Quantitative Assessment of Fundus Tessellated Density in Highly Myopic Glaucoma Using Deep Learning.

Purpose: To characterize the fundus tessellated density (FTD) in highly myopic glaucoma (HMG) and high myopia (HM) for discovering early signs and diagnostic markers. Methods: This retrospective cross-sectional study included hospital in-patients with HM (133 eyes) and HMG (73 eyes) with an axial length ≥26 mm at Zhongshan Ophthalmic Center. Using deep learning, FTD was quantified as the average exposed choroid area per unit area on fundus photographs in the global, macular, and disc regions. FTD-associated factors were assessed using partial correlation. Diagnostic efficacy was analyzed using the area under the curve (AUC). Results: HMG patients had lower global (0.20 ± 0.12 versus 0.36 ± 0.09) and macular FTD (0.25 ± 0.14 vs. 0.40 ± 0.09) but larger disc FTD (0.24 ± 0.11 vs. 0.19 ± 0.07) than HM patients in the tessellated fundus (all P < 0.001). In the macular region, nasal FTD was lowest in the HM (0.26 ± 0.13) but highest in the HMG (0.32 ± 0.13) compared with the superior, inferior, and temporal subregions (all P < 0.05). A fundus with a macular region nasal/temporal (NT) FTD ratio > 0.96 (AUC = 0.909) was 15.7 times more indicative of HMG than HM. A higher macular region NT ratio with a lower horizontal parapapillary atrophy/disc ratio indicated a higher possibility of HMG than HM (AUC = 0.932). Conclusions: FTD differs in degree and distribution between HMG and HM. A higher macular NT alone or with a lower horizontal parapapillary atrophy/disc ratio may help differentiate HMG. Translational Relevance: Deep learning-based FTD measurement could potentially assist glaucoma diagnosis in HM.

Interventions for psychiatric disorders among university students: An umbrella review of systematic reviews and meta-analyses / Intervenciones para los trastornos psiquiátricos entre estudiantes universitarios: una revisión general de revisiones sistemáticas y metanálisis

Background: Mental disorders are considered to be the main reason for the increase of the disease burden. College students seem to be more vulnerable to the adverse effects of stress, which makes them more at risk of suffering from mental disorders. This umbrella review aimed to evaluate the credibility of published evidence regarding the effects of interventions on mental disorders among university students. Methods: To identify systematic reviews and meta-analyses investigating the effects of interventions on mental disorders in the university student population, extensive searches were carried out in databases including PubMed, Embase, and the Cochrane Database, spanning from inception to July 21, 2023. Subsequently, a thorough reanalysis of crucial parameters such as summary effect estimates, 95 % confidence intervals, heterogeneity I2 statistic, 95 % prediction intervals, small-study effects, and excess significance bias was performed for each meta-analysis found. Results: Nineteen articles involving 74 meta-analyses were included. Our grading of the current evidence showed that interventions based on exercise, Cognitive-behavioural Intervention (CBI), mindfulness-based interventions (MBI), and other interventions like mood and anxiety interventions (MAI) were effective whereas exercise intervention had the highest effect size for both depression and anxiety among university students. However, the credibility of the evidence was weak for most studies. Besides, suggestive evidence was observed for the positive effects of CBI on sleep disturbance(SMD: -0.603, 95 % CI: -0.916, -0.290; P-random effects<0.01) and MAI on anxiety (Hedges'g = -0.198, 95 % CI: -0.302, -0.094; P-random effects<0.01). Conclusion: Based on our findings, it appears that exercise interventions, CBI, and MAI have the potential to alleviate symptoms related to mental disorders...(AU)

Visual impairment burden in retinopathy of prematurity: trends, inequalities, and improvement gaps.

Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment, and the increase in number and survival of premature infants may inflate its burden globally. We aimed to comprehensively assess the trends and inequalities in the burden of ROP-related visual impairment and to identify improvement gaps to facilitate appropriate actions in neonatal care systems. We obtained ROP data from the Global Burden of Disease 2019 study. We employed joinpoint regression analysis to assess the trends of the burden of ROP-related visual impairment, measured by age-standardised prevalence rates, health equity analysis methods to evaluate cross-country burden inequalities, and data envelopment and stochastic frontier analyses to identify improvement gaps based on the development status, i.e., sociodemographic index (SDI). Between 1990 and 2019, the age-standardised prevalence rates of ROP-related visual impairment significantly increased worldwide (average annual percentage change: 0.23 [95% confidence interval, 0.21-0.26] among males and 0.26 [0.25-0.27] among females), primarily in developed regions. Although significant SDI-related cross-country inequalities were identified, these reduced over time (slope index of inequality: -57.74 [-66.22 to -49.25] in 1990 to -29.68 [-38.39 to -20.97] in 2019; health concentration index: -0.11 [-0.13 to -0.09] in 1990 to -0.07 [-0.09 to -0.06] in 2019). Notably, some less-developed countries exhibited superior performance despite limited resources, whereas others with a higher SDI delivered lagging performance.  Conclusion: The global burden of ROP-related visual impairment has steadily increased between 1990 and 2019, with disproportionate burden concentration among less-developed countries, requiring appropriate preventive and intervention measures. What is Known: • Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment. • The prevalence of ROP is anticipated to increase due to the growing number of extremely premature infants. What is New: • The prevalence of ROP-related visual impairment has increased worldwide, primarily in developed regions, with declining but persisting cross-country inequalities. • The increasing burden of ROP-related visual impairment should be considered as part of global and national health agendas, requiring interventions with proven efficacy.

Interventions for psychiatric disorders among university students: An umbrella review of systematic reviews and meta-analyses.

Background: Mental disorders are considered to be the main reason for the increase of the disease burden. College students seem to be more vulnerable to the adverse effects of stress, which makes them more at risk of suffering from mental disorders. This umbrella review aimed to evaluate the credibility of published evidence regarding the effects of interventions on mental disorders among university students. Methods: To identify systematic reviews and meta-analyses investigating the effects of interventions on mental disorders in the university student population, extensive searches were carried out in databases including PubMed, Embase, and the Cochrane Database, spanning from inception to July 21, 2023. Subsequently, a thorough reanalysis of crucial parameters such as summary effect estimates, 95 % confidence intervals, heterogeneity I2 statistic, 95 % prediction intervals, small-study effects, and excess significance bias was performed for each meta-analysis found. Results: Nineteen articles involving 74 meta-analyses were included. Our grading of the current evidence showed that interventions based on exercise, Cognitive-behavioural Intervention (CBI), mindfulness-based interventions (MBI), and other interventions like mood and anxiety interventions (MAI) were effective whereas exercise intervention had the highest effect size for both depression and anxiety among university students. However, the credibility of the evidence was weak for most studies. Besides, suggestive evidence was observed for the positive effects of CBI on sleep disturbance(SMD: -0.603, 95 % CI: -0.916, -0.290; P-random effects<0.01) and MAI on anxiety (Hedges'g = -0.198, 95 % CI: -0.302, -0.094; P-random effects<0.01). Conclusion: Based on our findings, it appears that exercise interventions, CBI, and MAI have the potential to alleviate symptoms related to mental disorders. Despite the overall weak credibility of the evidence and the strength of the associations, these interventions offer a promising avenue for further exploration and research in the future. More high-quality randomized controlled trials should be taken into account to verify the effects of these interventions on various mental disorders.

Composition of gut microbiota and non-alcoholic fatty liver disease: A systematic review and meta-analysis.

The present systematic review and meta-analysis aimed to summarize the associations between gut microbiota composition and non-alcoholic fatty liver disease. To compare the differences between individuals with or without NAFLD, the standardized mean difference and 95% confidence interval were computed for each α-diversity index and relative abundance of gut microbes. The ß-diversity indices were summarized in a qualitative manner. A total of 54 studies with 8894 participants were included. Overall, patients with NAFLD had moderate reduction in α-diversity indices including Shannon (SMD = -0.36, 95% CI = [-0.53, -0.19], p < 0.001) and Chao 1 (SMD = -0.42, 95% CI = [-0.68, -0.17], p = 0.001), but no significant differences were found for Simpson, observed species, phylogenetic diversity, richness, abundance-based coverage estimator, and evenness (p ranged from 0.081 to 0.953). Over 75% of the included studies reported significant differences in ß-diversity. Although there was substantial interstudy heterogeneity, especially for analyses at the phylum, class, and family levels, the majority of the included studies showed alterations in the depletion of anti-inflammatory microbes (i.e., Ruminococcaceae and Coprococcus) and the enrichment of proinflammatory microbes (i.e., Fusobacterium and Escherichia) in patients with NAFLD. Perturbations in gut microbiota were associated with NAFLD, commonly reflected by a reduction in beneficial species and an increase in the pathogenic species.

Empagliflozin targets Mfn1 and Opa1 to attenuate microglia-mediated neuroinflammation in retinal ischemia and reperfusion injury.

BACKGROUND: Neuroinflammation and mitochondrial dysfunction play crucial roles in retinal ischemia and reperfusion (IR) injury. Recent studies have identified mitochondrial function as a promising target for immunomodulation. Empagliflozin (EMPA), an anti-diabetic drug, has exhibited great potential as both an anti-inflammatory agent and a protector of mitochondrial health. This study aimed to assess the therapeutic efficacy of EMPA in retinal IR injury. METHODS: To evaluate the protective effects of EMPA, the drug was injected into the vitreous body of mice post-retinal IR. Single-cell RNA sequencing (scRNA-seq) analysis was conducted to uncover the underlying mechanisms, and the results were further validated through in vivo and in vitro experiments. RESULTS: EMPA effectively protected retinal ganglion cells (RGCs) from IR injury by attenuating local retinal inflammation. The scRNA-seq analysis revealed that EMPA downregulated the nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) signaling pathway and restored mitochondrial dynamics by upregulating the expression of mitochondrial fusion-related genes, Mitofusin 1 (Mfn1) and optic atrophy 1 (Opa1). These findings were further corroborated by Western blotting. In vitro experiments provided additional insights, demonstrating that EMPA suppressed lipopolysaccharide (LPS)-induced cell inflammation and NLRP3 inflammasome activation. Moreover, EMPA enhanced mitochondrial fusion, neutralized mitochondrial reactive oxygen species (mtROS), and restored mitochondrial membrane potential (MMP) in BV2 microglia. Notably, genetic ablation of Mfn1 or Opa1 abolished the anti-inflammatory effects of EMPA. CONCLUSIONS: Our findings highlight the positive contribution of Mfn1 and Opa1 to the anti-inflammatory therapeutic effect of EMPA. By restoring mitochondrial dynamics, EMPA effectively mitigates microglia-mediated neuroinflammation and prevents RGC loss in retinal IR injury.

27­Gauge vitrectomy vs. 25­gauge vitrectomy in the management of proliferative diabetic retinopathy with preoperative intravitreal injection of conbercept.

Small-gauge vitrectomy has become popular due to its notable advantages, including less trauma, shortened convalescence and improved manoeuvrability. The aim of the present study was to compare the surgical outcomes of 27-gauge (27-G) vitrectomy with those of 25-gauge (25-G) vitrectomy in the management of proliferative diabetic retinopathy (PDR) with preoperative intravitreal injection of conbercept. The data of 48 consecutive patients with PDR (48 eyes) were retrospectively collected. The patients underwent conbercept intravitreal injection and pars plana vitrectomy with a 27-G group (23 eyes) or 25-G group (25 eyes) vitrectomy system. The operating time, suturing rate, endodiathermy rate, postoperative best-corrected visual acuity (BCVA), intraocular pressure (IOP) and complications were recorded. The mean postoperative BCVA at final follow-up was significantly improved compared with that at the baseline in both groups (P<0.001 for both). The differences in the mean BCVA changes between the two groups were not significant (P>0.99), and no differences were observed in the final central foveal thickness (P=0.51) between the two groups. The final IOP remained stable compared with that at the baseline in the 27-G group (P=0.36) and the 25-G group (P=0.05). The suturing rate was significantly decreased in the 27-G group compared with the 25-G group (P=0.04). There were no significant differences between the two groups in terms of the operating time (P=0.18), rate of endodiathermy use (P>0.99), iatrogenic retinal breaks (P=0.42) or postoperative recurrent vitreous haemorrhage (P>0.99). In addition, no case of ocular hypotony was observed in either group. In conclusion, 27-G vitrectomy was as efficient and safe as 25-G vitrectomy in the management of PDR in terms of operating time and complications. With reference to the literature, preoperative conbercept injection appears to assist in decreasing the incidence of intraoperative and postoperative complications.

The Association Between Eye Disease and Incidence of Dementia: Systematic Review and Meta-Analysis.

OBJECTIVES: To better demonstrate the relationship between common eye diseases and the risk of dementia, we conducted a systematic review and meta-analysis of cohort studies to investigate the relationship between common eye diseases and dementia. DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: Patients with common eye diseases. METHODS: We conducted a systematic search of articles published up to August 25, 2022, of online databases including PubMed, EMBASE, and Web of Science. We included cohort studies that evaluated the association of glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and cataracts with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD). Relative risks (RRs) and 95% CIs were pooled using random effects model, and heterogeneity was assessed by the I2 statistic. Subgroup analysis and sensitivity analysis were also performed. RESULTS: In total, 25 studies were included in the meta-analysis, with a total of 11,410,709 participants. Pooled estimates suggested an increased risk of all-cause dementia associated with AMD (RR, 1.29; 95% CI, 1.13-1.48), glaucoma (RR, 1.16; 95% CI, 1.03-1.32), DR (RR, 1.40; 95% CI, 1.21-1.63), and cataract (RR,1.23; 95% CI, 1.09-1.40); an increased risk of AD associated with AMD (RR, 1.27; 95% CI, 1.06-1.52), glaucoma (RR, 1.18; 95% CI, 1.02-1.38), DR (RR, 1.21; 95% CI, 1.04-1.41), and cataracts (RR,1.22; 95% CI, 1.07-1.38). No association was observed between incident VaD and any eye diseases. The results of subgroup analyses were consistent with those in meta-analysis of DR and risk of all-cause dementia. Meta-regressions suggested geographic regions as potential sources of heterogeneity for the association between AMD and all-cause dementia, AMD and AD, glaucoma and dementia, glaucoma, and AD, respectively. CONCLUSIONS AND IMPLICATIONS: AMD, glaucoma, DR, and cataract may be associated with an increased risk of all-cause dementia and AD, but not VaD. However, the results should be interpreted cautiously because of the high heterogeneity and unstable findings in some subgroup analyses.

Predicting the Risk of Type 2 Diabetes Mellitus with the New Chinese Diabetes Risk Score in a Cohort Study.

Objectives: The New Chinese Diabetes Risk Score (NCDRS) is a noninvasive tool to assess the risk of type 2 diabetes mellitus (T2DM) in the Chinese population. Our study aimed to evaluate the performance of the NCDRS in predicting T2DM risk with a large cohort. Methods: The NCDRS was calculated, and participants were categorized into groups by optimal cutoff or quartiles. Hazard ratios (HRs) and 95% confidential intervals (CIs) in Cox proportional hazards models were used to estimate the association between the baseline NCDRS and the risk of T2DM. The performance of the NCDRS was assessed by the area under the curve (AUC). Results: The T2DM risk was significantly increased in participants with NCDRS ≥25 (HR = 2.12, 95% CI 1.88-2.39) compared with NCDRS <25 after adjusting for potential confounders. T2DM risk also showed a significant increasing trend from the lowest to the highest quartile of NCDRS. The AUC was 0.777 (95% CI 0.640-0.786) with a cutoff of 25.50. Conclusion: The NCDRS had a significant positive association with T2DM risk, and the NCDRS is valid for T2DM screening in China.

Prevalence and associated factors of depressive and anxiety symptoms among healthcare workers in the post-pandemic era of COVID-19 at a tertiary hospital in Shenzhen, China: A cross-sectional study.

Background: Healthcare workers were at high risk of psychological problems during the COVID-19 pandemic, but it remains not well-investigated in the post-pandemic era of COVID-19, with regular epidemic prevention and control embedded in burdened healthcare work. This study aimed to investigate the prevalence and potential risk factors of the symptoms of depression and anxiety among healthcare workers at a tertiary hospital in Shenzhen. Method: Our cross-sectional study was conducted among 21- to 64-year-old healthcare workers in December 2021 at a tertiary hospital in Shenzhen, using a simple random sampling strategy. A wide range of socio-demographic characteristics, individual information, and psychological condition of the subjects were extracted. Healthcare workers' psychological conditions were tested with the Center for Epidemiologic Studies Depression (CESD-10), General Anxiety Disorder (GAD-7), Insomnia Severity Index (ISI), Work-Family Conflict Scale (WFCS), 10-item Connor-Davidson Resilience Scale (CD-RISC-10), and 17-item of Maslach's Burnout Inventory-Human Services Survey (MBI-HSS-17). Data were collected based on these questionnaires. Descriptive statistics were used to assess the difference between healthcare workers with depressive and anxiety symptoms among different groups. Hierarchical logistic regression analyses were conducted to investigate the association between focused variables and mental health outcomes. Results: A total of 245 healthcare workers were enrolled. The proportion of depressive symptoms, anxiety symptoms and their co-occurrence were 34.7, 59.6, and 33.1%, respectively. Logistic regression showed that for the three outcomes, no history of receiving psychological help and self-rated good or higher health were protective factors, whereas more severe insomnia and job burnout were risk factors. Junior or lower job title and higher psychological resilience were related to a lower prevalence of depressive symptoms, while relatively longer working hours and larger work-family conflict were positively associated with the anxiety symptoms. Psychological resilience was inversely associated with the co-occurrence of depressive and anxiety symptoms. Conclusions: Our study revealed a high proportion of psychological problems and proved that several similar factors which were significant during the pandemic were also associated with the symptoms of depression and anxiety among healthcare workers in the post-pandemic era of COVID-19. These results provide scientific evidence for psychological interventions for healthcare workers.

Eliciting national and subnational sets of disability weights in mainland China: Findings from the Chinese disability weight measurement study.

Background: The disability weight (DW) quantifies the severity of health states from disease sequela and is a pivotal parameter for disease burden calculation. We conducted a national and subnational DW measurement in China. Methods: In 2020-2021, we conducted a web-based survey to assess DWs for 206 health states in 31 Chinese provinces targeting health workers via professional networks. We fielded questions of paired comparison (PC) and population health equivalence (PHE). The PC data were analysed by probit regression analysis, and the regression results were anchored by results from the PHE responses on the DW scale between 0 (no loss of health) and 1 (health loss equivalent to death). Findings: We used PC responses from 468,541 respondents to estimate DWs of health states. Eight of 11 domains of health had significantly negative coefficients in the regression of the difference between Chinese and Global Burden of Disease (GBD) DWs, suggesting lower DW values for health states with mention of these domains in their lay description. We noted considerable heterogeneity within domains, however. After applying these Chinese DWs to the 2019 GBD estimates for China, total years lived with disability (YLDs) increased by 14·9% to 177 million despite lower estimates for musculoskeletal disorders, cardiovascular diseases, mental disorders, diabetes and chronic kidney disease. The lower estimates of YLDs for these conditions were more than offset by higher estimates of common, low-severity conditions. Interpretation: The differences between the GBD and Chinese DWs suggest that there might be some contextual factors influencing the valuation of health states. While the reduced estimates for mental disorders, alcohol use disorder, and dementia could hint at a culturally different valuation of these conditions in China, the much greater shifts in YLDs from low-severity conditions more likely reflects methodological difficulty to distinguish between health states that vary a little in absolute DW value but a lot in relative terms. Funding: This work was supported by the National Natural Science Foundation of China [grant number 82173626], the National Key Research and Development Program of China [grant numbers 2018YFC1315302], Wuhan Medical Research Program of Joint Fund of Hubei Health Committee [grant number WJ2019H304], and Ningxia Natural Science Foundation Project [grant number 2020AAC03436].

Reduction of Laser-Induced Choroidal Neovascularization in Mice With Erythropoietin RNA Interference.

Purpose: The purpose of this study was to evaluate the pathological involvement of erythropoietin (EPO) in experimental choroidal neovascularization (CNV) and its association with neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) in the Chinese population. Methods: Treatment effect of recombinant EPO protein were assessed by human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation, and ex vivo choroid-sprouting ability. The effect of intravitreal injection of Epo siRNA against neovascularization was evaluated in the laser-induced CNV mouse model. In addition, the association of EPO variants with neovascular AMD and PCV was determined. Results: Exogenous supplementation of EPO significantly enhanced the migration and tube formation of HUVECs and promoted ex vivo choroid sprouting in mouse retinal pigment epithelium (RPE)-choroid-sclera complex culture. In the experimental CNV mouse model, Epo expression was found to be significantly upregulated by 3.5-folds in RPE-choroid-sclera complex at day 10 after laser induction as compared to the baseline. Immunofluorescence analysis showed that Epo was mainly expressed around the vascular endothelial cells in the RPE-choroid-sclera complex. Intravitreal injection of siRNA targeting Epo reduced 40% Epo expression and 40% CNV lesion areas as compared to the scramble control. However, EPO variants were not associated with neovascular AMD nor PCV in the Chinese population. Conclusions: This study revealed the promotion of human endothelial cell tube formation in vitro and choroid sprouting ex vivo by EPO, and the reduction of laser-induced CNV in vivo by Epo RNA interference. Translational Relevance: Targeting EPO could be a potential additional treatment for CNV-related diseases.

Application of Optical Coherence Tomography to a Mouse Model of Retinopathy.

Optical coherence tomography (OCT) offers a noninvasive method for the diagnosis of retinopathy. The OCT machine can capture retinal crosssectional images from which the retinal thickness can be calculated. Although OCT is widely used in clinical practice, its application in basic research is not as prevalent, especially in small animals such as mice. Because of the small size of their eyeballs, it is challenging to conduct fundus imaging examinations in mice. Therefore, a specialized retinal imaging system is required to accommodate OCT imaging on small animals. This article demonstrates a small-animal-specific system for OCT examination procedures and a detailed method for image analysis. The results of retinal OCT examination of very-low-density lipoprotein receptor (Vldlr) knockout mice and C57BL/6J mice are presented. The OCT images of C57BL/6J mice showed retinal layers, while those of Vldlr knockout mice showed subretinal neovascularization and retinal thinning. In summary, OCT examination could facilitate the noninvasive detection and measurement of retinopathy in mouse models.

Associations and pathways between residential greenness and metabolic syndromes in Fujian Province.

Background: Greenness exposure is beneficial to human health, but its potential mechanisms through which the risk for metabolic syndrome (MetS) could be reduced have been poorly studied. We aimed to estimate the greenness-MetS association in southeast China and investigate the independent and joint mediation effects of physical activity (PA), body mass index (BMI), and air pollutants on the association. Methods: A cross-sectional study was conducted among the 38,288 adults based on the Fujian Behavior and Disease Surveillance (FBDS), established in 2018. MetS was defined as the presence of three or more of the five components: abdominal obesity, elevated triglyceride, reduced high-density lipoprotein cholesterol (HDL-C), high blood pressure, and elevated fasting glucose. The residential greenness exposure was measured as the 3-year mean values of the normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) within the 250, 500, and 1,000 meters (m) buffer zones around the residential address of each participant. Logistic regression models were used to estimate the greenness-MetS association. The causal mediation analysis was used to estimate the independent and joint mediation effects of PA, BMI, particulate matter with an aerodynamic diameter of 2.5 µm (PM2.5), particulate matter with an aerodynamic diameter ≤ 10 µm (PM10), nitrogen dioxide (NO2), and sulfur dioxide (SO2). Results: Each interquartile range (IQR) increase in greenness was associated with a decrease of 13% (OR = 0.87 [95%CI: 0.83, 0.92] for NDVI500m and OR = 0.87 [95%CI: 0.82, 0.91] for EVI500m) in MetS risk after adjusting for covariates. This association was stronger in those aged < 60 years (e.g., OR = 0.86 [95%CI: 0.81, 0.92] for NDVI500m), males (e.g., OR = 0.73 [95%CI: 0.67, 0.80] for NDVI500m), having an educational level of primary school or above (OR = 0.81 [95%CI: 0.74, 0.89] for NDVI500m), married/cohabitation (OR = 0.86 [95%CI: 0.81, 0.91] for NDVI500m), businessman (OR = 0.82 [95%CI: 0.68, 0.99] for NDVI500m), other laborers (OR = 0.77 [95%CI: 0.68, 0.88] for NDVI500m), and non-smokers (OR = 0.77 [95%CI: 0.70, 0.85] for NDVI500m). The joint effect of all six mediators mediated about 48.1% and 44.6% of the total effect of NDVI500m and EVI500m on the MetS risk, respectively. Among them, BMI showed the strongest independent mediation effect (25.0% for NDVI500m), followed by NO2 and PM10. Conclusion: Exposure to residential greenness was associated with a decreased risk for MetS. PA, BMI, and the four air pollutants jointly interpreted nearly half of the mediation effects on the greenness-MetS association.

CXCL5/CXCR2 modulates inflammation-mediated neural repair after optic nerve injury.

BACKGROUND: Previous studies reported that mild inflammation promotes retinal ganglion cell (RGC) survival and axonal regeneration after optic nerve (ON) injury with involvement of infiltrating macrophages and neutrophils. Here we aimed to evaluate the involvement and regulation of the main inflammatory chemokine pathway CXCL5/CXCR2 in the inflammation-mediated RGC survival and axonal regeneration in mice after ON injury. METHODS: The expressions and cellular locations of CXCL5 and CXCR2 were confirmed in mouse retina. Treatment effects of recombinant CXCL5 and CXCR2 antagonist SB225002 were studied in the explant culture and the ON injury model with or without lens injury. The number of RGCs, regenerating axons, and inflammatory cells were determined, and the activation of Akt andSTAT3 signaling pathways were evaluated. RESULTS: Cxcr2 and Cxcl5 expressions were increased after ON and lens injury. Addition of recombinant CXCL5 promoted RGC survival and neurite outgrowth in retinal explant culture with increase in the number of activated microglia, which was inhibited by SB225002 or clodronate liposomes. Recombinant CXCL5 also alleviated RGC death and promoted axonal regeneration in mice after ON injury, and promoted the lens injury-induced RGC protection with increase in the number of activated CD68+ cells. SB225002 inhibited lens injury-induced cell infiltration and activation, and attenuated the promotion effect on RGC survival and axonal regeneration through reduction of lens injury-induced Akt activation. CONCLUSIONS: CXCL5 promotes RGC survival and axonal regeneration after ON injury and further enhances RGC protection induced by lens injury with CD68+ cell activation, which is attenuated by CXCR2 antagonist. CXCL5/CXCR2 could be a potential therapeutic target for RGC survival promotion after ON injury.

Association between serum prostate-specific antigen concentrations and the risk of developing type 2 diabetes mellitus in Chinese men: A cohort study.

AIMS/INTRODUCTION: The current literature suggests that men with diabetes have a lower prostate-specific antigen concentration than men without diabetes, but the causal association remains unclear. We aimed to investigate the association between serum prostate-specific antigen concentrations and the risk of type 2 diabetes mellitus in a cohort study of a Chinese population. MATERIALS AND METHODS: We designed a cohort study that comprised 16,811 initially non-diabetic Chinese men who received annual health checkups between 2009 and 2016. The outcome of this study was type 2 diabetes mellitus, identified by medical diagnosis, self-reportage, medication use, fasting glucose, 2-h post oral glucose or glycated hemoglobin measurements. Cox proportional hazards models were carried out to evaluate the association. RESULTS: During a median follow-up period of 3.8 years (interquartile range 1.91-5.73 years), 1,260 participants developed incident type 2 diabetes mellitus. The multivariable model, adjusted for various potential confounders, showed that serum prostate-specific antigen concentrations were inversely related to type 2 diabetes mellitus risk (P for trend = 0.014). Compared with the lowest quartile of serum prostate-specific antigen, the hazard ratio and 95% confidence intervals of type 2 diabetes mellitus risk for quartile 2-4 were 0.84 (0.66-1.07), 0.75 (0.59-0.94) and 0.77 (0.62-0.96), respectively. Subgroup analyses suggested the inverse relationship was more prominent in overweight or obese participants (P for interaction = 0.013). CONCLUSIONS: High serum prostate-specific antigen concentration was associated with a low risk of type 2 diabetes mellitus in Chinese men. Future studies are required to confirm these findings and investigate underlying mechanisms.

Sodium Butyrate Inhibits Neovascularization Partially via TNXIP/VEGFR2 Pathway.

Control of neovascularization with small molecules is a promising tactics. Here, we tested the roles of sodium butyrate (NaBu) on the neovascularization and primary explained its underlining molecular links. We used models including cell and ex vivo culture of choroid and mouse, as well as the biochemical and cellular techniques, to confirm our hypothesis. We found that treating HUVEC cells with NaBu (both 2.5 mM and 5 mM) significantly inhibited its ability in tube formation and proliferation. This inhibitory effect was also observed in choroid sprouting experiments, compared to the control. Interestingly, the choroid sprouting suppressed by NaBu can proliferate again after removing it, indicating that the cell cycle progression might be arrested. The laser-induced choroid neovascularization (CNV) was significantly alleviated by assessing the CNV size (decreased to 0.73 fold) in contrast with the vehicle control group after 2.5 mM NaBu injection for 7 days. Mechanistically, we found an enhanced TXNIP expression in response to NaBu treatment in all the three models. Overexpressing TXNIP in HUVEC cells blocked its tube formation and inhibited its proliferation; on the other hand, knocking down its expression with shRNA reversed those phenotypes in context of NaBu treatment. Further investigation showed the expression of VEGF receptor 2 (VEGFR2) in HUVEC cells was regulated by TXNIP undergoing NaBu treatment. We therefore argued that NaBu inhibited neovascularization partially through TXNIP-regulated VEGFR2 signal pathway.

Thunder-Fire Moxibustion for Cervical Spondylosis: A Systematic Review and Meta-Analysis.

BACKGROUND: Cervical spondylosis (CS) refers to the degenerative changes in the cervical spinal column, which affect the majority of middle-aged and elderly people. Thunder-fire moxibustion originated from thunder-fire miraculous needle, which has been applied widely for treating pain syndromes for thousands of years. The aim of our research is to provide evidence to assess the efficacy and safety of thunder-fire moxibustion in treating CS. Methods and analysis. Retrieved literature databases included Cochrane Library, MEDLINE, Web of Science, EBSCO, EBASE, Springer, PubMed, WFDP, CNKI, VIP, and CBM. The period of retrieval was from the establishment of the database to December 2018. Randomized controlled trials which compared thunder-fire moxibustion and other therapies in CS were included. The quality of inclusive trials was accessed though a Cochrane risk of bias tool. According to the test results of heterogeneity, a random effect model or fixed effect model was used to analyze the data. RESULTS: Meta-analysis was conducted for the total effective rate of thunder-fire moxibustion, traditional Chinese medicine syndrome score, pain score, satisfaction score, and score of the symptoms and functional rehabilitation of cervical vertigo. The analysis results were as follows: compared with other therapies, the efficacy of thunder-fire moxibustion was statistically significant, total effective rate increased (OR = 2.48; 95% CI [1.80, 3.41]; P < 0.00001), traditional Chinese medicine syndrome score decreased (SMD = -3.05; 95% CI[-4.18, -1.93]; P < 0.00001), traditional Chinese medicine syndrome score decreased (SMD = -3.05; 95% CI[-4.18, -1.93]; P < 0.00001), traditional Chinese medicine syndrome score decreased (SMD = -3.05; 95% CI[-4.18, -1.93]; P < 0.00001), traditional Chinese medicine syndrome score decreased (SMD = -3.05; 95% CI[-4.18, -1.93]; P < 0.00001), traditional Chinese medicine syndrome score decreased (SMD = -3.05; 95% CI[-4.18, -1.93]. CONCLUSION: Based on the existing evidence, the curative effect and safety of thunder-fire moxibustion on CS were statistically significant. We should interpret the results scrupulously because of the low evidence level. Large-scale, high-quality, rigorous RCTs with long-term follow-up should be performed in the future.

Longitudinal evaluation of immediate inflammatory responses after intravitreal AAV2 injection in rats by optical coherence tomography.

Gene therapy has been proposed as a feasible strategy for RGC survival and optic nerve regeneration. Some preclinical and clinical studies revealed intraocular inflammation after intravitreal injection of adeno-associated virus (AAV) by slit-lamp or indirect ophthalmoscope. Here we evaluate the longitudinal profile of immediate inflammatory responses after AAV2 injection in rat retina and vitreous body by optical coherence tomography (OCT). Adult Fischer F344 rats were intravitreally injected once with saline, AAV2 or zymosan. Retinal thickness and cell infiltration were recorded by OCT longitudinally for 2 months and verified by histological analysis. The transduction rate of single intravitreal AAV2 injection was 21.3 ± 4.9% of whole retina, and the transduction efficiency on RGCs was 91.5 ± 2.5% in the transduced area. Significant increase in cell infiltration was observed from Day 1-3 after AAV2 injection, compared to very few infiltrating cells observed in the saline-injected group. The infiltrating cells ceased at Day 5 after intravitreal injection and remained absent at 2 months. The thicknesses of total and inner retina were increased along Day 1-3 after AAV2 injection, but reverted to normal afterwards. The surviving RGCs in the AAV2-injected groups at Day 14 showed no significant difference compared to saline-injected group. In summary, this study revealed the immediate inflammatory responses and retinal edema after intravitreal AAV2 injection in normal rats, without influencing long-term retinal thickness and RGC survival. OCT can be implemented for the time-lapse in vivo evaluation of inflammatory response after AAV-mediated gene therapy through intravitreal injection.