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.

Imaging-based body fat distribution and diabetic retinopathy in general US population with diabetes: an NHANES analysis (2003-2006 and 2011-2018).

BACKGROUND: Limited studies have investigated the correlation between fat distribution and the risk of diabetic retinopathy (DR) in the general population with diabetes. The relationship between obesity and DR remains inconclusive, possibly due to using simple anthropometric measures to define obesity. This study investigates the relationships between the android-to-gynoid fat ratio (A/G ratio, measured using dual-energy X-ray absorptiometry) and DR within the US population with diabetes. METHODS: The study used a population-based, cross-sectional approach based on the 2003-2006 and 2011-2018 data of the National Health and Nutrition Examination Survey (NHANES). Multivariable logistic regression analyses were performed on participants with diabetes to evaluate the contribution of body mass index (BMI), waist-to-height ratio (WHtR), and A/G ratio to the prevalence of DR. RESULTS: The prevalence of DR was 22.2, 21.2, and 17.6% among participants with A/G ratios <1.0, 1.0-1.2, and ≥1.2, respectively. After adjusting sex, age, ethnicity, diabetes duration, hemoglobin A1c level, blood pressure level, and non-high-density lipoprotein cholesterol level, a higher A/G ratio (≥1.2) was independently associated with decreased odds of DR (odds ratio [OR], 0.565; 95% CI: 0.372-0.858) compared with the A/G ratio of 1.0-1.2. Associations between a higher A/G ratio and DR remained statistically significant after adjusting for BMI (OR, 0.567; 95% CI: 0.373-0.861) and WHtR (OR, 0.586; 95% CI: 0.379-0.907). Moreover, these associations remained statistically significant in analyses using the ethnic-specific tertiles for the A/G ratio. In sex-stratified models, these correlations remained in males. There was a significant inverse association between the A/G ratio and diabetes duration in males, which persisted after multivariable adjustments (p < 0.05). CONCLUSIONS: A novel finding indicates that a higher A/G ratio is associated with a reduced likelihood of DR in males with diabetes. The results from NHANES underscore the importance of considering imaging-based fat distribution as a critical indicator in clinical practice.

Cytosolic delivery of cytochrome c conjugates induces apoptosis at nanomolar levels through a caspase-3-dependent pathway.

Cytochrome c (CytC) is conjugated with a small molecule TG6 to give TG6-CytC, which is directly delivered into cytosol, triggering the release of endogenous CytC from mitochondria, and inducing a caspase-3-dependent apoptosis with an IC50 down to 2.4 nM. This work shows an efficient strategy for intracellular protein delivery.

Risk factors and clinical prediction models for osteoporosis in pre-dialysis chronic kidney disease patients.

BACKGROUND: Osteoporosis in pre-dialysis chronic kidney disease (CKD) patients has been overlooked, and the risk factors of osteoporosis in these patients have not been adequately studied. OBJECTIVE: To identify risk factors for osteoporosis in pre-dialysis CKD patients and develop predictive models to estimate the likelihood of osteoporosis. METHODS: Dual-energy X-ray absorptiometry was used to measure bone mineral density, and clinical examination results were collected from 326 pre-dialysis CKD patients. Binary logistic regression was employed to explore the risk factors associated with osteoporosis and develop predictive models. RESULTS: In this cohort, 53.4% (n = 174) were male, 46.6% (n = 152) were female, and 21.8% (n = 71) were diagnosed with osteoporosis. Among those diagnosed with osteoporosis, 67.6% (n = 48) were female and 32.4% (n = 23) were male. Older age and low 25-(OH)-Vitamin D levels were identified as risk factors for osteoporosis in males. For females, older age, being underweight, higher bone alkaline phosphatase (NBAP), and advanced CKD (G5) were significant risk factors, while higher iPTH was protective. Older age, being underweight, and higher NBAP were risk factors for osteoporosis in the G1-4 subgroup. In the G5 subgroup, older age and higher NBAP increased the risk, while high 25-(OH)-Vitamin D or iPTH had protective effects. Nomogram models were developed to assess osteoporosis risk in pre-dialysis patients based on gender and renal function stage. CONCLUSION: Risk factors for osteoporosis vary by gender and renal function stages. The nomogram clinical prediction models we constructed may aid in the rapid screening of patients at high risk of osteoporosis.

ASSOCIATION OF MACULAR STRUCTURE WITH MICROPERIMETRY SENSITIVITY FOLLOWING VITRECTOMY FOR PROLIFERATE DIABETIC RETINOPATHY.

PURPOSE: To evaluate macular sensitivity using microperimetry in patients with proliferate diabetic retinopathy following vitrectomy and to investigate the relationship between the sensitivity and foveal microstructures with optical coherence tomography/angiography. METHODS: Eighty-four eyes of 84 patients with proliferative diabetic retinopathy, who were indicated for vitrectomy, had no intraocular surgery history 3 months preoperatively, and were able to ensure fundus examination after the vitrectomy, were included. A logMAR best-corrected visual acuity, macular sensitivity of microperimetry, macular retinal thickness, and macular vessel perfusion using optical coherence tomography/angiography were examined at 1 week, 1 month, and 3 months postoperatively. RESULTS: The logMAR best-corrected visual acuity and mean macular sensitivity of patients with proliferative diabetic retinopathy improved postoperatively (P < 0.05). There was a significant correlation between best-corrected visual acuity and mean sensitivity (P < 0.05). Postoperative mean macular sensitivity was significantly correlated with outer retinal thickness in the 0 to 6 mm macular area (P < 0.05) and also significantly correlated with deep capillary plexus perfusion (P < 0.05). Fixation stability and mean macular sensitivity did not show any correlation with glycated hemoglobin, triglyceride, serum total cholesterol, carbamide, and creatinine and duration of diabetes mellitus (P > 0.05). CONCLUSION: Postoperative mean macular sensitivity was significantly correlated with outer retinal thickness and deep capillary plexus perfusion for patients with proliferative diabetic retinopathy. The authors found that the visual performance of patients can be evaluated by the outer retinal thickness and deep capillary plexus perfusion, so optical coherence tomography/angiography examination can be an important prognostic factor for visual performance in patients.Clinical Trial Registration: This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn; Registration No.: ChiCTR2100043399).

Together in sickness and in health: Spillover of physical, mental, and cognitive health among older English couples.

Using data from eight waves of the English Longitudinal Study of Aging, we study the cross-domain and cross-spouse spillover of health among married adults aged 50 and above in England. We apply the system generalized method of moments to linear dynamic panel models for physical, mental, and cognitive health, controlling for individual heterogeneity and the influence of marriage market matching and shared environments. Our findings reveal bidirectional spillovers between memory abilities and mobility difficulty among men, as well as between depressive symptoms and mobility difficulty among women. Worsening mobility increases the risk of depression in men, but not vice versa. Additionally, gender-specific cross-spouse effects are observed. Women's mental health is significantly influenced by their spouse's mental health, while this effect is weaker for men. Conversely, men's mental health is notably affected by their spouse's physical health. These results highlight the importance of considering spillovers within families and across health domains when developing policies to promote health and reduce health disparities among the elderly population.

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.

Statin-Associated Liver Dysfunction and Muscle Injury: epidemiology, Mechanisms, and Management Strategies.

Surveillance of drug safety is an important aspect in the routine medical care. Adverse events caused by real-world drug utilization has become one of the leading causes of death and an urgent issue in the field of toxicology. Cardiovascular disease is now the leading cause of fatal diseases in most countries, especially in the elderly population who often suffer from multiple diseases and need long-term multidrug therapy. Among which, statins have been widely used to lower bad cholesterol and regress coronary plaque mainly in patients with hyperlipidemia and atherosclerotic cardiovascular diseases (ASCVD). Although the real-world benefits of statins are significant, different degrees and types of adverse drug reactions (ADR) such as liver dysfunction and muscle injury, have a great impact on the original treatment regimens as well as the quality of life. This review describes the epidemiology, mechanisms, early identification and post-intervention of statin-associated liver dysfunction and muscle injury based on the updated clinical evidence. It provides systematic and comprehensive guidance and necessary supplement for the clinical safety of statin use in cardiovascular diseases.

Enlarged perivascular spaces in alcohol-related brain damage induced by dyslipidemia.

Perivascular spaces (PVSs) as the anatomical basis of the glymphatic system, are increasingly recognized as potential imaging biomarkers of neurological conditions. However, it is not clear whether enlarged PVSs are associated with alcohol-related brain damage (ARBD). We aimed to investigate the effect of long-term alcohol exposure on dyslipidemia and the glymphatic system in ARBD. We found that patients with ARBD exhibited significantly enlargement of PVSs in the frontal cortex and basal ganglia, as well as a notable increased levels of total cholesterol (TC) and triglycerides (TG). The anatomical changes of the glymphatic drainage system mentioned above were positively associated with TC and TG. To further explore whether enlarged PVSs affects the function of the glymphatic system in ARBD, we constructed long alcohol exposure and high fat diet mice models. The mouse model of long alcohol exposure exhibited increased levels of TC and TG, enlarged PVSs, the loss of aquaporin-4 polarity caused by reactive astrocytes and impaired glymphatic drainage function which ultimately caused cognitive deficits, in a similar way as high fat diet leading to impairment in glymphatic drainage. Our study highlights the contribution of dyslipidemia due to long-term alcohol abuse in the impairment of the glymphatic drainage system.

Vascular smooth muscle-specific LRRC8A knockout ameliorates angiotensin II-induced cerebrovascular remodeling by inhibiting the WNK1/FOXO3a/MMP signaling pathway.

Hypertensive cerebrovascular remodeling involves the enlargement of vascular smooth muscle cells (VSMCs), which activates volume-regulated Cl- channels (VRCCs). The leucine-rich repeat-containing family 8 A (LRRC8A) has been shown to be the molecular identity of VRCCs. However, its role in vascular remodeling during hypertension is unclear. In this study, we used vascular smooth muscle-specific LRRC8A knockout (CKO) mice and an angiotensin II (Ang II)-induced hypertension model. The results showed that cerebrovascular remodeling during hypertension was ameliorated in CKO mice, and extracellular matrix (ECM) deposition was reduced. Based on the RNA-sequencing analysis of aortic tissues, the level of matrix metalloproteinases (MMPs), such as MMP-9 and MMP-14, were reduced in CKO mice with hypertension, which was further verified in vivo by qPCR and immunofluorescence analysis. Knockdown of LRRC8A in VSMCs inhibited the Ang II-induced upregulation of collagen I, fibronectin, and matrix metalloproteinases (MMPs), and overexpression of LRRC8A had the opposite effect. Further experiments revealed an interaction between with-no-lysine (K)-1 (WNK1), which is a "Cl--sensitive kinase", and Forkhead transcription factor O3a (FOXO3a), which is a transcription factor that regulates MMP expression. Ang II induced the phosphorylation of WNK1 and downstream FOXO3a, which then increased the expression of MMP-2 and MMP-9. This process was inhibited or potentiated when LRRC8A was knocked down or overexpressed, respectively. Overall, these results demonstrate that LRRC8A knockout in vascular smooth muscle protects against cerebrovascular remodeling during hypertension by reducing ECM deposition and inhibiting the WNK1/FOXO3a/MMP signaling pathway, demonstrating that LRRC8A is a potential therapeutic target for vascular remodeling-associated diseases such as stroke.

Modifiable lifestyle, mental health status and diabetic retinopathy in U.S. adults aged 18-64 years with diabetes: a population-based cross-sectional study from NHANES 1999-2018.

BACKGROUND: The relationship between integrated lifestyles, mental status and their impact on overall well-being has attracted considerable attention. This study aimed to evaluate the association between lifestyle factors, depression and diabetic retinopathy (DR) in adults aged 18-64 years. METHODS: A cohort of 3482 participants diagnosed with diabetes was drawn from the National Health and Nutrition Examination Survey (NHANES) spanning the years 1999-2018. DR was defined based on self-reported diabetic retinopathy diagnoses by professional physicians, relying on Diabetes Interview Questionnaires. Subgroup analysis was employed to assess lifestyle and psychological factors between participants with DR and those without, both overall and stratified by diabetic duration. Continuous variables were analyzed using the student's t test, while weighted Rao-Scott χ2 test were employed for categorical variables to compare characteristics among the groups. RESULTS: Of the 3482 participants, 767 were diagnosed with diabetic retinopathy, yielding a weighted DR prevalence of 20.8%. Patients with DR exhibited a higher prevalence of heavy drinking, depression, sleep deprivation, and insufficient physical activity compared to those without DR. Furthermore, multivariable logistic regression analysis revealed that sleeping less than 5 h (OR = 3.18, 95%CI: 2.04-4.95, p < 0.001) and depression (OR = 1.35, 95%CI:1.06-1.64, p = 0.025) were associated with a higher risk of DR, while moderate drinking (OR = 0.49, 95%CI: 0.32-0.75, p = 0.001) and greater physical activity (OR = 0.64, 95%CI: 0.35-0.92, p = 0.044) were identified as protective factors. CONCLUSIONS: Adults aged 18-64 years with DR exhibited a higher prevalence of lifestyle-related risk factors and poorer mental health. These findings underscore the need for concerted efforts to promote healthy lifestyles and positive emotional well-being in this population.

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.

Left bundle branch pacing better preserves ventricular mechanical synchrony than right ventricular pacing: a two-centre study.

AIMS: Left bundle branch pacing (LBBP) has been shown to better maintain electrical synchrony compared with right ventricular pacing (RVP), but little is known about its impact on mechanical synchrony. This study investigates whether LBBP better preserves left ventricular (LV) mechanical synchronicity and function compared with RVP. METHODS AND RESULTS: Sixty patients with pacing indication for bradycardia were included: LBBP (n = 31) and RVP (n = 29). Echocardiography was performed before and shortly after pacemaker implantation and at 1-year follow-up. The lateral wall-septal wall (LW-SW) work difference was used as a measure of mechanical dyssynchrony. Septal flash, apical rocking, and septal strain patterns were also assessed. At baseline, LW-SW work difference was small and similar in two groups. SW was markedly decreased, while LW work remained mostly unchanged in RVP, resulting in a larger LW-SW work difference compared with LBBP (1253 ± 687 mmHg·% vs. 439 ± 408 mmHg·%, P < 0.01) at last follow-up. In addition, RVP more often induced septal flash or apical rocking and resulted in more advanced strain patterns compared with LBBP. At 1 year follow-up, LV ejection fraction (EF) and global longitudinal strain (GLS) were more decreased in RVP compared with LBBP (ΔLVEF: -7.4 ± 7.0% vs. 0.3 ± 4.1%; ΔLVGLS: -4.8 ± 4.0% vs. -1.4 ± 2.5%, both P < 0.01). In addition, ΔLW-SW work difference was independently correlated with LV adverse remodelling (r = 0.42, P < 0.01) and LV dysfunction (ΔLVEF: r = -0.61, P < 0.01 and ΔLVGLS: r = -0.38, P = 0.02). CONCLUSION: LBBP causes less LV mechanical dyssynchrony than RVP as it preserves a more physiologic electrical conduction. As a consequence, LBBP appears to preserve LV function better than RVP.

Dual action of macrophage miR-204 confines cyclosporine A-induced atherosclerosis.

BACKGROUND AND PURPOSE: Atherosclerosis induced by cyclosporine A (CsA), an inhibitor of the calcineurin/nuclear factor of activated T cells (NFAT) pathway, is a major concern after organ transplantation. However, the atherosclerotic mechanisms of CsA remain obscure. We previously demonstrated that calcineurin/NFAT signalling inhibition contributes to atherogenesis via suppressing microRNA-204 (miR-204) transcription. We therefore hypothesised that miR-204 is involved in the development of CsA-induced atherosclerosis. EXPERIMENTAL APPROACH: ApoE-/- mice with macrophage-miR-204 overexpression were generated to determine the effects of miR-204 on CsA-induced atherosclerosis. Luciferase reporter assays and chromatin immunoprecipitation sequencing were performed to explore the targets mediating miR-204 effects. KEY RESULTS: CsA alone did not significantly affect atherosclerotic lesions or serum lipid levels. However, it exacerbated high-fat diet-induced atherosclerosis and hyperlipidemia in C57BL/6J and ApoE-/- mice, respectively. miR-204 levels decreased in circulating monocytes and plaque lesions during CsA-induced atherosclerosis. The upregulation of miR-204 in macrophages inhibited CsA-induced atherosclerotic plaque formation but did not affect serum lipid levels. miR-204 limited the CsA-induced foam cell formation by reducing the expression of the scavenger receptors SR-BII and CD36. SR-BII was post-transcriptionally regulated by mature miR-204-5p via 3'-UTR targeting. Additionally, nuclear-localised miR-204-3p prevented the CsA-induced binding of Ago2 to the CD36 promoter, suppressing CD36 transcription. SR-BII or CD36 expression restoration dampened the beneficial effects of miR-204 on CsA-induced atherosclerosis. CONCLUSION AND IMPLICATIONS: Macrophage miR-204 ameliorates CsA-induced atherosclerosis, suggesting that miR-204 may be a potential target for the prevention and treatment of CsA-related atherosclerotic side effects.

Effects of a fortified balanced salt solution and Ringer's lactate solution on anterior chamber inflammation after phacoemulsification in diabetes.

PURPOSE: To compare the effects of a fortified balanced salt solution (fSS) and Ringer's lactate solution (Ringer) on anterior chamber (AC) inflammation in patients undergoing phacoemulsification. SETTING: Tianjin Medical University Eye Hospital, Tianjin, China. DESIGN: Prospective masked controlled trial. METHODS: 80 patients (40 patients with regular cataract and 40 cataract patients with diabetes mellitus [DM]) were randomized to receive either fSS (n = 40) or Ringer's solution (n = 40). Anterior-segment optical coherence tomography was used to evaluate AC cells and flare. Transepithelial electrical resistance (TEER) and zonula occludens-1 (ZO-1) immunofluorescence were used for tight junction examination. Monocytic leukemia cell line (Tohoku Hospital Pediatrics-1 [THP-1]) transmigration assay was performed to observe the effects of the 2 perfusates on the inflammatory response in vitro. RESULTS: In patients with regular cataracts, postoperative AC cells and flare on the 1st and 7th days were not significantly different between the Ringer and fSS groups. However, in cataract patients with DM, AC cells were higher in the Ringer group than in the fSS group ( P = .003) on postoperative day 1. The AC flare was also significantly higher in the Ringer group than in the fSS group ( P < .0001). No significant differences between the groups were observed on day 7. Compared with Ringer, fSS increased the TEER value and ZO-1 content and reduced the adhesion of THP-1 cells. CONCLUSIONS: The results of this study indicated that early postoperative AC inflammation is more severe in patients with cataracts and DM. In addition, fSS attenuates inflammation by protecting the blood-aqueous barrier and inhibiting the exudation of inflammatory cells.

Hypergraph convolutional network for longitudinal data analysis in Alzheimer's disease.

Alzheimer's disease (AD) is an irreversible and progressive neurodegenerative disease. Longitudinal structural magnetic resonance imaging (sMRI) data have been widely used for tracking AD pathogenesis and diagnosis. However, existing methods tend to treat each time point equally without considering the temporal characteristics of longitudinal data. In this paper, we propose a weighted hypergraph convolution network (WHGCN) to use the internal correlations among different time points and leverage high-order relationships between subjects for AD detection. Specifically, we construct hypergraphs for sMRI data at each time point using the K-nearest neighbor (KNN) method to represent relationships between subjects, and then fuse the hypergraphs according to the importance of the data at each time point to obtain the final hypergraph. Subsequently, we use hypergraph convolution to learn high-order information between subjects while performing feature dimensionality reduction. Finally, we conduct experiments on 518 subjects selected from the Alzheimer's disease neuroimaging initiative (ADNI) database, and the results show that the WHGCN can get higher AD detection performance and has the potential to improve our understanding of the pathogenesis of AD.

[Arthroscopic treatment of scaphoid fracture nonunion with bone graft and Kirschner wire combined with screw fixation].

Objective: To explore the effectiveness of arthroscopic treatment of scaphoid fracture nonunion with bone graft and Kirschner wire combined with screw fixation. Methods: The clinical data of 14 patients with scaphoid fracture nonunion who met the selection criteria between February 2021 and September 2022 were retrospectively analyzed. There were 13 males and 1 female with an average age of 32 years ranging from 17 to 54 years. The time from injury to operation ranged from 6 to 15 months, with an average of 9.6 months. According to the Slade-Geissler classification of scaphoid fracture nonunion, there were 3 cases of grade Ⅲ, 8 cases of grade Ⅳ, and 3 cases of grade Ⅴ. The preoperative visual analogue scale (VAS) score was 5.9±1.0, and the modified Mayo wrist score was 53.2±9.1. There were 2 cases of scaphoid nonunion advanced collapse, both of which were stage Ⅰ. All patients were treated with arthroscopic bone graft and Kirschner wire combined with screw fixation, and the fracture healing was observed by X-ray film monthly after operation, and the effectiveness was evaluated by VAS score and modified Mayo wrist score before and after operation. Results: All patients were followed up 6-14 months, with an average of 8.4 months. All fractures healed in 4-8 months, with an average of 6.3 months. The postoperative pain symptoms and wrist function of the patients significantly improved when compared with those before operation, and the VAS score at last follow-up was 2.4±1.3, and the modified Mayo wrist score was 87.1±6.7, which were significantly different from those before operation ( t=12.851, P<0.001; t=-14.410, P<0.001). According to the modified Mayo wrist evaluation, 9 cases were excellent, 3 cases were good, and 2 cases were fair. Conclusion: Arthroscopic bone graft and Kirschner wire combined with screw fixation is an effective surgical method for the treatment of scaphoid fracture nonunion.

BRD4 facilitates osteogenic differentiation of human bone marrow mesenchymal stem cells through WNT4/NF-κB pathway.

BACKGROUND: Human bone marrow mesenchymal stem cells (hBMSCs) are a major source of osteoblast precursor cells and are directly involved in osteoporosis (OP) progression. Bromodomain-containing protein 4 (BRD4) is an important regulator for osteogenic differentiation. Therefore, its role and mechanism in osteogenic differentiation process deserve further investigation. METHODS: hBMSCs osteogenic differentiation was evaluated by flow cytometry, alkaline phosphatase assay and alizarin red staining. Western blot was used to test osteogenic differentiation-related proteins, BRD4 protein, WNT family members-4 (WNT4)/NF-κB-related proteins, and glycolysis-related proteins. Metabolomics techniques were used to detect metabolite changes and metabolic pathways. BRD4 and WNT4 mRNA levels were determined using quantitative real-time PCR. Dual-luciferase reporter assay and chromatin immunoprecipitation assay were performed to detect BRD4 and WNT4 interaction. Glycolysis ability was assessed by testing glucose uptake, lactic acid production, and ATP levels. RESULTS: After successful induction of osteogenic differentiation, the expression of BRD4 was increased significantly. BRD4 knockdown inhibited hBMSCs osteogenic differentiation. Metabolomics analysis showed that BRD4 expression was related to glucose metabolism in osteogenic differentiation. Moreover, BRD4 could directly bind to the promoter of the WNT4 gene. Further experiments confirmed that recombinant WNT4 reversed the inhibition effect of BRD4 knockdown on glycolysis, and NF-κB inhibitors (Bardoxolone Methyl) overturned the suppressive effect of BRD4 knockdown on hBMSCs osteogenic differentiation. CONCLUSION: BRD4 promoted hBMSCs osteogenic differentiation by inhibiting NF-κB pathway via enhancing WNT4 expression.

Progressive Retinal Medullated Nerve Fiber Layer in a Young Boy.

This case report documents progression of myelinated retinal nerve fibers in a young boy from age 6 months to 2 years.

Association of BMI and waist circumference with diabetic microvascular complications: A prospective cohort study from the UK Biobank and Mendelian randomization analysis.

AIMS: To investigate the precise association between BMI and waist circumference (WC) and diabetic complications, including retinopathy (DR), nephropathy (DN) and peripheral neuropathy (DPN). METHODS: A multivariable-adjusted Cox proportional hazard model was used to evaluate the observed association from 30,541 UK Biobank participants with diabetes. A two-sample Mendelian randomization (MR) framework was applied to summary-level GWASs of BMI and WC comprising a total of 461,460 and 462,166 participants from UK Biobank to explore the potential causal association. RESULTS: Higher BMI and WC were associated with increased risks of DR, DN, and DPN (HR (95% CI), per-SD increase: BMI: DR 1.09 (1.04-1.13), DN 1.37 (1.33-1.41), DPN 1.27 (1.20-1.34); WC: DR 1.11 (1.07-1.16), DN 1.41 (1.36-1.46), DPN 1.38 (1.30-1.45)) in the UK Biobank cohort. Univariate MR indicated that increased BMI and WC were causal risk factors for these complications (OR (95% CI), per-SD increase: BMI: DR 1.33 (1.22-1.45), DN 1.74 (1.47-2.07), DPN 2.20 (1.67-2.90); WC: DR 1.43 (1.27-1.61), DN 2.03 (1.62-2.55), DPN 2.80 (1.99-3.92)), and the effect sizes remained significant after adjustment for glycated hemoglobin. CONCLUSIONS: Prospective observational and MR analyses provided evidence that high BMI and WC may represent potential causal risk factors for diabetic microvascular complications. Weight control might modify the risks of these complications independently of glycemic control and should be considered as a therapeutic recommendation.