Loneliness and social isolation are associated with an increased risk of glaucoma: a UK Biobank cohort study.

BACKGROUND: Loneliness and social isolation have been found to be associated with various health-related outcomes. Our study aimed to evaluate the association of loneliness and social isolation with the risk of glaucoma. METHODS: A total of 373,330 participants from the UK Biobank without glaucoma at recruitment were included in this study. Self-reported questionnaires were used to define loneliness and social isolation. Incident glaucoma events were identified by hospital inpatient admissions and self-reported data. COX proportional hazards models adjusted for sociodemographic, lifestyle, and health-related factors were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: During a median follow-up of 13.1 (interquartile range: 12.3-13.9) years, 6,489 participants developed glaucoma. After adjusting for confounding factors, loneliness (yes vs. no: adjusted HR: 1.16; 95% CI: 1.04-1.30; P = 0.009) and social isolation (yes vs. no: adjusted HR: 1.08; 95% CI: 1.01-1.16; P = 0.033) were associated with an increased risk of glaucoma. CONCLUSIONS: In this population-based prospective cohort study, loneliness and social isolation were associated with a higher risk of glaucoma.

The differences of metabolic profiles, socioeconomic status and diabetic retinopathy in U.S. working-age and elderly adults with diabetes: results from NHANES 1999-2018.

AIMS: Controlled metabolic factors and socioeconomic status (SES) was crucial for prevention of diabetic retinopathy (DR). The study aims to assess the metabolic factors control and SES among working-age adults (18-64 years) with diabetes compared to older adults (65 years and older). METHODS: Totals of 6738 participants with self-reported diagnosed diabetes from National Health and Nutrition Examination Survey were included, of whom 3482 were working-age and 3256 were elderly. The prevalence of DR, metabolic factors control, and the impact of SES and diabetic duration on DR was estimated. Subgroup analysis among working-age adults was employed across different diabetic duration and SES level. RESULTS: The prevalence of DR was 20.8% among working-age adults and 20.6% in elderly adults. Further, working-age adults possessed suboptimal control on glycemia (median HbA1c: 7.0% vs. 6.8%, p < 0.001) and lipids (Low-density lipoprotein < 100 mg/dL: 46.4% vs. 63.5%, p < 0.001), but better blood pressure control (< 130/80 mmHg: 53.5% vs. 37.5%, p < 0.001) compared to the elderly, judging based on age-specific control targets. Prolonged diabetic duration didn't improve glycemic and composite factors control. SES like education and income impacted metabolic factors control and adults with higher SES were more likely to control well. Diabetic duration was a significant risk factor (OR = 4.006, 95%CI= (2.752,5.832), p < 0.001) while higher income (OR = 0.590, 95%CI= (0.421,0.826), p = 0.002) and educational level (OR = 0.637, 95%CI= (0.457,0.889), p = 0.008) were protective against DR. CONCLUSIONS: Working-age adults with diabetes demonstrate suboptimal metabolic profile control, especially glycemia and lipids. Additional efforts are needed to improve metabolic factor control and reduce DR risk, particularly for those with longer diabetes duration, less education, and lower incomes.

Associations between brain structures, cognition and dual-task performance in patients with mild cognitive impairment: A study based on voxel-based morphology.

BACKGROUND: This study aimed to explore the associations between brain structures, cognition, and motor control in participants with mild cognitive impairment (MCI), with a focus on dual-task performance. METHODS: Thirty MCI patients and thirty healthy controls were enrolled. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Structural magnetic resonance imaging data were analyzed using voxel-based morphometry (VBM) to calculate brain parenchyma volume and gray matter volume (GMV). Participants performed single- and dual-task Timed Up and Go (TUG) tests, and the correlations between significant GMV differences and task execution time was analyzed. RESULTS: MCI patients showed significantly lower MoCA scores, particularly in visuospatial/executive, attention, and delayed recall domains (p < 0.05). Dual-task TUG execution time was significantly increased in MCI patients (p < 0.05). The GMV in the right anterior lobe of the cerebellum and both insulae was positively correlated with visuospatial/executive scores (FDR-corrected, p < 0.05). The GMV of the right cerebellar anterior lobe and insula were significantly reduced in MCI patients (p < 0.05). The GMV of the right cerebellar anterior lobe was negatively correlated with dual-task execution time (r = -0.32, p = 0.012). CONCLUSION: Smaller GMV in the right anterior lobe of the cerebellum was associated with impaired dual-task performance, which may provide more evidence for the neural mechanisms of cognitive and motor function impairments in MCI.

Potential Immune-Inflammatory Proteome Biomarkers for Guiding the Treatment of Patients with Primary Acute Angle-Closure Glaucoma Caused by COVID-19.

Primary acute angle-closure glaucoma (PAACG) is a sight-threatening condition that can lead to blindness. With the increasing incidence of COVID-19, a multitude of people are experiencing acute vision loss and severe swelling of the eyes and head. These patients were then diagnosed with acute angle closure, with or without a history of PACG. However, the mechanism by which viral infection causes PACG has not been clarified. This is the first study to explore the specific inflammatory proteomic landscape in SARS-CoV-2-induced PAACG. The expression of 92 inflammation-related proteins in 19 aqueous humor samples from PAACGs or cataract patients was detected using the Olink Target 96 Inflammation Panel based on a highly sensitive and specific proximity extension assay technology. The results showed that 76 proteins were significantly more abundant in the PAACG group than in the cataract group. Notably, the top eight differentially expressed proteins were IL-8, MCP-1, TNFRSF9, DNER, CCL4, Flt3L, CXCL10, and CD40. Generally, immune markers are related to inflammation, macrophage activation, and viral infection, revealing the crucial role of macrophages in the occurrence of PAACGs caused by SARS-CoV-2.

Diabetes-Related Macrovascular Complications Are Associated With an Increased Risk of Diabetic Microvascular Complications: A Prospective Study of 1518 Patients With Type 1 Diabetes and 20 802 Patients With Type 2 Diabetes in the UK Biobank.

BACKGROUND: Diabetic vascular complications share common pathophysiological mechanisms, but the relationship between diabetes-related macrovascular complications (MacroVCs) and incident diabetic microvascular complications remains unclear. We aimed to investigate the impact of MacroVCs on the risk of microvascular complications. METHODS AND RESULTS: There were 1518 participants with type 1 diabetes (T1D) and 20 802 participants with type 2 diabetes from the UK Biobank included in this longitudinal cohort study. MacroVCs were defined by the presence of macrovascular diseases diagnosed after diabetes at recruitment, including coronary heart disease, peripheral artery disease, stroke, and ≥2 MacroVCs. The primary outcome was incident microvascular complications, a composite of diabetic retinopathy, diabetic kidney disease, and diabetic neuropathy. During a median (interquartile range) follow-up of 11.61 (5.84-13.12) years and 12.2 (9.50-13.18) years, 596 (39.3%) and 4113 (19.8%) participants developed a primary outcome in T1D and type 2 diabetes, respectively. After full adjustment for conventional risk factors, Cox regression models showed significant associations between individual as well as cumulative MacroVCs and the primary outcome, except for coronary heart disease in T1D (T1D: diabetes coronary heart disease: 1.25 [0.98-1.60]; diabetes peripheral artery disease: 3.00 [1.86-4.84]; diabetes stroke: 1.71 [1.08-2.72]; ≥2: 2.57 [1.66-3.99]; type 2 diabetes: diabetes coronary heart disease: 1.59 [1.38-1.82]; diabetes peripheral artery disease: 1.60 [1.01-2.54]; diabetes stroke: 1.50 [1.13-1.99]; ≥2: 2.66 [1.92-3.68]). Subgroup analysis showed that strict glycemic (glycated hemoglobin <6.5%) and blood pressure (<140/90 mm Hg) control attenuated the association. CONCLUSIONS: Individual and cumulative MacroVCs confer significant risk of incident microvascular complications in patients with T1D and type 2 diabetes. Our results may facilitate cost-effective high-risk population identification and development of precise prevention strategies.

An interpretable model based on graph learning for diagnosis of Parkinson's disease with voice-related EEG.

Parkinson's disease (PD) exhibits significant clinical heterogeneity, presenting challenges in the identification of reliable electroencephalogram (EEG) biomarkers. Machine learning techniques have been integrated with resting-state EEG for PD diagnosis, but their practicality is constrained by the interpretable features and the stochastic nature of resting-state EEG. The present study proposes a novel and interpretable deep learning model, graph signal processing-graph convolutional networks (GSP-GCNs), using event-related EEG data obtained from a specific task involving vocal pitch regulation for PD diagnosis. By incorporating both local and global information from single-hop and multi-hop networks, our proposed GSP-GCNs models achieved an averaged classification accuracy of 90.2%, exhibiting a significant improvement of 9.5% over other deep learning models. Moreover, the interpretability analysis revealed discriminative distributions of large-scale EEG networks and topographic map of microstate MS5 learned by our models, primarily located in the left ventral premotor cortex, superior temporal gyrus, and Broca's area that are implicated in PD-related speech disorders, reflecting our GSP-GCN models' ability to provide interpretable insights identifying distinctive EEG biomarkers from large-scale networks. These findings demonstrate the potential of interpretable deep learning models coupled with voice-related EEG signals for distinguishing PD patients from healthy controls with accuracy and elucidating the underlying neurobiological mechanisms.

Walking pace and microvascular complications among individuals with type 2 diabetes: A cohort study from the UK Biobank.

INTRODUCTION: Walking pace is associated with various health-related outcomes. The aim of this study was to investigate the association between self-reported walking pace and the incidences of diabetic microvascular complications among participants with type 2 diabetes (T2D). METHODS: Self-reported walking pace was classified as brisk, average, or slow. The outcomes were the incidences of diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. COX proportional hazards models adjusted for sociodemographic, lifestyle, and health-related factors were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: A total of 14 518 participants with T2D in the UK Biobank (mean age 59.7 ± 7.0 years, 5028 [34.6%] women) were included. During a median follow-up of 12.5 (interquartile range: 11.6-13.4) years, 2980 participants developed diabetic microvascular complications. After adjusting for confounding factors, and compared with brisk walkers, slow walkers had a multivariable-adjusted HR of 1.98 (95% CI 1.58, 2.47) for composite diabetic microvascular complications, 1.54 (95% CI 1.11, 2.14) for diabetic retinopathy, 3.26 (95% CI 2.08, 5.11) for diabetic neuropathy, and 2.32 (95% CI 1.91, 2.82) for diabetic nephropathy. Average walking pace was associated with a higher risk for diabetic nephropathy (HR 1.51, 95 CI% 1.27-1.79) compared with brisk walking. Additionally, ≥1 diabetic microvascular complication occurred in 447 (14.7%) of participants with brisk walking pace, 1702 (19.5%) with average walking pace, and 831 (30.4%) with slow walking pace. Time from study recruitment to first diagnosis was shorter in participants who reported a slow walking pace, compared with brisk or average walkers. Among participants who had diabetic nephropathy as their first diagnosis, slow walking pace was associated with subsequent risk of a second diabetic microvascular complication (HR 3.88, 95 CI% 2.27-6.60). CONCLUSIONS: Self-reported slow walking pace is associated with a higher risk of diabetic microvascular complications among participants with T2D in this population-based cohort study.

Role of m6A methylation in retinal diseases.

Retinal diseases remain among the leading causes of visual impairment in developed countries, despite great efforts in prevention and early intervention. Due to the limited efficacy of current retinal therapies, novel therapeutic methods are urgently required. Over the past two decades, advances in next-generation sequencing technology have facilitated research on RNA modifications, which can elucidate the relevance of epigenetic mechanisms to disease. N6-methyladenosine (m6A), formed by methylation of adenosine at the N6-position, is the most widely studied RNA modification and plays an important role in RNA metabolism. It is dynamically regulated by writers (methyltransferases) and erasers (demethylases), and recognized by readers (m6A binding proteins). Although the discovery of m6A methylation can be traced back to the 1970s, its regulatory roles in retinal diseases are rarely appreciated. Here, we provide an overview of m6A methylation, and discuss its effects and possible mechanisms on retinal diseases, including diabetic retinopathy, age-related macular degeneration, retinoblastoma, retinitis pigmentosa, and proliferative vitreoretinopathy. Furthermore, we highlight potential agents targeting m6A methylation for retinal disease treatment and discuss the limitations and challenges of research in the field of m6A methylation.

Successful mechanical thrombectomy in acute bilateral M1 middle cerebral artery occlusion: a case report and literature review.

BACKGROUND: Acute bilateral occlusion of the middle cerebral artery (MCA) is a very rare condition, and most cases are accompanied by a poor prognosis. However, mechanical thrombectomy (MT) for bilateral MCA is challenging. Here, we report a case of acute unilateral MCA occlusion with sequential acute occlusion of the bilateral MCA during intravenous thrombolysis (IVT). We urgently performed bilateral MT of the MCA and effective recanalization. CASE PRESENTATION: The patient is a 73-year-old man who complained of a sudden adverse influence on speech and an inability to move his left limb for 2 h. He had a history of paroxysmal atrial fibrillation, but had never used any anticoagulants before. Head and neck computed tomography angiography (CTA) showed embolism in the right M1 MCA. During intravenous alteplase thrombolytic therapy, the patient suddenly became unconscious. Cerebral angiography showed occlusion of the M1 segment of the bilateral MCA in the patients. MT of the bilateral MCA was performed using a combination of a stent retriever and an aspiration catheter with mTici 3 revascularization. On the second day, the patient became conscious, although he had remaining symptoms of speech insufficiency and weakness of the left limb. The mRS score was 2 90 days after the operation. CONCLUSIONS: Acute bilateral occlusion of the M1 segment of the MCA is extremely rare and is accompanied by high morbidity and high mortality. Intravenous alteplase thrombolysis can increase the risk of atrial thrombus shedding in patients with atrial fibrillation, so patients with acute bilateral MCA occlusion in the M1 segment chose direct MT or bridging therapy, which remains controversial, and the sequence of MT remains to be discussed. Nevertheless, early endovascular treatment can decrease the morbidity and mortality of such patients.

Transient receptor potential channel 6 knockdown prevents high glucose-induced Müller cell pyroptosis.

BACKGROUND: Transient receptor potential channel 6 (TRPC6) is reported to be involved in the pathogenesis of diabetic complications, but its role in diabetic retinopathy (DR) remains unknown. The aim of our study was to determine the role and mechanism of TRPC6 in DR. METHODS: High glucose was used to construct a DR cell model using rat retinal Müller cells (rMC-1). Intracellular Ca2+, reactive oxygen species (ROS) and cell pyroptosis were evaluated by flow cytometry. Protein levels of NLRP3, pro-caspase-1, active caspase-1, gasdermin D (GSDMD), GSDMD-N, TRPC6 and H3K27ac were detected by Western blot. mRNA levels of EP300 and TRPC6 were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Levels of IL-1ß and IL-18 were estimated by enzyme linked immunosorbent assay (ELISA). The interaction between EP300 and TRPC6 was validated by a chromatin immunoprecipitation assay. RESULTS: The knockdown of TRPC6 reduced inflammation and cell pyroptosis in HG induced rMC-1 cells, whereas overexpression of TRPC6 had the opposite effects. The inhibition of ROS and NLRP3 reversed TRPC6-mediated cell pyroptosis in the DR cell model. In addition, EP300 increased the expression of H3K27ac and TRPC6 to promote cell pyroptosis, which was suppressed by the knockdown of TRPC6. CONCLUSIONS: Our study revealed a novel EP300/H3K27ac/TRPC6 signaling pathway that may contribute to HG induced Müller cell pyroptosis. TRPC6 played a novel role in Müller cell pyroptosis triggered by HG, and may be a potential target for DR treatment in the future.

The left inferior frontal gyrus is causally linked to vocal feedback control: evidence from high-definition transcranial alternating current stimulation.

Current models of speech motor control propose a role for the left inferior frontal gyrus (IFG) in feedforward control of speech production. There is evidence, however, that has implicated the functional relevance of the left IFG for the neuromotor processing of vocal feedback errors. The present event-related potential (ERP) study examined whether the left IFG is causally linked to auditory feedback control of vocal production with high-definition transcranial alternating current stimulation (HD-tACS). After receiving active or sham HD-tACS over the left IFG at 6 or 70 Hz, 20 healthy adults vocalized the vowel sounds while hearing their voice unexpectedly pitch-shifted by ±200 cents. The results showed that 6 or 70 Hz HD-tACS over the left IFG led to larger magnitudes and longer latencies of vocal compensations for pitch perturbations paralleled by larger ERP P2 responses than sham HD-tACS. Moreover, there was a lack of frequency specificity that showed no significant differences between 6 and 70 Hz HD-tACS. These findings provide first causal evidence linking the left IFG to vocal pitch regulation, suggesting that the left IFG is an important part of the feedback control network that mediates vocal compensations for auditory feedback errors.

Prevalence and predictors of developing vision-threatening diabetic retinopathy within the first three years of type 2 diabetes.

Purpose: To investigate the prevalence of diabetic retinopathy (DR) and vision-threatening DR (VTDR) in patients with type 2 diabetes mellitus (T2DM) stratified by the duration of diabetes and to identify the clinical variations and risk factors for VTDR occurring at different stages of T2DM. Methods: This was a retrospective comparative study. Patients were divided into short- (≤3 years), intermediate- (3-7 years), and long-duration (>7 years) groups. All patients were followed-up for DR and VTDR development. Risk factors were explored using logistic regression analysis. Results: A total of,2961 patients were included; among them, 1,036 (35.0%) patients developed DR, and 293 (9.9%) had VTDR. The frequency of VTDR in patients who developed DR in the short-duration group was significantly higher than that in the intermediate-duration group (25.7% vs. 15.0%; p = 0.019), but comparable with that of the long-duration group (25.7% vs. 31.8%; p = 0.138). Patients who developed VTDR within the first 3 years of T2DM were more likely to have a family history of diabetes (p = 0.024), had higher glycated hemoglobin (p = 0.025), were males (p = 0.042), and were notably older at the onset of diabetes (p <0.001) but younger when diagnosed with DR (p <0.001). Moreover, higher glycated hemoglobin (OR = 1.14; 95% CI: 1.00-1.29; p = 0.043) and diabetic nephropathy (DN) (OR = 2.31; 95% CI: 1.08-4.91; p = 0.030) were independent risk factors for developing VTDR during the first 3 years of T2DM. Conclusion: The risk of DR is not high in persons with ≤3 years' duration of T2DM, however, if afflicted, the risk of VTDR should never be neglected. More frequent retinal screening is warranted in patients with newly diagnosed T2DM.

The endosomal sorting complex required for transport repairs the membrane to delay cell death.

The endosomal sorting complex required for transport (ESCRT) machinery plays a key role in the repair of damaged plasma membranes with puncta form and removes pores from the plasma membrane in regulated cell death, apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy. ESCRT-I overexpression and ESCRT-III-associated charged multivesicular body protein (CHMP) 4B participate in apoptosis, and the ESCRT-1 protein TSG 101 maintains low levels of ALIX and ALG-2 and prevents predisposition to apoptosis. The ESCRT-III components CHMP2A and CHMP4B are recruited to broken membrane bubble sites with the requirement of extracellular Ca2+, remove membrane vesicles from cells, and delay the time required for active MLKL to mediate necroptosis, thus preserving cell survival. CHMP4B disturbed pyroptosis by recruiting around the plasma membrane neck to remove the GSDMD pores and preserve plasma membrane integrity depending on Ca2+ influx. The accumulation of the ESCRT-III subunits CHMP5 and CHMP6 in the plasma membrane is increased by the classical ferroptosis activators erastin-1 and ras-selective lethal small molecule 3 (RSL3) upon cytosolic calcium influx and repairs the ferroptotic plasma membrane. ESCRT-III- and VPS4-induced macroautophagy, ESCRT-0-initiated microautophagy. ESCRT-I, ESCRT-II, ESCRT-III, ALIX, and VPS4A are recruited to damaged lysosomes and precede lysophagy, indicating that ESCRT is a potential target to overcome drug resistance during tumor therapy.

Aqueous Humor Biomarkers of Retinal Glial Cell Activation in Patients With or Without Age-Related Cataracts and With Different Stages of Diabetic Retinopathy.

Purpose: To clarify the expression of biomarkers of retinal glial cell activation in the aqueous humor (AH) of patients with and without age-related cataracts (ARCs) at different stages of diabetic retinopathy (DR). Methods: Patients were stratified by the presence of ARCs and then grouped by the presence of diabetes mellitus (DM), nonproliferative DR (NPDR), proliferative DR (PDR), and controls. Water channel aquaporin 1 (AQP1), water channel aquaporin 4 (AQP4), inwardly rectifying potassium channel 4.1 (Kir4.1), and glial fibrillary acidic protein (GFAP) were assayed in AH samples by ELISAs. Results: We enrolled 82 patients. The AQP1 concentration was higher in AH from cataract control patients than in control patients without cataracts (P < 0.05). The APQ1 concentration was also higher in patients with DM, NPDR, and PDR than in controls (P < 0.05). The concentrations of AQP4 and GFAP were significantly increased in patients with NPDR and PDR (P < 0.05) but not in patients with DM. Kir4.1 concentration was significantly decreased in patients with NPDR and PDR (P < 0.05), but the decrease in patients with DM did not reach significance. There were no differences in AQP4, Kir4.1, and GFAP between patients with and without ARCs. Conclusions: Increased AQP1 in AH may be a biomarker for ARCs in patients without diabetes and a biomarker for retinal glial cell activation in patients with diabetes without cataracts. AQP4, Kir4.1, and GFAP levels in AH suggested that retinal glial cell activation was affected by the progression of DR.

COVID-19 Home Quarantine Accelerated the Progression of Myopia in Children Aged 7 to 12 Years in China.

Purpose: To investigate the effect of home quarantine during the COVID-19 pandemic on myopia progression in children and its associated factors. Methods: Myopic children aged 7 to 12 years with regular follow-up visits every half a year from April 2019 to May 2020 were included. Cycloplegic refraction was measured at baseline and at two follow-up visits. The first follow-up visit (visit 1) was conducted before the COVID-19 home quarantine, whereas the second (visit 2) was four months after the home quarantine. Myopia progression at visits 1 and 2 were compared. Factors associated with changes in myopia progression were tested with a multiple regression analysis. Results: In total, 201 myopic children were enrolled. There was a significantly greater change in spherical equivalent at visit 2 (-0.98 ± 0.52 D) than at visit 1 (-0.39 ± 0.58 D; P < 0.001). Students were reported to have spent more time on digital devices for online learning (P < 0.001) and less time on outdoor activities (P < 0.001) at visit 2 than at visit 1. Children using television and projectors had significantly less myopic shift than those using tablets and mobile phones (P < 0.001). More time spent on digital screens (ß = 0.211, P < 0.001), but not less time on outdoor activities (ß = -0.106, P = 0.110), was associated with greater myopia progression at visit 2. Conclusions: Changes in behavior and myopic progression were found during the COVID-19 home quarantine. Myopic progression was associated with digital screen use for online learning, but not time spent on outdoor activities. The projector and television could be better choices for online learning.

A Higher Serum Calcium Level is an Independent Risk Factor for Vision-Threatening Diabetic Retinopathy in Patients with Type 2 Diabetes: Cross-Sectional and Longitudinal Analyses.

OBJECTIVE: An elevated serum calcium level is associated with a higher risk of type 2 diabetes (T2D), but its role in microvascular complications remains unclear. This study was conducted to investigate the association between serum calcium levels and vision-threatening diabetic retinopathy (VTDR). METHODS: This study employed a cross-sectional and longitudinal design. The cross-sectional part included all patients treated for T2D at Shanghai General Hospital between 2007 and 2016, while the longitudinal part involved an overlapping cohort of diabetic patients without VTDR who were followed from their admission until December 2019. Multivariable logistic and Cox proportional hazard regression analyses were performed, respectively. VTDR was defined as severe nonproliferative diabetic retinopathy, proliferative diabetic retinopathy, or clinically significant macular edema. RESULTS: A total of 3269 patients were included in the cross-sectional analysis, and 649 patients were included in the longitudinal analysis. In the cross-sectional analysis, higher corrected serum calcium (odds ratio: 1.31 per 0.1 mmol/L, 95% confidence interval: 1.16-1.49), younger age, longer diabetes duration, albuminuria, impaired renal function, and lower serum magnesium were independently associated with VTDR. In the longitudinal analysis, 95 subjects developed VTDR during follow-up (9.7 years, interquartile range: 7.4-10.9 years). Higher corrected serum calcium (hazard ratio: 1.38 per 0.1 mmol/L, 95% confidence interval: 1.10-1.72), younger age, longer diabetes duration, sub-VTDR, albuminuria, lower serum magnesium, and higher glycated hemoglobin were identified as independent risk factors for VTDR. CONCLUSIONS: A higher serum calcium level may be an independent risk factor for VTDR in patients with T2D.

Higher Serum Uric Acid Levels Are Associated With an Increased Risk of Vision-Threatening Diabetic Retinopathy in Type 2 Diabetes Patients.

Purpose: To investigate the association between serum uric acid (SUA) levels and vision-threatening diabetic retinopathy (VTDR) in patients with type 2 diabetes. Methods: This cross-sectional study evaluated 3481 patients with type 2 diabetes from four communities in China between 2016 and 2019. VTDR was defined as severe nonproliferative, proliferative diabetic retinopathy, or clinically significant macular edema evaluated by fundus photography and optical coherence tomography. Potential association between SUA and VTDR was examined using multivariable logistic regression. Sub-group analyses based on sex were constructed. Results: A total of 305 participants had VTDR. Both higher SUA (odds ratio [OR], 1.22 per 100 µmol/L; 95% confidence interval [CI], 1.04-1.44; P = 0.013) and hyperuricemia (OR, 1.47; 95% CI, 1.07-2.04; P = 0.019) were positively associated with VTDR after adjustment for relevant covariates. Compared with those in the lowest SUA quartile, participants in the third (OR, 1.60; 95% CI, 1.07-2.39; P = 0.022) and fourth (OR, 2.05; 95% CI, 1.37-3.08; P = 0.001) sex-specific SUA quartiles showed a significantly increased risk of VTDR after adjustment. No sex-related difference was observed. Conclusions: Higher SUA levels were associated with an increased risk of VTDR in patients with type 2 diabetes in both sexes, although females seemed to be more sensitive to high SUA than males. Prospective cohort studies are needed to verify SUA as a biomarker for predicting the risk of VTDR. Whether decreased SUA levels could decrease the risk of VTDR also requires further investigation.

Efficacy and Mechanism of Butylphthalide Combined with Atorvastatin Calcium Tablets in the Diagnosis of Cerebral Infarction Using Iodol/Fe3O4 Nanometric Contrast Agent.

To determine serum proteolytic activity, NO (nitric oxide) levels, TAC (total antioxidant capacity), and TOS (total oxidant status) in acute hemorrhagic stroke, the in vivo oxidative stress response mechanism of atorvastatin was studied in a rat model with cerebral infarction. All patient contrast agents are Iodol/Fe3O4 nanometric contrast agents. Serum prolinease activity, catalase activity, NO levels, TAC, and TOS were spectrophotometrically determined and the OSI (oxidative stress index) calculated. In this study, the serum TAC level and catalase activity with acute hemorrhagic stroke were significantly lower than in the control group (each P = 0.001), while the level of NO, TOS, OSI, and protease were significantly higher than in the control group (P = 0.01). When patients were classified for acute hemorrhagic stroke by gender, there was no difference in serum prolinease activity, meanwhile, NO, TAC, and TOS levels, and OSI differed between men and women (as mentioned with details acknowledged by all, P = 0.05). The results of this study indicate that compared with the control group, elevated oxidative stress levels, decreased antioxidants levels, and elevated prolinease activity are correlated with acute hemorrhagic stroke. Additionally, further research is needed to elucidate the mechanisms of oxidative stress with acute hemorrhagic stroke.

Effect of miR-124 on PI3K/Akt signal pathway in refractory epilepsy rats.

This research aimed to investigate the effect of miR-124 on the PI3K/Akt signaling pathway in refractory epilepsy rats. Ten healthy SD rats were selected as a control group, thirty-six successfully established model rats were randomly divided into the model group, mir-124-agomir, mir-124-antagomir, mir-124-agomir+ LY294002 group (combined group), with 9 rats in each group. PI3K or (and) Akt expressions were intervened respectively. The changes in attack latency and cognitive function were observed, and the correlation among miR-124, PI3K, Akt, and attack latency was analyzed. Up-regulation of the level of miR-124 could increase the seizure interval of rats (P< 0.05), improve the cognitive function of rats (P< 0.05), and promote the expression of PI3K, AKT. The level of miR-124, PI3K, Akt was positively correlated with the latent time of seizures in rats, and the level of miR-124 was positively correlated with the level of PI3K, Akt (P< 0.05). In conclusion, miR-124 can play a protective role in temporal lobe epilepsy by promoting PI3K/Akt signaling pathway, including the protection of cognitive function, which may be a potential target for clinical treatment of intractable epilepsy in the future.

12-h abstinence-induced functional connectivity density changes and craving in young smokers: a resting-state study.

Studying the neural correlates of craving to smoke is of great importance to improve treatment outcomes in smoking addiction. According to previous studies, the critical roles of striatum and frontal brain regions had been revealed in addiction. However, few studies focused on the hub of brain regions in the 12 h abstinence induced craving in young smokers. Thirty-one young male smokers were enrolled in the present study. A within-subject experiment design was carried out to compare functional connectivity density between 12-h smoking abstinence and smoking satiety conditions during resting state in young adult smokers by using functional connectivity density mapping (FCDM). Then, the functional connectivity density changes during smoking abstinence versus satiety were further used to examine correlations with abstinence-induced changes in subjective craving. We found young adult smokers in abstinence state (vs satiety) had higher local functional connectivity density (lFCD) and global functional connectivity density (gFCD) in brain regions including striatal subregions (i.e., bilateral caudate and putamen), frontal regions (i.e., anterior cingulate cortex (ACC) and orbital frontal cortex (OFC)) and bilateral insula. We also found higher lFCD during smoking abstinence (vs satiety) in bilateral thalamus. Additionally, the lFCD changes of the left ACC, bilateral caudate and right OFC were positively correlated with the changes in craving induced by abstinence (i.e., abstinence minus satiety) in young adult smokers. The present findings improve the understanding of the effects of acute smoking abstinence on the hubs of brain gray matter in the abstinence-induces craving and may contribute new insights into the neural mechanism of abstinence-induced craving in young smokers in smoking addiction.