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Osteogenesis imperfecta (OI) is a genetic disorder caused by mutations of type I collagen-related genes, and excessive transforming growth factor-beta (TGF-β) signaling is a common mechanism. TGF-β/Smad signaling has inhibitory effects on osteoblast differentiation and maturation and is mainly transduced and regulated by the internalization of a tetrameric receptor complex comprising types I and II TGF-β receptors (TβRI and TβRII). During internalization, clathrin-mediated endocytosis enhances TGF-β/Smad signaling via Smad2/3 phosphorylation and receptors recycling, while caveolae-mediated endocytosis turns off TGF-β/Smad signaling by promoting receptor ubiquitination and degradation. In this study, using an animal model of OI (Colla2

Background In patients with established HF, low triiodothyronine syndrome (LT3S) is commonly present, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful marker for predicting death. This study was aimed to evaluate the prognostic value of LT3S in combination with NT-proBNP for risk of death in patients with heart failure (HF). Methods A total of 594 euthyroid patients hospitalized with acute decompensated HF were enrolled by design. Of these patients, 27 patients died during hospitalization and 100 deaths were identified in patients discharged alive during one year follow-up. Patients were divided into 2 groups on the base of the reference ranges of free T3 (FT3) levels: LT3S group (FT3 n = 426). Results In multivariable Cox regression, LT3S was significantly associated with 1 year all-cause mortality (adjusted hazard ratio, 1.85; 95 % confidence interval [CI], 1.21 to 2.82; P = 0.005), but not significant for in-hospital mortality (adjusted hazard ratio, 1.58; 95 % CI, 1.58 to 2.82; P = 0.290) after adjustment for clinical variables and NT-proBNP. Addition of LT3S and NT-proBNP to the prediction model with clinical variables significantly improved the C statistic for predicting 1 year all-cause mortality. Conclusions In patients with acute decompensated HF, the combination of LT3S and NT-proBNP improved prediction for 1 year all-cause mortality beyond established risk factors, but was not strong enough for in-hospital mortality.

Aims This study was to determine the cost‐effectiveness of dapagliflozin in heart failure with reduced ejection fraction (HFrEF) patients in China from a perspective of health care payers. Methods and results We built a Markov model to perform a cost‐effectiveness analysis comparing standard treatment + dapagliflozin (10 mg, q.d.) with standard treatment for HFrEF. The base case in our simulation was a 65‐year‐old HFrEF patient and was modelled over 15 years. Inputs of the model were derived from the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial and other relevant data from China. Costs, quality‐adjusted life year (QALY), and incremental cost‐effectiveness ratio (ICER) were estimated for adding dapagliflozin relative to standard treatment. Costs and QALY were discounted at a 4.2% rate annually. All costs are presented in 2017 US dollars. Dapagliflozin would be considered very cost‐effective if the ICER was lower than a willingness‐to‐pay (WTP) threshold of $8573.4. Uncertainty was assessed in our model using one‐way, two‐way, and probabilistic sensitivity analysis (PSA). In our base case, compared with standard treatment, adding dapagliflozin was more expensive ($5829.4 vs. $4377.1) but more effective (4.82 vs. 4.44 QALYs). The respondent ICER was $3827.6 per QALY gained at 15‐year follow‐up. When the simulated horizon was longer than 3.5 years, the respondent ICER became lower than the WTP threshold. The inputs with the largest impact on ICER were the cost of dapagliflozin, the cardiovascular mortality in both groups, and the cost of hospitalization for heart failure. Most results of sensitivity analysis were robust. PSA showed a similar result as the base case (ICER = $4412.5 per QALY gained). In Monte Carlo simulation, at a WTP threshold of $8573.4 per QALY, dapagliflozin was considered very cost‐effective in 53.10% of the simulations. Conclusions Dapagliflozin was a very cost‐effective treatment option for HFrEF patients in China according to the result of our model. Our findings will help doctors and health care payers to make decisions in clinical practice. Future real‐world studies of cost‐effectiveness of dapagliflozin based on Chinese population were also needed.

Mitochondrial dysfunction plays a major role in the pathogenesis of cardiovascular diseases. MicroRNAs (miRNAs) are small RNAs that act as negative regulators of gene expression, but how miRNAs affect mitochondrial function in the heart is unclear. Using a miRNA microarray assay, we found that miR-762 predominantly translocated in the mitochondria and was significantly upregulated upon anoxia/reoxygenation (A/R) treatment. Knockdown of endogenous miR-762 significantly attenuated the decrease in intracellular ATP levels, the increase in ROS levels, the decrease in mitochondrial complex I enzyme activity and the increase in apoptotic cell death in cardiomyocytes, which was induced by A/R treatment. In addition, knockdown of miR-762 ameliorated myocardial ischemia/reperfusion (I/R) injury in mice. Mechanistically, we showed that enforced expression of miR-762 dramatically decreased the protein levels of endogenous NADH dehydrogenase subunit 2 (ND2) but had no effect on the transcript levels of ND2. The luciferase reporter assay showed that miR-762 bound to the coding sequence of ND2. In addition, knockdown of endogenous ND2 significantly decreased intracellular ATP levels, increased ROS levels, reduced mitochondrial complex I enzyme activity and increased apoptotic cell death in cardiomyocytes, which was induced by A/R treatment. Furthermore, we found that the inhibitory effect of miR-762 downregulation was attenuated by ND2 knockdown. Thus, our findings suggest that miR-762 participates in the regulation of mitochondrial function and cardiomyocyte apoptosis by ND2, a core assembly subunit of mitochondrial complex I. Our results revealed that mitochondrial miR-762, as a new player in mitochondrial dysfunction, may provide a new therapeutic target for myocardial infarction.

Dysregulated autophagy is associated with many pathological disorders such as cardiovascular diseases. Emerging evidence has suggested that circular RNAs (circRNAs) have important roles in some biological processes. However, it remains unclear whether circRNAs participate in the regulation of autophagy. Here we report that a circRNA, termed autophagy-related circular RNA (ACR), represses autophagy and myocardial infarction by targeting Pink1-mediated phosphorylation of FAM65B. ACR attenuates autophagy and cell death in cardiomyocytes. Moreover, ACR protects the heart from ischemia/reperfusion (I/R) injury and reduces myocardial infarct sizes. We identify Pink1 as an ACR target to mediate the function of ACR in cardiomyocyte autophagy. ACR activates Pink1 expression through directly binding to Dnmt3B and blocking Dnmt3B-mediated DNA methylation of Pink1 promoter. Pink1 suppresses autophagy and Pink1 transgenic mice show reduced myocardial infarction sizes. Further, we find that FAM65B is a downstream target of Pink1 and Pink1 phosphorylates FAM65B at serine 46. Phosphorylated FAM65B inhibits autophagy and cell death in the heart. Our findings reveal a novel role for the circRNA in regulating autophagy and ACR-Pink1-FAM65B axis as a regulator of autophagy in the heart will be potential therapeutic targets in treatment of cardiovascular diseases.

Objective We hypothesized that discharge SBP had different associations with outcomes in non-HFrEF (left ventricular ejection fraction ≥40%) patients with or without high blood pressure (HBP) at admission. Methods Non-HFrEF patients hospitalized for decompensated heart failure were consecutively recruited and were categorized into HBP (admission SBP ≥130 mmHg) group and non-HBP group. The primary outcome was a composite of cardiovascular death and heart transplantation. Multivariate Cox and penalized spline analyses were used to assess the relationships between discharge SBP and outcomes. Results Nine hundred and sixty-four non-HFrEF patients were enrolled with a median follow-up of 71.8 months. Three hundred and sixty-five (37.9%) patients had HBP. In multivariate Cox analyses, non-HBP patients with higher discharge SBP were associated with a better outcome (per 10 mmHg increased, hazard ratio = 0.788, P = 0.001). However, an opposite relationship between discharge SBP and the primary outcome was observed in HBP group (per 10 mmHg increased, hazard ratio = 1.312, P = 0.002). Results of penalized spline regression models showed that there was a U-shaped association between discharge SBP and outcomes in the total cohort. Compared with 120 mmHg, the risk of the primary outcome increased when discharge SBP was below 99 mmHg in non-HBP group; in HBP group, a worse outcome was observed when discharged SBP was above 145 mmHg. Conclusion Non-HFrEF had a U-shaped association between discharge SBP and adverse events. Such an association was modified by admission HBP. Higher discharge SBP correlated with a worse outcome in non-HFrEF patients with admission HBP, as opposed to patients admitted without HBP.

The aim of this study was to investigate the effect on mortality of torsemide and a combination of loop diuretics (furosemide + torsemide) in contemporary practice in patients with chronic heart failure (HF).We investigated patients with HF in the Heart Failure Center of Fuwai Hospital from 2009 to 2013 who were discharged on furosemide, torsemide, or a combination of the 2 drugs. Using inverse probability weighting (IPW) to account for nonrandom selection of diuretic strategies, we assessed the association between different diuretic strategies and mortality.Among 956 patients, 19.7% (n = 188) received furosemide, 36.6% (n = 350) torsemide, and 43.7% (n = 418) the combination therapy. The torsemide-treated and combination-treated patients had worse heart function and higher furosemide equivalent. Univariable Cox proportional hazards models showed that the combination group had worse outcomes (all-cause HR = 2.044, P = 0.008; CV HR = 1.988, P = 0.011), while torsemide was associated with an outcome (all-cause HR = 1.640, P = 0.078; CV HR = 1.509, P = 0.147) similar to that of furosemide. After IPW, torsemide was associated with a nominally lower mortality compared with furosemide (all-cause HR = 0.738, P = 0.222; CV HR = 0.667, P = 0.110), and the association between the combination treatment and increased mortality was no longer statistically significant (all-cause HR = 1.207, P = 0.470;CV HR = 1.174, P = 0.540).We found that torsemide and the combination strategy had similar outcomes when compared with furosemide. However, considering the lack of diuretic randomized clinical trials (RCTs) conducted with the aim of exploring the effect on mortality of different diuretic treatments, prospective trials are needed to investigate the effect of different diuretic strategies in chronic HF.

Background Galectin-3 plays an important role in modulating cardiac inflammation and fibrosis. It also takes part in the pathways underlying cardiac remodeling. Therefore, LGALS3 gene, encoding galectin-3 protein, is a promising candidate for the genetic study of dilated cardiomyopathy (DCM). To date, there has been no research evaluating the association between LGALS3 gene polymorphisms and the susceptibility and prognosis of DCM. Methods and Results Genotyping of 4 single nucleotide polymorphisms (SNPs) in the LGALS3 gene, which were reported to be functional in the literature, was performed in 279 unrelated clinically diagnosed DCM patients and 363 apparently healthy controls from Northern Han Chinese population using iPLEX SNP Genotyping analysis on a Sequenom MassARRAY System. The frequency of G allelic polymorphism of rs1009977 and the C allelic polymorphism of rs4652 were lower in DCM patients (OR = 0.77, 95% CI [0.60–0.99], P = 0.045; OR = 0.79, 95% CI [0.63–0.99], P = 0.042, respectively). The minor variants of rs1009977 and rs4652 were associated with low susceptibility of DCM under additive genetic models (P = 0.045 and P = 0.040, respectively). The AA genotype of both rs2274273 and rs4644 was associated with lower left ventricular ejection fraction (recessive model, P = 0.018 for both; additive model, P = 0.039 for both). The G variant of rs1009977 was related with lower serum galectin-3 level in DCM patients under three genetic models (additive model, P = 0.020, dominant model, P = 0.020, recessive model, P = 0.037). The A variant of both rs2274273 and rs4644 was associated with lower level of galectin-3 in DCM patients under additive model (P = 0.032 for both) and dominant model (P = 0.012 for both). None of the 4 SNPs was associated with the cardiovascular or all-cause death rate of DCM. In Conclusion, LGALS3 gene polymorphisms might be associated with the susceptibility of DCM in a Northern Han Chinese population.

Increasing evidence suggests that long noncoding RNAs (lncRNAs) play crucial roles in various biological processes. However, little is known about the effects of lncRNAs on autophagy. Here we report that a lncRNA, termed cardiac autophagy inhibitory factor (CAIF), suppresses cardiac autophagy and attenuates myocardial infarction by targeting p53-mediated myocardin transcription. Myocardin expression is upregulated upon H2O2 and ischemia/reperfusion, and knockdown of myocardin inhibits autophagy and attenuates myocardial infarction. p53 regulates cardiomyocytes autophagy and myocardial ischemia/reperfusion injury by regulating myocardin expression. CAIF directly binds to p53 protein and blocks p53-mediated myocardin transcription, which results in the decrease of myocardin expression. Collectively, our data reveal a novel CAIF-p53-myocardin axis as a critical regulator in cardiomyocyte autophagy, which will be potential therapeutic targets in treatment of defective autophagy-associated cardiovascular diseases., Little is known about the role of long lncRNAs in autophagy. The authors identify lncCAIF, and show that it suppresses cardiac autophagy and attenuates myocardial infarction by targeting p53 -mediated transcription of myocardin.

Cardiomyocyte apoptosis is initiated by various cellular insults and accumulated cardiomyocyte apoptosis leads to the pathogenesis of heart failure. Excessive reactive oxygen species (ROS) provoke apoptotic cascades. Manganese superoxide dismutase (MnSOD) is an important antioxidant enzyme that converts cellular ROS into harmless products. In this study, we demonstrate that MnSOD is down-regulated upon hydrogen peroxide treatment or ischemia/reperfusion (I/R) injury. Enhanced expression of MnSOD attenuates cardiomyocyte apoptosis and myocardial infarction induced by I/R injury. Further, we show that miR-23a directly regulates the expression of MnSOD. miR-23a regulates cardiomyocyte apoptosis by suppressing the expression of MnSOD. Our study reveals a novel model regulating cardiomyocyte apoptosis which is composed of miR-23a and MnSOD. Our study provides a new method to tackling apoptosis related cardiac diseases.

To investigate whether the combination of measuring amino-terminal pro-B-type natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP) could provide additional prognostic value in hospitalized heart failure patients.We measured both BNP and NT-proBNP simultaneously at baseline in 1464 hospitalized heart failure patients who were admitted to our heart failure center. All patients were followed-up with the median follow-up period of 533 days. The primary endpoint is a composite of all-cause death (non-transplantation patients) or heart transplantation.The median molar ratio of NT-proBNP/BNP was 2.37, but the range of the molar ratio varied from 1.57 to 3.75 (lower quartile to higher quartile). Using the cut-off value of 1790 pg/mL for NT-proBNP and 495 pg/mL for BNP from the ROC curve analysis, univariate Cox proportional regression analysis showed that the low/high group (NT-proBNP1790 pg/mL and BNP ≥ 495 pg/mL), high/low group (NT-proBNP ≥ 1790 pg/mL and BNP495 pg/mL) and high/high group (NT-proBNP ≥ 1790 pg/mL and BNP ≥ 495 pg/mL) had significant higher risk of all-cause death or heart transplantation [HR (hazard ratio): 2.87, 95% CI (confidence interval): 1.69-4.89, p .001; HR: 2.68, 95% CI: 1.91-3.76, p .001; HR:5.07, 95% CI: 3.85-6.67, p .001] than low/low group (NT-proBNP1790 pg/mL and BNP495 pg/mL). In turn, the high/high group had higher risk of all-cause death or heart transplantation than low/high (HR: 1.70, 95% CI: 1.04-2.80, p = .035) and high/low groups (HR: 1.88, 95% CI: 1.42-2.49, p .001). The low/high and high/low groups had a similar risk of all-cause death or heart transplantation. Further multivariable Cox regression analysis also showed that both BNP and NT-proBNP above the cut-off values independently predicted the worst prognosis, while either one of the two biomarkers above the cut-off value indicated the moderate poor prognosis and both below the cut-off values indicated the best prognosis (p for trend0.001).The plasma levels of NT-proBNP and BNP do not always increase proportionally in heart failure patients. The combination of testing NT-proBNP and BNP may add prognostic value to predict adverse events in hospitalized heart failure patients.

Background There has been no research evaluating the association between human Neuregulin (NRG) 1/ErbB2/ErbB4 gene polymorphisms and heart failure risk. Methods and Results Genotyping of 13 single nucleotide polymorphisms (SNPs) in the NRG-1/ErbB2/ErbB4 genes was performed in 569 unrelated heart failure patients and 682 healthy controls from a Northern Han Chinese population with the use of iPlex SNP Genotyping analysis on a Sequenom Massarray System. In the ErbB4 gene, the variants rs10932374 and rs1595064 were associated with reduced risk of heart failure under allelic, recessive and additive genetic models, and the variants rs13003941 and rs1595065 were associated with increased risk of heart failure under allelic, dominant, and additive models. The G-G-C-C-T haplotype of rs10932374-rs13003941-rs1595064-rs1595065-rs3748960 in the ErbB4 gene increased the risk of heart failure (odd ratio 1.35, 95% confidence interval [CI] 1.06–1.70; P = .014). The T variant of rs13003941 was associated with larger left ventricle (dominant model, P = .014; additive model, P = .048), and increased risk of overall death (relative risk [RR] 1.48, 95% CI 1.01–2.18; P = .045) and cardiovascular death (RR 1.56, 95% CI 1.04–2.33; P = .03) after adjusting for age and sex. NRG-1/ErbB2 gene polymorphisms were not associated with heart failure risk or prognosis. Conclusion ErbB4 gene polymorphisms were associated with the risk, severity, and prognosis of heart failure in a Northern Han Chinese population.

The aim of this study was to investigate the effect on mortality of torsemide and a combination of loop diuretics (furosemide + torsemide) in contemporary practice in patients with chronic heart failure (HF).We investigated patients with HF in the Heart Failure Center of Fuwai Hospital from 2009 to 2013 who were discharged on furosemide, torsemide, or a combination of the 2 drugs. Using inverse probability weighting (IPW) to account for nonrandom selection of diuretic strategies, we assessed the association between different diuretic strategies and mortality.Among 956 patients, 19.7% (n = 188) received furosemide, 36.6% (n = 350) torsemide, and 43.7% (n = 418) the combination therapy. The torsemide-treated and combination-treated patients had worse heart function and higher furosemide equivalent. Univariable Cox proportional hazards models showed that the combination group had worse outcomes (all-cause HR = 2.044, P = 0.008; CV HR = 1.988, P = 0.011), while torsemide was associated with an outcome (all-cause HR = 1.640, P = 0.078; CV HR = 1.509, P = 0.147) similar to that of furosemide. After IPW, torsemide was associated with a nominally lower mortality compared with furosemide (all-cause HR = 0.738, P = 0.222; CV HR = 0.667, P = 0.110), and the association between the combination treatment and increased mortality was no longer statistically significant (all-cause HR = 1.207, P = 0.470;CV HR = 1.174, P = 0.540).We found that torsemide and the combination strategy had similar outcomes when compared with furosemide. However, considering the lack of diuretic randomized clinical trials (RCTs) conducted with the aim of exploring the effect on mortality of different diuretic treatments, prospective trials are needed to investigate the effect of different diuretic strategies in chronic HF.

Background Contemporary data on the epidemiology of heart failure (HF) in China are scarce. The China-HF Registry was designed to investigate clinical characteristics, management, and outcomes of patients hospitalized for HF in China. Methods and Results Data were collected prospectively on 13,687 patients with a primary discharge diagnosis of HF who were enrolled from 132 participating hospitals from January 2012 to September 2015. Data from the China-HF Registry was compared with previously published literature. The mean age was 65 ± 15 years, 59.1% were male, and 36.0% had preserved ejection fraction. Age, body mass index, and systolic blood pressure were lower than in high-income countries. Common comorbidities included hypertension (50.9%), coronary heart disease (49.6%), and atrial fibrillation (24.4%). The overall use of diuretics, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB), and β-blockers at admission was 30.1%, 27.0%, and 25.6%, respectively, which was lower than in other registries. For patients discharged alive, ACEI/ARB, β-blocker, and mineralocorticoid receptor antagonist use in patients with reduced ejection fraction was 67.5%, 70.0%, and 74.1%, respectively; device use was much lower. The median length of hospital stay was 10 (range 7–15) days, and in-hospital mortality was 4.1 ± 0.3%. Predictors of mortality included low systolic blood pressure, acute myocardial infarction, infection, right bundle branch block, and elevated total bilirubin and blood urea nitrogen level. Conclusions Several important findings in patient profile and treatment patterns among Chinese patients with HF were noted compared with published literature. These data underscore the need for regional characterization of HF for global clinical trials and for the identification of several quality improvement opportunities.

This study was designed to investigate the plasma level of soluble ST2 (sST2) and related influencing factors, and establish its reference value in the healthy community-based population in Beijing area of China.We measured plasma sST2 level by enzyme-linked immunosorbent assay between March 2012 and August 2012 in 1 334 healthy subjects in communities, including 597 males and 737 females. Empiric and quantile regression methods were used to determine the reference range of plasma sST2. A multiple linear regression model was established to analyze the factors that might affect the level of plasma sST2.Gender is the most important factor affecting the plasma level of sST2 in healthy people. Plasma level of sST2 is significantly higher in men than in women (P0.01). Within each age strata, i.e.45, 45-54, 55-64, ≥ 65 years old, the plasma levels of sST2 were significantly higher in men than age-matched female (all P0.01). Age, body mass index (BMI), systolic blood pressure, diastolic blood pressure, and smoking did not affect plasma sST2 level. Reference range of sST2 was 5.7-53.5 µg/L for men and 4.4-42.4 µg/L for women (95% nonparametric reference interval). The one-side upper 95th percentile value of sST2 to discriminate the cardiovascular disease from healthy state was 47.2 µg/L for men and 37.2 µg/L for women.This study established the normal reference range of plasma sST2 in healthy community-based population. The major influencing factor of sST2 level in healthy population is gender.

To investigate the prevalence and prognostic value of hyponatremia on admission in hospitalized patients for heart failure (HF) from the first HF management center in China.Consecutive adult (age of 18 years or older) symptomatic HF patients (NYHA functional class II-IV) admitted between March 2009 and March 2012 in our center were included in the present analysis. Hyponatremia was defined as a serum sodium level135 mmol/L. Association between hyponatremia on admission and in-hospital mortality as well as all-cause death and heart failure death during 1-year follow-up after discharge was analyzed.A total of 1 048 hospitalized patients for HF with complete baseline data were enrolled and the prevalence of hyponatremia on admission was 9.2% (96/1 048). Blood pressure was significantly lower while NYHA functional class and N-terminal pro-B type natriuretic peptide levels were significantly higher in hyponatremic patients than non-hyponatremic patients (all P0.05). Kaplan-Meier survival analysis showed that patients with hyponatremia on admission had significant higher in-hospital mortality (P0.01), all-cause death rate (P0.01) and HF death rate (P0.01) during 1-year follow-up post discharge compared with non-hyponatremic patients with. Multiple Cox proportional hazard analysis showed that hyponatremia on admission remained as independent predictor for all-cause death (hazard risk (HR) = 2.105, 95% confidence interval (CI) 1.460-3.036, P0.01) and HF death (HR = 2.458, 95% CI: 1.704-3.545, P0.01) after adjustment for other covariates.Hyponatremia is relatively common in patients hospitalized with HF in China and hyponatremia on admission is associated with higher in-hospital mortality and all-cause death and HF death one year after discharge.

Background: Qiliqiangxin (QL) capsule is a traditional Chinese medicine which has been approved for the treatment of chronic heart failure. Evidences proved that QL capsules further reduced the NT-proBNP levels and improved left ventricular ejection fraction in CHF patients but the evidence supporting its underlying mechanism is still unclear. Methods and Results: Myocardial infarction (MI) -Heart failure (HF) Sprague-Dawley ratsmodel and neonatal rat cardiac myocytes (NRCMs) were used. Animals were assigned into 4 groups, normal group (n=6), shame-operation group (n=6), MI rats 4 weeks after left anterior descending coronary artery ligation were randomized into vehicle group (n=8), QL group (n=8). QL significantly attenuated cardiac dysfunction and ventricle remodeling as echocardiography and hemodynamic measurements showed improvement in left ventricular ejection fraction, fractional shortening, ±dp/dt and left ventricular end diastolic and systolic diameters in QL treated group compared with the vehicle group. Improvements ininterstitial fibrosisand mitochondrial structures were also exhibited by Sirius Red staining, RT-PCR and electron microscopy. QL treatment improved apoptosis and VEGF expression in rats marginal infract area. Complementary experiments analyzed the improved apoptosis and up-regulate of VEGF in ischemia-hypoxia cultivated NRCMs is in an Akt dependent manner and can be reversed by Akt inhibitor. Conclusion: QL capsule can improve cardiac dysfunction and ventricular remodeling in MI-HF ratsmodel, this cardiac protective efficacy may be concerned with attenuated apoptosis and cardiac fibrosis. Up-regulated VEGF expression and Akt phosphorylation may take part in this availability.

To investigate the plasma level of amino-terminal pro-brain natriuretic peptide (NT-proBNP) and related influencing factors in a community-based healthy population in Beijing area.We measured plasma NT-proBNP level by fluoroimmunoassay between March 2012 and July 2012 from 1 034 healthy subjects (including 486 men and 548 women). Empiric method was used to determine the reference value and influencing factors were analyzed.Age and gender are important factors affecting the level of NT-proBNP in healthy subjects. NT-proBNP plasma level is significantly higher in women than in men within each age strata below 75 years old, i.e.45, 45-54, 55-64 and 65-74 years old (P = 0.005, 0.001, 0.001, 0.011 respectively), but NT-proBNP plasma level is similar between male and female older than 75 years (P = 0.504). NT-proBNP level also increases with age irrespective of gender. Body mass index (BMI) is another independent influencing factor of NT-proBNP (P0.001), while estimated glomerular filtration rate is not influencing factor. The reference range of NT-proBNP is133 ng/L for men and289 ng/L for women aged55 years old,185 ng/L for men and333 ng/L for women aged between 55 and 64 years old, and465 ng/L for men and378 ng/L for women aged ≥ 75 years old.The major influencing factors of NT-proBNP level in the healthy population are age, gender and BMI. It essential to establish normal reference range of NT-proBNP according to these factors for Chinese population.

Aim: To evaluate the associations of soluble ST2 (sST2) and galectin-3 with death relative to renal function in patients with heart failure (HF). Methods: Eleven-hundred-and-sixty-one patients hospitalized for HF with 1-year follow up were enrolled for biomarkers analysis. Results: Patients were divided into two groups based on eGFR of either > or ≤60 ml/min/1.73 m2. sST2 was independently associated with death in both categories of renal function, while galectin-3 lost this significance after addition of NT-proBNP to the model of patients with eGFR ≤60 ml/min/1.73 m2. Conclusion: In patients with HF, sST2 improved prediction for death beyond risk factors without being influenced by renal function, however, the prognostic value of galectin-3 is less clear below an eGFR of 60 ml/min/1.73 m2.

To explore the predict value of plasma soluble ST2 (sST2) on one-year mortality for hospitalized patients with chronic heart failure (HF).A total of 1 244 consecutive hospitalized patients admitted to Heart Failure Center Fuwai Hospital between March 2009 and July 2012 and with HF as their primary diagnosis were included. Plasma sST2 was measured in all patients and patients were followed up for 1 year, and the primary endpoint was defined as all-cause death.There were 193 deaths during follow up. sST2 concentrations at admission were positively correlated with NT-proBNP, NYHA functional class and heart rate, and negatively correlated with left ventricular ejection fraction, blood sodium, total cholesterol and glomerular filtration rate at admission. sST2 concentrations were significantly higher in non-survivors compared with survivors (P0.001). Multivariable Cox regression analyses showed that sST2 independently predicted 1-year mortality (per 1 log unit, hazard ratio 1.87, 95% confidence interval: 1.56 to 2.25, P0.001). In receiver operating characteristic analyses, the area under the curve for ST2 was 0.776 which was similar to that of N-terminal pro-B-type natriuretic peptide (NT-proBNP) (AUC = 0.775). The prognostic value was improved when combining these two biomarkers together (AUC = 0.813).sST2 concentration at admission is correlated with clinical and biochemical indexes and associated with 1-year mortality for hospitalized patients with HF.

Objectives Galectin-3 has been shown to be involved in the process of cardiac fibrosis and to predict adverse events in heart failure (HF), but the association of galectin-3 with cause-specific death has not been well established. The purpose of this study was to investigate the prognostic value of baseline galectin-3 for all-cause, cardiovascular (CV), and in-hospital death in patients with HF. Methods and Results From March 2009 to April 2013, we consecutively measured galectin-3 in a large cohort of 1,440 hospitalized patients with HF. Cox proportional hazards regression, discrimination, and reclassification analyses were used to evaluate the association between galectin-3 and death. During a median follow-up of 582 days, 283 deaths were identified, of which 64 were patients who died during hospitalization. Compared with the lowest galectin-3 tertile, the highest 2 tertiles were significantly associated with all-cause, CV, and progressive HF death, but not significant for sudden and in-hospital death when analyzed by multivariable Cox regression. The utility of combining galectin-3 and N-terminal pro–B-type natriuretic peptide was assessed by dichotomizing these 2 biomarkers according to their median values. The highest risk of death due to all-cause, CV, and progressive HF was observed when both biomarkers were elevated after adjustment for established risk factors. Addition of galectin-3 to the prediction model for all-cause and CV death significantly improved discrimination and reclassification. Conclusions Galectin-3 independently predicted death and added additional prognostic value beyond established risk factors in hospitalized patients with HF. The utility of galectin-3 alone as a risk predictor was not strong enough to assess sudden or in-hospital death.

Tumor necrosis factor receptor-associated factor 1 (TRAF1), an adapter in signal transduction, is involved in immunity and in apoptotic processes in various cell types. However, little is known about its function and the molecular mechanism of its activation during liver injury. This study tested the hypothesis that TRAF1 is a mediator of cell injury after hepatic ischemia/reperfusion injury (I/R). In a mouse hepatic I/R injury model, we found that TRAF1 expression was highly induced. TRAF1 deficiency was liver protective, whereas sustained TRAF1 overexpression aggravated liver injury in response to hepatic I/R injury. Mechanistic studies demonstrated that a deficiency of TRAF1 in cultured hepatocytes led to the inhibition of NF-κB-mediated inflammatory responses, suppression of the ASK/JNK pro-death pathway and promotion of cellular regeneration capacity. In contrast, the converse occurred in hepatocyte-specific TRAF1 transgenic mice. TRAF1 activated the ASK1/JNK pathway and promoted hepatic injury. Our study demonstrates that TRAF1 is a crucial early mediator of hepatic I/R injury and suggests that TRAF1 may be a potential gene therapy target for the treatment of liver injury.

Background sST2 has been shown to be a risk predictor in heart failure (HF). Our aim was to explore the characteristics and prognostic value of soluble ST2 (sST2) in hospitalized Chinese patients with HF. Methods and Results We consecutively enrolled 1528 hospitalized patients with HF. Receiver operating characteristic (ROC) and multivariable Cox proportional hazards analysis were used to assess the prognostic values of sST2. Adverse events were defined as all-cause death and cardiac transplantation. During a median follow-up of 19.1 months, 325 patients experienced adverse events. Compared with patients free of events, sST2 concentrations were significantly higher in patients with events (P55.6 ng/mL) independently predicted events in comparison to the lowest quartile (≤25.2 ng/mL) when adjusted by multivariable model. In ROC analysis, the area under the curve for sST2 was not different from that for NT-proBNP in short and longer term. Over time, sST2 also improved discrimination and reclassification of risk beyond NT-proBNP. Conclusions sST2 is a strong independent risk predictor in Chinese patients hospitalized with HF and can significantly provide additional prognostic value to NT-proBNP in risk prediction.

Emerging evidence has shown the potential of marked improvement in left ventricular ejection fraction (LVEF) in patients with recent-onset cardiomyopathy (ROCM) on medical therapy. This study was designed to determine the frequency and to identify predictors of normalization of LVEF in a cohort of Chinese patients with ROCM receiving contemporary medication. A consecutive series of patients admitted from October 2008 to November 2012 with the clinical diagnosis of ROCM and LVEF ≤ 40% by echocardiography at presentation were followed up at least 12 months to identify those with normalization of LVEF, defined as an increase in LVEF to a final level of ≥ 50%. An array of clinical and echocardiographic variables regarded as potentially relevant to normalization was evaluated to identify predictors using logistic regression analysis. After a mean follow-up of 31 ± 13 months, 48% of 128 patients had normalized their LVEF, showing a significant increase in LVEF from 32 ± 6% to 58 ± 5%, of which 68% occurred within 1 year after initial diagnosis. Multivariate analysis demonstrated that normalization of LVEF was associated with a history of hypertension, higher systolic blood pressure at presentation, shorter electrocardiographic QRS duration, smaller left ventricular end-diastolic diameter, and higher LVEF by echocardiography at baseline. In conclusion, nearly 1/2 of a relatively large number of Chinese patients with ROCM have shown normalization of LVEF on current medical therapy after a medium-term follow-up, which was associated with some clinical and echocardiographic parameters.