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Abstract Sirtuin 3 (SIRT3) is well known as a conserved nicotinamide adenine dinucleotide+ (NAD+)-dependent deacetylase located in the mitochondria that may regulate oxidative stress, catabolism and ATP production. Accumulating evidence has recently revealed that SIRT3 plays its critical roles in cardiac fibrosis, myocardial fibrosis and even heart failure (HF), through its deacetylation modifications. Accordingly, discovery of SIRT3 activators and elucidating their underlying mechanisms of HF should be urgently needed. Herein, we identified a new small-molecule activator of SIRT3 (named 2-APQC) by the structure-based drug designing strategy. 2-APQC was shown to alleviate isoproterenol (ISO)-induced cardiac hypertrophy and myocardial fibrosis in vitro and in vivo rat models. Importantly, in SIRT3 knockout mice, 2-APQC could not relieve HF, suggesting that 2-APQC is dependent on SIRT3 for its protective role. Mechanically, 2-APQC was found to inhibit the mammalian target of rapamycin (mTOR)-p70 ribosomal protein S6 kinase (p70S6K), c-jun N-terminal kinase (JNK) and transforming growth factor-β (TGF-β)/ small mother against decapentaplegic 3 (Smad3) pathways to improve ISO-induced cardiac hypertrophy and myocardial fibrosis. Based upon RNA-seq analyses, we demonstrated that SIRT3-pyrroline-5-carboxylate reductase 1 (PYCR1) axis was closely assoiated with HF. By activating PYCR1, 2-APQC was shown to enhance mitochondrial proline metabolism, inhibited reactive oxygen species (ROS)-p38 mitogen activated protein kinase (p38MAPK) pathway and thereby protecting against ISO-induced mitochondrialoxidative damage. Moreover, activation of SIRT3 by 2-APQC could facilitate AMP-activated protein kinase (AMPK)-Parkin axis to inhibit ISO-induced necrosis. Together, our results demonstrate that 2-APQC is a targeted SIRT3 activator that alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis, which may provide a new clue on exploiting a promising drug candidate for the future HF therapeutics.

Abstract Increased plasma homocysteine (Hcy) has been identified as one of the important risk factors for cardiovascular disease. However, the association between plasma Hcy and peripheral artery disease (PAD) is still controversial. This study aimed to investigate the association between plasma Hcy and PAD and the potential modifier factors in Chinese hypertensive adults. A total of 25 300 hypertensive patients aged 18 years or older were included in the analysis in this cross‐sectional study. The outcome was PAD, which defined as an ankle‐brachial index ≤0.90 in either limb. Multiple logistic regression was used to analyze the relationship between plasma Hcy and PAD. The median plasma Hcy was 14.00 (interquartile range: 11.60–17.80) μmol/L. There was a significant positive association between plasma Hcy and PAD (per SD increment; OR: 1.13; 95% CI: 1.06–1.19). Patients in the upper plasma Hcy tertile (≥16.16 μmol/L) were associated with a 53% increased risk of PAD compared with patients in the lower tertile (

Summary: A study was conducted to investigate whether an integrated management (IM) model led by public healthcare providers is effective in reducing cardiovascular disease (CVD)-specific and all-cause mortality rates in low-income rural populations with hypertension. The study recruited 14,234 patients with hypertension aged 18 years or older and allocated them to either an IM group or a usual care (UC) group. During a median follow-up of 48.0 months, the incidences of CVD-specific and all-cause deaths were lower in the IM group than in the UC group. The hazard ratios for CVD-specific mortality and all-cause mortality among patients in the IM group were 0.60 and 0.62, respectively. The results showed that the IM model led by public health providers resulted in clinically significant reductions in CVD-specific and all-cause mortality rates in low-income rural populations with hypertension.

BackgroundWhether the estimated pulse wave velocity (ePWV) in Chinese patients with hypertension can serve as an independent predictor of cardiovascular and all-cause mortality remains unknown. Therefore, this study investigated the associations between ePWV and cardiovascular and all-cause mortalities and explored potential effect modifiers influencing these relationships. Finally, we compared the ePWV with the brachial-ankle pulse wave velocity (baPWV) to determine which parameter better predicts mortality.MethodsThe population of this longitudinal cohort study was selected from the China H-type Hypertension Registry Study. The exposure and outcome variables were ePWV and all-cause and cardiovascular mortalities, respectively. The Cox proportional hazard regression model was applied to assess the associations between ePWV and all-cause and cardiovascular mortalities. The performances of ePWV and baPWV in predicting death were compared using the receiver operating characteristic (ROC) curve area, net reclassification improvement index (NRI), and integrated discrimination improvement index (IDI).ResultsThis prospective study enrolled 14,232 patients with hypertension. Following an average follow-up of 48 months, 806 individuals succumbed to all-cause mortality, with 397 cases specifically attributed to cardiovascular diseases. The Cox proportional regression analysis revealed a significant association between a 1 m/s increase in ePWV and a 37% higher risk of all-cause mortality (hazard ratio [HR]: 1.37, 95% confidence interval [CI]: 1.31–1.43) as well as a 52% higher risk of cardiovascular mortality (HR: 1.52, 95% CI: 1.43–1.62) in the fully adjusted model. The findings for ePWV according to quartile demonstrated hazard ratios for all-cause mortality for Q2 (10.25

Background: The associations of body fat parameters with arterial stiffness measured by brachial-ankle pulse wave velocity in hypertensive patients were scarce. Methods: This cross-sectional study analyzed 4322 hypertensive adults. The correlations between the anthropometric indexes (body mass index [BMI], waist circumference, waist-tohip ratio [WHR], waist-to-height ratio [WHtR], a body shape index [ABSI], body round index [BRI]) and ba-PWV values were analyzed using multivariable linear regression model. Results: In both sex categories, linear regression models showed that BMI levels were inversely related to baPWV (adjusted-β per SD increase in male: −0.51, 95% CI -0.66 to −0.36, P

Abstract 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)

BackgroundThe impact of triglyceride–glucose (TyG) index variations on chronic kidney disease (CKD) progression remains unexplored. To investigate the effects of the TyG index and its dynamic changes on CKD progression.MethodThis prospective cohort study included data from 8,418 hypertensive participants. The exposure variable in this study was defined as the difference between the TyG index at the last visit from that at baseline. The study’s outcome variable was the progression of CKD, defined as follows: for subjects with an estimated glomerular filtration rate (eGFR) ≥60 mL/min, a ≥30% decrease in eGFR with a final follow-up value

Skeletal muscle regeneration mainly depends on muscle satellite cells; however, these cells are not sufficient for supporting repair and regeneration in volumetric muscle loss (VML), Duchenne muscular dystrophy, and other muscle injuries or muscle diseases. As such, much work has been conducted in recent years to search for myogenic stem cells. Adipose-derived stem cells (ADSCs) have a wide range of sources, rapid growth, and multi-directional differentiation potential, and have become vital candidates for muscle regeneration. Multiple factors influence the myogenic differentiation capacity of ADSCs. This paper reviews the regulatory aspects and possible factors that have been identified in recent years to affect myogenic differentiation of ADSCs. Based on these factors, gene editing, and perfusion concepts, a method was proposed to achieve maximal differentiation efficiency of ADSCs. This study focused on the application of ADSCs in muscle regeneration and disease. Based on the importance of myogenic differentiation of ADSCs for the repair and regeneration of muscle damage, this study provides a basis for future research surrounding the efficient induction of myogenic differentiation of ADSCs in vitro.

Abstract Purpose The aim of this study was to evaluate the association of marital status with cognitive function and to examine the potential effect modifiers in Chinese hypertensive populations. Methods A total of 9,525 adult Chinese hypertensive patients were enrolled in this cross-sectional study. Cognitive function, as the dependent variable in our study, was assessed by the Chinese version of the Mini‐Mental State Examination (MMSE). We adjusted for potential confounding factors in multiple linear regression models to examine the relationship of marital status with cognitive function. In addition, we divided the population according to sex to explore whether there were sex-specific differences. Results Among the 9,525 study participants, the mean (SD) age for men was 63.5 (10.3) years, and the mean MMSE score was 24.9 ± 5.0, whereas for women, the mean (SD) age was 63.8 (9.3) years, and the mean MMSE score was 19.4 ± 6.4. Unmarried persons had lower scores on the MMSE and lower subscores in each of the cognitive domains. A stronger correlation between marital status and a lower MMSE score was statistically significant in men (unmarried men: β = -1.55; 95% CI: -1.89, -1.21) but not women (unmarried women: β = -0.22; 95% CI: -0.56, 0.12; p interaction = 0.006). Compared to men who were widowed or divorced, never married men were more likely to have lower MMSE scores (β = -2.30, 95% CI -3.10,—1.50; p

BackgroundRemnant cholesterol (RC) and chronic kidney disease (CKD) have not been definitively linked in individuals with different characteristics. This study aims to investigate the relationship between serum RC level and CKD and examine possible effect modifiers in Chinese patients with hypertension.MethodsOur study is based on the Chinese H-type Hypertension Project, which is an observational registry study conducted in real-world settings. The outcome was CKD, defined as an estimated glomerular filtration rate of less than 60 ml/min·1.73 m2. Multivariate logistic regression and smooth curve fitting were used to analyze the association between RC and CKD. Subgroup analyses were subsequently conducted to examine the effects of other variables.ResultsThe mean age of the 13,024 patients with hypertension at baseline was 63.8 ± 9.4 years, and 46.8% were male. A conspicuous linear positive association was observed between RC level and CKD (per SD increment; odds ratio [OR], 1.15; 95% confidence interval [CI], 1.08–1.23). Compared with the lowest quartile group of RC, the risk of CKD was 53% higher (OR, 1.53; 95% CI, 1.26–1.86) in the highest quartile group. Furthermore, a stronger positive association between RC level and CKD was found among participants with a higher body mass index (BMI

BackgroundFew studies have examined the relationship between fatty liver index (FLI) and hyperuricemia (HUA). This study explores the relationship between FLI and HUA in hypertensive patients.MethodsA total of 13,716 hypertensive subjects were included in the current study. FLI, a simple index calculated from triglycerides (TG), waist circumference (WC), body mass index (BMI), and γ -glutamyltransferase (GGT), was used as a useful predictor of nonalcoholic fatty liver disease (NAFLD) distribution. HUA was defined as serum uric acid ≥ 360 μmol/L for females and ≥ 420 μmol/L for males.ResultsThe mean value of total FLI was 31.8 ± 25.1. Multiple logistic analyses revealed a significant positive correlation between FLI and HUA (OR, 1.78; 95% CI: 1.69–1.87). A subgroup analysis demonstrated that the correlation between FLI (< 30 vs. ≥ 30) and HUA was significant in both sexes (P for interaction = 0.006). Further analyses stratified by sex indicated a positive correlation between FLI and HUA prevalence among male and female subjects. However, the correlation between FLI and HUA was stronger in female subjects than in males (male: OR, 1.70; 95% CI: 1.58–1.83; female: 1.85; 95% CI: 1.73–1.98).ConclusionThis study demonstrates a positive correlation between FLI and HUA in hypertensive adults, but stronger in females than males.

ObjectiveThe abbreviated TCB index (TCBI) is a novel indicator of nutritional status, calculated by multiplying the serum values of triglycerides (TG), total serum cholesterol (TC), and body weight. The research on the relationship between this index and stroke is limited. We aimed to investigate the association between TCBI and stroke in Chinese hypertensive patients.Methods and resultsA total of 13,358 adults with hypertension from the China H-type Hypertension Registry Study were enrolled. The TCBI was calculated as TG (mg/dL) * TC (mg/dL) * body weight (kg)/1,000. The primary outcome was an incidence of stroke. Multivariable adjusted models revealed an inverse association between TCBI and the prevalence of stroke. In the fully adjusted model, the results showed that the prevalence of stroke decreased by 13% (OR, 0.87; 95% CI, 0.78–0.98, p = 0.018) per SD increment of LgTCBI. When TCBI was assessed as a categorical variable, compared with those in group Q4 (TCBI ≥ 2,399), the participants in group Q3 (TCBI ≥ 1,476 and

Highlights This study is the first to find a significant positive association between the baseline visceral adiposity index (VAI) and peripheral arterial disease (PAD) in normal-weight adults with hypertension. The present study is also the first to indicate a stronger linear positive relationship between VAI and PAD in male participants but not in females.

Abstract Non-coding RNAs (ncRNAs) have been defined as a class of RNA molecules transcribed from the genome but not encoding proteins, such as microRNAs, long non-coding RNAs, Circular RNAs, and Piwi-interacting RNAs. Accumulating evidence has recently been revealing that ncRNAs become potential druggable targets for regulation of several small-molecule compounds, based on their complex spatial structures and biological functions in cancer therapy. Thus, in this review, we focus on summarizing some new emerging designing strategies, such as high-throughput screening approach, small-molecule microarray approach, structure-based designing approach, phenotypic screening approach, fragment-based designing approach, and pharmacological validation approach. Based on the above-mentioned approaches, a series of representative small-molecule compounds, including Bisphenol-A, Mitoxantrone and Enoxacin have been demonstrated to modulate or selectively target ncRNAs in different types of human cancers. Collectively, these inspiring findings would provide a clue on developing more novel avenues for pharmacological modulations of ncRNAs with small-molecule drugs for future cancer therapeutics.

Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.

Abstract Background The relationship between obesity indices and arterial stiffness (AS) has not been fully discovered nor has it been studied in depth in large hypertensive patient populations. The aim of this study was to explore the association between body mass index (BMI) and waist-hip ratio (WHR) levels and AS based on brachial-ankle pulse wave velocity (baPWV) in Chinese rural adults with hypertension. Methods This cross-sectional study analyzed 5049 Chinese rural adults with essential hypertension. BMI was calculated as the body weight in kilograms divided by the square of the height in meters (kg/m2). Central obesity was defined as WHR ≥ 0.9 for males and ≥ 0.85 for females. Measurement of arterial stiffness was carried out via brachial-ankle pulse wave velocity (baPWV). Results The prevalence of overweight, general obesity, central obesity and increased AS were 26.88%, 3.39%, 63.85% and 44.01%, respectively. Multivariate logistic regression analysis indicated that BMI levels were negatively associated with the prevalence of increased AS (adjusted-OR per SD increase: 0.74, 95% CI 0.67–0.81, P

BackgroundUncertainty still remained about the relationship between visceral adiposity index (VAI) and hyperuricemia. The aim of this study was to investigate whether VAI was an independent risk factor for hyperuricemia in hypertensive Chinese patients.MethodsA cross-sectional study including 13176 hypertensive participants (6478 males) recruited from Wuyuan County, Jiangxi province, was conducted. All patients received anthropometric measurements, completed questionnaires and provided blood samples for biochemical testing. VAI was calculated by waist circumference, BMI, triglyceride and high-density lipoprotein cholesterol. Hyperuricemia was defined as serum uric acid ≥ 7 mg/dL in men and ≥ 6 mg/dL in women.ResultsOverall, the average level of uric acid was 7.8 ± 2.0 mg/dL in males and 6.34 ± 1.78 in females and prevalence of hyperuricemia was 61.4% and 51.30%, respectively. In multivariate logistic regression analysis, the risk of hyperuricemia increased 1.77 times and 1.88 times with the increase of ln VAI in males (OR:1.77, 95% CI: 1.62, 1.94) and females (OR:1.88, 95% CI: 1.73, 2.04). For males, compared to quartile 1, the risk of hyperuricemia in the second, third and the forth quartile of visceral adiposity index were 1.34 (95% CI: 1.14, 1.57),1.82(95% CI: 1.54, 2.14) and 2.97 (95% CI: 2.48, 3.57). For females, compared to quartile 1, the risk of hyperuricemia in the second, third and the forth quartile of visceral adiposity index were 1.48 (95% CI: 1.28, 1.72), 1.99 (95% CI: 1.71, 2.32) and 2.92 (95% CI: 2.50, 3.42).ConclusionsThis study found that VAI was an independent risk factor for hyperuricemia among hypertensive patients, which may provide some strategies for reducing the level of uric acid.

BackgroundData are limited on the impact of combined lifestyle behaviors on mortality in Jiangxi Province, China.ObjectiveThe study examined the association between combined lifestyle behaviors and all-cause and cardiovascular disease (CVD) mortality in Jiangxi province.MethodsThe 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.ResultsDuring 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

Background and aimsThe relationship between the new obesity index weight-adjusted-waist index (WWI) and hyperuricemia is unclear. We aimed to explore the association of the WWI and hyperuricemia among the hypertensive population.MethodsA total of 14,078 hypertension participants with complete data were included in our study. WWI was calculated by waist circumference divided by the square root of weight. Specifically, men with 420 μmol/L and women with 360 μmol/L were considered to have hyperuricemia.ResultsThe prevalence of hyperuricemia was 61.1% in men and 51.4% in women. On the whole, multivariate logistic regression analyses found that there was a linear positive correlation of WWI with hyperuricemia in both men (OR: 1.37; 95%CI: 1.25, 1.49) and women (OR: 1.35; 95%CI: 1.26, 1.45). Subgroup analysis found that the relationship between WWI and hyperuricemia was stable in stratified subgroups (all P-interactions >.05).ConclusionWWI showed a positive association with hyperuricemia among hypertension patients.

Abstract Background Current studies support lipid ratios [the total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio; the triglyceride (TG)/HDL-C ratio; the low-density lipoprotein cholesterol (LDL -C)/HDL-C ratio; and non-HDL-C] as reliable indicators of cardiovascular disease, stroke, and diabetes. However, whether lipid ratios could serve as markers for hyperuricemia (HUA) remains unclear due to limited research. This study aimed to explore the association between lipid ratios and HUA in hypertensive patients. Methods The data from 14,227 Chinese hypertensive individuals in the study were analyzed. Multiple logistic regression analysis and smooth curve fitting models examined the relationship between lipid ratios and HUA. Results The results showed positive associations between the lipid ratios and HUA (all P

BackgroundIncreased plasma total homocysteine (tHcy) is an influencing factor of cognitive impairment in the general population. However, studies on the relationship between the risk of cognitive impairment and plasma tHcy levels in patients with hypertension are limited. This study aimed to explore the association between plasma tHcy levels and cognitive function assessed by MMSE scores among hypertensive patients in China.MethodsA total of 9,527 subjects from the Chinese Hypertension Registry Study participated in this study. Plasma tHcy levels were quantified by high-performance liquid chromatography using a fluorescence detector. Cognitive assessment was performed using the Mini-Mental State Examination (MMSE). Linear regression models, two piecewise linear regression models, and smoothing curve fitting were applied to determine the relationship between plasma tHcy levels and cognitive function.ResultsThis analysis included 9,527 Chinese hypertensive adults. Based on the results of linear regression models, a negative relationship was identified between plasma tHcy levels and MMSE scores [beta coefficient (β) per standard deviation (SD) increase: −0.26, 95% confidence interval (CI) −0.35, −0.16, P < 0.001]. The fully adjusted smooth curve fitting presented a nonlinear between plasma tHcy levels and MMSE scores. The threshold effect analysis showed that the inflection point of tHcy was about 27.1 μmol/L. The effect size [β (95% CI)] per SD increase in plasma tHcy concentrations on MMSE scores was −0.93 (−1.24, −0.6) on the left side and −0.07 (−0.24, 0.10) on the right side of the inflection point (P-value for log-likelihood ratio (LLR) test was

Autophagy, originally described as a mechanism for intracellular waste disposal and recovery, has been becoming a crucial biological process closely related to many types of human tumors, including breast cancer, osteosarcoma, glioma, etc., suggesting that intervention of autophagy is a promising therapeutic strategy for cancer drug development. Therefore, a high-quality database is crucial for unraveling the complicated relationship between autophagy and human cancers, elucidating the crosstalk between the key autophagic pathways, and autophagic modulators with their remarkable antitumor activities. To achieve this goal, a comprehensive database of autophagic modulators (AMTDB) was developed. AMTDB focuses on 153 cancer types, 1,153 autophagic regulators, 860 targets, and 2,046 mechanisms/signaling pathways. In addition, a variety of classification methods, advanced retrieval, and target prediction functions are provided exclusively to cater to the different demands of users. Collectively, AMTDB is expected to serve as a powerful online resource to provide a new clue for the discovery of more candidate cancer drugs.

Background and aims: Previous studies have indicated that Plasma total bilirubin (TBiL) might play an essential role in peripheral arterial disease (PAD). However, the effects of different levels of TBiL on PAD development remain uncertain. We aimed to examine the TBiL and the prevalence of PAD among Chinese adults with hypertension, with particular attention paid to sex differences.Methods: A total of 10,900 hypertensive subjects were included in the current study. The mean age of our study participants was 63.86 ± 9.25 years, and there were 5,129 males and 5,771 females. The outcome was peripheral arterial disease (PAD), defined as present when the ankle-brachial index (ABI) of either side was ≤0.90. The association between TBiL and PAD was examined using multivariate logistic regression analysis and the restricted cubic spline.Results: Of 10,900 hypertensive participants, 350 (3.21%) had PAD, and the mean plasma total bilirubin was 14.66 (6.86) μmol/L. The mean TBiL was 15.67 μmol/L in men and 13.76 μmol/L in women. The smoothing curve showed that a U-shaped curve association existed between TBiL and the prevalence of PAD in Chinese adults with hypertension. When stratified by sex, TBiL was significantly U-shaped associated with PAD among men but not women. Among males, the inflection point was 11.48 μmol/L; to the left inflection point, the effect size and 95% CI were 0.08, 0.01, 0.66, respectively; to the right inflection point, OR, 5.16; 95% CI,1.64, 16.25.Conclusions: We found an independent U-shaped association between TBiL and the prevalence of PAD among hypertensive subjects and a differential association between men and women. We further revealed a turning point by threshold effect analysis.

Objective: This prospective study examined the relationship between body mass index (BMI) and all-cause mortality in Chinese adults without morbid obesity.Methods: We prospectively examined the relationship between BMI and all-cause mortality in 12,608 Southern Chinese adults with age ≥35 years who participated in the National Key R&D Program from 2013–2014 to 2019–2020. Cox proportional hazards models were used to examine the association between BMI and all-cause mortality.Results: The prevalence of being underweight, normal weight, overweight and having moderate obesity was 7.36%, 55.83%, 28.51% and 8.31%, respectively. A total of 683 (5.65%) deaths occurred during a median follow-up period of 5.61 years. The Cox proportional hazards models indicated that a continuous BMI level was negatively associated with all-cause mortality [adjusted-hazard ratio (HR) per 1 kg/m2 increase: 0.96, 95% CI 0.93 to 0.98, p < 0.001]. Furthermore, the HRs of all-cause mortality in the underweight, overweight and moderate obesity groups were 1.31 (1.05, 1.64), 0.89 (0.73, 1.08) and 0.64 (0.44, 0.92), respectively in the confounder model relative to the normal weight group. Survival analysis further confirmed this inverse association of the four BMI categories with mortality.Conclusion: BMI was negatively associated with all-cause mortality in southern Chinese adults without morbid obesity. Compared to the normal weight category, adults in the moderate obesity category had lower all-cause mortality, whereas being underweight was associated with increased all-cause mortality.

Abstract We aimed to evaluate the relation of the ankle–brachial index (ABI) with the prevalence of stroke and to examine any possible effect modifiers among hypertensive patients without atrial fibrillation. A total of 10 750 subjects with hypertension aged 27‐96 years were included in the current study. The outcome was a stroke. Odds ratios of stroke concerning ABI were calculated using multivariate logistic regression models. Among 10 750 hypertensive participants, 690 (6.42%) had a stroke. Multivariate logistic analyses showed that ABI was negatively correlated with the prevalence of stroke (per SD increment; adjusted OR, 0.88; 95% CI, 0.82‐0.94). Compared with participants in Q 1, the odds ratios (95% CI) for those in the Q2 (1.05 to 1.10), Q3 (1.10 to 1.15), and Q4 (≥1.15) were 0.71 (0.56, 0.90), 0.87 (0.70, 1.08), and 0.81 (0.65, 1.01), respectively. However, compared with higher ABI value, lower ABI value (

Abstract Background The low-density lipoprotein cholesterol/high-density lipoprotein- cholesterol (LDL-C/HDL-C) ratio is an excellent predictor of cardiovascular disease (CVD). However, previous studies linking the LDL-C/HDL-C ratio to mortality have yielded inconsistent results and been limited by short follow-up periods. Therefore, the aim of the present study was to determine whether the LDL-C/HDL-C ratio could be an effective predictor of all-cause mortality in elderly hypertensive patients. Methods A total of 6941 hypertensive patients aged 65 years or older who were not treated with lipid-lowering drugs were selected from the Chinese Hypertension Registry for analysis. The endpoint of the study was all-cause mortality. The relationship between the LDL-C/HDL-C ratio and all-cause mortality was determined using multivariate Cox proportional hazards regression, smoothing curve fitting (penalized spline method), subgroup analysis and Kaplan–Meier survival curve analysis. Results During a median follow-up of 1.72 years, 157 all-cause deaths occurred. A U-shaped association was found between the LDL-C/HDL-C ratio and all-cause mortality. Patients were divided according to the quintiles of the LDL-C/HDL-C ratio. Compared to the reference group (Q3: 1.67–2.10), patients with both lower (Q1 and Q2) and higher (Q4 and Q5) LDL-C/HDL-C ratios had higher all-cause mortality (

Abstract Background Data on the relationship between nontraditional lipid profiles [total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)/HDL-C ratio, low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio, non-high-density lipoprotein cholesterol (non-HDL-C)] and the risk of peripheral artery disease (PAD) are limited. The present study investigated the relationship of nontraditional lipid indices with PAD in hypertensive patients. Methods This cross-sectional study was performed among 10,900 adults with hypertension. Participants were diagnosed with PAD when their ankle-brachial index (ABI) was

Objective: Elevated systolic blood pressure (SBP) can significantly increase the bleeding risk in patients with atrial fibrillation (AF). However, it is unclear whether elevated diastolic blood pressure (DBP), in the presence of well-controlled SBP is also associated with bleeding. Therefore, we aimed to examine the specific relationship between DBP and bleeding in patients with AF treated with anticoagulants and had well-controlled SBP. Methods: We analyzed data from 542 of 929 patients with nonvalvular AF (NVAF) treated with dabigatran from the Monitor System for the Safety of Dabigatran Treatment study (MISSION-AF) who had a SBP of 120–140 mm Hg at the time of enrollment. The association between DBP and bleeding was analyzed using multivariate logistic regression and smooth curve fitting (penalized spline method). Threshold saturation effect analysis was used to show the nonlinear relationship between DBP and bleeding. Results: After 3 months of follow-up, 49 bleeding events occurred. Compared with participants with DBP

BackgroundHypertension is a major cardiovascular risk factor for cognitive impairment. Lipid accumulation product (LAP), an index that represents fat overaccumulation in the body, has been shown to be associated with cardiovascular disease. Nevertheless, the relationship between LAP and cognitive function in hypertensive patients with normal weight has been infrequently studied.ObjectiveThis study aimed to assess the relationship between LAP and cognitive function in hypertensive patients with normal weight.MethodsThis study included 5,542 Chinese hypertensive patients with normal weight. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE). The relationship between LAP and MMSE scores was evaluated using multiple linear regression.ResultsThe mean age of the participants was 64.8 ± 9.3 years, and 2,700 were men (48.7%). The mean MMSE score was 24.5 ± 5.1 in men and 19.2 ± 6.5 in women. The mean LAP was 26.2 ± 25.5 in men and 42.5 ± 34 in women. Log10-LAP showed a significant positive association with MMSE score (men: β = 0.69, 95% CI 0.14–1.24, p = 0.015; women: β = 1.03, 95% CI 0.16–1.90, p = 0.020). When LAP was divided into 3 groups according to tertiles, participants in the third LAP tertile had higher MMSE scores for both men (p for trend = 0.04) and women (p for trend = 0.015).ConclusionLAP showed an independent positive association with MMSE in Chinese hypertensive patients with normal weight.

BackgroundWe aim to evaluate the four surrogate markers of insulin resistance (IR), including triglyceride-glucose index (TyG), lipid accumulation product index (LAP), visceral adiposity index (VAI), triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL), on prevalence of chronic kidney disease (CKD) and to examine any possible effect modifiers in Chinese hypertensive patients.MethodsA total of 13,055 hypertensive participants were included in this cross-sectional study. In addition, average age of the study population was 63.81 ± 9.46 years, and 47.66% of them are men. The primary outcome was CKD, defined as eGFR

Objectives. Cognitive decline could be seen as the sign of preclinical phase of dementia, which was found to be sex differentiated. Previous studies had discovered that there might be some link between abnormal sleep duration and cognitive performance. Additionally, hypertension was found to be one of the important risk factors for cognitive decline and abnormal sleep duration was also a significant risk factor for hypertension. Therefore, the purpose of this study was to investigate sex differences in the association of sleep duration with cognitive performance and to further explore potential effect modifiers that may exist. Methods. Data analyzed in this study was from the China H-type Hypertension Registry Study. Sleep duration was assessed with a sleep questionnaire and categorized as

BackgroundLipid accumulation product (LAP) index, as a new index to predict cardiovascular disease (CVD), has attracted the attention of many researchers. The relation of the LAP index with brachial-ankle pulse wave velocity (baPWV) has been evaluated in several previous studies and yielded inconsistent results. This study aimed to investigate the association between the LAP index and arterial stiffness in the Chinese population with hypertension.MethodsWe conducted a cross-sectional analysis in 4,926 Chinese population with hypertension (aged 64.42 ± 9.44 years). The LAP index was developed from population-based frequency plots of adult waist circumferences and circulating triglyceride concentrations according to men and women. Arterial stiffness was determined by measuring baPWV.ResultsThe multivariate linear regression analyses showed that the LAP index was independently and positively associated with baPWV [beta coefficients (β), 24.10 cm/s; 95% CI: 5.72, 42.49 cm/s]. Consistently, the multivariate logistic regression analyses showed a positive association between the LAP index risk of elevated baPWV (>75th percentile) [odds ratio (OR), 1.19; 95% CI 1.01, 1.41]. A restricted cubic spline showed that a significant linear association existed between the LAP index and baPWV. In different subgroups of diastolic blood pressure (DBP), there is interaction between the LAP index and baPWV (DBP

Background. Previous studies have revealed the triglyceride-glucose (TyG) index is closely related to hyperuricemia in the general population. However, this relationship in hypertensive patients has not been reported. The aims of this study are to investigate the relationship of the TyG index and hyperuricemia in adult Chinese hypertension. Methods. The China H-type Hypertension Registration (an observational, noninterventional, and real-world study) was conducted from March 01, 2018, to August 31, 2018, in 16 communities in Wuyuan of China. The TyG index was calculated from fasting triglycerides (mg/dL) and fasting glucose (mg/dL)/2. Hyperuricemia was categorized by uric acid concentration ≥420 μmol/L (7 mg/dL). Results. Overall average TyG index of 13,060 adults with hypertension was 8.87; age was 63.81 years. The TyG index was positively correlated with serum uric acid by multiple linear regression analyses (β = 38.03; 95% CI: 34.55 to 41.51). Coincidentally, logistic analyses also demonstrated the TyG index had a positive correlation with hyperuricemia (OR = 2.04; 95% CI: 1.87 to 2.24). Strong linear associations of the TyG index with serum uric acid and hyperuricemia were confirmed by restricted cubic spline analysis. Compared with subjects in the lowest quartile (7.13 to 8.44) of the TyG index, subjects in the 2nd–4th quartiles had 1.25 (95% CI: 1.10 to 1.41), 1.63 (95% CI: 1.43 to 1.86), and 2.79 (95% CI: 2.41 to 3.24) times greater incident risk of developing hyperuricemia. The TyG index had significant correlations between male patients and hyperuricemia (OR = 2.01) by subgroup analysis. Conclusion. Positive associations were found between the TyG index and serum uric acid and between the TyG index and hyperuricemia in adults with hypertension. This trial was registered at clinicaltrials.gov as ChiCTR1800017274.

Abstract Background Data are limited on whether TyG index is an independent predictor of arterial stiffness in hypertensive patients. The purpose of this study was to assess the association between the TyG index and arterial stiffness, and examined whether there were effect modifiers, in hypertensive patients. Methods This study included 4718 hypertensive adults, a subset of the China H-type Hypertension Registry Study. The TyG index was calculated as ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Arterial stiffness was determined by measuring brachial-ankle pulse wave velocity (baPWV). Results The overall mean TyG index was 8.84. Multivariate linear regression analyses showed that TyG index was independently and positively associated with baPWV (β, 1.02; 95% confidence interval [CI] 0.83, 1.20). Consistently, Multiple logistic analyses showed a positive association between TyG index risk of elevated baPWV (> 75th percentile) (odds ratio [OR], 2.12; 95% CI 1.80, 2.50). Analyses using restricted cubic spline confirmed that the associations of TyG index with baPWV and elevated baPWV were linear. Subgroup analyses showed that stronger associations between TyG index and baPWV were detected in men (all P for interaction

Two new cyclohexadepsipeptides japonamides A (1) and B (2) were isolated from the ethyl acetate extract of a marine-sponge-derived fungus Aspergillus japonicus based on molecular networking. Their structures were elucidated by comprehensive spectral analysis and their absolute configurations were confirmed by Marfey’s method. Compounds 1 and 2 showed no antifungal activities against Candida albicans SC5314 measured by the broth microdilution method but exhibited prominent synergistic antifungal activities in combination with fluconazole, ketoconazole, or rapamycin. The Minimum inhibitory concentrations (MICs) of rapamycin, fluconazole, and ketoconazole were significantly decreased from 0.5 to 0.002 μM, from 0.25 to 0.063 μM, and from 0.016 to 0.002 μM, in the presence of compounds 1 or 2 at 3.125 μM, 12.5 μM, and 6.25 μM, respectively. Surprisingly, the combination of compounds 1 or 2 with rapamycin showed a strong synergistic effect, with fractional inhibitory concentration index (FICI) values of 0.03.

Objectives: Cancer is well-known as a collection of diseases of uncontrolled proliferation of cells caused by mutated genes which are generated by external or internal factors. As the mechanisms of cancer have been constantly revealed, including cell cycle, proliferation, apoptosis and so on, a series of new emerging anti-cancer drugs acting on each stage have also been developed. It is worth noting that natural products are one of the important sources for the development of anti-cancer drugs. To the best of our knowledge, there is not any database summarizing the relationships between natural products, compounds, molecular mechanisms, and cancer types.Materials and methods: Based upon published literatures and other sources, we have constructed an anti-cancer natural product database (ACNPD) (http://www.acnpd-fu.com/). The database currently contains 521 compounds, which specifically refer to natural compounds derived from traditional Chinese medicine plants (derivatives are not considered herein). And, it includes 1,593 molecular mechanisms/signaling pathways, covering 10 common cancer types, such as breast cancer, lung cancer and cervical cancer.Results: Integrating existing data sources, we have obtained a large amount of information on natural anti-cancer products, including herbal sources, regulatory targets and signaling pathways. ACNPD is a valuable online resource that illustrates the complex pharmacological relationship between natural products and human cancers.Conclusion: In summary, ACNPD is crucial for better understanding of the relationships between traditional Chinese medicine (TCM) and cancer, which is not only conducive to expand the influence of TCM, but help to find more new anti-cancer drugs in the future.

Ischemic stroke: Compound in fruit and vegetables may offer benefit A metabolite commonly found in fruit and vegetables may provide protection against brain damage after a stroke, according to researchers in China. Lei Zhang and co-workers at Sun Yat-sen University in Guangdong employed the Connectivity Map (CMap), a tool for analyzing genome-wide data and identifying connections between diseases, genes, and potential treatments. They confirmed that the metabolite luteolin may benefit patients who have suffered ischemic stroke, which is caused by a blocked artery to the brain. Using an existing database comprising genetic details of stroke patients and controls, the team found that a major signaling pathway is inactivated and an enzyme called MMP9 is increased in stroke victims. Studies in cultured human brain cells and rats showed that luteolin can inhibit MMP9 and reactivate the signaling pathway.

Background. The association between triglyceride-rich lipoprotein cholesterol (TRL-C) and diabetes mellitus (DM) remains unclear because of limited research and data. The aim of this study was to explore the independent association between TRL-C and DM in hypertensive patients and to examine whether a healthy lifestyle would have an impact on this relationship. Methods. In this study, data from 13,721 hypertensive patients who were not treated with lipid-lowering drugs were analyzed. TRL-C was calculated from total cholesterol (TC) minus [LDL cholesterol + HDL cholesterol]. DM was defined as fasting plasma glucose of ≥7.0 mmol/L and/or self-reported history of hypoglycemic drug use. Results. After adjusting for potential confounding factors, the TRL-C was significantly positively associated with elevated DM (odds ratio (OR): 1.73 and 95% confidence interval (CI): 1.54–1.94). In subgroup analysis, a healthy lifestyle (HL) failed to modify the positive association between TRL-C and DM (HL: OR 1.93, 95%CI 1.58–2.36; non-HL: OR 1.72, 95%CI 1.50–1.98; P for interaction = 0.38). Conclusion. The results showed a positive association between TRL-C and DM in hypertensive patients. A healthy lifestyle failed to diminish the relationship between TRL-C and DM. The novel findings indicate that TRL-C might be a reliable marker of DM and may provide a new strategy for the prevention and treatment of DM.

Myocardial fibrosis is well-known to be the aberrant deposition of extracellular matrix (ECM), which may cause cardiac dysfunction, morbidity, and death. Traditional Chinese medicine formula Si-Miao-Yong-An Decoction (SMYAD), which is used clinically in cardiovascular diseases has been recently reported to able to resist myocardial fibrosis. The anti-fibrosis effects of SMYAD have been evaluated; however, its intricate mechanisms remain to be clarified. Here, we found that SMYAD treatment reduced the fibrosis injury and collagen fiber deposition that could improve cardiac function in isoprenaline (ISO)-induced fibrosis rat models. Combined with our systematic RNA-seq data of SMYAD treatment, we demonstrated that the remarkable up-regulation or down-regulation of several genes were closely related to the functional enrichment of TGF-β and AMPK pathways that were involved in myocardial fibrosis. Accordingly, we further explored the molecular mechanisms of SMYAD were mainly caused by AMPK activation and thereby suppressing its downstream Akt/mTOR and TGF-β/SMAD3 pathways. Moreover, we showed that the ECM deposition and secretion process were attenuated, suggesting that the fibrosis pathological features are changed. Interestingly, we found the similar AMPK-driven pathways in NIH-3T3 mouse fibroblasts treated with ISO. Taken together, these results demonstrate that SMYAD may be a new candidate agent by regulating AMPK-driven Akt/mTOR and TGF-β/SMAD3 pathways for potential therapeutic implications of myocardial fibrosis.

Background. Evidence regarding the nonlinear relationship between serum uric acid (SUA) and blood lipids in Chinese population with hypertension is limited. Therefore, the present study aimed to investigate whether there is a nonlinear association between SUA and lipids in Chinese hypertensive population with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2. Methods. A total of 13,355 hypertensive participants with eGFR ≥30 ml/min/1.73 m2 were selected from the Chinese Hypertension Registry Study. Multivariate linear regression was used to examine the linear relationship between SUA and lipids. Smooth curve fitting (penalized spline method) and threshold saturation effects were used to analyze the nonlinear association between SUA and lipids. Results. In the fully adjusted model, the results showed a positive correlation between SUA and TG (β = 0.15; 95% CI: 0.14, 0.16) and LDL-C (β = 0.06; 95% CI: 0.05, 0.07), respectively. However, the relationship between SUA and HDL-C was nonlinear. The inflection point of SUA was 7.24 mg/dL. On the left side of the inflection point (

Seven new withanolides (1−7) and four known ones (8−11) were isolated from the calyxes and fruits of Nicandra physaloides, an edible and medicinal plant. Their structures were identified by extensive spectroscopic analyses or comparison with literature data. The antioxidant effects and hepatoprotective mechanisms of compounds 1–11 on hydrogen peroxide (H2O2)-induced oxidative stress injury were investigated. Among them, compound 11 showed significant activity with EC50 value of 83.78 ± 0.30 μM. Further, 11 was found to markedly increase cellular survivals and activities of SOD, CAT and GSH, and to reduce the accumulation of reactive oxygen species (ROS) in H2O2-induced LO2 cells. In addition, compound 11 significantly activated Nrf2 nuclear translocation and enhanced the expression of target gene HO-1, suggesting its preliminary mechanism of protective effects. In summary, withanolide 11 might be used as a lead compound for developing a hepatopathy medicine owing to its antioxidative and hepatoprotective effects.

Background. Association between age at menarche (AAM) and hypertension remains a controversial topic, and data in China were sparse. Therefore, we aimed to investigate the association between AAM and hypertension in Chinese female population. Methods. In this cross-sectional study, 5,102 females aged ≥15 years were enrolled. Self-reported AAM was assessed by the questionnaire. Multiple linear regression analysis was used to evaluate the association between systolic blood pressure (SBP), diastolic blood pressure (DBP), and AAM. Logistic regression analysis was performed to evaluate the association between hypertension and AAM. Generalized additive model (GAM) and smooth curve fitting (penalized spline method) were conducted to explore the exact shape of curve between them. Results. The overall mean of AAM was 15.5 years. Each additional year of AAM was associated with a 15% higher risk of hypertension (odds ratio (OR) = 1.15, 95% confidence interval (CI): 1.11–1.19). Among females with hypertension, there was a significant positive association between AAM and SBP (β = 0.88, 95% CI: 0.29–1.46) and DBP (β = 0.80, 95% CI: 0.47–1.13). A significantly higher risk of hypertension was found in younger subjects (15–44 y: OR = 1.37, 95% CI: 1.21–1.55; P for interaction = 0.009) compared with those aged between 62 and 97 y.Conclusions. AAM was positively associated with hypertension and blood pressure, especially among females in early adulthood from southern China.