Evaluating the Causal Effects of Low Density Lipoprotein Cholesterol Levels on Ischemic Stroke: A Mendelian Randomization Study.

Background: Ischemic stroke (IS) is the leading cause of disability and mortality worldwide. Low-density lipoprotein cholesterol (LDL-C) levels hadno potential risk on ischemic stroke. However, higher LDL-C levels were closely related to IS. Based on two antagonistic viewpoints, a Mendelian randomization (MR) study was designed to evaluate the causal effects of LDL-C levels on IS. Methods: Datasets of LDL-C levels and ischemic stroke were acquired from genome-wide association studies (GWAS). Weighted median method was conducted for main analysis, and MR-Egger and inverse-variance weighted (IVW) methods were performed for auxiliary analyses. Heterogeneity and pleiotropic tests were utilized to confirm the reliability of this study. Results: A total of 359 single nucleotide polymorphisms (SNPs) were associated with LDL-C levels (P < 5 × 10-8) and 337 SNPs were available in ischemic stroke with eliminating outliers. LDL-C levels were significantly associated with ischemic stroke (OR = 1.104, 95%CI = 1.019 - 1.195, P = 1.52 × 10-2). MR-Egger and IVW showed directionally similar estimates (MR-Egger: OR = 1.120, 95%CI = 1.040 - 1.207, P = 3.12 × 10-3; IVW: OR = 1.120, 95%CI = 1.064 - 1.178, P = 1.17 × 10-5). Conclusion: LDL-C levels had causal effects on IS, providing insights into the design of future interventions to reduce the burden of ischemic stroke.

Uric acid levels and heart failure: A mendelian randomization study.

BACKGROUND AND AIMS: Uric acid, the end-product of purine metabolism within the human body, has been the subject of studies exploring its potential association with cardiovascular and cerebrovascular diseases. However, the precise relationship between uric acid levels and heart failure remains elusive. METHODS AND RESULTS: In this particular study, aggregated data from genome-wide association studies on uric acid and heart failure were utilized to perform a two-sample Mendelian randomization (MR) analysis utilizing R software. The aim was to uncover any causal link between these variables. The primary outcome was assessed using inverse variance weighted (IVW) methodology, while sensitivity analyses employed MR-Egger, weighted median (WME), and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) techniques. IVW results revealed a possible causal relationship between elevated uric acid levels and an increased risk of heart failure (OR: 1.09, 95 % CI: 1.01-1.17, P < 0.05). Encouragingly, the directions provided by MR-Egger and WME aligned with IVW findings, and no anomalies were detected in the remaining sensitivity analyses. CONCLUSION: These outcomes indicate the stability of the results of the study, thereby suggesting that heightened uric acid levels may contribute to an augmented risk of heart failure.

The effects of self-esteem and parental phubbing on adolescent internet addiction and the moderating role of the classroom environment: a hierarchical linear model analysis.

BACKGROUND: With the advent of the new media era, the understanding of adolescent internet addiction needs to be enriched. It is also necessary to distinguish the related factors of adolescent internet addiction at different levels to clarify the mechanisms of this phenomenon. METHODS: This study used hierarchical linear model analysis to explore the effects of student-level factors and school-level factors on adolescent internet addiction, along with cross-level moderating effects. A total of 1,912 students between the 4th and 8th grades in China participated in the study. Participants completed the Self-Esteem Scale, Parents Phubbing Scale, Classroom Environment Scale, and the Diagnostic Questionnaire of Internet Addiction. RESULTS: Correlational analyses revealed that internet addiction was found to be negatively correlated with both self-esteem and the teacher-student relationship (p < 0.01), while father phubbing, mother phubbing, and learning burden were shown to positively correlate with internet addiction (p < 0.01). Hierarchical linear model analysis suggested that student-level variables, including self-esteem, and mother phubbing, were significant predictors of internet addiction (ß = -0.077, p < 0.001 and ß = 0.028, p < 0.01, respectively). At the school level, learning burden significantly and negatively predicted internet addiction (ß = 0.073, p < 0.05). Furthermore, the relationship between self-esteem and internet addiction was significantly moderated by learning burden (ß = -0.007, p < 0.05). Meanwhile, the teacher-student relationship also had a significant moderating effect on the association between mother phubbing and internet addiction (ß = -0.005, p < 0.01). CONCLUSIONS: This study revealed the relationships between self-esteem, parental phubbing, and classroom environment with adolescent internet addiction, and these findings could provide insights into reducing adolescent internet addiction from the perspective of individuals, families, and schools.

Risk Factors for Primary Angle-closure Glaucoma: A Systematic Review and Meta-analysis of 45 Studies.

SIGNIFICANCE: This study summarized primary angle-closure glaucoma (PACG)-related factors across different dimensions. OBJECTIVES: This review aimed at systematically summarizing the associated factors of PACG in published literatures. METHODS: A systematic review and meta-analysis were conducted by searching the electronic databases including PubMed, EMBASE, and Web of Science from their inception to November 2021. The pooled risk estimates of continuous and categorical variables were calculated using weighted mean difference (WMD) and odds ratio (OR; 95% confidence intervals [CIs]), respectively. RESULTS: We included 45 studies in this review. In the meta-analysis, intraocular pressure (WMD, 3.13; 95% CI, 2.37 to 3.89), anterior chamber depth (WMD, -0.52; 95% CI, -0.70 to -0.34), axial length (WMD, -0.77; 95% CI, -1.26 to -0.28), retinal nerve fiber layer (WMD, -21.23; 95% CI, -30.21 to -12.25), and spherical equivalent (WMD, 1.02; 95% CI, 0.66 to 1.38) were the most common ophthalmic anatomic factors, and lower body weight (WMD, -3.65; 95% CI, -6.48 to -0.82) was the most significant general morphological indicators. The presence of cataract (OR, 3.77; 95% CI, 3.46 to 4.11) and hyperlipidemia (OR, 1.10; 95% CI, 1.02 to 1.20) were significantly associated with PACG. Increased level of triglyceride (WMD, 0.17; 95% CI, 0.06 to 0.27) was associated with PACG. In addition, an association between short-term antidepressant exposure (OR, 1.36; 95% CI, 1.08 to 1.70) and acute angle-closure glaucoma was observed. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: This review identified a few consistent factors related to PACG, providing important information for primary care physicians, general ophthalmologists, and public health professionals to counsel their patients on PACG risks.

Myopic maculopathy among Chinese children with high myopia and its association with choroidal and retinal changes: the SCALE-HM study.

AIMS: To investigate myopic maculopathy in Chinese children with high myopia and its association with choroidal and retinal changes. METHODS: This cross-sectional study included Chinese children aged 4-18 years with high myopia. Myopic maculopathy was classified by fundus photography and retinal thickness (RT) and choroidal thickness (ChT) in the posterior pole were measured by swept-source optical coherence tomography. A receiver operation curve was used to determine the efficacy of fundus factors in classifying myopic maculopathy. RESULTS: In total, 579 children aged 12.8±3.2 years with a mean spherical equivalent of -8.44±2.20 D were included. The proportions of tessellated fundus and diffuse chorioretinal atrophy were 43.52% (N=252) and 8.64% (N=50), respectively. Tessellated fundus was associated with a thinner macular ChT (OR=0.968, 95% CI: 0.961 to 0.975, p<0.001) and RT (OR=0.977, 95% CI: 0.959 to 0.996, p=0.016), longer axial length (OR=1.545, 95% CI: 1.198 to 1.991, p=0.001) and older age (OR=1.134, 95% CI: 1.047 to 1.228, p=0.002) and less associated with male children (OR=0.564, 95% CI: 0.348 to 0.914, p=0.020). Only a thinner macular ChT (OR=0.942, 95% CI: 0.926 to 0.959, p<0.001) was independently associated with diffuse chorioretinal atrophy. When using nasal macular ChT for classifying myopic maculopathy, the optimal cut-off value was 129.00 µm (area under the curve (AUC)=0.801) and 83.85 µm (AUC=0.910) for tessellated fundus and diffuse chorioretinal atrophy, respectively. CONCLUSION: A large proportion of highly myopic Chinese children suffer from myopic maculopathy. Nasal macular ChT may serve as a useful index for classifying and assessing paediatric myopic maculopathy. TRIAL REGISTRATION NUMBER: NCT03666052.

Machine Learning-Based Integration of Metabolomics Characterisation Predicts Progression of Myopic Retinopathy in Children and Adolescents.

Myopic retinopathy is an important cause of irreversible vision loss and blindness. As metabolomics has recently been successfully applied in myopia research, this study sought to characterize the serum metabolic profile of myopic retinopathy in children and adolescents (4-18 years) and to develop a diagnostic model that combines clinical and metabolic features. We selected clinical and serum metabolic data from children and adolescents at different time points as the training set (n = 516) and the validation set (n = 60). All participants underwent an ophthalmologic examination. Untargeted metabolomics analysis of serum was performed. Three machine learning (ML) models were trained by combining metabolic features and conventional clinical factors that were screened for significance in discrimination. The better-performing model was validated in an independent point-in-time cohort and risk nomograms were developed. Retinopathy was present in 34.2% of participants (n = 185) in the training set, including 109 (28.61%) with mild to moderate myopia. A total of 27 metabolites showed significant variation between groups. After combining Lasso and random forest (RF), 12 modelled metabolites (mainly those involved in energy metabolism) were screened. Both the logistic regression and extreme Gradient Boosting (XGBoost) algorithms showed good discriminatory ability. In the time-validation cohort, logistic regression (AUC 0.842, 95% CI 0.724-0.96) and XGBoost (AUC 0.897, 95% CI 0.807-0.986) also showed good prediction accuracy and had well-fitted calibration curves. Three clinical characteristic coefficients remained significant in the multivariate joint model (p < 0.05), as did 8/12 metabolic characteristic coefficients. Myopic retinopathy may have abnormal energy metabolism. Machine learning models based on metabolic profiles and clinical data demonstrate good predictive performance and facilitate the development of individual interventions for myopia in children and adolescents.

Uric acid levels and their association with vascular dementia and Parkinson's disease dementia: a meta-analysis.

OBJECTIVES: To explore the association between uric acid (UA) levels and vascular dementia (VaD) and Parkinson's disease dementia (PDD), a meta-analysis was conducted. METHODS: The relevant studies were identified by searching PubMed, Embase, Web of Science, and Cochrane Collaboration Database up to May 2022. Pooled analysis, sensitivity analysis, and publication bias examination were all conducted. All analyses were performed by using STATA 16. RESULTS: Twelve studies with a total of 2097 subjects were included. The pooled analysis showed that UA levels were not associated with VaD (WMD = - 10.99 µmol/L, 95% CI (- 48.05, 26.07), P = 0.561) but were associated with PDD (WMD = - 25.22 µmol/L, 95% CI (- 43.47, - 6.97), P = 0.007). The statistical stability and reliability were evaluated using sensitivity analysis and publication bias outcomes. CONCLUSION: UA levels are associated with PDD but not with VaD. This study will help to strengthen our knowledge of the pathophysiologies of VaD and PDD, and promote the development of prevention and treatment strategies.

Metabolomics facilitates the discovery of metabolic profiles and pathways for myopia: A systematic review.

BACKGROUND: Myopia is one of the major eye disorders and the global burden is increasing rapidly. Our purpose is to systematically summarize potential metabolic biomarkers and pathways in myopia to facilitate the understanding of disease mechanisms as well as the discovery of novel therapeutic measures. METHODS: Myopia-related metabolomics studies were searched in electronic databases of PubMed and Web of Science until June 2021. Information regarding clinical and demographic characteristics of included studies and metabolomics findings were extracted. Myopia-related metabolic pathways were analysed for differential metabolic profiles, and the quality of included studies was assessed based on the QUADOMICS tool. Pathway analyses of differential metabolites were performed using bioinformatics tools and online software such as the Metaboanalyst 5.0. RESULTS: The myopia-related metabolomics studies included in this study consisted of seven human and two animal studies. The results of the study quality assessment showed that studies were all phase I studies and all met the evaluation criteria of 70% or more. The myopia-control serum study identified 23 differential metabolites with the Sphingolipid metabolism pathway beings enriched. The high myopia-cataract aqueous humour study identified 40 differential metabolites with the Arginine biosynthesis pathway being enriched. The high myopia-control serum study identified 43 differential metabolites and 4 pathways were significantly associated with metabolites including Citrate cycle; Alanine, aspartate and glutamate metabolism; Glyoxylate and dicarboxylate metabolism; Biosynthesis of unsaturated fatty acids (all P value < 0.05). CONCLUSIONS: This study summarizes potential metabolic biomarkers and pathways in myopia, providing new clues to elucidate disease mechanisms.

X-ray CT image denoising with MINF: A modularized iterative network framework for data from multiple dose levels.

In clinical applications, multi-dose scan protocols will cause the noise levels of computed tomography (CT) images to fluctuate widely. The popular low-dose CT (LDCT) denoising network outputs denoised images through an end-to-end mapping between an LDCT image and its corresponding ground truth. The limitation of this method is that the reduced noise level of the image may not meet the diagnostic needs of doctors. To establish a denoising model adapted to the multi-noise levels robustness, we proposed a novel and efficient modularized iterative network framework (MINF) to learn the feature of the original LDCT and the outputs of the previous modules, which can be reused in each following module. The proposed network can achieve the goal of gradual denoising, outputting clinical images with different denoising levels, and providing the reviewing physicians with increased confidence in their diagnosis. Moreover, a multi-scale convolutional neural network (MCNN) module is designed to extract as much feature information as possible during the network's training. Extensive experiments on public and private clinical datasets were carried out, and comparisons with several state-of-the-art methods show that the proposed method can achieve satisfactory results for noise suppression of LDCT images. In further comparisons with modularized adaptive processing neural network (MAP-NN), the proposed network shows superior step-by-step or gradual denoising performance. Considering the high quality of gradual denoising results, the proposed method can obtain satisfactory performance in terms of image contrast and detail protection as the level of denoising increases, which shows its potential to be suitable for a multi-dose levels denoising task.

Antiplatelet therapy for secondary prevention of lacunar stroke: a systematic review and network meta-analysis.

PURPOSE: To comprehensively compare the efficacy of different antiplatelet therapies for secondary prevention of lacunar stroke (LS). METHODS: The relevant studies were identified by searching PubMed, EMBASE, Web of Science, and Cochrane Collaboration Database up to May 2022. Cardiovascular and cerebrovascular events were chosen to evaluate the efficacy of antiplatelet therapy for secondary prevention. Loop-specific approach and node-splitting analysis were used to evaluate consistency and inconsistency, respectively. The value of the surface under the cumulative ranking (SUCRA) was calculated and ranked. Funnel-plot symmetry was used to evaluate publication bias. The meta-analysis was performed by using STATA 16.0. RESULTS: Thirteen studies with a total of 33,011 subjects were included in this network meta-analysis. Compared with placebo, aspirin, clopidogrel, cilostazol, ticlopidine, aspirin plus dipyridamole, and aspirin plus clopidogrel were associated with reducing cardiovascular and cerebrovascular events. The SUCRA estimated relative ranking of treatments showed that cilostazol may be the most effective (RR 0.56, 95% CI 0.42-0.74, SUCRA 95.8). No significant inconsistency or publication bias was found in the study. CONCLUSIONS: This meta-analysis suggests that cilostazol may be a priority option for secondary prevention of patients with LS. These findings still need further study in the future.

Rope Jumping Strength Monitoring on Smart Devices via Passive Acoustic Sensing.

Rope jumping, as a fitness exercise recommended by many sports medicine practitioners, can improve cardiorespiratory capacity and physical coordination. Existing rope jump monitoring systems have limitations in terms of convenience, comfort, and exercise intensity evaluation. This paper presents a rope jump monitoring system using passive acoustic sensing. Our system exploits the off-the-shelf smartphone and headphones to capture the user's rope-jumping sound and breathing sound after exercise. Given the captured acoustic data, the system uses a short-time energy-based approach and the high correlation between rope jumping cycles to detect the rope-jumping sound frames, then applies a dual-threshold endpoint detection algorithm to calculate the number of rope jumps. Finally, our system performs regression predictions of exercise intensity based on features extracted from the jumping speed and the mel spectrograms of the user's breathing sound. The significant advantage of the system lies in the solution of the problem of poorly characterized mel spectrograms. We employ an attentive mechanism-based GAN to generate optimized breathing sound mel spectrograms and apply domain adversarial adaptive in the network to improve the migration capability of the system. Through extensive experiments, our system achieves (on average) 0.32 and 2.3% error rates for the rope jumping count and exercise intensity evaluation, respectively.

Metabolomics and Biomarkers in Retinal and Choroidal Vascular Diseases.

The retina is one of the most important structures in the eye, and the vascular health of the retina and choroid is critical to visual function. Metabolomics provides an analytical approach to endogenous small molecule metabolites in organisms, summarizes the results of "gene-environment interactions", and is an ideal analytical tool to obtain "biomarkers" related to disease information. This study discusses the metabolic changes in neovascular diseases involving the retina and discusses the progress of the study from the perspective of metabolomics design and analysis. This study advocates a comparative strategy based on existing studies, which encompasses optimization of the performance of newly identified biomarkers and the consideration of the basis of existing studies, which facilitates quality control of newly discovered biomarkers and is recommended as an additional reference strategy for new biomarker discovery. Finally, by describing the metabolic mechanisms of retinal and choroidal neovascularization, based on the results of existing studies, this study provides potential opportunities to find new therapeutic approaches.

A review of study designs and data analyses in metabolomics studies in myopia.

Metabolomics analyzes the entire range of small molecule metabolites in biological systems to reveal the response signals that are transmitted from "genetics and environment", which could help us understand complex phenotypes of diseases. Metabolomics has been successfully applied to the study of eye diseases including age-related macular degeneration, glaucoma, and diabetic retinopathy. In this review, we summarize the findings of myopic metabolomics and discuss them from a design and analysis perspective. Finally, we provide new ideas for the future development of myopia metabolomics research based on the broader ocular metabolomics study.

Safety and preliminary efficacy of argatroban plus dual antiplatelet therapy for acute mild to moderate ischemic stroke with large artery atherosclerosis.

OBJECTIVE: Previous studies suggest the benefit of dual antiplatelet therapy (DAPT) for acute ischemic stroke with large artery atherosclerosis (LAA) etiology, but there is no study about the effect of DAPT plus anticoagulant in this population. METHODS: A prospective single arm trial was performed to determine the effect of DAPT combined with argatroban on acute mild to moderate ischemic stroke patients with LAA, which was compared with historical populations. The main outcome was the proportion of early neurological deterioration (END). The secondary outcomes included scores of 0 to 1 and 0 to 2 on the modified Rankin Scale (mRS) at 90 days, and changes in National Institutes of Health Stroke Scale (NIHSS) from baseline to day 7 after admission. The safety outcomes included intracranial hemorrhage at 7 days, organ hemorrhage, and all-cause mortality at 90 days. RESULTS: A total of 120 patients with argatroban plus DAPT were prospectively enrolled and 529 patients with only DAPT were retrospectively collected. There was no significant difference in baseline characteristics between groups. Compared with control group, combined treatment group had lower proportion of END (4.2% vs. 10.0%, adjusted p = .046), more reduction in NIHSS score from the baseline to day 7 after admission (1.06 ± 2.03 vs. 0.39 ± 1.97, adjusted p = .003), and higher proportion of mRS (0-2) at 90 days (87.5% vs. 79.2%, adjusted p = .048). No intracranial hemorrhage was found between groups. CONCLUSIONS: This is the first report that short-term argatroban combined with DAPT seems to be safe and may effectively prevent END and improve neurological prognosis for acute mild to moderate ischemic stroke patients with LAA; however, interpretation of the conclusion required caution due to nonrandomized controlled trial with medium sample size.

Mechanical Thrombectomy for Mild Acute Ischemic Stroke with Large-Vessel Occlusion: A Systematic Review and Meta-Analysis.

BACKGROUND: The functional prognosis of mechanical thrombectomy (MT) for mild acute ischemic stroke (AIS) with large-vessel occlusion (LVO) is controversial. To explore a more precise estimation, a meta-analysis was conducted. METHODS: The relevant studies were identified by searching PubMed, Embase, Web of Science, and Cochrane Collaboration Database until October 2021. The pooled analysis, subgroup analysis, sensitivity analysis, and publication bias examination were all conducted. The meta-analysis was performed by using Stata 12.0. RESULTS: Eleven studies were included with a total of 1,929 subjects, including 794 patients receiving MT and 1,135 patients receiving medical management. The pooled analysis showed that MT might be not associated with functional prognosis among mild AIS with LVO (excellent functional prognosis: risk ratio (RR) = 1.07, 95% confidence interval (CI) = 0.94-1.21, p = 0.294; favorable functional prognosis: RR = 1.01, 95% CI = 0.96-1.06, p = 0.823). The statistical stability and reliability were demonstrated by the sensitivity analysis and publication bias outcomes. CONCLUSION: Our meta-analysis suggests that MT may be not associated with functional prognosis of mild AIS with LVO.

Organic NIR-II dyes with ultralong circulation persistence for image-guided delivery and therapy.

Nanocarriers hold great promise for the controlled release of therapeutic payloads to target organs/tissues and extended duration of anticancer agents in the bloodstream. However, limited data on their in vivo pharmacokinetics and delivery process hamper clinical applications. Here we report a series of micellar nanocarriers self-assembled from new-generation thiophenthiadiazole (TTD)-based NIR-II fluorophores HLAnP (n = 1-4) for simultaneous bioimaging and drug delivery. The NIR-II HLA4P nanocarrier displays exceptional non-fouling performance, minimal immunogenicity, ultralong blood half-life, and high tumor accumulation even with different administration routes. When used as a drug carrier, HLA4P with encapsulated doxorubicin (DOX) realized accurate tumor targeting and continuous real-time in vivo NIR-II tracking of drug delivery and therapy, showing a sustained release rate, improved therapeutic effect, and diminished cardiotoxicity as compared to free DOX. This study provides a new perspective on the design of dual-functional NIR-II fluorophores for diagnostic and therapeutic applications.

Self-assembled NIR-II Fluorophores with Ultralong Blood Circulation for Cancer Imaging and Image-guided Surgery.

Complete excision of the last remaining 1-2% of tumor tissue without collateral damage remains particularly challenging. Herein, we report thiophenthiadiazole (TTD)-derived fluorophores L6-PEGnk (n = 1, 2, 5) as new-generation NIR-II (1000-1700 nm) probes with exceptional nonfouling performance and significantly high fluorescence quantum yields in water. L6-PEG2k can self-assemble into vesicular micelles and exhibited minimal immunogenicity, low binding affinities, ultralong blood circulation (t1/2 = 59.5 h), and a supercontrast ratio in vivo. Most importantly, L6-PEG2k achieved excellent in vivo CT-26 and U87MG tumor targeting and accumulation (>20 d) through intraperitoneal or intravenous injection. A subcutaneous U87MG tumor and orthotopic brain glioma were successfully resected under NIR-II FIGS in our animal model via intraperitoneal injection in an extended time window (48-144 h). This study highlights the potential of using L6-PEG2K as self-assembling molecular probes with long-circulation persistence for routine preoperative tumor assessment and precise intraoperative image-guided resection.

Relationship between behavioral inhibition/activation system and Internet addiction among Chinese college students: The mediating effects of intolerance of uncertainty and self-control and gender differences.

Background: Internet addiction is a global public health issue among college students that is associated with a range of negative outcomes. Especially the COVID-19 pandemic has forced them to shift most of their studies and life activities from offline to online, leading to a growing problem of Internet dependence and even Internet addiction. Although previous studies have indicated that the Behavioral Inhibition/Activation System (BIS/BAS) have important effects on college students' Internet addiction, the mechanisms underlying these associations and gender differences are still unclear. Aims: The present study investigated the mediating roles of intolerance of uncertainty and self-control in the association between BIS/BAS and Internet addiction following the Interaction of Person-Affect-Cognition-Execution model. Gender differences in such associations between variables were also tested. Method: A total of 747 Chinese college students were surveyed by using Young's Diagnostic Questionnaire for Internet Addiction, BIS/BAS Scales, the Intolerance of Uncertainty Scale and the Brief Self-Control Scale. Results: The results from the structural equation modeling analysis showed that BIS was positively related to Internet addiction and that BAS had a negative association with Internet addiction. Moreover, intolerance of uncertainty and self-control mediated the relationships between BIS/BAS and Internet addiction. Multi-group analysis further revealed that the associations between BAS and Internet addiction and between intolerance of uncertainty and Internet addiction were stronger among the male students than among female students. The relationship between self-control and Internet addiction was greater in the female sample than in the male sample. Conclusions: These findings extend our understanding of how BIS/BAS influence Internet addiction among college students and suggest that not only should training approaches based on intolerance of uncertainty and self-control be fully considered, but different intervention programs should be focused on gender sensitivity to maximize the intervention effect.

Metabolomics in Diabetic Retinopathy: A Systematic Review.

Purpose: Diabetic retinopathy (DR), a common microvascular complication of diabetes, is the leading cause of acquired blindness in the working-age population. Individuals with diabetes still develop DR despite appropriate glycemic and blood pressure control, highlighting the pressing need to identify useful biomarkers for risk stratification. The purpose of this review is to systematically summarize potential metabolic biomarkers and pathways of DR, which could facilitate developing an understanding of the disease mechanisms, as well as new therapeutic measures. Methods: We searched PubMed and Web of Science for relevant metabolomics studies on humans published before September 30, 2020. Information regarding authors, title, publication date, study subjects, analytical platforms, methods of statistical analysis, biological samples, directions of change of potential metabolic biomarkers, and predictive values of metabolic biomarker panels was extracted, and the quality of the studies was assessed. Pathway analysis, including enrichment analysis and topology analysis, was derived from integrating differential metabolites using MetaboAnalyst 3.0, based on the Kyoto Encyclopedia of Genes and Genomes and Human Metabolome Database. Results: We found nine studies focused on the identification of potential biomarkers. Repeatedly identified metabolites including l-glutamine, l-lactic acid, pyruvic acid, acetic acid, l-glutamic acid, d-glucose, l-alanine, l-threonine, citrulline, l-lysine, and succinic acid were found to be potential biomarkers of DR. It was observed that l-glutamine and citrulline changed in all biological samples. Dysregulation of metabolic pathways involved amino acid and energy metabolism. Conclusions: This review summarizes potential biomarkers and metabolic pathways, providing insights into new pathogenic pathways for this microvascular complication of diabetes.

Metabolomics in Glaucoma: A Systematic Review.

Purpose: Glaucoma remains a poorly understood disease, and identifying biomarkers for early diagnosis is critical to reducing the risk of glaucoma-related visual impairment and blindness. The aim of this review is to provide current metabolic profiles for glaucoma through a summary and analysis of reported metabolites associated with glaucoma. Methods: We searched PubMed and Web of Science for metabolomics studies of humans on glaucoma published before November 11, 2020. Studies were included if they assessed the biomarkers of any types of glaucoma and performed mass spectrometry-based or nuclear magnetic resonance-based metabolomics approach. Pathway enrichment analysis and topology analysis were performed to generate a global view of metabolic signatures related to glaucoma using the MetaboAnalyst 3.0. Results: In total, 18 articles were included in this review, among which 13 studies were focused on open-angle glaucoma (OAG). Seventeen metabolites related to OAG were repeatedly identified, including seven amino acids (arginine, glycine, alanine, lysine, methionine, phenylalanine, tyrosine), two phosphatidylcholine (PC aa C34:2, PC aa C36:4), three complements (acetylcarnitine, propionylcarnitine, butyrylcarnitine), carnitine, glutamine, hypoxanthine, spermine, and spermidine. The pathway analysis implied a major role of amino metabolism in OAG pathophysiology and revealed the metabolic characteristics between different biological samples. Conclusions: In this review, we summarize existing metabolomic studies related to glaucoma biomarker identification and point out a series of metabolic disorders in OAG patients, providing information on the molecular mechanism changes in glaucoma. Additional studies are needed to validate existing findings, and future research will need to explore the potential overlap between different biological fluids.