Tissue-resident C1q + macrophages exert anti-aging potential through the Sirt1 pathway.

OBJECTIVE: Resident immune cells are at the forefront of sensory organ-specific signals, and changes in these cells are closely related to the aging process. The Sirt pathway can regulate NAD + metabolism during aging, thereby affecting the accumulation of ROS. However, the role of the Sirt pathway in resident immune cells in aged tissues is currently unclear. METHODS: We investigated Sirt1 signalling in resident immune cells during chronic inflammation in an aged mouse model. Integrated single-cell RNA sequencing data from young and aged mice were used to refine the characterization of immune cells in aged tissues RESULTS: We found that C1q + macrophages could affect chronic inflammation during aging. C1q + macrophages acted in an opposing manner to Il1b + macrophages and were responsible for anti-inflammatory effects during aging. Sirt1 agonists inhibited the decrease in C1qb in macrophages during aging, and anti-aging drugs could affect the expression of C1qb in macrophages via the Sirt1 pathway. CONCLUSIONS: In this study, we first identified the relevance of C1q + macrophages in chronic inflammation during aging. The potential anti-aging effect of C1q + macrophages was mediated by the Sirt1 pathway, suggesting new strategies for aging immunotherapy.

Association between bilirubin and chronic kidney disease in hypertensive patients: The China hypertension registry study.

Limited data exists on the association between Direct bilirubin (DBIL) and Indirect bilirubin (IBIL) with the risk of chronic kidney disease (CKD) among patients with hypertension. This study aimed to assess the relationship between DBIL and IBIL with the risk of CKD in a cohort of Chinese adults diagnosed with hypertension. This study included 14 182 Chinese patients with hypertension between the ages of 27 and 96. CKD, the outcome variable, was defined by an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 . The study employed multivariate linear and multivariate logistic regression analysis to evaluate the correlation between DBIL and IBIL with the risk of CKD. The prevalence of CKD in the study population was 9.77%. Multivariate logistic regression analysis showed that the increase in DBIL (OR: 0.66; 95% CI: 0.61, 0.71) and IBIL (OR: 0.75; 95% CI: 0.71, 0.81) were independently and negatively correlated with CKD. Further analyses using a restricted cubic spline (smooth-fitting curve) confirmed the linearly negative association between DBIL and IBIL with the risk of CKD. The subgroup analysis showed that the correlation between IBIL and CKD was stronger among men and populations <65 years of age (p for interaction <.05). DBIL and IBIL were independently and negatively associated with CKD. Furthermore, the correlation between DBIL and IBIL with CKD in the hypertensive population is more significant in those under 65 years of age. These findings may inform future strategies for the management of CKD.

[Associations Between Insulin Resistance Indexes and Hyperuricemia in Hypertensive Population].

Objective To explore the relationship between insulin resistance (IR) indexes and hyperuricemia (HUA) among the people with hypertension. Methods From July to August in 2018,hypertension screening was carried out in Wuyuan county,Jiangxi province,and the data were collected through questionnaire survey,physical measurement,and biochemical test.Logistic regression was performed to analyze the relationship between HUA and IR indexes including metabolic score for IR (METS-IR),triglyceride-glucose (TyG) index,TyG-body mass index (BMI),TyG-waist circumference (WC),visceral adiposity index (VAI),triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C),and lipid accumulation product (LAP).The penalty spline method was used for the curve fitting between IR indexes and HUA.The area under the receiver operating characteristic curve (AUC) was employed to reveal the correlation between each index and HUA. Results The 14 220 hypertension patients included 6 713 males and 7 507 females,with the average age of (63.8±9.4) years old,the average uric acid level of (418.9±120.6) mmol/L,and the HUA detection rate of 44.4%.The HUA group had higher proportions of males,current drinking,current smoking,diabetes,and using antihypertensive drugs,older age,higher diastolic blood pressure,WC,BMI,homocysteine,total cholesterol,TG,low-density lipoprotein cholesterol,blood urea nitrogen,creatinine,aspartate aminotransferase,alanine aminotransferase,total protein,albumin,total bilirubin,direct bilirubin, METS-IR, TyG, TyG-BMI, TyG-WC, VAI, TG/HDL-C, and LAP, and lower systolic blood pressure and HDL-C than the normal uric acid group (all P<0.05).Multivariate Logistic regression showed that METS-IR (OR=1.049,95%CI=1.038-1.060, P<0.001), TyG (OR=1.639,95%CI=1.496-1.797, P<0.001), TyG-BMI (OR=1.008,95%CI=1.006-1.010, P<0.001), TyG-WC (OR=1.003,95%CI=1.002-1.004, P<0.001), lnVAI (OR=1.850, 95%CI=1.735-1.973, P<0.001), ln(TG/HDL-C) (OR=1.862,95%CI=1.692-2.048, P<0.001),and lnLAP (OR=1.503,95%CI=1.401-1.613,P<0.001) were associated with the risk of HUA.Curve fitting indicated that METS-IR,TyG,TYG-BMI,TYG-WC,lnVAI,ln(TG/HDL-C),and lnLAP were positively correlated with HUA (all P<0.001),and the AUC of TyG index was higher than that of other IR indexes (all P<0.05). Conclusion Increased IR indexes,especially TyG,were associated with the risk of HUA among people with hypertension.

Associations of combined lifestyle behaviors with all-cause and cardiovascular mortality in adults: A population-based cohort study in Jiangxi Province of China.

Background: Data are limited on the impact of combined lifestyle behaviors on mortality in Jiangxi Province, China. Objective: The study examined the association between combined lifestyle behaviors and all-cause and cardiovascular disease (CVD) mortality in Jiangxi province. Methods: The baseline survey was completed in Jiangxi Province from November 2013 to August 2014. We conducted a follow-up on 12,608 participants of 35 years of age or older from July 2019 to October 2020. Four known lifestyle behaviors were evaluated: alcohol consumption, smoking, diet (AHEI scores), and physical activity. Cox regression analysis was performed to determine the association of combined lifestyle behaviors with all-cause and CVD mortality. Results: During 65,083 person-years of follow-up, among the 11,622 participants (mean age 59.1 years; 40.1% men) 794 deaths occurred, including 375 deaths from CVD disease in this study. Compared to the favorable lifestyle group, the adjusted HR of all-cause mortality was 1.25 (95% CI, 1.03-1.53) for the intermediate lifestyle group and 1.37 (95% CI, 1.11-1.71) for the unfavorable lifestyle group. Compared to the favorable lifestyle group, the adjusted HR of CVD mortality was 1.50 (95% CI, 1.11-2.03) for the intermediate lifestyle group and 1.58 (95% CI, 1.14-2.20) for the unfavorable lifestyle group. Significant interactions of lifestyle and BMI (P for interaction <0.05) with the risk of all-cause mortality and CVD mortality were observed. Conclusion: In the current study, we reaffirm the associations of combined lifestyle factors with total and CVD mortality in Jiangxi Province, our data suggest that an unfavorable lifestyle was associated with a substantially increased risk of all-cause and CVD mortality.

Associations among vitamin D, tobacco smoke, and hypertension: A cross-sectional study of the NHANES 2001-2016.

The interrelationships among vitamin D, tobacco smoking, and hypertension are currently unknown. This study was conducted to determine the relationship between vitamin D levels and hypertension and the effect of tobacco smoke exposure levels on this relationship among US adults. We performed a cross-sectional analysis of adult participants from the 2001-2016 National Health and Nutrition Examination Survey (NHANES). Serum 25-hydroxyvitamin D concentration was used as a biomarker of vitamin D status, and tobacco smoke exposure levels were objectively evaluated by serum cotinine levels. Among 22,875 eligible adults who were not receiving antihypertensive medications, the prevalence of hypertension, vitamin D deficiency (<50 mmol/L), and cotinine ≥3 ng/mL was 13.9%, 34.9%, and 29.4%, respectively. Serum cotinine and vitamin D levels were independently associated with hypertension risk after controlling for confounders (P < 0.05). When stratified by the cotinine group (<0.05, 0.05-3 and ≥3 ng/mL), we found that the risk of hypertension associated with vitamin D deficiency was higher among subjects with cotinine levels ≥3 ng/mL compared with the other strata [OR (95% CI) 1.30 (1.09, 1.54) vs. 1.53 (1.19, 1.96) vs. 1.64 (1.30, 2.06); P for heterogeneity test <0.05]. Furthermore, serum cotinine levels were negatively correlated with vitamin D levels. These findings suggested that the increased risk of hypertension could be partly attributed to low vitamin D levels induced by tobacco smoke exposure, in addition to the effects of tobacco smoke exposure and vitamin D deficiency themselves.

Homozygous familial hypercholesterolemia in China: Genetic and clinical characteristics from a real-world, multi-center, cohort study.

BACKGROUND: There is a lack of large-scale data on the clinical and genotype characteristics of homozygous familial hypercholesterolemia (HoFH) patients in Asia. OBJECTIVE: To define the characteristics of phenotypic and genetic HoFH probands from mainland China. METHODS: We collected data from patients with suspected HoFH from ten clinical hospitals across mainland China from 2003 to 2019. Clinical data and DNA testing were obtained in all patients. The Kaplan-Meier method was used to generate survival curves, and the groups were compared with the log-rank test. RESULTS: A total of 108 unrelated probands with suspected HoFH (mean age 14.9 years) were included. The three most common variants were W483X (c.1448 G>A), A627T (c.1879 G>A), H583Y (c.1747 C>T). The majority (64.8%) were compound heterozygotes (n = 70), 23 (21.3%) were true HoFH patients. True HoFH showed higher LDL-C levels compared to compound HoFH (16.8±3.6 mmol/L vs. 15.0±3.1 mmol/L, P = 0.022). During follow-up, only 21.2% patients exhibited an LDL-C reduction of more than 50%. Kaplan-Meier analysis showed that the true HoFH probands had significantly worse survival rates compared to other genotype probands (13-year survival; 20.3% vs. 76.7%, respectively; P = 0.016). In addition, true HoFH shows that 2.8-fold (P = 0.022) increase any death and 3.0-fold (P = 0.023) increase cardiovascular death risk in relative to other FH. CONCLUSIONS: This report shows that HoFH has devastating consequences, and that patients are often only diagnosed after they have been exposed to severely elevated LDL-C for years. Systematic screening and early intensive treatment are an absolute requirement for these young individuals with HoFH.

Association of weight-adjusted-waist index with all-cause and cardiovascular mortality in China: A prospective cohort study.

BACKGROUND AND AIMS: As a new simple anthropometric index, the weight-adjusted-waist index (WWI) appears to be superior to body mass index (BMI) and waist circumference (WC) in assessing both muscle and fat mass. We aimed to explore the association of WWI with all-cause and cardiovascular mortality in southern China. METHODS AND RESULTS: A total of 12,447 participants (mean age, 59.0 ± 13.3 years; 40.6% men) in Jiangxi Province from the China Hypertension Survey study were included. WWI was defined as WC divided by the square root of weight. The outcome was all-cause and cardiovascular mortality. During a median follow-up of 5.6 years, 838 all-cause deaths occurred, with 390 cardiovascular deaths. Overall, there was a nonlinear positive relationship of WWI with all-cause and cardiovascular mortality. Accordingly, compared with participants in quartiles 1-3 (<11.2 cm/√kg), a significant higher risk of all-cause mortality (HR: 1.36, 95% CI: 1.17, 1.58) and cardiovascular mortality (HR: 1.43, 95% CI: 1.15, 1.77) were found in quartile 4 (≥11.2 cm/√kg). Further adjustment for BMI and WC did not substantially alter the results. No significant interactions were found in any of the subgroups (sex, age, area, physical activity, current smoking, current alcohol drinking, hypertension, and stroke). CONCLUSION: Higher WWI levels (≥11.2 cm/√kg) were associated with increased the risk of all-cause and cardiovascular mortality in southern China. These findings, if confirmed by further studies, suggested that WWI may serve as a simple and effective anthropometric index in clinical practice.

Association between serum folate levels and blood concentrations of cadmium and lead in US adults.

BACKGROUND: Folate may be involved in the detoxification of heavy metals. This has been demonstrated in animal studies, in in vivo and in vitro studies, and clinical evaluations. However, knowledge regarding the associations between serum folate and blood concentrations of cadmium and lead is limited. OBJECTIVE: We aimed to investigate the relationship between serum folate levels and blood concentrations of cadmium and lead in US adults. METHODS: Data on 15,501 adults were obtained from the 1999-2006 National Health and Nutrition Examination Survey (NHANES) and used for the analysis. Information on serum folate concentrations and blood levels of lead and cadmium was derived from laboratory measurements in the NHANES. Multivariable linear regression was used to examine the relationship between serum folate levels and blood concentrations of cadmium and lead in US adults, controlling for confounders. RESULTS: The serum folate concentration was negatively correlated with blood levels of cadmium and lead (P-trends <0.01). When stratified by sex (male and female) and estimated glomerular filtration rate (eGFR ≤60 and >60 mL/min/1.73 m2), the association between serum folate concentrations and blood levels of cadmium and lead was found to be more stable in adults with eGFR > 60 mL/min/1.73 m2, both in males and females. SIGNIFICANCE: These findings warrant future studies to explore the mechanisms responsible for the beneficial role of folate in regulating cadmium and lead concentrations in the blood.

Disparities in Secondary Prevention between Stroke and Coronary Heart Disease in China: Cross-Sectional Community-Based Study, 2014-2016.

BACKGROUND: Health care quality and insurance coverage have improved with economic development in China, but the burden of cardiovascular diseases (CVDs) continues to increase with ongoing gaps in prevention. We aimed to compare the uptake of secondary CVD prevention between stroke and coronary heart disease (CHD) patients in China. METHODS: In a cross-sectional community-based survey of 47,841 adults (age ≥45 years) in 7 regions of China between 2014 and 2016, we identified those with a history of stroke or CHD to quantify disparities in conventional secondary CVD prevention strategies in multivariable logistic regression models. RESULTS: There were 4,105 and 1,022 participants with a history of stroke and CHD, respectively. Compared to participants with CHD, those with a history of stroke were significantly less likely to be taking blood-pressure-lowering (39.7% vs. 53%), lipid-lowering (13.7% vs. 36.8%), and antiplatelet (20.8% vs. 50.6%) agents, at least one (48.9% vs. 70.8%) or all 3 recommended medicines (6.1% vs. 24.0%), and were less likely to achieve a lipid-cholesterol target (30.3% vs. 44.0%). Participants with a history of stroke achieved less optimal secondary prevention goals for medication use, either from any (adjusted odds ratio [aOR] 0.54, 95% confidence interval [CI] 0.44-0.66) or all 3 medications (aOR 0.27, 95% CI 0.20-0.36), as well as better blood pressure (aOR 0.81, 95% CI 0.66-0.98) and low-density lipoprotein cholesterol (aOR 0.34, 95% CI 0.27-0.43) levels of control. There were no significant differences in weight, smoking, or physical activity between the groups. CONCLUSION: Stroke patients had lower use of secondary CVD-preventive medication and achieved lower levels of risk factor control than those of CHD patients in China. Nationwide disease-specific strategies, and better education of participants and health care providers, may narrow these gaps.

Hsp22 ameliorates lipopolysaccharide-induced myocardial injury by inhibiting inflammation, oxidative stress, and apoptosis.

Sepsis-induced myocardial dysfunction (SIMD) is ubiquitous in septic shock patients and is associated with high morbidity and mortality rates. Heat shock protein 22 (Hsp22), which belongs to the small HSP family of proteins, is involved in several biological functions. However, the function of Hsp22 in lipopolysaccharide (LPS)-induced myocardial injury is not yet established. This study was aimed at investigating the underlying mechanistic aspects of Hsp22 in myocardial injury induced by LPS. In this study, following the random assignment of male C57BL/6 mice into control, LPS-treated, and LPS + Hsp22 treated groups, relevant echocardiograms and staining were performed to scrutinize the cardiac pathology. Plausible mechanisms were proposed based on the findings of the enzyme-linked immunosorbent assay and Western blotting assay. A protective role of Hsp22 against LPS-induced myocardial injury emerged, as evidenced from decreased levels of creatinine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and enhanced cardiac function. The post-LPS administration-caused spike in inflammatory cytokines (IL-1ß, IL-6, TNF-α and NLRP3) was attenuated by the Hsp22 pre-treatment. In addition, superoxide dismutase (SOD) activity and B-cell lymphoma-2 (Bcl2) levels were augmented by Hsp22 treatment resulting in lowering of LPS-induced oxidative stress and cardiomyocyte apoptosis. In summary, the suppression of LPS-induced myocardial injury by Hsp22 overexpression via targeting of inflammation, oxidative stress, and apoptosis in cardiomyocytes paves the way for this protein to be employed in the therapy of SIMD.

Knockdown of transient receptor potential melastatin 2 reduces renal fibrosis and inflammation by blocking transforming growth factor-ß1-activated JNK1 activation in diabetic mice.

BACKGROUND: Diabetic nephropathy is a major complication of diabetes. We explore the protective effect of TRPM2 knockdown on the progression of diabetic nephropathy. METHODS: A type 2 diabetes animal model was established in C57BL/6N mice by long-term high-fat diet (HFD) feeding combined with a single injection of 100 mg/kg streptozotocin (STZ). Genetic knockdown of TRPM2 in mouse kidneys was accomplished by the intravenous injection via the tail vein of adeno-associated virus type 2 carrying TRPM2 shRNA. RESULTS: Mice with HFD/STZ-induced diabetes exhibited kidney dysfunction, as demonstrated by increased blood creatinine and urea nitrogen levels, accompanied by glomerulus derangement, tubule damage and extracellular matrix deposition in the interstitium. The protein expression of TRPM2, transforming growth factor-ß1 (TGF-ß1), connective tissue growth factor, α-smooth muscles actin, fibronectin, collagen I and collagen III, and the mRNA expression and contents of inflammatory factors, including interleukin-1ß, interleukin-6, interferon-α, tumour necrosis factor -α and monocyte chemotactic protein -1, were significantly elevated in the renal tissues of the HFD/STZ-induced diabetes group compared to those of the two control groups. Furthermore, fluorescent staining of TRPM2 was markedly increased in the renal tubular epithelial cells from diabetic mice. Knockdown of TRPM2 significantly attenuated HFD/STZ-induced renal inflammatory responses and fibrosis, which was accompanied by activation of TGF-ß1-activated c-Jun N-terminal protein kinase-1 (JNK1) signalling. JNK1 inactivation reversed hyperglycaemia-induced fibrosis and inflammation in HK-2 cells. CONCLUSION: TRPM2 silencing significantly attenuated fibrosis and inflammation in the kidneys of mice with HFD/STZ-induced diabetes, which was largely achieved via the inhibition of TGF-ß1-activated JNK1 activation.

Pim-2 kinase inhibits inflammation by suppressing the mTORC1 pathway in atherosclerosis.

BACKGROUND: Inflammatory immunity theory has raised considerable concern in the pathogenesis of atherosclerosis. Proviral integration site of murine 2 (Pim-2) kinases functions in apoptosis pathways and the anti-inflammatory response. Here, we investigated whether Pim-2 kinase inhibits atherosclerotic inflammation by suppressing the mTORC1 pathway. METHODS: An atherosclerosis animal model was established by feeding ApoE -/- mice a high-fat diet. THP-1-derived macrophages were subjected to ox-LDL (50 µg/ml, 24h) conditions in vitro to mimic the in vivo conditions. RESULT: The protein expression of Pim-2 was upregulated in ox-LDL-treated THP-1-derived macrophages and an atherosclerotic mouse model. Additionally, ox-LDL upregulated the protein expression of p-mTOR, p-S6K1 and p-4EBP1, intracellular lipid droplets, free cholesterol and cholesterylester and the mRNA expression of inflammatory cytokines, including IL-6, MCP-1, TLR-4 and TNF-α, in THP-1-derived macrophages. Functionally, overexpressed Pim-2 (Pim-2 OE) attenuated atherosclerotic inflammation associated with the mTORC1 signaling pathway in vitro and in vivo, whereas knocked down Pim-2 (Pim-2 KD) markedly promoted atherosclerotic inflammation associated with upregulation of the mTORC1 signaling pathway. The plaque areas and lesions in the whole aorta and aortic root sections were alleviated in ApoE -/- mice with Pim-2 OE, but aggravated by Pim-2 KD. Additionally, an mTOR agonist (MHY1485) counteracted the anti-inflammatory effect of Pim-2 in ox-LDL-treated THP-1-derived macrophages after Pim-2 OE, whereas rapamycin rescued atherosclerotic inflammation in ox-LDL-treated THP-1-derived macrophages after Pim-2 KD. Furthermore, si-mTOR and si-Raptor alleviated the atherosclerotic proinflammatory effect in ox-LDL-treated THP-1-derived macrophages in a the background of Pim-2 KD. CONCLUSIONS: These results indicated that Pim-2 kinase inhibits atherosclerotic inflammation by suppressing the mTORC1 pathway.

De-ubiquitination of p300 by USP12 Critically Enhances METTL3 Expression and Ang II-induced cardiac hypertrophy.

Stresses, such as neurohumoral activation, induced pathological cardiac hypertrophy is the main risk factor for heart failure. The ubiquitin-proteasome system (UPS) plays a key role in maintaining protein homeostasis and cardiac function. However, research on the role and mechanism of deubiquitinating enzymes (DUBs) in cardiac hypertrophy is limited. Here, we observe that the deubiquitinating enzyme ubiquitin-specific protease 12(USP12) is upregulated in Ang II-induced hypertrophic hearts and primary neonatal rat cardiomyocytes (NRCMs). Inhibition of USP12 ameliorate Ang II-induced myocardial hypertrophy, while overexpression of USP12 have the opposite effect. USP12 deficiency also significantly attenuate the phenotype of Ang II-induced cardiac hypertrophy in vivo. Moreover, we demonstrate that USP12 aggravate Ang II-induced cardiac hypertrophy by enhancing METTL3, a methyltransferase which catalyze N6-methyladenosine (m6A) modification on messenger RNA and acts as a harmful factor in pathological cardiac hypertrophy. Upregulation of METTL3 reverse the reduction of myocardial hypertrophy induced by USP12 silencing in NRCMs. In contrast, knockdown of METTL3 attenuate the aggravation of myocardial hypertrophy in USP12-overexpressing NRCMs. Furthermore, we discover that USP12 promote the expression of METTL3 via upregulating p300. Mechanistically, USP12 binds and stabilizes p300, thereby activating the transcription of its downstream gene METTL3. Finally, our data show that USP12 is partially dependent on the stabilization of p300 to activate METTL3 expression and promote myocardial hypertrophy. Taken together, our results demonstrate that USP12 acts as a pro-hypertrophic deubiquitinating enzyme via enhancing p300/METTL3 axis, indicating that targeting USP12 could be a potential treatment strategy for pathological cardiac hypertrophy.

A Review of Novel Cardiac Biomarkers in Acute or Chronic Cardiovascular Diseases: The Role of Soluble ST2 (sST2), Lipoprotein-Associated Phospholipase A2 (Lp-PLA2), Myeloperoxidase (MPO), and Procalcitonin (PCT).

While the received traditional predictors are still the mainstay in the diagnosis and prognosis of CVD events, increasing studies have focused on exploring the ancillary effect of biomarkers for the aspiring of precision. Under which circumstances, soluble ST2 (sST2), lipoprotein-associated phospholipase A2 (Lp-PLA2), myeloperoxidase (MPO), and procalcitonin (PCT) have recently emerged as promising markers in the field of both acute and chronic cardiovascular diseases. Existent clinical studies have demonstrated the significant associations between these markers with various CVD outcomes, which further verified the potentiality of markers in helping risk stratification and diagnostic and therapeutic work-up of patients. The current review article is aimed at illuminating the applicability of these four novels and often neglected cardiac biomarkers in common clinical scenarios, including acute myocardial infarction, acute heart failure, and chronic heart failure, especially in the emergency department. By thorough classification, combination, and discussion of biomarkers with clinical and instrumental evaluation, we hope the current study can provide insights into biomarkers and draw more attention to their importance.

Visceral Adiposity Index Is Inversely Associated with Renal Function in Normal-Weight Adults with Hypertension: The China H-Type Hypertension Registry Study.

BACKGROUND: Risk of chronic kidney disease (CKD) is higher in normal-weight metabolically unhealthy people, especially when combined with hypertension. In this context, whether the visceral adiposity index (VAI), which reflects body fat distribution and metabolism, can be used to identify the risk of CKD among normal-weight hypertensive patients is unclear. OBJECTIVES: This study aimed to evaluate the association between VAI and renal function in normal-weight hypertensive patients. METHODS: In this cross-sectional study, 8591 hypertensive patients with normal BMI from the China H-type Hypertension Registry Study were analyzed. The VAI was calculated with serum triglycerides, serum HDL cholesterol, waist circumference, and BMI. VAI was ln-transformed for analysis on account of the skewed distribution. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epidemiology Collaboration equation. CKD was defined as an eGFR <60 mL · min-1 · 1.73 m-2. Multivariable linear and multivariable logistic regression analyses were performed to evaluate the association of VAI with eGFR and CKD. RESULTS: The prevalence rate of CKD was 10.1%. Multivariable linear regression analyses showed that an elevated lnVAI reduced eGFR by 2.63 mL · min-1 · 1.73 m-2 (95% CI: -3.54, -1.72 mL · min-1 · 1.73 m-2). Multivariable logistic regression analysis showed that an elevated lnVAI was independently associated with the prevalence of CKD (OR: 1.59; 95% CI: 1.31, 1.93). As possible confounding factors were removed the association became greater. The higher the VAI was, the greater the decrease in eGFR and the higher the risk of CKD. No significant interactions were found in any of the subgroups (age, sex, physical activity, current smoking, current drinking, fasting glucose, LDL cholesterol, blood pressure, and antihypertensive drugs). CONCLUSIONS: VAI, as a simple surrogate measure of visceral fat accumulation, is independently and inversely associated with renal function in normal-weight Chinese hypertensive adults.This trial was registered at chictr.org.cn as ChiCTR1800017274.

Potential Target Genes in the Development of Atrial Fibrillation: A Comprehensive Bioinformatics Analysis.

BACKGROUND Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide. Although it is not life-threatening, the accompanying rapid and irregular ventricular rate can lead to hemodynamic deterioration and obvious symptoms, especially the risk of cerebrovascular embolism. Our study aimed to identify novel and promising genes that could explain the underlying mechanism of AF development. MATERIAL AND METHODS Expression profiles GSE41177, GSE79768, and GSE14975 were acquired from the Gene Expression Omnibus Database. R software was used for identifying differentially expressed genes (DEGs), and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were subsequently performed. A protein-protein interaction network was constructed in Cytoscape software. Next, a least absolute shrinkage and selection operator (LASSO) model was constructed and receiver-operating characteristic curve analysis was conducted to assess the specificity and sensitivity of the key genes. RESULTS We obtained 204 DEGs from the datasets. The DEGs were mostly involved in immune response and cell communication. The primary pathways of the DEGs were related to the course or maintenance of autoimmune and chronic inflammatory diseases. The top 20 hub genes (high scores in cytoHubba) were selected in the PPI network. Finally, we identified 6 key genes (FCGR3B, CLEC10A, FPR2, IGSF6, S100A9, and S100A12) via the LASSO model. CONCLUSIONS We present 6 target genes that are potentially involved in the molecular mechanisms of AF development. In addition, these genes are likely to serve as potential therapeutic targets.

Saturation Effects of Plasma Homocysteine on Chronic Kidney Disease in Chinese Adults With H-type Hypertension: A Cross-sectional Study.

OBJECTIVE: Data on the association between homocysteine (Hcy) and the risk of chronic kidney disease (CKD) in patients with H-type hypertension were limited. This study aimed to examine the relation of Hcy with the prevalence of CKD and estimated glomerular filtration rate (eGFR) among Chinese adults with H-type hypertension. METHODS: A total of 12,873 Chinese adults with H-type hypertension aged 27-75 years were enrolled in the final analysis. Hcy concentrations were divided into 11 groups at 2 µmol/L interval. The outcome was CKD, defined as eGFR <60 mL/min/1.73 m2. RESULTS: The prevalence of CKD was 7.58%, and the mean Hcy was 17.58 ± 10.96 µmol/L. The smoothing curve indicated that with the increase of Hcy, the prevalence of CKD increases first and then flattens, eGFR decreases first and then flattens, which supports the L-shaped association of Hcy with the prevalence of CKD and eGFR. Moreover, we further found the inflection point of Hcy was 22 µmol/L. OR (95% CI) of risk of CKD was 1.31 (1.28, 1.35) on the left side of an inflection point and 1.00 (0.99, 1.01) on the right of an inflection point, ß (95% CI) of eGFR was -1.58 (-1.65, -1.50) on the left side of an inflection point and 0.00 (-0.03, 0.03) on the right of an inflection point, respectively. Similar results were found in various subgroups. CONCLUSIONS: Our study suggested saturation effects of Hcy on the prevalence of CKD and eGFR among Chinese patients with H-type hypertension.

Nonlinear association between blood lead and hyperhomocysteinemia among adults in the United States.

Evidence regarding the association between blood lead levels (BLL) and hyperhomocysteinemia (HHcy) in US adults was limited. We aimed to investigate the association of BLL with the risk of HHcy, and to examine possible effect modifiers using US National Health and Nutrition Examination Survey (NHANES) database. We performed a cross-sectional study using data from up to 9,331 participants aged ≥ 20 years of NHANES from 2001 to 2006. BLL was measured by atomic absorption spectrometry. HHcy was defined as plasma homocysteine level > 15 µmol/L. The weighted prevalence of HHcy was 6.87%. The overall mean BLL was 1.9 µg/dL. Overall, there was a nonlinear positive association between Ln-transformed BLL (LnBLL) and the risk of HHcy. The Odds ratios (95% CI) for participants in the second (0.04-0.49 µg/dL), third (0.5-0.95 µg/dL) and fourth quartiles (> 0.95 µg/dL) were 1.12 (95% CI: 0.71, 1.76), 1.13 (95% CI: 0.73, 1.77), and 1.67 (95% CI: 1.07, 2.61), respectively, compared with those in quartile 1. Consistently, a significantly higher risk of HHcy (OR: 1.49; 95% CI: 1.19, 1.88) was found in participants in quartile 4 compared with those in quartiles 1-3. Furthermore, a strongly positive association between LnBLL and HHcy was observed in participants with estimated glomerular filtration rate (eGFR) < 60 mL/min-1/1.73 m-2. Our results suggested that a higher level of BLL (LnBLL > 0.95 µg/dL) was associated with increased risk of HHcy compared with a lower level of BLL (LnBLL ≤ 0.95 µg/dL) among U.S. adults, and the association was modified by the eGFR.

Prognostic role of neutrophil-to-lymphocyte ratio in aortic disease: a meta-analysis of observational studies.

OBJECTIVE: Recent studies have reported that neutrophil-to-lymphocyte ratio (NLR) is associated with cardiovascular disease. The aim of the present study was to investigate the prognostic value of NLR in aortic disease. METHODS: We systematically searched electronic databases (Cochrane, PubMed, Elsevier, Medline, and Embase) from their inception to March 2020. Observational studies that evaluated the relationship between NLR and aortic disease were eligible for critical appraisal. Data were extracted from applicable articles, risk ratio (RR), weighted mean differences (MD) and 95% confidence intervals (CI) were calculated by RevMan 5.3, and statistical heterogeneity was assessed by the I2 statistic. RESULTS: Fourteen studies enrolling 4066 individuals were included in the meta-analysis. Compared with the control group, NLR was significantly higher in the aortic disease group (MD 3.44, 95%CI: 0.81-6.07, P = 0.01, I2 = 99%). The NLR was also significantly higher in non-survivors with aortic disease, compared to the survivors (MD 4.62, 95%CI: 2.75-6.50, P < 0.00001, I2 = 60%). Compared with the aortic disease patients with a low NLR, mortality was significantly higher in those with a high NLR (RR 2.63, 95%CI: 1.79-3.86, P < 0.00001, I2 = 67%). CONCLUSION: Based on current evidence, an elevated NLR was associated with aortic disease and in-hospital mortality. Raised NLR also demonstrated a significantly increased the risk of mortality after surgical repair in aortic disease patients. NLR may be a good prognostic biomarker in aortic disease and deserve further research in this area.

Interleukin-35 pretreatment attenuates lipopolysaccharide-induced heart injury by inhibition of inflammation, apoptosis and fibrotic reactions.

Previous studies have demonstrated that targeting inflammation is a promising strategy for treating lipopolysaccharide (LPS)-induced sepsis and related heart injury. Interleukin-35 (IL-35), which consists of two subunits, Epstein-Barr virus-induced gene 3 (EBI3) and p35, is an immunosuppressive cytokine of the IL-12 family and exhibits strong anti-inflammatory activity. However, the role of IL-35 in LPS-induced heart injury reains obscure. In this study, we explored the role of IL-35 in heart injury induced by LPS and its potential mechanisms. Mice were treated with a plasmid encoding IL-35 (pIL-35) and then injected intraperitoneally (ip) with LPS (10 mg/kg). Cardiac function was assessed by echocardiography 12 h later. LPS apparently decreased the expression of EBI3 and p35 and caused cardiac dysfunction and pathological changes, which were significantly improved by pIL-35 pretreatment. Moreover, pIL-35 pretreatment significantly decreased the levels of cardiac proinflammatory cytokines including TNF-α, IL-6, and IL-1ß, and the NLRP3 inflammasome. Furthermore, decreased number of apoptotic myocardial cells, increased BCL-2 levels and decreased BAX levels inhibited apoptosis, and LPS-induced upregulation of the expression of cardiac pro-fibrotic genes (MMP2 and MMP9) and fibrotic factor (Collagen type I) was inhibited. Further investigation indicated that pIL-35 pretreatment might suppressed the activation of the cardiac NF-κBp65 and TGF-ß1/Smad2/3 signaling pathways in LPS-treated mice. Similar cardioprotective effects of IL-35 pretreatment were observed in mouse myocardial fibroblasts challenged with LPS in vitro. In summary, IL-35 pretreatment can attenuate cardiac inflammation, apoptosis, and fibrotic reactions induced by LPS, implicating IL-35 as a promising therapeutic target in sepsis-related cardiac injury.