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ObjectivesThis study aimed to find novel oxidative stress (OS)-related biomarkers of osteoporosis (OP), together with targeting the macromolecule Mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2) protein to further discover potential novel materials based on an advanced structural biology approach.MethodsGene expression profiles of GSE35958 were obtained from the Gene Expression Omnibus (GEO) database, which were included for weighted gene co-expression network analysis (WGCNA) and differential analysis to identify the most correlated module, to identify OS-related hub genes in the progression of OP. Functional annotations were also analyzed on the interested module to get a comprehensive understanding of these genes. Then, a series of advanced structural biology methods, including high-throughput screening, pharmacological characteristic prediction, precise molecular docking, molecular dynamics simulation, etc., was implemented to discover novel natural inhibitor materials against the MAPKAPK2 protein.ResultsThe brown module containing 720 genes was identified as the interested module, and a group set of genes was determined as the hub OS-related genes, including PPP1R15A, CYB5R3, BCL2L1, ABCD1, MAPKAPK2, HSP90AB1, CSF1, RELA, P4HB, AKT1, HSP90B1, and CTNNB1. Functional analysis demonstrated that these genes were primarily enriched in response to chemical stress and several OS-related functions. Then, Novel Materials Discovery demonstrated that two compounds, ZINC000014951634 and ZINC000040976869, were found binding to MAPKAPK2 with a favorable interaction energy together with a high binding affinity, relatively low hepatoxicity and carcinogenicity, high aqueous solubility and intestinal absorption levels, etc., indicating that the two compounds were ideal potential inhibitor materials targeting MAPKAPK2.ConclusionThis study found a group set of OS-related biomarkers of OP, providing further insights for OS functions in the development of OP. This study then focused on one of the macromolecules, MAPKAPK2, to further discover potential novel materials, which was of great significance in guiding the screening of MAPKAPK2 potential materials.

ObjectiveTo explore the correlation between the incidence of atrial fibrillation (AF) and thyroid dysfunction in patients with hypertrophic obstructive cardiomyopathy (HOCM).MethodsThyroid function testing in 755 consecutive patients with HOCM were examined at the National Center for Cardiovascular Diseases (China) from October 2009 to December 2013. Patients were divided into four groups according to the TSH levels: TSH10.00mIU/L(n=17).ResultsA total of 107 patients were diagnosed with AF (14%).(1) Compared to HOCM patients without AF,HOCM patients with AF have older age (P

BackgroundThe triglyceride-glucose index (TyG index) is a valuable marker for predicting adverse cardiovascular events in diabetic patients. However, for nondiabetic patients, whether the TyG index is independently related to poor prognosis remains unclear. This cohort study assessed the association of the TyG index with future cardiovascular risk in nondiabetic subjects who received percutaneous coronary intervention (PCI).MethodsWe consecutively enrolled 5,489 nondiabetic patients who underwent PCI. All experimental subjects were divided into three groups based on their TyG index, which was determined by the equation ln (fasting triglyceride (mg/dl) × fasting blood glucose (mg/dl)/2). The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, and target vessel revascularization (TVR).ResultsA total of 386 MACCE were documented during a median 29-month follow-up. The Kaplan–Meier survival results indicated that among the three groups, there was no obvious difference in any endpoints. Further Cox regression analyses suggested that the TyG index was not independently related to adverse cardiovascular outcomes for nondiabetic patients who underwent PCI (HR: 0.77, 95% CI 0.56–1.16, P = 0.210 for MACCE). Subgroup analysis suggested that the TyG index was independently relevant to MACCE for patients with low-density lipoprotein cholesterol (LDL-C) lower than 1.8 mmol/L.ConclusionThe TyG index is not an effective predictive factor for adverse cardiovascular prognosis in nondiabetic patients who underwent PCI. However, in subjects with LDL-C lower than 1.8mmol/L, it may predict future cardiovascular risk.

BackgroundThis study aims to investigate the role of free triiodothyronine (fT3) in predicting poor prognosis of adult patients with acute myocarditis.MethodsA total of 173 consecutive adult patients with acute myocarditis completed thyroid function evaluations. They were divided into two groups according to fT3 levels: low fT3 group (n = 54, fT3 < 3.54 pmol/liter) and normal fT3 group (n = 119, fT3 ≥ 3.54 pmol/liter). The primary endpoint was major adverse cardiac events (MACE).ResultsDuring the 3.5 ± 2.8 years follow-up, the rate of MACE was 29.6% versus 3.5% in low fT3 group versus normal fT3 group, respectively (P < 0.0001). Long-term at 8 years MACE-free survival were lower in low fT3 group versus normal fT3 group (52.9% versus 92.3%, log-rank P < 0.0001), respectively. Univariate Cox analysis showed that left ventricular ejection fraction (LVEF) < 50% [hazard ratio (HR) 10.231, 95% confidence interval (CI): 3.418–30.624, P < 0.0001) and low fT3 level (HR 0.360, 95% CI: 0.223–0.582, P < 0.0001) were strongest two predictors of MACE. After adjustment for traditional risk predictors, the prognostic value of fT3 status was still significant (HR 0.540, 95% CI: 0.316–0.922, P = 0.024). Compared with normal fT3 group, those in low fT3 group were at a much higher risk of MACE (HR 5.074, 95% CI: 1.518–16.964, P = 0.008).ConclusionsLow T3 syndrome was a strong predictor of poor prognosis in adult patients with acute myocarditis. These findings suggest that fT3 level could serve as a biomarker for risk stratification in acute myocarditis patients.

BackgroundHigh lipoprotein(a) (Lp[a]) levels are associated with increased risks of cardiovascular events in Percutaneous Coronary Intervention (PCI) patients with diabetes mellitus (DM). Peri-procedural myocardial infarction (PMI) occurs commonly during the PCI, whereas the relationship between Lp(a) and PMI remains unclear. Our study aimed to evaluate the association between Lp(a) value and the incidence of PMI in a larger-scale diabetic cohort undergoing PCI throughout 2013.MethodsA total of 2,190 consecutive patients with DM were divided into two groups according to the median Lp(a) level of 175 mg/L: Low Lp(a) group (N = 1095) and high Lp(a) group (N = 1095). PMI was defined based on the 2018 universal definition of myocardial infarction.ResultsPatients with high Lp(a) levels exhibited higher rates of PMI compared to those with low Lp(a) levels (2.3% versus 0.8%, P = 0.006). The multivariable logistic analysis showed that PMI was independently predicted by Lp(a) as a dichotomous variable (OR 2.64, 95%CI 1.22–5.70) and as a continuous variable (OR 1.57, 95% CI 1.12–2.20). However, further investigation found that this association was only maintained in men, whose Lp(a) levels were significantly associated with the frequency of PMI, both as a dichotomous variable (OR 3.66, 95%CI 1.34–10.01) and as a continuous variable (OR 1.81, 95%CI 1.18–2.78). Lp(a) wasn’t a risk factor of PMI in women.ConclusionsHigh Lp(a) levels had forceful correlations with the increased frequency of PMI in male diabetic patients undergoing PCI. Lp(a) might act as a marker of risk stratification and a therapeutic target to reduce PCI-related ischemic events.