Association between obstructive sleep apnea and 24-h urine protein quantification in patients with hypertension.

The association between obstructive sleep apnea (OSA) and proteinuria is undetermined, with few studies on hypertension, a high-risk group for renal impairment. Therefore, we aimed to explore whether OSA is an independent risk factor for proteinuria in patients with hypertension. We investigated the cross-sectional association between OSA and proteinuria. Participants were divided into groups by apnea hypopnea index (AHI) category. Multivariable Logistic regression analysis was used to evaluate the association between OSA severity, objectively measured sleep dimensions, and proteinuria which is mainly defined by 24-h urine protein quantification > 300 mg/24 h. Sensitivity analyses were performed by excluding those with comorbidities (primary aldosteronism and homocysteine ≥ 15 µmol/L). Of the 2106 participants, the mean age was 47.57 ± 10.50 years, 67.2% were men, and 75.9% were OSA patients. In total participants, compared with those without OSA, patients with mild OSA, moderate OSA, and severe OSA showed 1.09 (95% CI 0.80-1.40), 1.24 (95% CI 0.89-1.74) and 1.47 (95% CI 1.04-2.08) fold risk for proteinuria with a trend test P trend < 0.05. Each 10-unit increase in the AHI, oxygen desaturation index (ODI), and time spent with oxygen saturation < 90% (T90) was found to be associated with 13%, 10%, and 2% higher likelihood of proteinuria in the crude model, significant in adjusted models. The more severe the OSA is, the higher the risk of proteinuria. AHI and T90 are independently associated with a higher risk of structural renal damage in the population with hypertension.

Association between serum phosphate, magnesium, calcium and aortic valve sclerosis: a propensity score-matched case-control study.

OBJECTIVES: Aortic valve sclerosis has been proposed to signify greater cardiovascular risk; the correlation between serum trace elements and aortic valve sclerosis has been reported. Therefore, an in-depth exploration of the risk factors for aortic valve sclerosis and early intervention may reduce the risk of cardiovascular disease. METHODS: In this study, Patients with aortic valve sclerosis and non-aortic valve sclerosis who underwent echocardiographic diagnosis in the People's Hospital of Xinjiang Uygur Autonomous Region during the period from 2019 to 2021 were selected for this study. The correlation between aortic valve sclerosis and serum phosphorus, calcium, and magnesium levels was explored using the propensity score matching technique by pairing the two groups of patients 1:1. RESULTS: A total of 1,533 non-aortic valve sclerosis and 1,533 aortic valve sclerosis patients were included. Logistic regression analysis showed that serum magnesium [OR: 0.346; 95%CI: 0.227, 0.528] and serum calcium [OR: 7.022; 95%CI: 4.755, 10.369] were influential factors. Patients with low, intermediate, and high serum magnesium levels had a significantly lower risk of aortic valve sclerosis compared to patients with very low micronutrient levels (p < 0.05). Comparatively, patients with low or high serum calcium levels had an elevated risk of aortic valve sclerosis (p < 0.05). CONCLUSION: Serum magnesium may have a protective role against aortic valve sclerosis, while both low and high levels of serum calcium could be risk factor for the condition. These serum micronutrients may be indications of cardiovascular disease risk prediction or prevention, and more research is required.

Aldosterone is Associated With New-onset Cerebrovascular Events in Patients With Hypertension and White Matter Lesions: A Cohort Study.

OBJECTIVE: White matter lesions (WMLs) increase the risk of stroke, stroke recurrence, and death. Higher plasma aldosterone concentration (PAC) increases the risk of stroke, acute myocardial infarction, and hypertension. The objective is to evaluate the relationship between PAC and cerebrovascular events in patients with hypertension and WMLs. METHODS: We conducted a retrospective cohort study that included 1041 participants hospitalized. The outcome was new-onset cerebrovascular events including intracerebral hemorrhage and stroke. A Cox regression model was used to evaluate the relationship between baseline PAC and the risk of cerebrovascular events. RESULTS: The mean age of participants was 60.9 ± 10.2 years and 565 (53.4%) were males. The median follow-up duration was 42 months (interquartile range: 25-67), and 92 patients experienced new-onset cerebrovascular events. In a multivariate-adjusted model, with PAC as a continuous variable, higher PAC increased the risk of cerebrovascular events; patient risk increased per 1 (hazard ratio [HR: 1.03], 95% confidence interval [CI]: 1.01-1.06, P < .01), per 5 (HR: 1.17, 95% CI: 1.06-1.31, P < .01), and per 10 ng/dL (HR: 1.41, 95%: 1.14-1.75, P < .01) increase in PAC. When PAC was expressed as a categorical variable (quartile: Q1-Q4), patients in Q4 (HR: 2.12, 95% CI: 1.18-3.79, P < .05) exhibited an increased risk of cerebrovascular events compared to Q1. Restrictive spline regression showed a linear association between PAC and the risk of new-onset cerebrovascular events after adjusting for all possible variables. CONCLUSIONS: Our study identified a linear association between PAC and the risk of new-onset cerebrovascular events in patients with hypertension and WMLs.

Dictamnine Ameliorates DNFB-Induced Atopic Dermatitis Like Skin Lesions in Mice by Inhibiting M1 Macrophage Polarization and Promoting Autophagy.

Autophagy and M1 macrophage polarization play important roles in the regulation of inflammation in atopic dermatitis (AD). Dictamnine is one of the main ingredients in Cortex Dictamni, a widely used traditional Chinese medicine for the treatment of dermatitis. In the present study, we investigated the anti-inflammatory effects of dictamnine on AD like skin lesions and M1 macrophage polarization. A 2,4-dinitrofluorobenzene (DNFB) triggered AD like skin lesions models in mice was established to identify the ameliorative effects of dictamnine on AD in vivo. In addition, an M1 macrophage polarization model was co-stimulated by lipopolysaccharide (LPS) and interferon-γ (IFN-γ) using phorbol myristate acetate (PMA) differentiated THP-1 cells, to investigate the effect of dictamnine on promoting autophagy and inhibiting inflammatory factor release. Dictamnine suppressed DNFB-induced skin inflammation by inhibiting M1 macrophage polarization, up-regulating the expression of microtubule-associated protein 1A/1B-light chain 3 (LC3) expression, and promoting macrophage autophagy at inflammatory sites. Dictamnine also could reduce the release of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), and interleukin-8 (IL-8), and down-regulate the mRNA expression of these genes in LPS-IFN-γ triggered M1 polarized macrophages. Dictamnine ameliorates AD like skin lesions by inhibiting M1 macrophage polarization and promoting autophagy. Hence, dictamnine is expected to be a potential therapeutic candidate for AD.

Fisetin alleviates chronic urticaria by inhibiting mast cell activation via MRGPRX2.

OBJECTIVES: The activation of mast cell (MC) plays an important part in the pathogenesis of chronic urticaria (CU), and the expression of MRGPRX2 (Mas-related G-protein coupled receptor X2) and the circulating levels of SP (substance P) in skin MC of CU patients increased. Fisetin is a natural flavonoid with anti-inflammatory and antiallergic pharmacological effects. This study aimed to investigate the inhibitory effect of fisetin on CU via MRGPRX2 and its possible molecular mechanisms. METHODS: OVA/SP co-stimulated and SP-stimulated CU like murine models were used to evaluate the effect of fisetin on CU. MRGPRX2/HEK293 cells and LAD2 cells were used to perform the antagonism effect of fisetin on MC via MRGPRX2. KEY FINDINGS: The results indicated that fisetin prevented urticaria-like symptoms in murine CU models, and inhibited MCs activation by suppressing calcium mobilization and degranulation of cytokines and chemokines via binding to MRGPRX2. The bioinformatics analysis showed that fisetin might have an interaction relationship with Akt in CU. The western blotting experiments showed that fisetin downregulated the phosphorylation levels of Akt, P38, NF-κB, and PLCγ in C48/80 activated LAD2 cells. CONCLUSIONS: Fisetin alleviates CU progression by inhibiting mast cell activation via MRGPRX2, which may be a novel therapeutic candidate for CU.

The relationship between obstructive sleep apnea and risk of renal impairment in patients with hypertension, a longitudinal study.

OBJECTIVE: Association of obstructive sleep apnea (OSA) with renal damage is undetermined, especially in the population with hypertension, a high-risk group for chronic kidney disease. Therefore, we aimed to explore whether OSA is an independent risk factor for renal impairment in patients with hypertension, by considering the effects of gender, age, obesity and OSA severity. METHODS: The longitudinal observational study included patients with hypertension and suspected OSA without renal damage at baseline who visited Hypertension Center between January 2011 and December 2018, and followed up till renal outcomes, death, loss to follow-up, or May 31, 2022, using annual health check-ups, hospital readmission or out-patient visits. Main renal outcome was chronic kidney disease (CKD), defined as estimated glomerular filtration rate <60 ml/min per 1.73 m2 and/or positive proteinuria. Cox proportional hazard models were used to evaluate the association, and repeated after propensity score matching. Sensitivity analysis were performed by excluding those with primary aldosteronism. RESULTS: 7961 patients with hypertension were included with 5022 ones with OSA, and 82% were followed up. During median follow-up of 3.42 years, 1486 patients developed CKD. Per 1000 person-year incidence of CKD was 56.72 in OSA group. In Cox regression analysis, OSA and severe OSA group respectively showed 1.21 (95% CI: 1.08-1.35) and 1.27 (95% CI: 1.09-1.47) fold risk for CKD in total, compared with non-OSA group. Overall results remained consistent in propensity score matching and sensitivity analysis. CONCLUSION: OSA is independently associated with higher risk of chronic kidney disease in hypertension.

TXLNG improves insulin resistance in obese subjects in vitro and in vivo by inhibiting ATF4 transcriptional activity.

Lipotoxicity contributes to insulin resistance and dysfunction of pancreatic ß-cells. Insulin promotes 3T3-L1 preadipocyte differentiation and facilitates glucose entry into muscle, adipose, and other tissues. In this study, differential gene expression was analyzed using four datasets, and taxilin gamma (TXLNG) was the only shared downregulated gene in all four datasets. TXLNG expression was significantly reduced in obese subjects according to online datasets and in high-fat diet (HFD)-induced insulin-resistant (IR) mice according to experimental investigations. TXLNG overexpression significantly improved IR induced by HFD in mouse models by reducing body weight and epididymal adipose weight, decreasing mRNA expression of pro-inflammatory factors interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), and reducing adipocyte size. High-glucose/high-insulin-stimulated adipocytes exhibited decreased TXLNG and increased signal transducer and activator of transcription 3 (STAT3) and activating transcription factor 4 (ATF4). IR significantly decreased glucose uptake, cell surface glucose transporter type 4 (GLUT4) levels, and Akt phosphorylation, while increasing the mRNA expression levels of IL-6 and TNF-α in adipocytes. However, these changes were significantly reversed by TXLNG overexpression, while they were exacerbated by TXLNG knockdown. TXLNG overexpression had no effect on ATF4 protein levels, while ATF4 overexpression increased ATF4 protein levels. Furthermore, ATF4 overexpression notably abolished the improvements in IR adipocyte dysfunction caused by TXLNG overexpression. In conclusion, TXLNG improves IR in obese subjects in vitro and in vivo by inhibiting ATF4 transcriptional activity.

Elevated random glucose levels at admission are associated with all-cause mortality and cardiogenic shock during hospitalisation in patients with acute myocardial infarction and without diabetes: A retrospective cohort study.

BACKGROUND: Elevated glucose levels at admission are associated with a worse prognosis in patients with acute myocardial infarction (AMI); additionally, such elevation has a higher prognostic value for patients without diabetes. METHODS: We retrospectively recruited 2412 AMI patients without diabetes from 1 August 2011 to 10 January 2022. The primary outcome was all-cause mortality during hospitalisation, and the secondary outcomes were cardiogenic shock, ventricular tachycardia, ventricular fibrillation, atrioventricular block and new stroke. RESULTS: The mean age of participants was 65 years and 78.6% were male. Of the 2412 patients, all-cause mortality occurred in 236 patients (9.8%) during hospitalisation. In multivariate-adjusted models that corrected for variable weights, the risk of all-cause mortality increased with an increase in random glucose levels at admission; specifically, the risk of all-cause mortality increased per 1 mg/dL (odds ratio [OR] 1.006, 95% confidence interval [CI]: 1.004-1.008), per 9 mg/dL (OR: 1.06, 95% CI: 1.04-1.08), and per 18 mg/dL (OR: 1.12, 95% CI: 1.07-1.16) increases in admission glucose levels. When admission glucose levels were expressed as a categorical variable, increased levels of glucose (relative to the reference glucose value <140 mg/dL) led to an increased risk of all-cause mortality; specifically, the OR of all-cause mortality for 140-200 mg/dL glucose was 1.55 (95% CI: 1.09-2.17) and the OR for glucose >200 mg/dL was 3.08 (95% CI: 2.00-4.62) (P for trend <0.001). The risk of cardiogenic shock also increased with glucose levels with an OR of 1.68 (95% CI: 1.21-2.31) for 140-200 mg/dL glucose and an OR of 3.72 (95% CI: 2.50-5.46) for >200 mg/dL, compared with that of glucose <140 mg/dL. In multivariate-adjusted spline regression models, an increased risk of all-cause mortality was observed in patients with glucose ≥122 mg/dL (OR: 1.81, 95% CI: 1.38-2.38, p < 0.001) compared with the reference cohort. Furthermore, patients with glucose ≥111 mg/dL (OR: 2.36, 95% CI: 1.80-3.12) had a higher risk of cardiogenic shock than patients with glucose <111 mg/dL. CONCLUSIONS: Patients with AMI and without diabetes who had elevated random glucose levels at admission had a higher risk of all-cause mortality and cardiogenic shock during hospitalisation. In particular, patients with glucose ≥122 mg/dL had an increased risk of all-cause mortality, and those with glucose ≥111 mg/dL had an increased risk of cardiogenic shock.

Proteomics analysis of coronary blood microparticles in patients with acute myocardial infarction.

BACKGROUND: Acute myocardial infarction (AMI) is the leading cause of death for patients with cardiovascular disease (CVD). Although researchers have made substantial efforts to elucidate its pathogenesis, the molecular mechanisms underlying AMI remain unknown. The aim of this study was to use proteomics to identify differentially expressed proteins (DEPs) and the possible biological functions and metabolic pathways related to coronary blood microparticles (MPs) in patients with AMI and stable coronary artery disease (SCAD); this study will allow for the identification of individuals at risk of acute thrombosis. METHODS: The study was performed on 5 AMI patients and 5 SCAD patients. DEPs were identified, and Gene Ontology (GO) enrichment and KEGG pathway enrichment analyzes were performed to determine the relative abundance and biological function of the significant DEPs that were identified in the present study. RESULTS: The current analysis identified 198 DEPs in the coronary blood of AMI patients and SCAD patients, including 85 proteins that were significantly upregulated and 113 proteins that were significantly downregulated. GO enrichment analysis demonstrated that GDP binding and GTP binding were enriched in molecular function. Similarly, KEGG pathway enrichment analysis revealed that the identified proteins were involved in pantothenate and coenzyme A biosynthesis, starch and sucrose metabolism, and the AMPK signalling pathway. CONCLUSIONS: The proteome of coronary MPs differs between patients with AMI and patients with SCAD. In summary, the GO terms and KEGG pathways enriched by the DEPs may reflect the possible molecular mechanisms underlying the pathogenesis of acute thrombosis in patients with AMI.