Background: Qiliqiangxin (QLQX) capsule is a Traditional Chinese Medicine (TCM) that has been approved in China for the treatment of chronic heart failure (CHF). Our previous study showed with a background of standard HF treatment, QLQX capsules further reduced the levels of NT-proBNP and the incidence of composite cardiac events (CCEs) in CHF patients. This study aims to further assess the reduction in mortality when using QLQX compared with placebo for heart failure with reduced ejection fraction (HFrEF) patients. Methods: This study is a randomized, double-blind, placebo-controlled, parallel-group, multi-center, event-driven clinical study of approximately 3080 patients for a targeted 620 events. Patients must have a diagnosis of heart failure for at least 3 months prior to screening. Patients will be randomized 1:1 to receive the placebo or QLQX in addition to their standard medications of CHF. The primary efficacy outcome event is a composite cardiovascular death and re-hospitalization due to the worsening of heart failure. Discussion: The QUEST study is a randomized control study of TCM in chronic heart failure. It will determine the place of QLQX as an new treatment approach and provide additional and innovative information regarding TCM - and the specific used of QLQX in HFrEF. Trial registration: The trial was registered at http://www.chictr.org.cn. ( Registration No.: ChiCTR1900021929); Date: 2019-03-16.

Purpose: The current study aimed to develop a convenient and accurate prognostic dynamic nomogram model for the risk of all-cause death in acute heart failure (AHF) patients that incorporates clinical characteristics including N-terminal pro-brain natriuretic peptide (NT-pro BNP) and growth stimulation expresses gene 2 protein (ST2). Patients and Methods: We prospectively studied 537 consecutive AHF patients and derived a clinical prediction model. The least absolute shrinkage and selection operator regression model combined with clinical characteristics were used for dimensional reduction and feature selection. Multivariate Cox proportional hazard analysis and “Dynnom” package were used to build the dynamic nomogram for prediction of 1-,2-,and 5-year overall survival for AHF. With bootstrap validation, the time-dependent concordance index (C-index) and calibration curves were used to assess predictive discrimination and accuracy. The contributions of NT-pro BNP and ST2 to the nomogram were evaluated using integrated discrimination improvement (IDI) and net reclassification improvement (NRI), while decision curve analysis (DCA) was used to assess clinical value. Results: Patients were randomly divided into derivation (74.9%, n=402) and validation (25.1%, n=135) cohorts. Optimal independent prognostic factors for 1-,2-, and 5-year all-cause mortality were BS-ACMR (B: NT-pro BNP; S: ST2; A: age; C: complete right bundle branch block; M: mean arterial pressure; and R: red cell distribution width > 14.5%); these were incorporated into the dynamic nomogram (https://bs-acmr-nom.shinyapps.io/dynnomapp/) with bootstrap validation. The C-indexes in the derivation (0.793) and validation (0.782) cohorts were consistent with comparable performance parameters. The calibration curve showed good agreement between the nomogram-predicted and actual survival. Adding NT-pro BNP and ST2 provided a significant net benefit and improved performance over other less adequate schemes in terms of DCA of survival probability compared to those neglecting either of these two factors. Conclusion: The study constructed a dynamic BS-ACMR nomogram, which is a convenient, practical and effective clinical decision-making tool for providing accurate prognosis in AHF patients.

Di(2-ethylhexyl) phthalate (DEHP) a parent compound that is metabolized into 4 phthalate metabolites, which correlate to adverse cardio-metabolic risk factors. This study aimed to explore the links between urinary DEHP metabolites and serum lipids in the U.S. general adult population. In this cross-sectional study, data on 11 urinary phthalate metabolites from the 2005–2018 National Health and Nutrition Examination Surveys (NHANES) were analyzed. Multivariate linear regression and restricted cubic spline (RCS) were used to examine the relationship between phthalate metabolites [specific DEHPs: mono-(2-ethyl-5-carboxy-pentyl) phthalate (MECPP), mono-(2-ethyl-5-hydroxy-hexyl) phthalate (MEHHP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl-5-oxo-hexyl) phthalate (MEOHP)] and serum lipids (triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]). To identify mixed exposure effects of phthalate metabolites, quantile g-computation (QG-C) and weighted quantile sum (WQS) regression were employed for the lipid profiles. A total of 9141 adults were included in the analysis. MECPP, MEHHP, MEHP, and MEOHP in the highest quartile had a negative relationship with HDL-C compared to the lowest quartile (All P for trend <0.05). TG showed a significant positive relation with MECPP, MEHHP, and MEOHP (All P for trend 0.05). The WQS index of DEHP metabolites showed independent correlations with HDL-C [β = −0.26, 95%CI (−0.43, −0.09), P = 0.002], TC [β = 0.55, 95%CI (0.13, 0.98), P = 0.011], and TG [β = 2.40, 95%CI (0.85, 3.96), P = 0.003]. Our study suggests that environmental DEHP exposure may affect serum HDL-C and TG levels in the general adult population. Further research is warranted to confirm these findings and illuminate the underlying mechanisms of DEHP exposure on lipids.

Insulin-like growth factor-binding protein 5 (IGFBP5) has been shown to be useful for the diagnosis and treatment of multiple tumors and cerebrovascular diseases. However, it is unknown whether IGFBP5 is involved in myocardial repair following myocardial infarction (MI). Here we show high expression of IGFBP5 in multiple models of ischemic and hypoxic injury. IGFBP5 affected the proliferation of neonatal rat cardiomyocytes (NRCMs) and the cardiomyocyte apoptosis induced by oxygen-glucose deprivation (OGD). Subsequently, heart-specific IGFBP5 knockdown inhibited myocardial apoptosis and increased cardiomyocyte proliferation in mice with MI. During the chronic remodeling stage, heart-specific regulation of IGFBP5 ameliorated pathological cardiac remodeling and dysfunction. Mechanistically, IGFBP5 regulated cardiomyocyte survival through the insulin-like growth factor 1 (IGF1) receptor (IGF1R)/protein kinase B (PKB/AKT) pathway. In summary, our results provide mechanistic insights into the effect of IGFBP5 on cardiomyocyte during cardiac repair. IGFBP5 may represent a therapeutic target for myocardial ischemic injury.