Porous Se@SiO2 nanospheres alleviate diabetic retinopathy by inhibiting excess lipid peroxidation and inflammation.

BACKGROUND: Lipid peroxidation is a characteristic metabolic manifestation of diabetic retinopathy (DR) that causes inflammation, eventually leading to severe retinal vascular abnormalities. Selenium (Se) can directly or indirectly scavenge intracellular free radicals. Due to the narrow distinction between Se's effective and toxic doses, porous Se@SiO2 nanospheres have been developed to control the release of Se. They exert strong antioxidant and anti-inflammatory effects. METHODS: The effect of anti-lipid peroxidation and anti-inflammatory effects of porous Se@SiO2 nanospheres on diabetic mice were assessed by detecting the level of Malondialdehyde (MDA), glutathione peroxidase 4 (GPX4), decreased reduced/oxidized glutathione (GSH/GSSG) ratio, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL) -1ß of the retina. To further examine the protective effect of porous Se@SiO2 nanospheres on the retinal vasculopathy of diabetic mice, retinal acellular capillary, the expression of tight junction proteins, and blood-retinal barrier destruction was observed. Finally, we validated the GPX4 as the target of porous Se@SiO2 nanospheres via decreased expression of GPX4 and detected the level of MDA, GSH/GSSG, TNF-α, IFN-γ, IL -1ß, wound healing assay, and tube formation in high glucose (HG) cultured Human retinal microvascular endothelial cells (HRMECs). RESULTS: The porous Se@SiO2 nanospheres reduced the level of MDA, TNF-α, IFN-γ, and IL -1ß, while increasing the level of GPX4 and GSH/GSSG in diabetic mice. Therefore, porous Se@SiO2 nanospheres reduced the number of retinal acellular capillaries, depletion of tight junction proteins, and vascular leakage in diabetic mice. Further, we identified GPX4 as the target of porous Se@SiO2 nanospheres as GPX4 inhibition reduced the repression effect of anti-lipid peroxidation, anti-inflammatory, and protective effects of endothelial cell dysfunction of porous Se@SiO2 nanospheres in HG-cultured HRMECs. CONCLUSION: Porous Se@SiO2 nanospheres effectively attenuated retinal vasculopathy in diabetic mice via inhibiting excess lipid peroxidation and inflammation by target GPX4, suggesting their potential as therapeutic agents for DR.

Correlation between mental status and prevalence of asthenopia in Chinese college students.

BACKGROUND: The purpose of this study was to identify the possible association between mental status and the risk of self-reported asthenopia among college students in China. METHODS: Ten thousand students were randomly assessed in the study using a self-reported asthenopia questionnaire. Their demographic characteristics and mental status were recorded. Univariate analysis was performed to preliminarily select potential risk and protective factors. Then, multivariate logistic regression was used to estimate odds ratios for the selected risk factors of interest. RESULTS: Among the 8370 students who completed the survey, the prevalence of asthenopia was 61.0%. Multivariate analysis revealed a significant relationship between asthenopia and depressive symptoms (OR 1.511 95% CI: 1.350-1.691), obsessive-compulsive symptoms (OR 1.477, 95% CI: 1.338-1.632), gender and study load. The place college students spent their off-hours (OR 0.841, 95% CI: 0.784-0.902) was found to be the strongest factor for decreasing the occurrence of asthenopia complaints. CONCLUSION: Asthenopia appears common in Chinese college students. In addition to depressive symptoms, we should pay attention to obsessive-compulsive symptoms when considering means of preventing asthenopia. Harmonious social relationships, outdoor off-hour activities and exercising more than three times per week are crucial to relieving visual fatigue. Further study is still needed in this area.

Associations between the vessel density in deep vascular plexus and macular edema recurrences in patients with retinal vein occlusion.

INTRODUCTION: To study the relationships between vessel density (VD) in different retinal vascular plexus and retinal vein occlusion-macular edema (RVO-ME) recurrence using wide-field swept source optical coherence tomography angiography (OCTA) Methods: Patients with a history of central (CRVO) or branch retinal vein occlusion (BRVO) with macular edema in the Department of Ophthalmology, Shanghai General Hospital, from May 25, 2020 to January 12, 2023, were retrospectively reviewed and recruited. All patients were followed up for at least 6 months and divided in the release group and the recurrence group. The optical coherence tomography and OCTA examination were performed. Demographics, retinal structural and angiographic data were collected and compared between two groups. The ordinal logistic regression was performed to assess the risk factors for RVO-ME. RESULTS: A total of 85 patients were enrolled in this study. Among them, 30 patients had CRVO while 55 had BRVO. The VD in the 6-9 mm ring in deep vascular plexus (DVP) was significantly higher in the recurrence group (25.414 ± 6.068% in the release group vs 27.574 ± 7.767% in the recurrence group, P = 0.036). More patients with mean VD of the 6-9 mm ring in DVP no less than 30% was observed in the recurrence group (observed n = 20, expected n = 14.4, P = 0.043). The ordinal logistic regression reported that patients with mean VD of the 6-9 mm ring in DVP ≥30% had risk of RVO-ME increased to 11.508 (95% CI: 1.745 to 75.944, P = 0.011), when compared to the patients with mean VD of the 6-9 mm ring in DVP <20%, even with RVO type, baseline central macular thickness weighed. CONCLUSION: High vessel density of the 6-9 mm ring in DVP, especially those ≥30%, was associated with macular edema recurrences in patients with retinal vein occlusion.

Automatic Segmentation of Hyperreflective Foci in OCT Images Based on Lightweight DBR Network.

Hyperreflective foci (HF) reflects inflammatory responses for fundus diseases such as diabetic macular edema (DME), retina vein occlusion (RVO), and central serous chorioretinopathy (CSC). Shown as high contrast and reflectivity in optical coherence tomography (OCT) images, automatic segmentation of HF in OCT images is helpful for the prognosis of fundus diseases. Previous traditional methods were time-consuming and required high computing power. Hence, we proposed a lightweight network to segment HF (with a speed of 57 ms per OCT image, at least 150 ms faster than other methods). Our framework consists of two stages: an NLM filter and patch-based split to preprocess images and a lightweight DBR neural network to segment HF automatically. Experimental results from 3000 OCT images of 300 patients (100 DME,100 RVO, and 100 CSC) revealed that our method achieved HF segmentation successfully. The DBR network had the area under curves dice similarity coefficient (DSC) of 83.65%, 76.43%, and 82.20% in segmenting HF in DME, RVO, and CSC on the test cohort respectively. Our DBR network achieves at least 5% higher DSC than previous methods. HF in DME was more easily segmented compared with the other two types. In addition, our DBR network is universally applicable to clinical practice with the ability to segment HF in a wide range of fundus diseases.

Green Tandem [5C + 1C] Cycloaromatization of α-Alkenoyl Ketene Dithioacetals and Nitroethane in Water: Eco-Friendly Synthesis of Ortho-Acylphenols.

For the first time, an eco-friendly and sustainable tandem [5C + 1C] cycloaromatization of α-alkenoyl ketene dithioacetals and nitroethane in water for the efficient synthesis of ortho-acylphenols was reported. In refluxing water, a range of α-alkenoyl ketene dithioacetals and nitroethane smoothly underwent tandem Michael addition/cyclization/aromatization reactions in the presence of 2.0 equivalents of DBU to provide various ortho-acylphenols in excellent yields. The green approach to ortho-acylphenols not only avoided the use of harmful organic solvents, which could result in serious environmental and safety issues, but also exhibited fascinating features such as good substrate scope, excellent yields, simple purification for desired products, ease of scale-up, and reusable aqueous medium.

Fibroblast growth factor 21 attenuates salt-sensitive hypertension-induced nephropathy through anti-inflammation and anti-oxidation mechanism.

BACKGROUND: Patients with salt-sensitive hypertension are often accompanied with severe renal damage and accelerate to end-stage renal disease, which currently lacks effective treatment. Fibroblast growth factor 21 (FGF21) has been shown to suppress nephropathy in both type 1 and type 2 diabetes mice. Here, we aimed to investigate the therapeutic effect of FGF21 in salt-sensitive hypertension-induced nephropathy. METHODS: Changes of FGF21 expression in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mice were detected. The influence of FGF21 knockout in mice on DOCA-salt-induced nephropathy were determined. Recombinant human FGF21 (rhFGF21) was intraperitoneally injected into DOCA-salt-induced nephropathy mice, and then the inflammatory factors, oxidative stress levels and kidney injury-related indicators were observed. In vitro, human renal tubular epithelial cells (HK-2) were challenged by palmitate acid (PA) with or without FGF21, and then changes in inflammation and oxidative stress indicators were tested. RESULTS: We observed significant elevation in circulating levels and renal expression of FGF21 in DOCA-salt-induced hypertensive mice. We found that deletion of FGF21 in mice aggravated DOCA-salt-induced nephropathy. Supplementation with rhFGF21 reversed DOCA-salt-induced kidney injury. Mechanically, rhFGF21 induced AMPK activation in DOCA-salt-treated mice and PA-stimulated HK-2 cells, which inhibited NF-κB-regulated inflammation and Nrf2-mediated oxidative stress and thus, is important for rhFGF21 protection against DOCA-salt-induced nephropathy. CONCLUSION: These findings indicated that rhFGF21 could be a promising pharmacological strategy for the treatment of salt-sensitive hypertension-induced nephropathy.

Influence of temperature-salinity-depth structure of the upper-ocean on the frequency shift of Brillouin LiDAR.

Brillouin-based LiDAR is an alternative remote sensing technique for measuring the distribution profiles of temperature, salinity, and sound speed in the upper ocean mixed layer. Its principle is based on the dependence of Brillouin frequency shift on the temperature, salinity, and depth of ocean. Therefore, it is necessary to investigate the effect of various seawater parameters on Brillouin frequency shift for ocean remote sensing by using the Brillouin LiDAR. Here we theoretically and experimentally investigate the influence of temperature, salinity, and pressure (depth) of seawater on Brillouin frequency shift in the upper ocean for the first time. Numerical simulations of the distribution profiles of temperature, salinity, and Brillouin frequency shift in the upper-ocean mixed layers of East China Sea and South China Sea were performed, respectively, by employing the Brillouin equations and the World Ocean Atlas 2018 (WOA18). A special ocean simulation system was designed to carry out the stimulated Brillouin scattering (SBS) experiments for validating the numerical simulations. The results show that the seawater temperature is the most important factor for the Brillouin frequency shift in the upper-ocean mixed layer compared with the salinity and pressure. At the same salinity and pressure, the frequency shift increases by more than 10 MHz for every 1 °C increase in temperature. Also, the differences of Brillouin frequency shift between experimental and theoretical values at the same parameter conditions were analyzed. The experimental results coincide well with the theoretical simulations. This work is essential to future applications of Brillouin LiDAR in remote sensing of the temperature, salinity, or sound velocity profiles of ocean.

Serum Metabolomics Reveals Personalized Metabolic Patterns for Macular Neovascular Disease Patient Stratification.

The macular neovascular disease is a group disorder with complex pathogenesis of neovascularization for vision impairment and irreversible blindness, posing great challenges to precise diagnosis and management. We prospectively recruited participants with age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV), and pathological myopia (PM) and compared with cataract patients without fundus diseases as a control group. The serum metabolome was profiled by gas chromatography coupled with time-of-flight mass spectrometry (GC-TOFMS) analysis. Multivariate statistical methods as well as data mining were performed for interpretation of macular neovascularization. A total of 446 participants with macular neovascularization and 138 cataract subjects as the control group were enrolled in this study. By employing GC-TOFMS, 131 metabolites were identified and 33 differentiating metabolites were highlighted in patients with macular neovascularization. For differential diagnosis, three panels of specific metabolomics-based biomarkers provided areas under the curve of 0.967, 0.938, and 0.877 in the discovery phase (n = 328) and predictive values of 87.3%, 79%, and 85.7% in the test phase (n = 256). Personalized pathway dysregulation scores measurement using Lilikoi package in R language revealed the pentose phosphate pathway and mitochondrial electron transport chain as the most important pathways in AMD; purine metabolism and glycolysis were identified as the major disturbed pathways in PCV, while the altered thiamine metabolism and purine metabolism may contribute to PM phenotypes. Serum metabolomics are powerful for characterizing metabolic disturbances of the macular neovascular disease. Differences in metabolic pathways may reflect an underlying macular neovascular disease and serve as therapeutic targets for macular neovascular treatment.

Boundary Restored Network for Subpleural Pulmonary Lesion Segmentation on Ultrasound Images at Local and Global Scales.

To evaluate the application of machine learning for the detection of subpleural pulmonary lesions (SPLs) in ultrasound (US) scans, we propose a novel boundary-restored network (BRN) for automated SPL segmentation to avoid issues associated with manual SPL segmentation (subjectivity, manual segmentation errors, and high time consumption). In total, 1612 ultrasound slices from 255 patients in which SPLs were visually present were exported. The segmentation performance of the neural network based on the Dice similarity coefficient (DSC), Matthews correlation coefficient (MCC), Jaccard similarity metric (Jaccard), Average Symmetric Surface Distance (ASSD), and Maximum symmetric surface distance (MSSD) was assessed. Our dual-stage boundary-restored network (BRN) outperformed existing segmentation methods (U-Net and a fully convolutional network (FCN)) for the segmentation accuracy parameters including DSC (83.45 ± 16.60%), MCC (0.8330 ± 0.1626), Jaccard (0.7391 ± 0.1770), ASSD (5.68 ± 2.70 mm), and MSSD (15.61 ± 6.07 mm). It also outperformed the original BRN in terms of the DSC by almost 5%. Our results suggest that deep learning algorithms aid fully automated SPL segmentation in patients with SPLs. Further improvement of this technology might improve the specificity of lung cancer screening efforts and could lead to new applications of lung US imaging.

Correlation of retinal layer changes with vision gain in diabetic macular edema during conbercept treatment.

BACKGROUNDS: To assess the changes in individual retinal layer thickness and visual function associated with gains in visual acuity after an intravitreal conbercept injection in the diabetic macular edema (DME) on spectral domain optical coherence tomography (SD-OCT) and microperimetry during 1-year follow-up. METHODS: Retrospective observational study. Twenty patients with clinically significant DME in the study eye were imaged by SD-OCT every 3 months and MP1 microperimeter in the third month while receiving anti-vascular endothelial growth factor (VEGF) (conbercept) treatment. In each patient, seven retinal layers were segmented in 98 scans covering a 6 mm × 6 mm area of the macula at baseline and during 1 year of treatment. An automatic, full-threshold microperimetry of the central field (10° × 10°, 40 stimulated points) with the MP1 microperimeter. Thickness and microperimetry changes were quantitatively measured and evaluated for their correlation with increases in visual acuity. RESULTS: Although thicknesses of the inner nuclear layer (INL) and the outer nuclear layer (ONL) were reduced the most after treatment (p < 0.05), decreases of the ganglion cell layer (GCL) (r = 0.591, p = 0.006) and inner plexiform layer (IPL) (r = 0.663, p = 0.001) in central subfield area was associated with best-corrected visual acuity (BCVA) gain, and had the best estimation of BCVA gain (adjust R2 = 0.544). Mean macular sensitivity in the central subfield was also well correlated with BCVA gain (r = 0.531, p = 0.016). CONCLUSIONS: Neural recovery occurred after the resolution of edema during conbercept treatment, due to the decreases in GCL and IPL associating with gains in vision and improved microperimetry.

A light-emitting diode (LED)-based multispectral imaging system in evaluating retinal vein occlusion.

BACKGROUND AND OBJECTIVE: Retinal vein occlusion (RVO), the second most common retinal vascular disorder worldwide, is considered to be a critical cause of visual loss. The aim of this study was to describe the characteristics of eyes with RVO using a light-emitting diode (LED)-based multispectral imaging (MSI) system and to compare its performance in terms of reliability and diagnostic power with those of fundus fluorescein angiography (FFA), optical coherence tomography (OCT), and fundus photography (FP). MATERIALS AND METHODS: Fifty-six eyes of 28 patients with RVO disease were evaluated by MSI, FP, FFA, and spectral domain OCT. All images were analyzed by an experienced reading center grader. Nonperfusion area, occlusion area, and intraretinal edema from occlusions and FP abnormalities (presence of cotton-wool spots, epiretinal membrane, hard exudates, and retinal hemorrhage) were documented. The diagnostic power of MSI was evaluated by the area under receiver operating characteristic (ROC) curve (AUC). RESULTS: Of the 56 eyes, 15 had branch RVO (BRVO), 13 had central RVO (CRVO), and 28 were normal. The ROC curve analysis showed that MSI was a better discriminator of RVO than FP (AUC = 0.911 vs. 0.768, P = 0.0318). The sensitivity (and 95% confidence intervals) of MSI for nonperfusion area was 42.3% (18.8-70.4), 80.0% (51.4-94.7) for retinal hemorrhage, 90.0% (54.1-99.5) for cotton-wool spots, 90.9% (57.1-99.5) for hard exudates, and 21.1% (7.0-46.1) for intraretinal edema. MSI was capable of finding abnormalities such as nonperfusion area, retinal hemorrhage, cotton-wool spots, hard exudates, and epiretinal membrane. MSI oxy-deoxy maps showed low oxygen levels in the affected vein, especially in CRVOs, and could be used in detecting the nonperfusion area. CONCLUSION: MSI reveals highly defined vascular abnormalities in shortwave images and oxy-deoxy maps, which is compatible with FP, FFA, and OCT findings and indicates, preliminarily, the advantages of the noninvasiveness, simplicity, and effectiveness of MSI in evaluating RVO diseases. Lasers Surg. Med. 47:549-558, 2015. © 2015 Wiley Periodicals, Inc.

The role of left atrium posterior wall isolation in patients undergoing catheter ablation for atrial fibrillation.

The posterior left atrium (LAPW) is an important substrate for initiation and maintenance of atrial fibrillation (AF). While it has been proposed as a potential target for preventing recurrence of atrial tachyarrhythmias, it remains unclear whether electrical silence of LAPW offers additional benefits over pulmonary vein isolation (PVI) alone. We conducted a systematic review of PubMed, Medline, Embase, and Cochrane databases and identified 21 eligible studies, encompassing 1514 patients assigned to PVI + posterior wall isolation (PWI) group and 1629 patients assigned to PVI group. Over a median follow-up of 12 months, adjunctive PWI significantly improved the atrial tachyarrhythmia-free survival by 14 % in comparison to PVI alone [relative risk (RR): 1.14, 95 % confidence interval (CI): 1.04 to 1.25, p = 0.004]. This improvement was mainly attributed to a pronounced benefit for patients with persistent AF. In addition, patients undergoing PVI + PWI had a longer procedure time [weighted mean difference (WMD): 23.85, 95 % CI: 12.68 to 35.01, p < 0.001], ablation time (WMD: 9.27, 95 % CI: 5.19 to 13.54, p < 0.001), and a nearly negligible increase in fluoroscopic exposure (WMD: 2.69, 95 % CI: -0.23 to 5.62, p = 0.071). There was no increased risk of procedure-related complications between these approaches (RR: 1.06, 95 % CI: 0.71 to 1.57, p = 0.787). Compared with PVI alone, PWI adjunctive to PVI exhibited a higher procedure success of sinus rhythm maintenance in persistent AF during an index catheter ablation. Meanwhile, elongated procedure time and ablation time did not compromise the safety of extensive ablation strategy with additional PWI.

Accumulation of branched-chain amino acids deteriorates the neuroinflammatory response of Müller cells in diabetic retinopathy via leucine/Sestrin2-mediated sensing of mTOR signaling.

AIMS: This study aimed to investigate branched-chain amino acid (BCAA) catabolism in diabetic retinopathy (DR). METHODS: Wild-type and db/db mice were fed BCAAs (5 or 10 mg/kg/day) for 12 weeks, and hyperglycemia-exposed Müller cells were treated with BCAAs (2 or 5 mmol/L) for 24 and 48 h. BCAA levels were measured using MS/MS. Western blotting was performed to detect proteins. Flow cytometry, oxygen consumption rate, and Cell Counting Kit-8 assays were used to evaluate Müller cell viability. Each experiment was conducted at least thrice. RESULTS: BCAAs and branched-chain α-keto acids (BCKAs) were increased in the retina and systemic tissues of diabetic mice, and these changes were further enhanced to approximately 2-fold by extra BCAAs compared to wild-type group. In vitro, BCAAs and BCKAs were induced in hyperglycemic Müller cells, and augmented by BCAA supplementation. The aberrant BCAA catabolism was accompanied by mTORC1 activation and subsequently induced TNF-ɑ, VEGFA, GS, and GFAP in retinas and Müller cells under diabetic conditions. The cell apoptosis rate increased by approximately 50%, and mitochondrial respiration was inhibited by hyperglycemia and BCAA in Müller cells. Additionally, mTORC1 signaling was activated by leucine in Müller cells. Knockdown of Sestrin2 or LeuRS significantly abolished the leucine-induced mTORC1 phosphorylation and protected Müller cell viability under diabetic conditions. CONCLUSIONS: We found that BCAA catabolism is hindered in DR through mTORC1 activation. Leucine plays a key role in inducing mTORC1 by sensing Sestrin2 in Müller cells. Targeting Sestrin2 may ameliorate the toxic effects of BCAA accumulation on Müller cells in DR.

Metadata information and fundus image fusion neural network for hyperuricemia classification in diabetes.

OBJECTIVE: In diabetes mellitus patients, hyperuricemia may lead to the development of diabetic complications, including macrovascular and microvascular dysfunction. However, the level of blood uric acid in diabetic patients is obtained by sampling peripheral blood from the patient, which is an invasive procedure and not conducive to routine monitoring. Therefore, we developed deep learning algorithm to detect noninvasively hyperuricemia from retina photographs and metadata of patients with diabetes and evaluated performance in multiethnic populations and different subgroups. MATERIALS AND METHODS: To achieve the task of non-invasive detection of hyperuricemia in diabetic patients, given that blood uric acid metabolism is directly related to estimated glomerular filtration rate(eGFR), we first performed a regression task for eGFR value before the classification task for hyperuricemia and reintroduced the eGFR regression values into the baseline information. We trained 3 deep learning models: (1) metadata model adjusted for sex, age, body mass index, duration of diabetes, HbA1c, systolic blood pressure, diastolic blood pressure; (2) image model based on fundus photographs; (3)hybrid model combining image and metadata model. Data from the Shanghai General Hospital Diabetes Management Center (ShDMC) were used to develop (6091 participants with diabetes) and internally validated (using 5-fold cross-validation) the models. External testing was performed on an independent dataset (UK Biobank dataset) consisting of 9327 participants with diabetes. RESULTS: For the regression task of eGFR, in ShDMC dataset, the coefficient of determination (R2) was 0.684±0.07 (95 % CI) for image model, 0.501±0.04 for metadata model, and 0.727±0.002 for hybrid model. In external UK Biobank dataset, a coefficient of determination (R2) was 0.647±0.06 for image model, 0.627±0.03 for metadata model, and 0.697±0.07 for hybrid model. Our method was demonstrably superior to previous methods. For the classification of hyperuricemia, in ShDMC validation, the area, under the curve (AUC) was 0.86±0.013for image model, 0.86±0.013 for metadata model, and 0.92±0.026 for hybrid model. Estimates with UK biobank were 0.82±0.017 for image model, 0.79±0.024 for metadata model, and 0.89±0.032 for hybrid model. CONCLUSION: There is a potential deep learning algorithm using fundus photographs as a noninvasively screening adjunct for hyperuricemia among individuals with diabetes. Meanwhile, combining patient's metadata enables higher screening accuracy. After applying the visualization tool, it found that the deep learning network for the identification of hyperuricemia mainly focuses on the fundus optic disc region.

The protective effect of vagus nerve stimulation against myocardial ischemia/reperfusion injury: pooled review from preclinical studies.

Aims: Myocardial ischemia-reperfusion (I/R) injury markedly undermines the protective benefits of revascularization, contributing to ventricular dysfunction and mortality. Due to complex mechanisms, no efficient ways exist to prevent cardiomyocyte reperfusion damage. Vagus nerve stimulation (VNS) appears as a potential therapeutic intervention to alleviate myocardial I/R injury. Hence, this meta-analysis intends to elucidate the potential cellular and molecular mechanisms underpinning the beneficial impact of VNS, along with its prospective clinical implications. Methods and Results: A literature search of MEDLINE, PubMed, Embase, and Cochrane Database yielded 10 articles that satisfied the inclusion criteria. VNS was significantly correlated with a reduced infarct size following myocardial I/R injury [Weighed mean difference (WMD): 25.24, 95% confidence interval (CI): 32.24 to 18.23, p < 0.001] when compared to the control group. Despite high heterogeneity (I2 = 95.3%, p < 0.001), sensitivity and subgroup analyses corroborated the robust efficacy of VNS in limiting infarct expansion. Moreover, meta-regression failed to identify significant influences of pre-specified covariates (i.e., stimulation type or site, VNS duration, condition, and species) on the primary estimates. Notably, VNS considerably impeded ventricular remodeling and cardiac dysfunction, as evidenced by improved left ventricular ejection fraction (LVEF) (WMD: 10.12, 95% CI: 4.28; 15.97, p = 0.001) and end-diastolic pressure (EDP) (WMD: 5.79, 95% CI: 9.84; -1.74, p = 0.005) during the reperfusion phase. Conclusion: VNS offers a protective role against myocardial I/R injury and emerges as a promising therapeutic strategy for future clinical application.

Using the meteorological early warning model to improve the prediction accuracy of water damage geological disasters around pipelines in mountainous areas.

This paper focuses on the threat of water damage geological disasters brought by the complex terrain along the long-distance natural gas pipeline. The role of rainfall factors in the occurrence of such disasters has been fully considered, a meteorological early warning model for water damage geological disasters in mountainous areas based on slope units has been constructed to improve the prediction accuracy of such disasters and timely early warning and forecasting. An actual natural gas pipeline in a typical mountainous area of Zhejiang Province is taken as an example. The hydrology-curvature combined analysis method is chosen to divide the slope units, and the SHALSTAB model is used to fit the slope soil environment to calculate the stability level. Finally, the stability level is coupled with rainfall data to calculate the early warning index for water damage geological disasters in the study area. The results show that compared with the separate SHALSTAB model, the early warning results coupled with rainfall are more effective in predicting water damage geological disasters. The early warning results are compared with the actual disaster points, among the nine actual disaster points, most of the slope units around seven disaster points are in the state of needing early warning, the early warning accuracy rate reaches 77.8 %. The proposed early warning model can carry out targeted deployment in advance according to the divided slope units, and the prediction accuracy of geological disasters induced by heavy rainfall weather is significantly higher and more suitable for the actual location of the disaster point, which can provide a basis for accurate disaster prevention in the research area and areas with similar geological environments.

Higher-order aberrations and their association with axial elongation in highly myopic children and adolescents.

BACKGROUND: Vision-dependent mechanisms play a role in myopia progression in childhood. Thus, we investigated the distribution of ocular and corneal higher-order aberrations (HOAs) in highly myopic Chinese children and adolescents and the relationship between HOA components and 1-year axial eye growth. METHODS: Baseline cycloplegic ocular and corneal HOAs, axial length (AL), spherical equivalent (SE), astigmatism and interpupillary distance (IPD) were determined for the right eyes of 458 highly myopic (SE ≤-5.0D) subjects. HOAs were compared among baseline age groups (≤12 years, 13-15 years and 16-18 years). Ninety-nine subjects completed the 1-year follow-up. Linear mixed model analyses were applied to determine the association between HOA components, other known confounding variables (age, gender, SE, astigmatism and IPD) and axial growth. A comparison with data from an early study of moderate myopia were conducted. RESULTS: Almost all ocular HOAs and few corneal HOAs exhibited significant differences between different age groups (all p<0.05). After 1 year, only ocular HOA components was significantly negative associated with a longer AL, including secondary horizontal comatic aberration (p=0.019), primary spherical aberration (p<0.001) and spherical HOA (p=0.026). Comparing with the moderate myopia data, the association of comatic aberration with AL growth was only found in high myopia. CONCLUSION: In highly myopic children and adolescents, lower levels of annual ocular secondary horizontal comatic aberration changes, besides spherical aberrations, were associated with axial elongation. This suggests that ocular HOA plays a potential role in refractive development in high myopia.

Individualized Statistical Modeling of Lesions in Fundus Images for Anomaly Detection.

Anomaly detection in fundus images remains challenging due to the fact that fundus images often contain diverse types of lesions with various properties in locations, sizes, shapes, and colors. Current methods achieve anomaly detection mainly through reconstructing or separating the fundus image background from a fundus image under the guidance of a set of normal fundus images. The reconstruction methods, however, ignore the constraint from lesions. The separation methods primarily model the diverse lesions with pixel-based independent and identical distributed (i.i.d.) properties, neglecting the individualized variations of different types of lesions and their structural properties. And hence, these methods may have difficulty to well distinguish lesions from fundus image backgrounds especially with the normal personalized variations (NPV). To address these challenges, we propose a patch-based non-i.i.d. mixture of Gaussian (MoG) to model diverse lesions for adapting to their statistical distribution variations in different fundus images and their patch-like structural properties. Further, we particularly introduce the weighted Schatten p-norm as the metric of low-rank decomposition for enhancing the accuracy of the learned fundus image backgrounds and reducing false-positives caused by NPV. With the individualized modeling of the diverse lesions and the background learning, fundus image backgrounds and NPV are finely learned and subsequently distinguished from diverse lesions, to ultimately improve the anomaly detection. The proposed method is evaluated on two real-world databases and one artificial database, outperforming the state-of-the-art methods.

A simple system for measuring the transmittance curve of x-ray filters at low x-ray energies.

To prevent the x-ray detectors from the interference of optical photons, x-ray filters are widely used in x-ray space missions. As the flux of low energy x-rays would be significantly attenuated by the filters, it is important to derive the transmittance of the filters below 10 keV. In this paper, we present a simple experimental apparatus and data processing method to measure the transmittance curve of x-ray filters in the energy range from 1.6 to 10 keV. The measured spectra were further processed with Geant4 Monte Carlo simulation results and a direct demodulation algorithm. The obtained transmittance is in good accordance with the theoretical calculation and the synchrotron radiation test result, which proves that the proposed system with the algorithm is a reasonable way to characterize the x-ray transmittance performance of filters above 1.6 keV.

Protective effects of peptide FK18 against neuro-excitotoxicity in SH-SY5Y cells.

Excitotoxic neuronal injury is associated with numerous acute and chronic neurological disorders, such as Alzheimer's disease and glaucoma. Neuroprotection is a direct and effective therapeutic approach, with small-molecule bioactive peptides displaying certain advantages, including high membrane permeability, low immunogenicity and convenient synthesis and modification. FK18 is a novel peptide derived from basic fibroblast growth factor, which is a protein with neuroprotective effects. The present study aims to evaluate the neuroprotective effect of FK18 against excitotoxic injury. For this purpose, cell viability was determined by the MTS assay, cell apoptosis was assessed by flow cytometry and the TUNEL assay; expression of antiapoptotic proteins Bcl-2, proapoptotic protein Bax and caspase-3 as well as the phosphorylation of Akt and Erk was estimated by western blotting. The results of the present study demonstrated that FK18 effectively increased the viability of, and attenuated glutamate-induced apoptosis of SH-SY5Y cells. In addition, FK18 significantly increased Akt phosphorylation and decreased Erk phosphorylation in SH-SY5Y cells. FK18 also increased the Bcl-2/Bax ratio and decreased the level of cleaved-caspase-3 in SY5Y cells, which was reversed by the Akt pathway inhibitor LY294002, but not by the Erk pathway inhibitor U0126. The findings of the present study suggested that FK18 may be a promising therapeutic agent for the inhibition of neuronal cell death in multiple neurological diseases involving excitotoxicity.