MicroRNA-221-3p inhibits the inflammatory response of keratinocytes by regulating the DYRK1A/STAT3 signaling pathway to promote wound healing in diabetes.

Diabetic foot ulcer (DFU), a serious complication of diabetes, remains a clinical challenge. MicroRNAs affect inflammation and may have therapeutic value in DFU. Here, we find that an miR-221-3p mimic reduces the inflammatory response and increases skin wound healing rates in a mouse model of diabetes, whereas miR-221-3p knockout produced the opposite result. In human keratinocytes cells, miR-221-3p suppresses the inflammatory response induced by high glucose. The gene encoding DYRK1A is a target of miR-221-3p. High glucose increases the expression of DYRK1A, but silencing DYRK1A expression decreases high glucose-induced inflammatory cytokine release via dephosphorylation of STAT3, a substrate of DYRK1A. Application of miR-221-3p mimic to human keratinocytes cells not only decreases DYRK1A expression but also inhibits high glucose-induced production of inflammatory cytokines to promote wound healing. This molecular mechanism whereby miR-221-3p regulates inflammation through the DYRK1A/STAT3 signaling pathway suggests targets and therapeutic approaches for treating DFU.

Concentrated Solar Light Photoelectrochemical Water Splitting for Stable and High-Yield Hydrogen Production.

Photoelectrochemical water splitting is a promising technique for converting solar energy into low-cost and eco-friendly H2 fuel. However, the production rate of H2 is limited by the insufficient number of photogenerated charge carriers in the conventional photoelectrodes under 1 sun (100 mW cm-2 ) light. Concentrated solar light irradiation can overcome the issue of low yield, but it leads to a new challenge of stability because the accelerated reaction alters the surface chemical composition of photoelectrodes. Here, it is demonstrated that loading Pt nanoparticles (NPs) on single crystalline GaN nanowires (NWs) grown on n+ -p Si photoelectrode operates efficiently and stably under concentrated solar light. Although a large number of Pt NPs detach during the initial reaction due to H2 gas bubbling, some Pt NPs which have an epitaxial relation with GaN NWs remain stably anchored. In addition, the stability of the photoelectrode further improves by redepositing Pt NPs on the reacted Pt/GaN surface, which results in maintaining onset potential >0.5 V versus reversible hydrogen electrode and photocurrent density >60 mA cm-2 for over 1500 h. The heterointerface between Pt cocatalysts and single crystalline GaN nanostructures shows great potential in designing an efficient and stable photoelectrode for high-yield solar to H2 conversion.

Hematite Hollow-Sphere-Array Photoanodes for Efficient Photoelectrochemical Water Splitting.

Constructing 3D nanophotonic structures is regarded as an effective method to realize efficient solar-to-hydrogen conversion. These photonic structures can enhance the absorbance of photoelectrodes by the light trapping effect, promote the charge separation by designable charge transport pathway and provide a high specific surface area for catalytic reaction. However, most 3D structures reported so far mainly focused on the influence of light absorption and lacked a systematic investigation of the overall water splitting process. Herein, hematite hollow-sphere-array photoanodes are fabricated through a facile hydrothermal method with polystyrene templates. Validating by simulations and experiments, the hollow sphere array is proved to enhance the efficiency of light harvesting, charge separation and surface reaction at the same time. With an additional annealing treatment in oxygen, a photocurrent density of 2.26 mA cm-2 at 1.23 V versus reversible hydrogen electrode can be obtained, which is 3.70 times larger than that with a planar structure in otherwise the same system. This work gains an insight into the photoelectrochemical water splitting process, which is valuable for the further design of advancing solar driven water splitting devices.

Liver indicators affecting the relationship between BMI and hypertension in type 2 diabetes: a mediation analysis.

BACKGROUND: Body mass index (BMI) is an important risk factor for hypertension in diabetic patients. However, the underlying mechanisms remain poorly understood. Although liver-derived biological intermediates may play irreplaceable roles in the pathophysiology of diabetes, few studies have explored them in the association between BMI and hypertension in diabetes. OBJECTIVE: To investigate the role of liver enzymes in mediating the relationship between BIM exposure and hypertension in type 2 diabetes mellitus (T2DM). METHODS: We included a total of 1765 participants from the China National Diabetic Chronic Complications Study Cohort. Associations between liver enzymes and hypertension were estimated using multivariable regression models. The function of liver indicators in the relationship between BMI and hypertension was assessed using mediation analysis. Mediation analysis was conducted, taking into account age, diabetes duration, current smoking, fasting plasma glucose level, glycated hemoglobin, anti-diabetic therapy, and family history of diseases, including diabetes, hypertension, obesity, and hyperlipidemia. RESULTS: For men, the association of BMI with hypertension was partially mediated by alanine aminotransferase (ALT), with a proportion of mediation was 68.67%, by aspartate aminotransferase (AST) was 27.02%, and by γ-glutamyltransferase (GGT) was 38.58%, by AST/ALT was 63.35%; for women, the proportion mediated by ALT was 36.93%, and by AST was 37.47%, and GGT was 44.60%, and AST/ALT was 43.73% for BMI (all P < 0.05). CONCLUSION: The effect of BMI on hypertension is partly mediated by liver indicators (ALT, AST, GGT, and AST/ALT) in diabetic patients. Our results may provide opportunities to identify new targets for hypertension interventions.

Water-promoted selective photocatalytic methane oxidation for methanol production.

Converting relatively inert methane into active chemical fuels such as methanol with high selectivity through an energy-saving strategy has remained a grand challenge. Photocatalytic technology consuming solar energy is an appealing alternative for methane reforming. However, the low efficiency and the undesirable formation of low-value products, such as carbon dioxide and ethane, limit the commercial application of photocatalytic technology. Herein, we find a facile and practical water-promoted pathway for photocatalytic methane reforming into methanol, enabling methanol production from methane and oxygen with a high selectivity (>93%) and production rate (21.4 µmol cm-2 h-1 or 45.5 mmol g-1 h-1) on metallic Ag nanoparticle-loaded InGaN nanowires (Ag/InGaN). The experimental XPS and theoretical PDOS analyses reveal that water molecules adsorbed on Ag nanoparticles (AgNPs) can promote the electron transfer from InGaN to AgNPs, which enables the formation of partial Ag species with a lower oxidation state in AgNPs. Through the in situ IR spectrum and the reaction pathway simulation studies, these newly formed Ag species induced by water adsorption were demonstrated to be responsible for the highly selective methanol production due to the effective formation of a C-O bond and the optimal desorption of the formed methanol from the surface indium site of the InGaN photocatalyst. This unique water promotion effect leads to a 55-fold higher catalytic rate and 9-fold higher selectivity for methanol production compared to photocatalytic methane reforming without water addition. This finding offers a new pathway for achieving clean solar fuels by photocatalysis-based methane reforming.

MiR-29c alleviates hyperglycemia-induced inflammation via targeting TGF-ß in cardiomyocytes.

This study aims to investigate whether miR-29c is involved in regulating transforming growth factor-ß (TGF-ß) mediated inflammation in diabetic cardiomyopathy (DCM). Our data showed increased inflammation and oxidative stress in diabetic myocardium together with decrease of miR-29c and elevation of TGF-ß expression. In vitro experiments, we transfected miR-29c mimic and antagomir into HL-1 cells to explore the effect of miR-29c on inflammation in hyperglycemic conditions. Overexpression of miR-29c down-regulated the elevated TNF-α level, ROS production and NADPH oxidase activity which caused by high glucose. However, above changes were reversed by miR-29c antagomir. Interestingly, TGF-ß protein rather than mRNA expression was changed significantly after transfection with miR-29c mimic, indicating that the modulation of TGF-ß mediated by miR-29c was at the posttranslational level. Meanwhile, we found that 3'-UTR of TGF-ß was the direct target of miR-29c confirmed by dual-luciferase assay. In conclusion, our study revealed that miR-29c could alleviate hyperglycemic-induced inflammation and ROS production via targeting TGF-ß in cardiomyocytes, which provides a potential target for the treatment of DCM.

Association of sleep behaviors, insulin resistance surrogates, and the risk of hypertension in Chinese adults with type 2 diabetes mellitus.

Objective: Our aim was to evaluate the association between midday napping, combined sleep quality, and insulin resistance surrogates and the risk of hypertension in patients with type 2 diabetes mellitus (T2DM). Methods: Data were collected using a standardized questionnaire. Binary logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) for the risk of hypertension. Systolic and diastolic blood pressure were grouped as categorical variables and unpaired two-sided Student's t-test and Spearman correlation analysis were performed to estimate the association between different blood pressure levels and insulin resistance surrogates. Results: The overall prevalence rate of hypertension was 50%. Age (OR = 1.056, 95% CI:1.044-1.068), poor sleep quality (OR = 1.959, 95% CI:1.393-2.755), hyperlipidemia (OR = 1.821, 95% CI:1.462-2.369), family history of hypertension (OR = 2.811, 95% CI:2.261-3.495), and obesity (OR = 5.515, 95% CI:1.384-21.971) were significantly associated with an increased risk of hypertension. Midday napping for 1-30 min was negatively correlated with the risk of hypertension (OR = 0.534, 95% CI:0.305-0.936, P <0.05). Conclusion: Poor sleep quality and obesity are independent risk factors for hypertension. Midday napping (1-30 min) is associated with a decreased risk of hypertension in patients with T2DM.

Prognostic implications of left ventricular hypertrophy defined by the thresholds from the international and Chinese guidelines.

To compare the predictive value of mortality between left ventricular hypertrophy (LVH) defined by Chinese thresholds and defined by international guidelines in hypertension individuals and investigate better indexation methods for LVH in Chinese population. We included 2454 community hypertensive patients with Left ventricular mass (LVM) and relative wall thickness. LVM was indexed to body surface area (BSA), height2 7 and height 1 7 . The outcomes were all-cause and cardiovascular mortality. Cox proportional hazards models were used to explore the association between LVH and the outcomes. C-statistics and time-dependent receiver operating characteristic curve (ROC) was used to evaluate the value of those indicators. During a median follow-up of 49 months (interquartile range 2-54 months), 174 participants (7.1%) died from any cause (n = 174), with 71 died of cardiovascular disease. LVM/BSA defined by the Chinese thresholds was significantly associated with cardiovascular mortality (HR: 1.63; 95%CI: 1.00-2.64). LVM/BSA was significantly associated with all-cause mortality using Chinese thresholds (HR: 1.56; 95%CI: 1.14-2.14) and using Guideline thresholds (HR: 1.52; 95%CI: 1.08-2.15). LVM/Height1.7 was significantly associated with all-cause mortality using Chinese thresholds (HR: 1.60; 95%CI: 1.17-2.20) and using Guideline thresholds (HR: 1.54; 95%CI: 1.04-2.27). LVM/Height2.7 was not significantly associated with all-cause mortality. C-statistics indicated that LVM/BSA and LVM/Height1.7 by Chinese thresholds had better predictive ability for mortality. Time-ROC indicated that only LVM/Height1.7 defined by Chinese threshold had incremental value for predicting mortality. We found that in community hypertensive populations, race-specific thresholds should be used to classify LV hypertrophy related to mortality risk stratification. LVM/BSA and LVM/Height1.7 are acceptable normalization method in Chinese hypertension.

Control status of ambulatory blood pressure and its relationship with arterial stiffness in the China nationwide registry of treated hypertensive patients: the REACTION-ABP study.

The control rate of ambulatory blood pressure (BP) is unclear in Chinese hypertensive patients, and whether it would be associated with the ambulatory arterial stiffness indices is also unknown. From June 2018 until December 2022, 4408 treated hypertensive patients (52.8% men, average age 58.2 years) from 77 hospitals in China were registered. Ambulatory BPs were measured with validated monitors and analyzed with a web-based standardized Shuoyun system ( www.shuoyun.com.cn ). The BP control rate was the highest in the office (65.7%), moderate in the daytime (45.0%), low in the morning (34.1%), and the lowest in the nighttime (27.6%, P < 0.001). Only 21.0% had their 24 h BP perfectly controlled. The stepwise regression analyses identified that the factors associated with an imperfect 24 h BP control included male sex, smoking and drinking habits, a higher body mass index, serum total cholesterol and triglycerides, and the use of several specific types of antihypertensive drugs. After adjustment for the above-mentioned factors, the 24 h pulse pressure (PP) and its components, the elastic and stiffening PPs, were all significantly associated with an uncontrolled office and ambulatory BP status with the standardized odds ratios ranging from 1.09 to 4.68 (P < 0.05). The ambulatory arterial stiffness index (AASI) was only associated with an uncontrolled nighttime and 24 h BP status. In conclusion, the control rates of 24 h ambulatory BP, especially that in the nighttime and morning time windows, were low in Chinese hypertensive patients, which might be associated with arterial stiffness in addition to other common risk factors.

Association of serum uric acid levels with cardiovascular and all-cause mortality in hypertensive patients in China: a cohort study.

PURPOSE: The present study aimed to assess the association of elevated serum uric acid (SUA) and hypouricemia with all-cause mortality and cardiovascular mortality in Chinese hypertensive patients. METHODS: In the present prospective cohort, 9325 hypertensive patients from Dongguan, China were enrolled from 2014 to 2018 for analysis. Participants were categorised by quintiles of SUA. The HRs and 95% CIs for the association between SUA, all-cause and cardiovascular mortality were evaluated using the multivariate Cox regression model. After adjusting for multiple confounders, restricted cubic spline analysis was conducted to demonstrate the shape of relationship. RESULTS: After a median follow-up of 4.18 years for 9325 participants, there were 409 (4.4%) and 151 (1.6%) reported cases of all-cause and cardiovascular mortality, respectively. By using the third quintile of SUA (6.68 mg/dL to <7.55 mg/dL for men, 5.63 mg/dL to <6.42 mg/dL for women) as reference, the highest quintiles of SUA were associated with an elevated risk of all cause (HR: 1.34, 95% CI 1.00 to 1.80) in the crude model, but the association was not significant after adjusting for multiple comparisons. The association between low SUA and mortality and the dose-response analysis on the non-linearity of SUA-mortality relationship were not statistically significant. CONCLUSIONS: Although the association between SUA levels, all-cause and cardiovascular disease mortality did not appear to be significant among Chinese hypertensive patients, the findings might be confounded by their medical conditions. Further studies are needed to verify the optimal SUA levels for hypertensive patients.

Melatonin Alleviates Hyperglycemia-Induced Cardiomyocyte Apoptosis via Regulation of Long Non-Coding RNA H19/miR-29c/MAPK Axis in Diabetic Cardiomyopathy.

Recent studies revealed that non-coding RNAs (ncRNAs) play a crucial role in pathophysiological processes involved in diabetic cardiomyopathy (DCM) that contribute to heart failure. The present study was designed to further investigate the anti-apoptotic effect of melatonin on cardiomyocytes in diabetic conditions, and to elucidate the potential mechanisms associated with ncRNAs. In animal models, we induced diabetes in SD rats by single intraperitoneal injection of streptozotocin (STZ) solution (55 mg/kg) at 18:00 in the evening, after a week of adaptive feeding. Our results indicate that melatonin notably alleviated cardiac dysfunction and cardiomyocyte apoptosis. In the pathological situation, lncRNA H19 level increased, along with a concomitant decrease in miR-29c level. Meanwhile, melatonin significantly downregulated lncRNA H19 and upregulated miR-29c levels. In our in vitro experiments, we treated H9c2 cells with high-concentration glucose medium (33 mM) to simulate the state of diabetes. It was verified that positive modulation of miR-29c and inhibition of lncRNA H19, as well as mitogen-activated protein kinase (MAPK) pathways, distinctly attenuated apoptosis in high-glucose-treated H9c2 cells. A luciferase activity assay was conducted to evaluate the potential target sites of miR-29c on lncRNA H19 and MAPK13. LncRNA H19 silencing significantly downregulated the expression of miR-29c target gene MAPK13 by inducing miR-29c expression. Most importantly, our results show that melatonin alleviated apoptosis by inhibiting lncRNA H19/MAPK and increasing miR-29c level. Our results elucidate a novel protective mechanism of melatonin on diabetic cardiomyocyte apoptosis, which involved the regulation of lncRNA H19/miR-29c and MAPK pathways, providing a promising strategy for preventing DCM in diabetic patients.

Prevalence and prognosis of left ventricular diastolic dysfunction in community hypertension patients.

Left ventricular diastolic dysfunction (LVDD) is common in hypertension and is a predictor of increased cardiovascular risk, however the effect of LVDD, detected by new guideline, on major adverse cardiac events (MACE) is unknown in hypertensive patients without known cardiovascular disease. The present study aims to evaluate LVDD in a community hypertension cohort study and assess the effect of LVDD on MACE. we studied 283 asymptomatic nonischemic patients with hypertension who had baseline echocardiogram between 2012 and 2014. Patients were followed for MACE (myocardial infarction, coronary revascularization procedures, heart failure, stroke, all-cause mortality) with mean follow-up of 5.4 years. A Cox proportional hazards model was used to assess the association of LVDD with MACE. At baseline, 35 of the 283 hypertensions were diagnosed with LVDD (12.3%) and 25 patients were women (15.5%). Women had higher frequency of LVDD than men (8%). During follow-up, there were 26.6% patients occurring MACE in the LVDD group at baseline, 9.9% patients occurring MACE in the group with normal diastolic function. In multivariable Cox regression analyses, LVDD was a stronger predictor of MACE (HR: 2.5; 95% CI: 1.20 to 5.25; c- statistics 0.805) than E/e' ratio (HR: 1.13; 95% CI: 1.04 to 1.22). LVDD was strongly associated with MACE in hypertension patients.

Association of Nondiabetic Glucometabolic Status and Aortic Stiffness in Community Hypertension Patients.

BACKGROUND: Diabetes is most commonly associated with aortic stiffness, but the importance of nondiabetic glucometabolic status for aortic stiffness (AS) in hypertension patients is unclear. METHODS: We included 1065 hypertension patients without diabetes in a cohort study. Carotid-femoral pulse wave velocity (cfPWV) >10 m/s can broadly be defined as AS. Pearson correlation analysis and multiple regression analysis are used to reveal the relationship between elevated fasting blood glucose (FBG) and AS. RESULTS: The 1065 hypertension patients (mean age 60 years) included 48% male, 22% smokers, 94.3% with anti-hypertensive drugs, 17.9% with AS, 80% with abdominal obesity, 42% with elevated triglycerides (TG), and 27% with elevated FBG. The mean values for office systolic blood pressure (SBP)/diastolic blood pressure (DBP) and central SBP/DBP were 130/85mmHg and 132/86mmHg. Mean cfPWV was 8.7m/s. Multiple regression analysis revealed that age, office SBP, and elevated FBG were independently related to AS in the whole hypertension. Elevated FBG had 1.6-fold risk of AS in hypertension patients compared with below the cutoff. In subgroup analysis, elevated FBG increased 2.68-fold risk for AS in those without metabolic syndrome (MS), not in MS. The area under curve (AUC) of office SBP was higher than central SBP for AS in receiver operating characteristic (ROC) analysis. CONCLUSION: We found that elevated FBG was an independent risk factor for AS in hypertension patients without MS, although there was a high proportion of abdominal obesity. Office SBP was better than central SBP to assess AS in community hypertension.

Influences of achieved SBP on age and sex-related left ventricular structural alteration in community hypertensive populations.

OBJECTIVE: To evaluate age and sex-related left ventricular (LV) structural alteration in community hypertensive populations, and to explore whether achieved systolic blood pressure (SBP) (< 120, < 130 and <140 mmHg) would modify the association between age and sex with LV structural alteration. METHOD: A total of 1419 community hypertensive people (mean age 61 years, women 50.5%) without cardiovascular disease and left ventricular hypertrophy (LVH) at baseline were included. LV structural measures were assessed using transthoracic echocardiography at baseline and at follow-up. Age and sex-related LV structural alteration was evaluated using linear and Cox regression analysis as appropriate. RESULTS: Per 10 years increase in age was associated with positive alteration of LV mass (LVM) index (coefficient-ß: 2.63) and LV mass-to-volume (LVMV) ratio (coefficient-ß: 0.04). Female sex was associated with positive alteration of LVM index (coefficient-ß: 4.87) and LVMV ratio (coefficient-ß: 0.05). After a median follow-up of 4years, compared to men, women had a higher rate of LVH (36.8% vs. 11.5%, P  < 0.001). The association between age and incident LVH was nonsignificant when achieved SBP <120 mmHg. The association between female sex and LVM index alteration was nonsignificant when achieved SBP <120mmHg and <130mmHg. CONCLUSION: Age and female sex were associated with a phenotype of LV remodeling which was featured by increased LVM index and concentric remodeling. Women had a higher risk of developing LVH. A lower achieved SBP conferred greater effects on mitigating age and sex-related LV structural alteration. VIDEO ABSTRACT: http://links.lww.com/HJH/B907.

MiR-221-3p targets HIPK2 to promote diabetic wound healing.

Diabetic foot ulcer is a severe complication of diabetes and is prone to being a chronic non-healing wound. We previously demonstrated that endothelial progenitor cell-derived exosomes, which contain miR-221-3p, alleviate diabetic ulcers. Here, to explore the mechanisms underlying this wound healing, we investigated the potential angiogenic effects of miR-221-3p in vitro using cultured human umbilical vein endothelial cells (HUVECs) and in vivo using a streptozotocin-induced mouse model of diabetes. We found that miR-221-3p promoted HUVEC viability, migration, and capillary-like tube formation. HUVECs cultured in high glucose showed up-regulated expression of homeodomain-interacting protein kinase 2 (HIPK2), a predicted target of miR-221-3p that may decrease angiogenesis. Knockdown of HIPK2 enhanced high glucose-suppressed HUVEC viability, migration, and tube formation, counteracting the effects of high glucose. Using a dual luciferase reporter assay, we found that HIPK2 was indeed a direct target of miR-221-3p. Subcutaneous injection of miR-221-3p agomir into diabetic mice promoted wound healing and suppressed HIPK2 expression in wound margin tissue. These findings indicate that HIPK2, as a direct target of miR-221-3p, contributes to the regulatory role of miR-221-3p in diabetic wound healing and may be a novel therapeutic target for diabetic foot ulcer.

Role of moesin in the effect of glucagon-like peptide-1 on advanced glycation end products-induced endothelial barrier dysfunction.

Glucagon-like peptide-1 (GLP-1) analogues have been found to exert protective effect on endothelial barrier dysfunction in vascular diseases. Moesin phosphorylation participates in the process of advanced glycation end products (AGEs) induced disruption of endothelial barrier integrity. Whether and how GLP-1 modulating moesin phosphorylation in endothelium under diabetic condition needs further clarification. Consistent with previous studies, our data showed that hyperglycemia and AGEs promoted moesin phosphorylation in ECs in vivo and vitro experiments. With or without AGEs incubation, overexpression of moesin and activated mutant moesin T558D increased ECs permeability, whereas knockdown of moesin decreased ECs permeability. Inhibition of Rho/ROCK, p38/MAPK and PKC ß signal pathways also decreased moesin phosphorylation in ECs incubated with AGEs. Importantly, GLP-1 inhibited moesin phosphorylation in AGE-induced ECs in a dose-dependent manner. Intriguingly, the effects of GLP-1 elicited on moesin phosphorylation in ECs under diabetic condition were blunted by inhibition of cAMP/PKA and stimulation of Rho/ROCK, p38 and PKC ß signaling pathways. Therefore, this study verified that the stabilizing effect of GLP-1 on the moesin phosphorylation mediated endothelial barrier function is mediated by GLP-1R/cAMP/PKA activation and subsequent down-regulation of Rho/ROCK, p38 and PKC ß signaling pathways.

Body Roundness Index Is a Superior Obesity Index in Predicting Diabetes Risk Among Hypertensive Patients: A Prospective Cohort Study in China.

Objective: Individuals with both hypertension and diabetes have been confirmed to significantly increase the risk of cardiovascular disease morbidity and mortality compared with those with only hypertension or diabetes. This study aimed to evaluate the potential of different anthropometric indices for predicting diabetes risk among hypertensive patients. Methods: The study group consisted of 6,990 hypertensive adults without diabetes who were recruited in China. Demographic and clinical assessment, physical examinations, laboratory tests, and anthropometric measurements, including body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), and novel indices (ABSI, AVI, BAI, BRI, CI, WWI, and WHHR), were performed at baseline and during the (median) 3-year follow-up. Cox regression analyses were conducted to estimate effects from these indices for the onset of diabetes. Receiver operator characteristic (ROC) analyses were conducted to assess the predictive capacities of the anthropometric indices and determine the optimal cut-points. Results: A total of 816 (11.7%) developed diabetes during our prospective study. Multivariate Cox regression analyses revealed weight, WC, WHR, WHtR, BAI, BRI, and WWI as the independent risk factor for diabetes among hypertensive patients, regardless of whether it was treated as a continuous or categorical variable (P < 0.05). Further Cox analyses combining BMI and different central obesity indices showed that elevated WC, WHR, WHtR, AVI, BRI, CI, regardless of the general obesity status, were found to be each independently associated with increased diabetes risk (P < 0.05). Dynamic increases of BRI < 5.24 to BRI ≥ 5.24 were associated with increased risk (HR = 1.29; 95% CI, 1.02, 1.64), and its reversal was associated with reduced risk (HR = 1.56; 95% CI, 1.23, 1.98) compared with the others (HR = 1.95; 95% CI, 1.63, 2.32). ROC analysis indicated that the areas under the ROC curves (AUC) of the anthropometric indices ranged from 0.531 to 0.63, with BRI (cut-off value = 4.62) and WHtR having the largest area. Conclusions: Based on this novel study, BRI was the most superior predictor and independent determinant for diabetes onset among the hypertensive population. Hypertensive patients with BRI > 4.62, regardless of general obesity status, were at high risk of diabetes. Thus, the prompt screening and diagnosis of diabetes should be carried out among these patients for timely integrated intervention.

Relationship Between Change in Serum Uric Acid and Ischemic Stroke in Chinese Hypertensive Patients.

Background: Limited studies focused on the association between serum uric acid (SUA) change with ischemic stroke, and their results remain controversial. The present study aimed to investigate the relationship between change in SUA with ischemic stroke among hypertensive patients. Method: This was a retrospective cohort study. We recruited adult hypertensive patients who had two consecutive measurements of SUA levels from 2013 to 2014 and reported no history of stroke. Change in SUA was assessed as SUA concentration measured in 2014 minus SUA concentration in 2013. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The Kaplan-Meier analysis and log-rank test were performed to quantify the difference in cumulative event rate. Additionally, subgroup analysis and interaction tests were conducted to investigate heterogeneity. Results: A total of 4,628 hypertensive patients were included, and 93 cases of ischemic stroke occurred during the mean follow-up time of 3.14 years. Participants were categorized into three groups according to their SUA change tertiles [low (SUA decrease substantially): <-32.6 µmol/L; middle (SUA stable): ≥-32.6 µmol/L, <40.2 µmol/L; high (SUA increase substantially): ≥40.2 µmol/L]. In the fully adjusted model, setting the SUA stable group as reference, participants in the SUA increase substantially group had a significantly elevated risk of ischemic stroke [HR (95% CI), 1.76 (1.01, 3.06), P = 0.0451], but for the SUA decrease substantially group, the hazard effect was insignificant [HR (95% CI), 1.31 (0.75, 2.28), P = 0.3353]. Age played an interactive role in the relationship between SUA change and ischemic stroke. Younger participants (age < 65 years) tended to have a higher risk of ischemic stroke when SUA increase substantially. Conclusion: SUA increase substantially was significantly correlated with an elevated risk of ischemic stroke among patients with hypertension.

Association Between Vascular Overload Index and New-Onset Ischemic Stroke in Elderly Population with Hypertension.

BACKGROUND: Vascular overload index (VOI) is a marker of arterial stiffness and arteriolar resistance, which predicts the increasing risks of cardiovascular and cerebrovascular disease. This study aimed to evaluate the association between VOI and new-onset ischemic stroke in an elderly population with hypertension. METHODS: This retrospective cohort study included 3315 hypertensive participants aged 60 years or more. Ischemic stroke was diagnosed according to cranial computed tomography, magnetic resonance imaging of the brain or cerebrovascular angiography. The calculation of VOI was based on systolic and diastolic blood pressure. VOI was divided by quartiles (<7.88 mmHg, 7.88-16.10 mmHg, 16.10-27.14 mmHg, ≥27.14 mmHg) and evaluated the association with new-onset ischemic stroke by multivariable Cox regression models. RESULTS: A total of 3315 participants (55.5% female) aged 71.4±7.20 years were included in the analysis. The median follow-up period was 5.5 years, and 206 participants reached the endpoint, new-onset ischemic stroke. With per standard deviation increment in VOI, the risks of new-onset ischemic stroke increased in non-adjusted model (Hazard ratio [HR], 1.11; 95% confidence interval [CI]: 1.03-1.22; p = 0.001), adjusted model (HR, 1.11; 95% CI: 1.04-1.22; p = 0.003) and fully-adjusted model (HR, 1.15; 95% CI: 1.08-1.26; p<0.001), respectively. In multivariate fully adjusted model, the risks of ischemic stroke increased in higher quartiles in comparison to the first quartiles (p for trend <0.001). CONCLUSION: In an elderly hypertensive population, VOI is significantly associated with the incidence of new-onset ischemic stroke. Elevated VOI is the cardiovascular risk factor and increases the probability of new-onset ischemic stroke.

Eruptive xanthoma model reveals endothelial cells internalize and metabolize chylomicrons, leading to extravascular triglyceride accumulation.

Although tissue uptake of fatty acids from chylomicrons is primarily via lipoprotein lipase (LpL) hydrolysis of triglycerides (TGs), studies of patients with genetic LpL deficiency suggest additional pathways deliver dietary lipids to tissues. Despite an intact endothelial cell (EC) barrier, hyperchylomicronemic patients accumulate chylomicron-derived lipids within skin macrophages, leading to the clinical finding eruptive xanthomas. We explored whether an LpL-independent pathway exists for transfer of circulating lipids across the EC barrier. We found that LpL-deficient mice had a marked increase in aortic EC lipid droplets before and after a fat gavage. Cultured ECs internalized chylomicrons, which were hydrolyzed within lysosomes. The products of this hydrolysis fueled lipid droplet biogenesis in ECs and triggered lipid accumulation in cocultured macrophages. EC chylomicron uptake was inhibited by competition with HDL and knockdown of the scavenger receptor-BI (SR-BI). In vivo, SR-BI knockdown reduced TG accumulation in aortic ECs and skin macrophages of LpL-deficient mice. Thus, ECs internalize chylomicrons, metabolize them in lysosomes, and either store or release their lipids. This latter process may allow accumulation of TGs within skin macrophages and illustrates a pathway that might be responsible for creation of eruptive xanthomas.