Diabetic cardiomyopathy (DCM) is a pathophysiological condition induced by diabetes mellitus that often causes heart failure (HF). However, their mechanistic relationships remain unclear. This study aimed to identify immune gene signatures and molecular mechanisms of DCM. Microarray data from the Gene Expression Omnibus (GEO) database from patients with DCM were subjected to weighted gene co-expression network analysis (WGCNA) identify co-expression modules. Core expression modules were intersected with the immune gene database. We analyzed and mapped protein-protein interaction (PPI) networks using the STRING database and MCODE and filtering out 17 hub genes using cytoHubba software. Finally, potential transcriptional regulatory factors and therapeutic drugs were identified and molecular docking between gene targets and small molecules was performed. We identified five potential immune biomarkers: proteosome subunit beta type-8 (PSMB8), nuclear factor kappa B1 (NFKB1), albumin (ALB), endothelin 1 (EDN1), and estrogen receptor 1 (ESR1). Their expression levels in animal models were consistent with the changes observed in the datasets. EDN1 showed significant differences in expression in both the dataset and the validation model by real-time quantitative PCR (qPCR) and Western blotting(WB). Subsequently, we confirmed that the potential transcription factors upstream of EDN1 were PRDM5 and KLF4, as its expression was positively correlated with the expression of the two transcription factors. To repurpose known therapeutic drugs, a connectivity map (CMap) database was retrieved, and nine candidate compounds were identified. Finally, molecular docking simulations of the proteins encoded by the five genes with small-molecule drugs were performed. Our data suggest that EDN1 may play a key role in the development of DCM and is a potential DCM biomarker.

Carotenoid levels are inversely associated with blood pressure (BP). This study focused on the effects of individual and combined serum carotenoids on BP and hypertension, which have not been established to date. Data from National Health and Nutrition Examination Survey (NHANES) 2001–2006 were analyzed in this cross-sectional study. Multivariate logistic, linear, and weighted quantile sum (WQS) regression analyses were applied to explore the associations of six serum carotenoids (α-carotene, β-cryptoxanthin, lutein/zeaxanthin, trans-lycopene, trans-β-carotene, and cis-β-carotene), individually and in combination, with BP/hypertension. The linearity of correlations was further assessed using restricted cubic spline (RCS) regression. A total of 11,336 adults were included for analysis. Data from multivariate models showed that all six carotenoids were independently and negatively associated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP; all p < 0.05). Compared to the first quartile, the fourth quartile of α-carotene (odds ratio [OR] = 0.64 [0.52–0.77]), β-cryptoxanthin (OR = 0.74 [0.60–0.90]), trans-β-carotene (OR = 0.50 [0.40–0.61]), and cis-β-carotene (OR = 0.47 [0.35–0.64]) were significantly and inversely related to hypertension (all p < 0.05). Moreover, WQS analysis revealed that the combination of all six serum carotenoids was negatively associated with BP and hypertension (all P<0.001), among which trans-β-carotene was the most significant contributor to the protective effect against hypertension (weight, 59.50%). Dose-response analyses demonstrated a linear inverse association of all carotenoids with hypertension (p for non-linearity > 0.05). Our collective findings indicate that higher levels of all six mixed serum carotenoids are correlated with decreased prevalence of hypertension, among which β-carotene exerts the most significant effect, which may provide a basis and direction for further studies.

Background Early reperfusion of the coronary artery has become the first choice for patients with ST-segment elevation myocardial infarction (STEMI). How to deal with patients who miss the time window for early reperfusion is still controversial. Based on real-world data, this study was conducted to explore whether percutaneous coronary intervention (PCI) has an advantage over standard drug therapy in patients who miss the optimal treatment window. Methods Consecutive patients who were diagnosed with STEMI and met the inclusion criteria between 2009 and 2018 in our center were retrospectively included in this cohort study. The primary endpoint events were major adverse cardiac events (MACEs), including heart failure, sudden cardiac death, malignant arrhythmia, thrombi and bleeding events during the period of admission. Secondary endpoint events were components of MACEs. At the same time, we also evaluated angina pectoris at admission and discharge through Canadian Cardiovascular Society (CCS) grading. Results This study enrolled 417 STEMI patients and divided them into four groups (PCI < 3 days, 14.87%; 3 days<PCI < 7 days, 21.104%; PCI > 7 days, 34.29%; MED, 29.74%). During the period of admission, MACEs occurred in 52 cases. The incidence of MACEs was 11.29, 7.95, 4.20 and 25.81% in the four respective groups (p < 0.0001). The MED group had higher rates of MACEs (OR = 3.074; 95% CI 0.1.116–8.469, p = 0.03) and cardiac death (OR = 3.027; 95% CI 1.121–8.169, p = 0.029) compared to the PCI group. Although both treatments were effective in improving CCS grade at discharge, the PCI group improved more significantly (p < 0.0001). Conclusions In the real world, delayed PCI can be more effective in patients with angina symptoms at discharge and reduce the incidence of MACEs and cardiac death during hospitalization. The timing of intervention was independent of the occurrence of MACEs during hospitalization and of improvement in symptoms.

Aims The early identification and appropriate management may provide clinically meaningful and substained benefits in patients with acute heart failure (AHF). This study aimed to develop an integrative nomogram with myocardial perfusion imaging (MPI) for predicting the risk of all‐cause mortality in AHF patients. Methods and results Prospective study of 147 patients with AHF who received gated MPI (59.0 [47.5, 68.0] years; 78.2% males) were enrolled and followed for the primary endpoint of all‐cause mortality. We analysed the demographic information, laboratory tests, electrocardiogram, and transthoracic echocardiogram by the least absolute shrinkage and selection operator (LASSO) regression for selection of key features. A multivariate stepwise Cox analysis was performed to identify independent risk factors and construct a nomogram. The predictive values of the constructed model were compared by Kaplan–Meier curve, area under the curves (AUCs), calibration plots, continuous net reclassification improvement, integrated discrimination improvement, and decision curve analysis. The 1, 3, and 5 year cumulative rates of death were 10%, 22%, and 29%, respectively. Diastolic blood pressure [hazard ratio (HR) 0.96, 95% confidence interval (CI) 0.93–0.99; P = 0.017], valvular heart disease (HR 3.05, 95% CI 1.36–6.83; P = 0.007), cardiac resynchronization therapy (HR 0.37, 95% CI 0.17–0.82; P = 0.014), N‐terminal pro‐B‐type natriuretic peptide (per 100 pg/mL; HR 1.02, 95% CI 1.01–1.03; P < 0.001), and rest scar burden (HR 1.03, 95% CI 1.01–1.06; P = 0.008) were independent risk factors for patients with AHF. The cross‐validated AUCs (95% CI) of nomogram constructed by diastolic blood pressure, valvular heart disease, cardiac resynchronization therapy, N‐terminal pro‐B‐type natriuretic peptide, and rest scar burden were 0.88 (0.73–1.00), 0.83 (0.70–0.97), and 0.79 (0.62–0.95) at 1, 3, and 5 years, respectively. Continuous net reclassification improvement and integrated discrimination improvement were also observed, and the decision curve analysis identified the greater net benefit of the nomogram across a wide range of threshold probabilities (0–100% at 1 and 3 years; 0–61% and 62–100% at 5 years) compared with dismissing the included factors or using either factor alone. Conclusions A predictive nomogram for the risk of all‐cause mortality in patients with AHF was developed and validated in this study. The nomogram incorporated the rest scar burden by MPI is highly predictive, and may help to better stratify clinical risk and guide treatment decisions in patients with AHF.

The relationship between aldehyde exposure and metabolic syndrome is unclear; hence, we aimed to investigate the association between serum aldehyde concentrations and metabolic syndrome. We analyzed the data of 1471 participants from the National Health and Nutrition Examination Survey enrolled from 2013 to 2014. The association of serum aldehyde concentrations with metabolic syndrome was assessed via generalized linear models as well as restricted cubic splines, and endpoint events were further analyzed. After adjusting for covariates, both moderate (odds ratio [OR] = 2.73, 95% confidence interval [CI]: 1.34–5.56) and high (OR = 2.08, 95% CI: 1.06–4.07) concentrations of isovaleraldehyde were associated with the risk of metabolic syndrome. Interestingly, although a moderate concentration of valeraldehyde was associated with the risk of metabolic syndrome (OR = 1.08, 95% CI: 0.70–1.65), a high concentration was not (OR = 0.55, 95% CI: 0.17–1.79). Restricted cubic splines revealed a non-linear association between valeraldehyde and metabolic syndrome, and threshold effect analysis revealed that the inflection point for valeraldehyde concentration was 0.7 ng/mL. The results of the subgroup analysis revealed differences in the relationship of aldehyde exposure with components of metabolic syndrome. High isovaleraldehyde concentrations may increase the risk of metabolic syndrome, and valeraldehyde demonstrated a J-shaped relationship with the risk of metabolic syndrome.

The aim of this study was to assess the associations of urinary thiocyanate, nitrate, and perchlorate concentrations with dyslipidemia, individually and in combination, which has not previously been studied. Data from the 2001-2002 and 2005-2016 National Health and Nutrition Examination Surveys (NHANES) were analyzed in this cross-sectional study. The dependent variables were continuous serum lipid variables (triglycerides [TG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], highdensity lipoprotein cholesterol [HDL-C], non-HDL-C, and apolipoprotein B [Apo B]) and binary serum lipid variables, with the latter re ecting dyslipidemia (elevated TG, ≥ 150 mg/dL; elevated TC, ≥ 200 mg/dL; elevated LDL-C, ≥ 130 mg/dL; lowered HDL-C, < 40 mg/dL in men and < 50 mg/dL in women; elevated non-HDL-C, ≥ 160 mg/dL; and elevated Apo B, ≥ 130 mg/dL). Multivariate logistic, linear, and weighted quantile sum (WQS) regression analyses were used to explore the associations of thiocyanate, nitrate, and perchlorate with the continuous and binary serum lipid variables. The linearity of the associations with the binary serum lipid variables was assessed using restricted cubic spline (RCS) regression. A total of 15,563 adults were included in the analysis. The multivariate linear and logistic regression analyses showed that thiocyanate was positively associated with multiple continuous (TG, TC, LDL-C, non-HDL-C, and Apo B, but not HDL-C) and binary (elevated TG, TC, LDL-C, and non-HDL-C) serum lipid variables, whereas perchlorate was negatively associated with elevated LDL-C. Multivariate RCS logistic regression revealed a linear dose-response relationship between thiocyanate and elevated TG, TC, LDL-C, non-HDL-C, and Apo B, but a nonlinear relationship with lowered HDL-C (in ection point = 1.622 mg/L). WQS regression showed that a mixture of thiocyanate, nitrate, and perchlorate was positively associated with all binary serum lipid variables except for Apo B. Our ndings indicate that urinary thiocyanate, nitrate, and perchlorate concentrations, individually and in combination, were associated with dyslipidemia.

Background: The phenomenon of slow coronary blood flow is common clinically and is related to the patient experiencing repeated chest distress. The mechanism of slow blood flow is still unclear, and the prognosis after combined interventional therapy is unknown. Therefore, we evaluated the role of interventional therapy in this part of the population through the results of a 2-year follow-up.Methods: A total of 4663 patients who underwent continuous coronary angiography (CAG) were identified. Those patients with primary slow coronary flow were included in the study (n=369). The population was then divided into the PCI group and the N-PCI group. CTFT is used to assess the severity of slow blood flow. The endpoint events were the occurrence of rehospitalization and out-of-hospital death within 2 years. The log-rank test, Kaplan-Meier method, and Cox regression were used to evaluate and analyze the final results.Results: A total of 36 patients were readmitted to hospital, and 14 died suddenly outside the hospital during the follow-up period. Among these patients, 6 and 2 patients comprised the PCI group, while 30 and 12 patients comprised the N-PCI group. Comparison of the two groups showed no significant superiority (15.1% vs 13%, P=0.73). In Cox regression analysis, high BMI (body mass index) was an independent predictor of adverse end events (P=0.024).Conclusions: Interventional therapy may not improve outcomes in patients with slow coronary blood flow. BMI plays an important role in the influence of prognosis. Further research is needed to investigate this conclusion.

This study sought to examine hitherto unresearched relationships between serum terpenes and the prevalence of dyslipidemia. Serum terpenes such as limonene, α-pinene and β-pinene from the 2013–2014 National Health and Nutrition Examination Survey (NHANES) were used as independent variables. Continuous lipid variables included total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], non-HDL-C, triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], residual cholesterol [RC], and apolipoprotein B [Apo B]. Binary lipid variables (elevated TC, ≥ 5.18 mmol/L; lowered HDL-C, < 1.04 mmol/L in men and < 1.30 mmol/L in women; elevated non-HDL-C, ≥ 4.2 mmol/L; elevated TG, ≥ 1.7 mmol/L; elevated LDL-C, ≥ 3.37 mmol/L; elevated RC, ≥ 1.0 mmol/L; and elevated Apo B, ≥ 1.3 g/L) suggest dyslipidaemia. Serum terpene relationships with lipid variables were investigated using multivariate logistic and weighted quantile sum (WQS) regression. The study for TC, HDL-C, and non-HDL-C included a total of 1,621 people, whereas the analysis for TG, LDL-C, RC, and Apo B comprised 761 participants. We found that tertiles of serum terpene were positively associated with binary (elevated TC, non-HDL-C, TG, LDL-C, RC, Apo B, and lowered HDL-C) and continuous (TC, non-HDL-C, TG, LDL-C, RC, and Apo B, but not HDL-C) serum lipid variables. There was no significant correlation between serum α-pinene tertiles and elevated Apo B. A WQS regression analysis revealed that all serum lipid variables were linked with a blend of three serum terpenes. According to our data, the prevalence of dyslipidemia was correlated with serum concentrations of three terpenes both separately and collectively.