (HCVECs). Meanwhile, LYC inhibited proliferation, androgen receptor (AR) expression and nuclear localization in hypoxic HCVECs. Then LYC-inhibited AR promotes the activation of microphthalmia-associated transcription factor (MITF) in hypoxic HCVECs. In addition, LYC down-regulated AR and induced MITF up-regulated pigment epithelium-derived factor (PEDF) transcription and expression in hypoxic HCVECs. Moreover, LYC-induced PEDF bound to laminin receptor (LR), inhibiting EndMT of hypoxic HCVECs via down-regulating protein kinase B (AKT)/β-catenin pathway. In vivo, LYC alleviated mouse laser-induced subretinal fibrosis secondary to CNV via up-regulating PEDF without any ocular or systemic toxicity. These results indicate that LYC inhibits EndMT of CVECs via modulating AR/MITF/PEDF/LR/AKT/β-catenin pathway, showing LYC is a promising therapeutic agent for CNV.

Introduction: Myopia is an increasingly serious health problem in China. The aim of this study was to investigate the prevalence of myopia and the factors associated with it among students in Nantong, China, to show the current status of myopia prevention. Methods: This school-based, cross-sectional study examined students from all high schools in an urban area of Nantong, China. At least two classes were randomly selected from each grade of each school. A self-reported questionnaire was used to collect the required information. Univariate analyses were performed to identify associations between myopia and various parameters. Noncycloplegic autorefraction and visual acuity were assessed for each student. Factors that were statistically significant in univariate analyses were selected for multivariate analyses. Myopia was defined as a spherical equivalent refraction of ≤−0.5 diopters. Results: The completion percentage of students out of the whole high school was 6.5%. The overall prevalence of myopia was 94%. The response percentage of the number of validated questionnaires was 90.2%, of which 50.2% (n = 1,466) were from male participants, and 49.8% (n = 1,452) were from female participants. The mean (SD) of age was 15.22 ± 1.75 years, ranging from 12 to 18 years. Factors such as female sex, older age, parental myopia, sitting in the back of the classroom, increased homework time, and minimal outdoor activity were significantly associated with a higher risk of myopia (p < 0.05). In the myopic population, most students (67.9%) did not take measures to prevent further progression of myopia. Conclusion: The prevalence of myopia among high school students was 94%. Female sex, older age, parental myopia, sitting in the back of the classroom, increased homework time, and minimal outdoor activity were significantly associated with a higher risk of myopia. Most students with myopia (67.9%) did not take measures to prevent further progression of myopia.

Diabetic retinopathy (DR) is one of the microvascular complications of diabetes mellitus and a major pathological feature of neovascular DR. These patients potentially experience vision impairment and blindness. Platelet-derived growth factor receptor β (PDGFRβ), fibroblast growth factor receptor 1 (FGFR1), and vascular endothelial growth factor receptor 2 (VEGFR2) are implicated in the DR pathogenesis. Nintedanib (BIBF1120) is an oral selective dual receptor tyrosine kinase (RTK) inhibitor of VEGFR2, FGFR1, and PDGFRβ. In this study, intravitreal injection of BIBF1120 blocked the phosphorylation of VEGFR2, FGFR1, PDGFRβ, and MAPK signaling pathway proteins in a streptozotocin (STZ)-induced diabetic retinopathy mouse model. In in vitro cell experiments, BIBF1120 did not change cellular activity under normal conditions, while it further suppressed the tube formation, migration, and proliferation of high glucose-induced human retinal microvascular endothelial cells (HRMECs). Additionally, BIBF1120 blocked the phosphorylation of p38, JNK, and ERK1/2 in high glucose-treating HRMECs. Our results indicate that the BIBF1120 treatment can be a novel potential drug to protect against DR.

Introduction Along with blood glucose levels, diabetic retinopathy (DR) development also involves endogenous risk factors, such as trimethylamine-N-oxide (TMAO), a product of intestinal flora metabolic disorder, which exacerbates diabetic microvascular complications. However, the effect of TMAO on retinal cells under high-glucose conditions remains unclear. Therefore, this study examined the effects of TMAO on high-glucose-induced retinal dysfunction in the context of NLRP3 inflammasome activation, which is involved in DR. Materials and Methods TMAO was assessed in the serum and aqueous humor of patients using ELISA. Human retinal microvascular endothelial cells (HRMECs) were treated for 72 h as follows: NG (normal glucose, D-glucose 5.5 mM), NG + TMAO (5 μM), HG (high glucose, D-glucose 30 mM), and HG + TMAO (5 μM). The CCK8 assay was then used to assess cell proliferation; wound healing, cell migration, and tube formation assays were used to verify changes in cell phenotype. ZO-1 expression was determined using immunofluorescence and western blotting. Reactive oxygen species (ROS) formation was assessed using DCFH-DA. NLRP3 inflammasome complex activation was determined using a western blot. Results The serum and aqueous humor from patients with PDR contained higher levels of TMAO compared to patients with nontype 2 diabetes (Control), non-DR (NDR), and non-PDR (NPDR). TMAO showed significant acceleration of high-glucose-induced cell proliferation, wound healing, cell migration, and tube formation. ZO-1 expression decreased remarkably with the combined action of TMAO and a high glucose compared to either treatment alone. TMAO also promoted high-glucose-activated NLRP3 inflammasome complex. Conclusion The combination of TMAO and high-glucose results in increased levels of ROS and NLRP3 inflammasome complex activation in HRMECs, leading to exacerbated retinal dysfunction and barrier failure. Thus, TMAO can accelerate PDR occurrence and development, thus indicating the need for early fundus monitoring in diabetic patients with intestinal flora disorders.