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.

Reductions in extracellular vesicle-associated microRNA-126 levels in coronary blood after acute myocardial infarction: A retrospective study.

Background: Acute Myocardial Infarction (AMI) is a kind of cardiovascular disease with high mortality and incidence. Extracellular vesicles (EVs) and microRNA-126 (miR-126) are known to play important role in the development and prognosis of several cardiovascular diseases. Therefore, this study aimed to investigate the changes in Extracellular vesicle (EV)-associated miR-126 levels in the coronary blood of patients with AMI to explore the relationship between miR-126 levels and AMI. Materials and methods: We analyzed EV-associated miR-126 in the coronary blood of patients with AMI and stable coronary artery disease (SCAD) using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: We tested the coronary blood of 20 patients with AMI and 20 with SCAD. The mean age of the patients was 58.8 ± 10.3 years and 32 (80%) were men. We observed that the EV-associated miR-126 levels were lower in patients with AMI [median = 0.13; interquartile range (IQR): 0.08-0.22] than in patients with SCAD (median = 0.37; IQR: 0.26-0.48) (P < 0.001). In addition, the levels of miR-126 were negatively associated with the Thrombolysis in Myocardial Infarction (TIMI) score (r = -0.66, P = 0.001). Conclusion: Reduction of EV-associated miR-126 levels in the coronary blood of patients with AMI may be involved in acute coronary thrombosis events.

The Use of Aspirin Increases the Risk of Major Adverse Cardiac and Cerebrovascular Events in Hypertensive Patients with Obstructive Sleep Apnea for the Primary Prevention of Cardiovascular Disease: A Real-World Cohort Study.

(1) Background: Hypertensive patients with obstructive sleep apnea (OSA) are at high risk for cardiovascular diseases (CVDs), and the utility of aspirin for primary cardiovascular prevention in this population remains uncertain. (2) Methods: In this retrospective cohort study using data from the Urumchi Hypertension Database (UHDATA), hypertensive patients older than 18 years old with a first-time diagnosis of OSA were divided into three groups depending on aspirin history. Major adverse cardiac and cerebrovascular events (MACCE) were the primary outcome. Secondary outcomes included MACCE components, ischemic events, cardiac events, cerebrovascular events, and gastrointestinal bleeding risk. The inverse probability of treatment weighting (IPTW) method was used to balance the confounding factors among the groups, and the Cox proportional hazards model was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). (3) Results: In persistent aspirin users, the risk of MACCE events (HR 2.11, 95%CI 1.23-3.63), ischemic events (HR 2.58, 95%CI 1.42-4.69), cerebrovascular events (HR 2.55, 95%CI 1.44-4.51), and non-fatal cerebral infarction (HR 3.14, 95%CI 1.69-5.84) was significantly elevated. (4) Conclusions: Continuous aspirin use increases the incidence of cardiovascular adverse events in hypertensive patients with OSA receiving aspirin for primary prevention of cardiovascular disease.

Elevated body mass index increases the risk of cardiovascular events in hypertensive patients accompanied with obstructive sleep apnea: A cohort study.

BACKGROUND: Effects of body mass index (BMI) on cardiovascular events are inconsistent. We aimed to investigate the association of BMI with cardiovascular events in hypertensives with obstructive sleep apnea (OSA). METHODS: Hypertensives with OSA diagnosed with polysomnography between 2011 and 2013 in UROSAH cohort were followed up till Jan 2021. Outcomes were non-fatal cardiovascular events and cardiac death. Cox regression was used to estimate the relationship of continuous and categorical BMI with total and specific outcomes. Sensitivity analyses were performed by excluding those on OSA treatment or underweight patients. Stratified analyses were conducted by parameters including sex and age. RESULTS: 2239 hypertensives with OSA were included with 405 normal weight (BMI<25 kg/m2), 1164 overweight (25-29.9 kg/m2) and 670 obesity (≥30 kg/m2). 206 non-fatal cardiovascular events and 18 cardiac death were recorded during 6.6 years follow-up. Compared with normal weight group, overweight (HR=1.53, 95%CI: 1.01-2.32, P = 0.047) and obesity groups (1.85, 1.19-2.86, P = 0.006) showed increased risk for cardiovascular events, significant in obesity group and marginal in overweight group in fully-adjusted model. In specific events, obesity showed significantly elevated HR for non-fatal cardiovascular events (1.64, 1.04-2.60, P = 0.035). Continuous BMI showed significantly increased HR for total and specific events in all models. Sensitivity analysis yielded consistent results. In stratification analysis, stronger association between obesity and cardiovascular events was observed in the young (HR=5.97, P interaction=0.030). CONCLUSIONS: BMI is in positive association with cardiovascular events in hypertensives with OSA, emphasizing importance of maintaining healthy BMI for prevention of adverse events in this population, on the basis of guideline-recommended treatment.

Establishment and validation of a nomogram that predicts the risk of type 2 diabetes in obese patients with non-alcoholic fatty liver disease: a longitudinal observational study.

OBJECTIVE: This study aimed to establish and validate a nomogram for better assessment of the risk of type 2 diabetes (T2D) in obese patients with non-alcoholic fatty liver disease (NAFLD) based on independent predictors. METHODS: Of 1820 eligible participants from the NAGALA cohort enrolled in the study. Multivariate Cox regression was employed to construct the nomogram. The performance was assessed by area under the receiver operating characteristic curve (AUC), C-index, calibration curve, decision curve analysis, and Kaplan-Meier analysis. RESULTS: Five predictors were selected from 17 variables. The AUC values at different time points all indicated that the model constructed with these five predictors had good predictive power. Decision curves indicated that the model could be applied to clinical applications. CONCLUSIONS: We established and validated a reasonable, economical nomogram for predicting the risk of T2D in obese NAFLD patients. This simple clinical tool can help with risk stratification and thus contribute to the development of effective prevention programs against T2D in obese patients with NAFLD.

Long-term prognostic value of macrophage migration inhibitory factor in ST-segment elevation myocardial infarction patients with metabolic syndrome after percutaneous coronary intervention.

Metabolic syndrome (MetS) is a major risk factor for cardiovascular disease and negatively affecting the prognosis of patients with ST elevation myocardial infarction (STEMI). Macrophage migration inhibitory factor (MIF) is a multipotent cytokine involved in various cardiovascular and inflammatory diseases. In this prospective study, we investigate the value of MIF in the long-term prognosis of STEMI combined with MetS after emergency PCI. Circulating MIF levels were measured at admission, and major adverse cardiovascular and cerebrovascular events (MACCE) were monitored during the follow-up period of 4.9 (3.9-5.8) years. MACCE occurred in 92 patients (22.9%), which was significantly higher in MetS (69/255, 27.1%) than in the non-MS subgroup (23/146, 15.8%, P < 0.05). Patients with MetS developed MACCE had the highest admission MIF level. Kaplan-Meier survival analysis using the cutoff value of admission MIF (143 ng/ml) showed that patients with a higher MIF level had a greater incidence of MACCE than those with lower MIF levels in both the MetS (P < 0.0001) and non-MetS groups (P = 0.016). After adjustment for clinical variables, the value of MIF ≥ 143 ng/ml still had the predictive power for the MetS group [HR 9.56, 95% CI (5.397-16.944),P < 0.001]; nevertheless, it was not the case in the non-MetS group. Our findings indicated that MetS is a critical risk factor for adverse clinical outcomes in patients with STEMI, and a high admission MIF level has predictive power for the long-term MACCE, which is superior in STEMI patients with MetS and better than other traditional predictors.

Dose-response association between plasma homocysteine and white matter lesions in patients with hypertension: a case-control study.

White matter lesions (WMLs) are common MRI changes that are indicative of cerebral small vessel disease (CSVD). Elevated plasma homocysteine (Hcy) levels are related to an increased risk of vascular disease. We aimed to analyze the relationship between Hcy levels and WMLs in patients with hypertension. A total of 1961 patients with WMLs and 15,463 patients without WMLs were matched at a 1:1 ratio by age and sex. Hyperhomocysteinemia (HHcy) was defined as an abnormally high level (>15 µmol/l) of Hcy in a plasma sample. In total, 1888 (WML group) and 1888 (No-WMLs group) patients were enrolled, with 51.6% of the sample being male and a mean age of 63 years. Multivariate logistic regression analysis showed a significant association between a higher level of plasma Hcy and a higher prevalence of WMLs (OR 1.03 95% CI, 1.02-1.04) when the Hcy level was used as a continuous variable. Patients with Hcy levels of 15-20 µmol/l (OR 1.54, 95% CI 1.31-1.81) and >20 µmol/l (OR 1.51, 95% CI 1.26-1.82) also had a significantly higher risk of WMLs than patients with Hcy levels <15 µmol/l. Multivariable-adjusted spline regression models showed that the risk of WMLs started to increase only in patients with Hcy levels above 13.85 µmol/l (P < 0.001). In subgroup analyses of WMLs, there was no significant interaction between the Hcy group and subgroup heterogeneity for the prevalence of WMLs (P > 0.05). Our study found a dose-response association between plasma homocysteine levels, especially a Hcy level >13.85 µmol/l, and the prevalence of WMLs, implying that lowering Hcy levels might be a target for prevention.

Invention and Clinical Application of an Oversleeve for Measuring Limb Volume in Postoperative Breast Cancer Patients.

BACKGROUND: Lymphedema is a common complication of breast cancer treatment, affecting 1/5 of breast cancer survivors, but there is no reliable way to detect subclinical lymphedema. OBJECTIVE: The purpose of this study was to determine the feasibility and reliability of using an oversleeve as a postoperative limb volume measurement tool in breast cancer patients. METHODS: Fifty patients were analyzed based on inclusion criteria. A body volume measurement kit was designed based on the drainage volume method and the circumference measurement method. Twenty-two normal healthy people were measured by the drainage volume (LV) and oversleeve measuring limb volume (OMLV) methods, so as to verify the accuracy of OMLV. Twenty-eight patients with lymphedema diagnosed by the circumdiameter measurement (CDM) method were measured with OMLV for comparison. The difference in measurements between OMLV and CDM was compared in 50 patients with early lymphedema diagnosed by the LV method. RESULTS: There was no significant difference between the sleeve method and the drainage volume method in the normal population (P = 0.74). All patients with lymphedema diagnosed by CDM met the diagnostic criteria by the OMLV method. In patients with early lymphedema diagnosed by LV, the diagnostic rate with OMLV was significantly higher than that with CDM (P = 0.008). CONCLUSION: Similar to LV in the diagnosis of lymphedema, OMLV can effectively improve the diagnostic rate of early lymphedema, providing a new option for the diagnosis and treatment of lymphedema.

Manipulative Reduction for Abnormal Uterine Inclination in Vaginal Delivery.

OBJECTIVE: To investigate the manipulative reduction in abnormal uterine inclination in vaginal delivery. METHODS: With the independently developed uterine inclination surveyor, 40 primiparas with abnormal uterine inclination were randomly divided into two groups: treatment group (Group A, 20 cases) and control group (Group B, 20 cases). The general condition of the primipara, the labor stages, the changes in uterine inclination after treatment, postpartum hemorrhage at 2 hours, and the general condition of fetuses were observed to study the therapeutic value of manual reduction in abnormal uterine inclination. RESULT: In the control group, one uterine inclination was not corrected with the change in labor process, and the pregnancy was terminated due to stagnation of the active phase. In the first stage of labor, the time spent in the treatment group (393.4 ± 31.3 mins) was significantly lower than that in the control group (440.7 ± 34.9 mins) (P = 0.001). Compared with the control group (49.8 ± 6.5 mins), the treatment group (42.6 ± 7.2 mins) also exhibited a significantly shortened second stage of labor (P = 0.02). Sixteen cases (16/20) in the treatment group returned to normal after manual reduction, and 9 cases (9/20) in the control group returned to normal with the progression of natural labor. Manual reduction could be used as an option to treat abnormal uterine inclination (P = 0.01). There was no significant difference in the third stage of labor (P = 0.2), 2-hour postpartum hemorrhage (P = 0.35), Apgar score (P = 0.64), or body weight (P = 0.76) between the two groups. CONCLUSION: Manual reduction in the treatment of abnormal uterine inclination has obvious effects, shortens the birth process, and is safe for the fetus.

Zinc Finger Protein 24 is a Prognostic Factor in Ovarian Serous Carcinoma.

OBJECTIVE: As a member of the zinc finger protein family, zinc finger protein 24 (ZNF24) contains a Cys2His2 zinc finger domain and acts as a transcription factor. ZNF24 has been reported to be downregulated in gastric cancer and breast cancer. However, little is known about its expression and function in ovarian serous carcinoma (OSC). PATIENTS AND METHODS: We collected 117 OSC patients during 2011 to 2017 and retrospectively retrieved their clinicopathologic characteristics as well as their survival data. Protein level was analyzed by immunohistochemistry, mRNA level was evaluated by RT-qPCR assay, and transcriptional data was obtained from TCGA data sets. The correlations between ZNF24 expression and patients' features were assessed using χ2 test. Univariate and multivariate analyses were used to identify the prognosis predicative potential of ZNF24 in OSC. The function of ZNF24 in the epithelial ovarian cancer cells was also verified by in vitro cellular experiments. RESULTS: Among the 117 cases, ZNF24 was downregulated in 52 OSC samples (44.6%) and significantly correlated with tumor stages. According to univariate and multivariate analyses, ZNF24 can act as an independent prognostic indicator for the overall survival of OSC patients, whose lower expression was associated with poorer clinical outcomes. Ectopic overexpression and knockdown assays indicated that ZNF24 can negatively regulate the OSC cell viability. CONCLUSIONS: OSC patients with low level of ZNF24 have worse overall survival compared with those possess high-ZNF24 expression. Downregulated ZNF24 may be involved in the proliferation of OSC, and ZNF24 expression can serve as an independent survival predictor.

Plasma aldosterone concentration is associated with white matter lesions in patients with primary aldosteronism.

PURPOSE: Primary aldosteronism (PA) is the most frequent form of secondary hypertension. Hypertension is a risk factor for cognitive decline and dementia. White matter lesions (WMLs) are linked to vascular risk factors, which increase the risk of dementia. We aimed to analyze the association of PA-related parameters and WMLs in patients with PA. METHODS: We conducted a retrospective analysis of all patients with PA in the Hypertension Center of the People's Hospital of Xinjiang Uygur Autonomous Region from January 1, 2011 to April 1, 2021. We analyzed the relationship between plasma aldosterone concentration (PAC), plasma renin activity (PRA), aldosterone-renin ratio (ARR), serum potassium, and WMLs. RESULTS: We enrolled 138 patients with WMLs and matched these to controls without WMLs at a 1:4 ratio. Among the analytic sample (N = 711) with ages ranging from 30 to 64 years, 69% were male. In the logistic regression analysis, PAC, PRA and serum potassium were treated as continuous variables. The results showed that PAC (OR 1.04, 95% CI 1.01, 1.06, P = 0.008) was positively associated with the risk of WMLs, and serum potassium (OR 0.26, 95% CI 0.16, 0.44, P < 0.001) was inversely associated with the risk of WMLs. PRA (OR 0.86, 95% CI 0.68, 1.08, P = 0.384) was not associated with the risk of WMLs after adjusting for confounders. The results of restricted cubic splines showed the dose-response association between increasing PAC, ARR, decreasing serum potassium, and the risk of WMLs. We also divided PAC, ARR and serum potassium into two groups according to the result of restricted cubic splines. After adjusting for confounders, patients who were in Q2 (≥23.12 ng/dl) of PAC (OR 2.07, 95% CI 1.36, 3.15), Q2 (≥56.81 (ng/dl per ng/ml*h) of ARR (OR 1.82, 95% CI 1.22, 2.72) and Q2 (≤3.58 mmol/l) of serum potassium (OR 2.99, 95% CI 1.95, 4.50) had a significantly higher risk of WMLs than their counterparts. In stratified analyses, there was no evidence of subgroup heterogeneity regarding the change in the risk of WMLs (P > 0.05 for interaction for all). CONCLUSION: Our results suggested that the PAC and serum potassium were related to the risk of WMLs in patients with PA. In particular, PAC ≥23.12 ng/dl significantly increased the risk of WMLs in patients with PA.

Positive Association Between Plasma Aldosterone Concentration and White Matter Lesions in Patients With Hypertension.

Background and Objective: White matter lesions (WMLs) are imaging changes in MRI of cerebral small vessel disease associated with vascular risk factors, increasing the risk of dementia, depression, and stroke. Aldosterone (ALD) or activation of mineralocorticoid receptor (MR) causes cerebrovascular injury in a mouse model. We aimed to analyze the relationship between ALD and WMLs in a population with hypertension. Methods: We conducted a retrospective review of all patients screened for causes of secondary hypertension. We enrolled 547 patients with WMLs and matched these to controls without WMLs at a 1:1 ratio. White matter lesion load was assessed by using a modified Scheltens' scale. Results: Among the analytic sample (N = 1,094) with ages ranging from 30 to 64 years, 62.2% were male. We divided plasma ALD concentration (PAC), plasma renin activity (PRA), and ALD-renin ratio (ARR) into the third tertile (Q3), second tertile (Q2), and first tertile (Q1). We also analyzed them simultaneously as continuous variables. Multivariate logistic regression analysis showed that participants in Q3 (>17.26 ng/dl) of PAC (OR 1.59, 95% CI 1.15, 2.19), Q3 (<0.80 ng/dl) of PRA (OR 2.50, 95% CI 1.81, 3.44), and Q3 (>18.59 ng/dl per ng/ml*h) of ARR (OR 2.90, 95% CI 2.10, 4.01) had a significantly higher risk of WMLs than those in Q1 (<12.48) of PAC, Q1 (>2.19) of PRA, and Q1 (<6.96) of ARR. In linear regression analysis, we separately analyzed the correlation between the modified Scheltens' scale score and log(PAC) (ß = 2.36; 95% CI 1.30, 3.41; p < 0.001), log(PRA) (ß = -1.76; 95% CI -2.09, -1.43; p < 0.001), and log(ARR) (ß = 1.86; 95% CI 1.55, 2.17; p < 0.001), which were all significantly correlated with white matter lesion load, after adjusting for confounding factors. Simple mediation analyses showed that systolic blood pressure (SBP) or diastolic blood pressure (DBP) mediated -3.83% or -2.66% of the association between PAC and white matter lesion load, respectively. In stratified analyses, there was no evidence of subgroup heterogeneity concerning the change in the risk of WMLs (p > 0.05 for interaction for all). Conclusion: Higher PAC, especially in PAC >17.26 ng/dl, increased the risk of WMLs. PAC was positively associated with white matter lesion load independent of SBP or DBP.

Poor sleep quality is associated with new-onset hypertension in a diverse young and middle-aged population.

BACKGROUND: Sleep disorders have been proposed as the potential risk factors for hypertension, thus we aimed to investigate the association of sleep quality with new-onset hypertension. METHODS: We evaluated sleep quality using Pittsburgh Sleep Quality Index (PSQI) and it's seven components in normotensive population aged 18 years old and over in Emin Xinjiang, China in 2016 and followed up till 2019 using annual health checkup data. Poor sleep quality was defined as a PSQI score>5, and good sleep quality was defined as a PSQI score⩽5. RESULTS: Among 9344 analytic sample 57.29% were female. A total of 2958 (31.66%) subjects developed hypertension during 22,960 person-years of follow-up. Poor sleep quality (HR 1.131, 95% CI 1.045, 1.224) showed had higher risk of development hypertension in total population in adjusted Cox models. Fairly bad subjective sleep quality (HR 1.148, 95% CI 1.015, 1.298), habitual sleep efficiency of <65%-75% group (HR 1.174, 95% CI 1.026, 1.344), and mild (HR 1.194, 95% CI 1.098, 1.299) and moderate (HR 1.264, 95% CI 1.080, 1.479) sleep disturbance increased the risk of developing hypertension compared to their counterparts. In age stratification, poor sleep quality (HR 1.100, 95% CI 1.007, 1.202) had higher risk of developing hypertension in the young and middle-aged population after adjusted all covariates. CONCLUSIONS: Poor sleep quality is associated with higher risk of new-onset hypertension in young and middle-aged population.