Delayed sternal Mycobacterium tuberculosis infection after left ventricular assist device implantation: A case report.

The incidence of Mycobacterium tuberculosis (Mtb) infection in patients with mechanical circulatory support devices is extremely rare. We present a case involving a 38-year-old male who experienced a delayed sternal Mtb infection following left ventricular assist device (LVAD) implantation. More than 5 months post-surgery, the patient was readmitted to the hospital presenting a subxiphoid abscess. The incision site displayed an unsatisfactory healing process after the incision and drainage of the abscess. Despite engaging in a rigorous treatment protocol, which included anti-infective therapy, vacuum-assisted closure, and surgical debridement, the patient's wound remained unhealed. Ultimately, after pus gene sequencing confirmed the diagnosis, the patient was administered a regimen combining anti-tuberculosis and anti-infective therapy, which culminated in the successful healing of the wound. This singular case study not only reveals the clinical progression of an unexpected Mtb infection post-implantation but also emphasizes the challenges encountered in diagnosis and management.

Effect of preoperative moderate-dose statin and duration on acute kidney injury after cardiac surgery: a retrospective cohort study.

BACKGROUND:The impact of preoperative statin use on postoperative acute kidney injury (AKI) is uncertain. We aimed to examine the association of statin therapy before cardiac surgery with postoperative AKI.METHODS:The retrospective cohort study consisted of 1581 patients undergoing cardiac surgery. Postoperative AKI were identified by the modified KDIGO definition. Propensity-score matching was employed to control for selection bias, and logistic regression was used to control for confounders. Subgroup and interaction analyses were performed to evaluate the robustness of the findings.RESULTS:The overall incidence of postoperative AKI and severe AKI were 42.19% and 12.27%, respectively. Preoperative moderate-dose statin was significantly associated with a reduced incidence of postoperative AKI (28.9% vs 43.0%, OR (95%CI): 0.54 (0.38, 0.77), p < 0.001) and severe AKI (6.9% vs 13.7%, OR (95%CI): 0.46 (0.26, 0.83), p = 0.009). The beneficial effect on postoperative AKI persisted after adjusting for major confounding factors (OR (95%CI): 0.47 (0.34, 0.66)). Decreased risk of postoperative AKI was observed in patients with preoperative statin duration of 7 ∼ 14 days (OR (95%CI): 0.41 (0.25, 0.65)) and over 14 days (OR (95%CI): 0.43 (0.28, 0.65)), but not in those with preoperative statin duration of <7 days. Similar favorable effects were noted in most subgroup patients, except for those with high-risk factors such as diabetes mellitus, previous congestive cardiac failure, arrhythmia, preoperative ACEI/ARB, aortic cross-clamping or IABP.CONCLUSION:Preoperative moderate-dose statin was significantly related to a decreased risk of postoperative AKI, especially in patients who received statins for a longer duration. Further large-scale multicenter randomized controlled trials are needed to ascertain the impact of statin dose, duration, and timing on postoperative AKI in cardiac surgery patients.

Expert consensus on the use of human serum albumin in adult cardiac surgery.

Interpretable machine learning models for early prediction of acute kidney injury after cardiac surgery.

OBJECTIVE:Postoperative acute kidney injury (PO-AKI) is a common complication after cardiac surgery. We aimed to evaluate whether machine learning algorithms could significantly improve the risk prediction of PO-AKI.METHODS:The retrospective cohort study included 2310 adult patients undergoing cardiac surgery in a tertiary teaching hospital, China. Postoperative AKI and severe AKI were identified by the modified KDIGO definition. The sample was randomly divided into a derivation set and a validation set based on a ratio of 4:1. Exploiting conventional logistic regression (LR) and five ML algorithms including decision tree, random forest, gradient boosting classifier (GBC), Gaussian Naive Bayes and multilayer perceptron, we developed and validated the prediction models of PO-AKI. We implemented the interpretation of models using SHapley Additive exPlanation (SHAP) analysis.RESULTS:Postoperative AKI and severe AKI occurred in 1020 (44.2%) and 286 (12.4%) patients, respectively. Compared with the five ML models, LR model for PO-AKI exhibited the largest AUC (0.812, 95%CI: 0.756, 0.860, all P < 0.05), sensitivity (0.774, 95%CI: 0.719, 0.813), accuracy (0.753, 95%CI: 0.719, 0.781) and Youden index (0.513, 95%CI: 0.451, 0.573). Regarding severe AKI, GBC algorithm showed a significantly higher AUC than the other four ML models (all P < 0.05). Although no significant difference (P = 0.173) was observed in AUCs between GBC (0.86, 95%CI: 0.808, 0.902) and conventional logistic regression (0.803, 95%CI: 0.746, 0.852), GBC achieved greater sensitivity, accuracy and Youden index than conventional LR. Notably, SHAP analyses showed that preoperative serum creatinine, hyperlipidemia, lipid-lowering agents and assisted ventilation time were consistently among the top five important predictors for both postoperative AKI and severe AKI.CONCLUSION:Logistic regression and GBC algorithm demonstrated moderate to good discrimination and superior performance in predicting PO-AKI and severe AKI, respectively. Interpretation of the models identified the key contributors to the predictions, which could potentially inform clinical interventions.

Peak Blood Lactate at 24 h after ECMO Can Predict 30-day Mortality in Infants after Complex Cardiac Surgery.

OBJECTIVE:Peak blood lactate at 24 h after extracorporeal membrane oxygenation (ECMO) can predict 30-day mortality in infants after complex cardiac surgery.METHODS:Twenty-eight infants with ECMO after complex congenital heart disease surgery were selected from March 2019 to March 2022 in our hospital. The infants were divided into survival group (n = 11) and non-survival group (n = 17) according to 30-day survival after discharge from hospital. The risk factors at 30-day mortality after discharge were analyzed by Cox regression analysis.RESULTS:When compared to the non-survival group, there were significant differences in peak blood lactate at 24 h after ECMO, liver dysfunction and multiple organ dysfunction syndrome (MODS) in the survival group (p < 0.05). Cox regression analysis showed that peak blood lactate at 24 h after ECMO (HR = 1.074, 95% CI: 1.005-1.149, p = 0.036) and MODS (HR = 4.120, 95% CI: 1.373-12.362, p = 0.012) were related risk factors affecting the prognosis of infants. The best cutoff value for the peak blood lactate at 24 h after ECMO was 10.2 mmol/L. The area under the curve (AUC) for predicting the 30-day survival rate of the ECMO assisted infants after discharge from hospital was 0.770 (95% CI: 0.592-0.948, p = 0.018), with a sensitivity of 94.1% and specificity of 54.5%.CONCLUSION:The peak blood lactate at 24 h after ECMO can predict the 30-day mortality after discharge of infants treated with ECMO after complex cardiac surgery. The best cut-off value for peak blood lactate at 24 h after ECMO was 10.2 mmol/L.

Preliminary Study of Genome-Wide Association Identified Novel Susceptibility Genes for Hemorheological Indexes in a Chinese Population.

Background:Genome-wide association studies for various hemorheological characteristics have not been reported. We aimed to identify genetic loci associated with hemorheological indexes in a cohort of healthy Chinese Han individuals.Methods:Genotyping was performed using Applied Biosystems Axiom™ Precision Medicine Diversity Array in 838 individuals, and 6,423,076 single nucleotide polymorphisms were available for genotyping. The relations were examined in an additive genetic model using mixed linear regression and combined with identical by descent matrix.Results:We identified 38 genetic loci (p < 5 × 10-6) related to hemorheological traits. In which, LOC102724502-OLIG2 rs28371438 was related to the levels of nd30 (p = 8.58 × 10-07), nd300 (p = 1.89 × 10-06), erythrocyte rigidity (p = 1.29 × 10-06), assigned viscosity (p = 6.20 × 10-08) and whole blood high cut relative (p = 7.30 × 10-08). The association of STK32B rs4689231 for nd30 (p = 3.85 × 10-06) and nd300 (p = 2.94 × 10-06) and GTSCR1-LINC01541 rs11661911 for erythrocyte rigidity (p = 9.93 × 10-09) and whole blood high cut relative (p = 2.09 × 10-07) was found. USP25-MIR99AHG rs1297329 was associated with erythrocyte rigidity (p = 1.81 × 10-06) and erythrocyte deformation (p = 1.14 × 10-06). Moreover, the association of TMEM232-SLC25A46 rs3985087 and LINC00470-METTL4 rs9966987 for fibrinogen (p = 1.31 × 10-06 and p = 4.29 × 10-07) and plasma viscosity (p = 1.01 × 10-06 and p = 4.59 × 10-07) was found.Conclusion:These findings may represent biological candidates for hemorheological indexes and contribute to hemorheological study.

GAS5/METTL14/ESR1 genetic variants are related to the susceptibility of coronary heart disease.

The prevention and treatment of coronary heart disease (CHD) is a difficult problem to be solved urgently. Genetic factors play a crucial role in CHD development. This study aimed to investigate the association of GAS5/METTL14/ESR1 polymorphisms with CHD susceptibility. We carried out a case-control study that included 506 patients and 506 healthy subjects to detect the correlation between GAS5/METTL14/ESR1 polymorphisms and CHD risk in a Chinese population. Odds ratios (OR) and 95% confidence intervals (CI) were computed to assess the associations. Our study showed that GAS5 rs17359906 (OR 2.32, p = 0.020) and rs75315904 (OR 0.41, p = 0.039) were related to the risk of CHD in females. ESR1 rs6927072 (OR 1.76, p = 0.007) and rs4870061 (OR 0.74, p = 0.036) correlated with CHD risk in age ≤ 60 years. GAS5 rs17359906 (OR 0.10, p = 0.032) and ESR1 rs3020308 (OR 2.73, p = 0.041) were associated with an increased susceptibility to CHD in smokers. We also found that METTL14 rs4834698 (OR 1.57, p = 0.044) and ESR1 rs4870061 (OR 0.62, p = 0.040) were associated with CHD susceptibility in non-drinkers. Besides, METTL14 rs17050450 (OR 0.48, p = 0.029) and ESR1 rs3853248 (OR 1.61, p = 0.018) had the susceptibility of CHD patients with diabetes. Our study indicated that GAS5/METTL14/ESR1 polymorphisms were associated with CHD risk, which might provide a new understanding of CHD in a Chinese population.

Influence of Baseline HbA1c and Antiplatelet Therapy on 1-Year Vein Graft Outcome.

Background:The influence of baseline HbA1c levels on vein graft outcomes post coronary artery bypass grafting (CABG) remains unclear.Objective:The purpose of this study was to assess the association between baseline HbA1c and 1-year vein graft patency, and the effects of antiplatelet therapy on the 1-year vein graft patency after CABG in patients with baseline HbA1c <6.5% vs ≥6.5%.Methods:We examined the subgroups with baseline HbA1c <6.5% vs ≥6.5% from the DACAB trial (NCT02201771), in which 500 patients were randomly allocated to receive ticagrelor plus aspirin (T+A), ticagrelor alone (T), or aspirin alone (A) for 1 year after CABG. The primary outcome was the vein graft patency (FitzGibbon grade A) at 1 year.Results:A total of 405 patients with available baseline HbA1c data were included in this subgroup analysis. Of them, there were 233 patients (678 vein grafts) with baseline HbA1c <6.5% and 172 patients (512 vein grafts) with baseline HbA1c ≥6.5%. Compared with the HbA1c <6.5% subgroup, the HbA1c ≥6.5% subgroup showed worse 1-year vein graft patency (adjusted odds ratio [OR] for nonpatency: 1.69, 95% confidence interval [CI]: 1.08-2.64). T+A showed higher vein graft patency than A in both HbA1c <6.5% (adjusted OR for nonpatency: 0.34, 95% CI: 0.15-0.75) and HbA1c ≥6.5% subgroups (adjusted OR for nonpatency: 0.45, 95% CI: 0.19-1.09), without an interaction effect (P for interaction = 0.335), whereas T did not show more significant improvement than A in both subgroups.Conclusions:In the DACAB trial, lower baseline HbA1c was associated with higher vein graft patency 1 year after CABG. T+A improved 1-year vein graft patency vs A, irrespective of baseline HbA1c.

Long Noncoding RNA SNHG4 Attenuates the Injury of Myocardial Infarction via Regulating miR-148b-3p/DUSP1 Axis.

Objective:Long noncoding RNAs (lncRNAs), including some members of small nucleolar RNA host gene (SNHG), are important regulators in myocardial injury, while the role of SNHG4 in myocardial infarction (MI) is rarely known. This study is aimed at exploring the regulatory role and mechanisms of SNHG4 on MI.Methods:Cellular and rat models of MI were established. The expression of relating genes was measured by qRT-PCR and/or western blot. In vitro, cell viability was detected by MTT assay, and cell apoptosis was assessed by caspase-3 level, Bax/Bcl-2 expression, and/or flow cytometry. The inflammation was evaluated by TNF-α, IL-1β, and IL-6 levels. The myocardial injury in MI rats was evaluated by echocardiography, TTC/HE/MASSON/TUNEL staining, and immunohistochemistry (Ki67). DLR assay was performed to confirm the target relationships.Results:SNHG4 was downregulated in hypoxia-induced H9c2 cells and MI rats, and its overexpression enhanced cell viability and inhibited cell apoptosis and inflammation both in vitro and in vivo. SNHG4 overexpression also decreased infarct and fibrosis areas, relieved pathological changes, and improved heart function in MI rats. In addition, miR-148b-3p was an action target of SNHG4, and its silencing exhibited consistent results with SNHG4 overexpression in vitro. DUSP1 was a target of miR-148b-3p, which inhibited the apoptosis of hypoxia-induced H9c2 cells. Both miR-148b-3p overexpression and DUSP1 silencing weakened the effects of SNHG4 overexpression on protecting H9c2 cells against hypoxia.Conclusions:Overexpression of SNHG4 relieved MI through regulating miR-148b-3p/DUSP1, providing potential therapeutic targets.

Histone Deacetylase 1 Depletion Alleviates Coronary Heart Disease Via the MicroRNA-182-Mediated Transforming Growth Factor β/Smad Signaling Pathway.

Histone deacetylase (HDAC) determines the acetylation status of histones, thereby regulating gene expression. HDAC inhibitors have been demonstrated to suppress cardiomyocyte growth in vitro and in vivo. We assessed here whether HDAC1 exerts an aggravating effect on coronary heart disease (CHD). Epigenetic probe array revealed that HDAC1 was overexpressed in patients with CHD. HDAC1 was then downregulated in rat cardiomyocytes, and microRNA microarray analysis was performed to detect downstream targets of HDAC1, followed by chromatin immunoprecipitation validation. HDAC1 inhibited miR-182 expression through deacetylation. miR-182 was poorly expressed in patients with CHD. Using enzyme-linked immunosorbent assay, Reverse transcription-quantitative PCR, hematoxylin-eosin staining, terminal deoxynucleotidyl transferase (TdT)-mediated 2'-deoxyuridine 5'-triphosphate (dUTP) nick-end labeling assay, and immunohistochemistry, we observed that HDAC1 downregulation promoted cardiac function, restored lipid levels, reduced myocardial injury markers and inflammatory factors, and alleviated myocardial tissue damage and apoptosis in CHD rats. By contrast, miR-182 downregulation exacerbated injury in rats in the presence of HDAC1 knockdown. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes of miR-182 were mainly enriched in the transforming growth factor (TGF)-β/Smad pathway. Western blot also validated that HDAC1/miR-182 modulated the TGF-β/Smad pathway activity. Our results demonstrated that HDAC1 repressed miR-182 and activated the TGF-β/Smad pathway to promote CHD.

Delayed sternal Mycobacterium tuberculosis infection after left ventricular assist device implantation: A case report.

The incidence of Mycobacterium tuberculosis (Mtb) infection in patients with mechanical circulatory support devices is extremely rare. We present a case involving a 38-year-old male who experienced a delayed sternal Mtb infection following left ventricular assist device (LVAD) implantation. More than 5 months post-surgery, the patient was readmitted to the hospital presenting a subxiphoid abscess. The incision site displayed an unsatisfactory healing process after the incision and drainage of the abscess. Despite engaging in a rigorous treatment protocol, which included anti-infective therapy, vacuum-assisted closure, and surgical debridement, the patient's wound remained unhealed. Ultimately, after pus gene sequencing confirmed the diagnosis, the patient was administered a regimen combining anti-tuberculosis and anti-infective therapy, which culminated in the successful healing of the wound. This singular case study not only reveals the clinical progression of an unexpected Mtb infection post-implantation but also emphasizes the challenges encountered in diagnosis and management.

Effect of preoperative moderate-dose statin and duration on acute kidney injury after cardiac surgery: a retrospective cohort study.

BACKGROUND:The impact of preoperative statin use on postoperative acute kidney injury (AKI) is uncertain. We aimed to examine the association of statin therapy before cardiac surgery with postoperative AKI.METHODS:The retrospective cohort study consisted of 1581 patients undergoing cardiac surgery. Postoperative AKI were identified by the modified KDIGO definition. Propensity-score matching was employed to control for selection bias, and logistic regression was used to control for confounders. Subgroup and interaction analyses were performed to evaluate the robustness of the findings.RESULTS:The overall incidence of postoperative AKI and severe AKI were 42.19% and 12.27%, respectively. Preoperative moderate-dose statin was significantly associated with a reduced incidence of postoperative AKI (28.9% vs 43.0%, OR (95%CI): 0.54 (0.38, 0.77), p < 0.001) and severe AKI (6.9% vs 13.7%, OR (95%CI): 0.46 (0.26, 0.83), p = 0.009). The beneficial effect on postoperative AKI persisted after adjusting for major confounding factors (OR (95%CI): 0.47 (0.34, 0.66)). Decreased risk of postoperative AKI was observed in patients with preoperative statin duration of 7 ∼ 14 days (OR (95%CI): 0.41 (0.25, 0.65)) and over 14 days (OR (95%CI): 0.43 (0.28, 0.65)), but not in those with preoperative statin duration of <7 days. Similar favorable effects were noted in most subgroup patients, except for those with high-risk factors such as diabetes mellitus, previous congestive cardiac failure, arrhythmia, preoperative ACEI/ARB, aortic cross-clamping or IABP.CONCLUSION:Preoperative moderate-dose statin was significantly related to a decreased risk of postoperative AKI, especially in patients who received statins for a longer duration. Further large-scale multicenter randomized controlled trials are needed to ascertain the impact of statin dose, duration, and timing on postoperative AKI in cardiac surgery patients.

Expert consensus on the use of human serum albumin in adult cardiac surgery.

Interpretable machine learning models for early prediction of acute kidney injury after cardiac surgery.

OBJECTIVE:Postoperative acute kidney injury (PO-AKI) is a common complication after cardiac surgery. We aimed to evaluate whether machine learning algorithms could significantly improve the risk prediction of PO-AKI.METHODS:The retrospective cohort study included 2310 adult patients undergoing cardiac surgery in a tertiary teaching hospital, China. Postoperative AKI and severe AKI were identified by the modified KDIGO definition. The sample was randomly divided into a derivation set and a validation set based on a ratio of 4:1. Exploiting conventional logistic regression (LR) and five ML algorithms including decision tree, random forest, gradient boosting classifier (GBC), Gaussian Naive Bayes and multilayer perceptron, we developed and validated the prediction models of PO-AKI. We implemented the interpretation of models using SHapley Additive exPlanation (SHAP) analysis.RESULTS:Postoperative AKI and severe AKI occurred in 1020 (44.2%) and 286 (12.4%) patients, respectively. Compared with the five ML models, LR model for PO-AKI exhibited the largest AUC (0.812, 95%CI: 0.756, 0.860, all P < 0.05), sensitivity (0.774, 95%CI: 0.719, 0.813), accuracy (0.753, 95%CI: 0.719, 0.781) and Youden index (0.513, 95%CI: 0.451, 0.573). Regarding severe AKI, GBC algorithm showed a significantly higher AUC than the other four ML models (all P < 0.05). Although no significant difference (P = 0.173) was observed in AUCs between GBC (0.86, 95%CI: 0.808, 0.902) and conventional logistic regression (0.803, 95%CI: 0.746, 0.852), GBC achieved greater sensitivity, accuracy and Youden index than conventional LR. Notably, SHAP analyses showed that preoperative serum creatinine, hyperlipidemia, lipid-lowering agents and assisted ventilation time were consistently among the top five important predictors for both postoperative AKI and severe AKI.CONCLUSION:Logistic regression and GBC algorithm demonstrated moderate to good discrimination and superior performance in predicting PO-AKI and severe AKI, respectively. Interpretation of the models identified the key contributors to the predictions, which could potentially inform clinical interventions.

Peak Blood Lactate at 24 h after ECMO Can Predict 30-day Mortality in Infants after Complex Cardiac Surgery.

OBJECTIVE:Peak blood lactate at 24 h after extracorporeal membrane oxygenation (ECMO) can predict 30-day mortality in infants after complex cardiac surgery.METHODS:Twenty-eight infants with ECMO after complex congenital heart disease surgery were selected from March 2019 to March 2022 in our hospital. The infants were divided into survival group (n = 11) and non-survival group (n = 17) according to 30-day survival after discharge from hospital. The risk factors at 30-day mortality after discharge were analyzed by Cox regression analysis.RESULTS:When compared to the non-survival group, there were significant differences in peak blood lactate at 24 h after ECMO, liver dysfunction and multiple organ dysfunction syndrome (MODS) in the survival group (p < 0.05). Cox regression analysis showed that peak blood lactate at 24 h after ECMO (HR = 1.074, 95% CI: 1.005-1.149, p = 0.036) and MODS (HR = 4.120, 95% CI: 1.373-12.362, p = 0.012) were related risk factors affecting the prognosis of infants. The best cutoff value for the peak blood lactate at 24 h after ECMO was 10.2 mmol/L. The area under the curve (AUC) for predicting the 30-day survival rate of the ECMO assisted infants after discharge from hospital was 0.770 (95% CI: 0.592-0.948, p = 0.018), with a sensitivity of 94.1% and specificity of 54.5%.CONCLUSION:The peak blood lactate at 24 h after ECMO can predict the 30-day mortality after discharge of infants treated with ECMO after complex cardiac surgery. The best cut-off value for peak blood lactate at 24 h after ECMO was 10.2 mmol/L.

Preliminary Study of Genome-Wide Association Identified Novel Susceptibility Genes for Hemorheological Indexes in a Chinese Population.

Background:Genome-wide association studies for various hemorheological characteristics have not been reported. We aimed to identify genetic loci associated with hemorheological indexes in a cohort of healthy Chinese Han individuals.Methods:Genotyping was performed using Applied Biosystems Axiom™ Precision Medicine Diversity Array in 838 individuals, and 6,423,076 single nucleotide polymorphisms were available for genotyping. The relations were examined in an additive genetic model using mixed linear regression and combined with identical by descent matrix.Results:We identified 38 genetic loci (p < 5 × 10-6) related to hemorheological traits. In which, LOC102724502-OLIG2 rs28371438 was related to the levels of nd30 (p = 8.58 × 10-07), nd300 (p = 1.89 × 10-06), erythrocyte rigidity (p = 1.29 × 10-06), assigned viscosity (p = 6.20 × 10-08) and whole blood high cut relative (p = 7.30 × 10-08). The association of STK32B rs4689231 for nd30 (p = 3.85 × 10-06) and nd300 (p = 2.94 × 10-06) and GTSCR1-LINC01541 rs11661911 for erythrocyte rigidity (p = 9.93 × 10-09) and whole blood high cut relative (p = 2.09 × 10-07) was found. USP25-MIR99AHG rs1297329 was associated with erythrocyte rigidity (p = 1.81 × 10-06) and erythrocyte deformation (p = 1.14 × 10-06). Moreover, the association of TMEM232-SLC25A46 rs3985087 and LINC00470-METTL4 rs9966987 for fibrinogen (p = 1.31 × 10-06 and p = 4.29 × 10-07) and plasma viscosity (p = 1.01 × 10-06 and p = 4.59 × 10-07) was found.Conclusion:These findings may represent biological candidates for hemorheological indexes and contribute to hemorheological study.

GAS5/METTL14/ESR1 genetic variants are related to the susceptibility of coronary heart disease.

The prevention and treatment of coronary heart disease (CHD) is a difficult problem to be solved urgently. Genetic factors play a crucial role in CHD development. This study aimed to investigate the association of GAS5/METTL14/ESR1 polymorphisms with CHD susceptibility. We carried out a case-control study that included 506 patients and 506 healthy subjects to detect the correlation between GAS5/METTL14/ESR1 polymorphisms and CHD risk in a Chinese population. Odds ratios (OR) and 95% confidence intervals (CI) were computed to assess the associations. Our study showed that GAS5 rs17359906 (OR 2.32, p = 0.020) and rs75315904 (OR 0.41, p = 0.039) were related to the risk of CHD in females. ESR1 rs6927072 (OR 1.76, p = 0.007) and rs4870061 (OR 0.74, p = 0.036) correlated with CHD risk in age ≤ 60 years. GAS5 rs17359906 (OR 0.10, p = 0.032) and ESR1 rs3020308 (OR 2.73, p = 0.041) were associated with an increased susceptibility to CHD in smokers. We also found that METTL14 rs4834698 (OR 1.57, p = 0.044) and ESR1 rs4870061 (OR 0.62, p = 0.040) were associated with CHD susceptibility in non-drinkers. Besides, METTL14 rs17050450 (OR 0.48, p = 0.029) and ESR1 rs3853248 (OR 1.61, p = 0.018) had the susceptibility of CHD patients with diabetes. Our study indicated that GAS5/METTL14/ESR1 polymorphisms were associated with CHD risk, which might provide a new understanding of CHD in a Chinese population.

Influence of Baseline HbA1c and Antiplatelet Therapy on 1-Year Vein Graft Outcome.

Background:The influence of baseline HbA1c levels on vein graft outcomes post coronary artery bypass grafting (CABG) remains unclear.Objective:The purpose of this study was to assess the association between baseline HbA1c and 1-year vein graft patency, and the effects of antiplatelet therapy on the 1-year vein graft patency after CABG in patients with baseline HbA1c <6.5% vs ≥6.5%.Methods:We examined the subgroups with baseline HbA1c <6.5% vs ≥6.5% from the DACAB trial (NCT02201771), in which 500 patients were randomly allocated to receive ticagrelor plus aspirin (T+A), ticagrelor alone (T), or aspirin alone (A) for 1 year after CABG. The primary outcome was the vein graft patency (FitzGibbon grade A) at 1 year.Results:A total of 405 patients with available baseline HbA1c data were included in this subgroup analysis. Of them, there were 233 patients (678 vein grafts) with baseline HbA1c <6.5% and 172 patients (512 vein grafts) with baseline HbA1c ≥6.5%. Compared with the HbA1c <6.5% subgroup, the HbA1c ≥6.5% subgroup showed worse 1-year vein graft patency (adjusted odds ratio [OR] for nonpatency: 1.69, 95% confidence interval [CI]: 1.08-2.64). T+A showed higher vein graft patency than A in both HbA1c <6.5% (adjusted OR for nonpatency: 0.34, 95% CI: 0.15-0.75) and HbA1c ≥6.5% subgroups (adjusted OR for nonpatency: 0.45, 95% CI: 0.19-1.09), without an interaction effect (P for interaction = 0.335), whereas T did not show more significant improvement than A in both subgroups.Conclusions:In the DACAB trial, lower baseline HbA1c was associated with higher vein graft patency 1 year after CABG. T+A improved 1-year vein graft patency vs A, irrespective of baseline HbA1c.

Long Noncoding RNA SNHG4 Attenuates the Injury of Myocardial Infarction via Regulating miR-148b-3p/DUSP1 Axis.

Objective:Long noncoding RNAs (lncRNAs), including some members of small nucleolar RNA host gene (SNHG), are important regulators in myocardial injury, while the role of SNHG4 in myocardial infarction (MI) is rarely known. This study is aimed at exploring the regulatory role and mechanisms of SNHG4 on MI.Methods:Cellular and rat models of MI were established. The expression of relating genes was measured by qRT-PCR and/or western blot. In vitro, cell viability was detected by MTT assay, and cell apoptosis was assessed by caspase-3 level, Bax/Bcl-2 expression, and/or flow cytometry. The inflammation was evaluated by TNF-α, IL-1β, and IL-6 levels. The myocardial injury in MI rats was evaluated by echocardiography, TTC/HE/MASSON/TUNEL staining, and immunohistochemistry (Ki67). DLR assay was performed to confirm the target relationships.Results:SNHG4 was downregulated in hypoxia-induced H9c2 cells and MI rats, and its overexpression enhanced cell viability and inhibited cell apoptosis and inflammation both in vitro and in vivo. SNHG4 overexpression also decreased infarct and fibrosis areas, relieved pathological changes, and improved heart function in MI rats. In addition, miR-148b-3p was an action target of SNHG4, and its silencing exhibited consistent results with SNHG4 overexpression in vitro. DUSP1 was a target of miR-148b-3p, which inhibited the apoptosis of hypoxia-induced H9c2 cells. Both miR-148b-3p overexpression and DUSP1 silencing weakened the effects of SNHG4 overexpression on protecting H9c2 cells against hypoxia.Conclusions:Overexpression of SNHG4 relieved MI through regulating miR-148b-3p/DUSP1, providing potential therapeutic targets.

Histone Deacetylase 1 Depletion Alleviates Coronary Heart Disease Via the MicroRNA-182-Mediated Transforming Growth Factor β/Smad Signaling Pathway.

Histone deacetylase (HDAC) determines the acetylation status of histones, thereby regulating gene expression. HDAC inhibitors have been demonstrated to suppress cardiomyocyte growth in vitro and in vivo. We assessed here whether HDAC1 exerts an aggravating effect on coronary heart disease (CHD). Epigenetic probe array revealed that HDAC1 was overexpressed in patients with CHD. HDAC1 was then downregulated in rat cardiomyocytes, and microRNA microarray analysis was performed to detect downstream targets of HDAC1, followed by chromatin immunoprecipitation validation. HDAC1 inhibited miR-182 expression through deacetylation. miR-182 was poorly expressed in patients with CHD. Using enzyme-linked immunosorbent assay, Reverse transcription-quantitative PCR, hematoxylin-eosin staining, terminal deoxynucleotidyl transferase (TdT)-mediated 2'-deoxyuridine 5'-triphosphate (dUTP) nick-end labeling assay, and immunohistochemistry, we observed that HDAC1 downregulation promoted cardiac function, restored lipid levels, reduced myocardial injury markers and inflammatory factors, and alleviated myocardial tissue damage and apoptosis in CHD rats. By contrast, miR-182 downregulation exacerbated injury in rats in the presence of HDAC1 knockdown. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the target genes of miR-182 were mainly enriched in the transforming growth factor (TGF)-β/Smad pathway. Western blot also validated that HDAC1/miR-182 modulated the TGF-β/Smad pathway activity. Our results demonstrated that HDAC1 repressed miR-182 and activated the TGF-β/Smad pathway to promote CHD.