Association Between Triglyceride Glucose Index and Chronic Kidney Disease in Normal-Weight Chinese Adults With Hypertension.

This study aimed to examine the association between the triglyceride-glucose (TyG) index and chronic kidney disease (CKD) in normotensive adults with hypertension and further investigate potential effect modifiers of this association. A total of 7975 normoweight hypertensive participants were enrolled from the Chinese H-type hypertension registry (CHHRS) cohort. The TyG index was calculated using the formula: ln (fasting triglyceride [mg/dL] × fasting plasma glucose [mg/dL])/2. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 of body surface area. Multivariate logistic regression analysis revealed a 50% increased risk of CKD (OR: 1.50, 95% CI: 1.26-1.79) for each unit increase in the TyG index. A linear dose-response relationship between the TyG index and CKD risk was observed using restricted cubic spline analysis. Compared to the first quartile of the TyG index, the fourth quartile showed a significantly higher risk of CKD (OR: 1.88; 95% CI: 1.41-2.50). Subgroup analysis identified a stronger association between the TyG index and CKD risk in males and individuals with a history of alcohol consumption (all p values for interaction < 0.05). In conclusions, the TyG index was significantly associated with an increased risk of CKD in normoweight adults with hypertension, particularly in males and those with a history of alcohol consumption.

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.

PLGA-coated methylene blue nanoparticles for photoacoustic imaging and photodynamic/photothermal cascaded precisely synergistic therapy of tumor.

Photodynamic therapy (PDT) and photothermal therapy (PTT) are synergetic treatment strategies in antitumor treatment to achieve the best anticancer efficacy. Although traditional photosensitizer materials such as methylene blue (MB) have been widely studied for PDT, the photothermal effect is rarely reported. Herein, mono-component nanoparticles lactic-co-glycolic acid-coated methylene blue (MBNPs) based on methylene blue (MB) and lactic-co-glycolic acid (PLGA) were prepared by a facile solution-based emulsification method at room temperature. The resulting nanoparticles possess high photothermal conversion efficiency and excellent photodynamic effect. For the first time, the in vitro and in vivo tests indicated an enhanced antitumor efficacy for MBNPs with combined PDT and PTT. This study provides an efficient approach to fabricate nano-MB and also demonstrates the great potential of lactic-co-glycolic acid-coated MB for biomedical applications. Most importantly, the strong tumor growth inhibition by synergistic PTT and PDT demonstrates an excellent cascaded synergistic effect of MBNPs for the tumor therapy.

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.

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.

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.

Cu-Doped-ZnO Nanocrystals Induce Hepatocyte Autophagy by Oxidative Stress Pathway.

As a novel nanomaterial for cancer therapy and antibacterial agent, Cu-doped-ZnO nanocrystals (CZON) has aroused concern recently, but the toxicity of CZON has received little attention. Results of hematology analysis and blood biochemical assay showed that a 50 mg/kg dosage induced the increase in white blood cells count and that the concentration of alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT), and Malonaldehyde (MDA) in the serum, liver, and lungs of the CZON group varied significantly from the control mice. Histopathological examinations results showed inflammation and congestion in the liver and lung after a single injection of CZON at 50 mg/kg. A transmission electron microscope (TEM) result manifested the autolysosome of hepatocyte of mice which received CZON at 50 mg/kg. The significant increase in LC3-II and decrease in p62 of hepatocyte in vivo could be seen in Western blot. These results indicated that CZON had the ability to induce autophagy of hepatocyte. The further researches of mechanism of autophagy revealed that CZON could produce hydroxyl radicals measured by erythrocyte sedimentation rate (ESR). The result of bio-distribution of CZON in vivo, investigated by ICP-OES, indicated that CZON mainly accumulated in the liver and two spleen organs. These results suggested that CZON can induce dose-dependent toxicity and autophagy by inducing oxidative stress in major organs. In summary, we investigated the acute toxicity and biological distribution after the intravenous administration of CZON. The results of body weight, histomorphology, hematology, and blood biochemical tests showed that CZON had a dose-dependent effect on the health of mice after a single injection. These results indicated that CZON could induce oxidative damage of the liver and lung by producing hydroxyl radicals at the higher dose.

TB@PLGA Nanoparticles for Photodynamic/Photothermal Combined Cancer Therapy with Single Near-Infrared Irradiation.

BACKGROUND: Phototherapy has significant potential as an effective treatment for cancer. However, the application of a multifunctional nanoplatform for photodynamic therapy (PDT) and photothermal therapy (PTT) at a single excitation wavelength remains a challenge. MATERIALS AND METHODS: The double emulsion solvent evaporation method was used to prepare toluidine blue@poly lactic-co-glycolic acid (TB@PLGA) nanoparticles (NPs). The biocompatibility of TB@PLGA NPs was evaluated, and a 660 nm luminescence was used as the light source. The photothermal effect, photothermal stability, and singlet oxygen yield of NPs in an aqueous solution verified the feasibility of NPs as a PTT/PDT synergistic therapy drug. RESULTS: TB@PLGA NPs were successfully prepared and characterized. In vitro experiments demonstrated that TB@PLGA NPs can cause massive necrosis of tumor cells and induce apoptosis through a photodynamic mechanism under 660 nm laser irradiation. The TB@PLGA NPs also achieved optimal tumor inhibition effect in vivo. CONCLUSION: The TB@PLGA NPs prepared in this study were applied as a dual-mode phototherapeutic agent under single laser irradiation. Both in vitro and in vivo experiments demonstrated the good potential of PTT/PDT for tumor inhibitors.

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.

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.

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.

Nicorandil reversed homocysteine-induced coronary microvascular dysfunction via regulating PI3K/Akt/eNOS pathway.

OBJECTIVE: Nicorandil exerts a protective effect against coronary microvascular dysfunction in acute myocardial infarction (AMI) patients. However, the mechanism and effect of nicorandil in hyperhomocysteinemia (HHcy) AMI patients remain unclear. METHODS: C57/BL6 mice with mild to moderate HHcy and human coronary artery endothelial cells (HCAECs) cotreated with HHcy (1 mmol/L) for 24 h and hypoxia for 6 h were selected as models. Small animal ultrasound detection was used to compare cardiac function. CD31 immunofluorescence staining and tomato lectin staining were used to assess the number of microcirculation changes in vivo. MTT, tube formation and western blotting assays were used to evaluate the effect of nicorandil on HCAECs and the PI3K/Akt/eNOS pathway. RESULTS: The results showed that nicorandil improved cell viability and p-PI3K/PI3K, p-Akt/Akt, and p-eNOS/eNOS expression in the vitro HHcy and hypoxia models. The beneficial effects of nicorandil on HCAECs could be inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and the nitric oxide synthase (NOS) inhibitor L-NAME. In vivo, nicorandil improved the left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the post-HHcy + MI model, and the levels of CD31 and tomato lectin expression were higher in the nicorandil treatment group. The effectiveness of nicorandil was inhibited in the PI3K and L-NAME groups. CONCLUSION: The results suggest that nicorandil improves Hcy-induced coronary microvascular dysfunction through the PI3K/Akt/eNOS signalling pathway.

U-Shaped Association of Serum Uric Acid With All-Cause and Cause-Specific Mortality in US Adults: A Cohort Study.

BACKGROUND: In addition to the controversy regarding the association of hyperuricemia with mortality, uncertainty also remains regarding the association between low serum uric acid (SUA) and mortality. We aimed to assess the relationship between SUA and all-cause and cause-specific mortality. METHODS: This cohort study included 9118 US adults from the National Health and Nutrition Examination Survey (1999-2002). Multivariable Cox proportional hazards models were used to evaluate the relationship between SUA and mortality. Our analysis included the use of a generalized additive model and smooth curve fitting (penalized spline method), and 2-piecewise Cox proportional hazards models, to address the nonlinearity between SUA and mortality. RESULTS: During a median follow-up of 5.83 years, 448 all-cause deaths occurred, with 100 cardiovascular disease (CVD) deaths, 118 cancer deaths, and 37 respiratory disease deaths. Compared with the reference group, there was an increased risk of all-cause, CVD, cancer, and respiratory disease mortality for participants in the first and third tertiles of SUA. We further found a nonlinear and U-shaped association between SUA and mortality. The inflection point for the curve was found at a SUA level of 5.7 mg/dL. The hazard ratios (95% confidence intervals) for all-cause mortality were 0.80 (0.65-0.97) and 1.24 (1.10-1.40) to the left and right of the inflection point, respectively. This U-shaped association was observed in both sexes; the inflection point for SUA was 6 mg/dL in males and 4 mg/dL in females. CONCLUSION: Both low and high SUA levels were associated with increased all-cause and cause-specific mortality, supporting a U-shaped association between SUA and mortality.

The efficacy of remote ischemic conditioning in preventing contrast-induced nephropathy among patients undergoing coronary angiography or intervention: An updated systematic review and meta-analysis.

BACKGROUND: Numerous trials have investigated the effect of remote ischemic conditioning (RIC) in preventing contrast-induced nephropathy (CIN) in patients receiving contrast medium (CM). This meta analysis aims to validate the role of RIC in preventing CIN. METHODS: We searched the PubMed, EMBASE, and Web of Science databases for eligible randomized controlled trials (RCTs) published before April 27, 2019. Two investigators independently extracted basic characteristics from each study. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to examine the treatment effect. RESULTS: A total of 18 studies comprising 2,503 patients were included in our meta-analysis. Compared with conventional therapy, RIC significantly reduced the risk of CIN (OR = 0.43, 95% CI: 0.33, 0.56, p < .05). Subgroup analyses showed that the protective effect of RIC was stronger in the low-osmolar contrast media group (OR = 0.32; 95% CI: 0.23, 0.45, p < .05) and the nondiabetic group (OR = 0.39; 95% CI: 0.29, 0.53 p < .05). RIC also significantly reduced major adverse cardiovascular events within the first 6 months (OR = 0.39; p < .05), but the influence was not present after long-term follow-up. CONCLUSIONS: Our meta-analysis showed that RIC could effectively reduce CIN risk and decrease the short-term incidence of relevant adverse events. Furthermore, the effects of CIN are more pronounced in nondiabetic patients and with the use of low-osmolar contrast medium. This meta-analysis of small trials suggests a possible protective effect of RIC on contrast-induced nephropathy and favors the performance of a large randomized trial to further investigate this strategy.

Cu2ZnSnS4 nanocrystals for microwave thermal and microwave dynamic combination tumor therapy.

Cu2ZnSnS4 nanocrystals (CZTS NCs) have been demonstrated to be effective in tumor therapy as a novel susceptible agent for microwave thermal and microwave dynamic therapy. CZTS NCs intensify the heating effect of microwaves with a significant temperature increase of about 15 °C compared to the control group and showed remarkable anti-tumor performance after 5 min of microwave irradiation. For the first time, we report the microwave absorption performance and singlet oxygen production of CZTS NCs used in microwave therapy, which reveals new opportunities for novel combined mechanisms of microwave thermal and microwave dynamic tumor therapies.

Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting in Unprotected Left Main Coronary Artery Stenosis.

BACKGROUND: The present study performed a meta-analysis of randomized and prospective trials to compare the outcomes of percutaneous coronary intervention (PCI) with stents versus coronary artery bypass graft surgery (CABG) for unprotected left main coronary artery (UPLM) stenosis. METHODS: The Cochrane Library, PubMed and EMBASE databases were systematically searched until July 2017. The Newcastle-Ottawa scale was used for quality assessment. RESULTS: A total of 19 studies with 16,900 participants were included. Pooled analysis showed no significant differences in all-cause mortality (odds ratio [OR] 0.94; 95% CI 0.74-1.20) and cardiac death (OR 1.04; 95% CI 0.74-1.47). However, subgroup analysis showed that PCI was associated with a low all-cause mortality rate at 30-day follow up (OR 0.48; 95% CI 0.26-0.89). The stroke rate in PCI was lower in short-term follow up (OR 0.45; 95% CI 0.23-0.88) and long-term follow up (OR 0.36; 95% CI 0.27-0.47). On the other hand, PCI was associated with higher risk of myocardial infarction (OR 1.59; 95% CI 1.34-1.88), repeat revascularization (OR 2.47; 95% CI 1.80-3.37) and target vessel revascularization (OR 2.10; 95% CI 1.72-2.57) compared to CABG in the pooled analysis. CONCLUSIONS: The current evidence suggests that the risk of stroke was significantly reduced in PCI compared to that in CABG. Therefore, PCI is the preferred treatment for patients with a high risk of stroke. Additionally, in short-term follow up, PCI was reported to be safe and effective for UPLM patients compared to CABG. However, CABG caused fewer complications long term.