Tree-based ensemble machine learning models in the prediction of acute respiratory distress syndrome following cardiac surgery: a multicenter cohort study.

BACKGROUND: Acute respiratory distress syndrome (ARDS) after cardiac surgery is a severe respiratory complication with high mortality and morbidity. Traditional clinical approaches may lead to under recognition of this heterogeneous syndrome, potentially resulting in diagnosis delay. This study aims to develop and external validate seven machine learning (ML) models, trained on electronic health records data, for predicting ARDS after cardiac surgery. METHODS: This multicenter, observational cohort study included patients who underwent cardiac surgery in the training and testing cohorts (data from Nanjing First Hospital), as well as those patients who had cardiac surgery in a validation cohort (data from Shanghai General Hospital). The number of important features was determined using the sliding windows sequential forward feature selection method (SWSFS). We developed a set of tree-based ML models, including Decision Tree, GBDT, AdaBoost, XGBoost, LightGBM, Random Forest, and Deep Forest. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and Brier score. The SHapley Additive exPlanation (SHAP) techinque was employed to interpret the ML model. Furthermore, a comparison was made between the ML models and traditional scoring systems. ARDS is defined according to the Berlin definition. RESULTS: A total of 1996 patients who had cardiac surgery were included in the study. The top five important features identified by the SWSFS were chronic obstructive pulmonary disease, preoperative albumin, central venous pressure_T4, cardiopulmonary bypass time, and left ventricular ejection fraction. Among the seven ML models, Deep Forest demonstrated the best performance, with an AUC of 0.882 and a Brier score of 0.809 in the validation cohort. Notably, the SHAP values effectively illustrated the contribution of the 13 features attributed to the model output and the individual feature's effect on model prediction. In addition, the ensemble ML models demonstrated better performance than the other six traditional scoring systems. CONCLUSIONS: Our study identified 13 important features and provided multiple ML models to enhance the risk stratification for ARDS after cardiac surgery. Using these predictors and ML models might provide a basis for early diagnostic and preventive strategies in the perioperative management of ARDS patients.

Hyperlipidemia induces vascular smooth muscle cell proliferation involving Wnt/ß-catenin signaling.

Hyperlipidemia has been shown to stimulate vascular smooth muscle cell (VSMC) proliferation. Wnt signaling pathway plays a critical role in embryonic development and cell proliferation. In this study, Sprague-Dawley rats fed with high-fat or normal diet for 12 weeks were sacrificed, and the thoracic aorta was harvested to determine wnt3a, ß-catenin, T-cell factor 4 (TCF4), and cyclin D1 expressions. VSMC proliferation within thoracic aorta and lipid accumulation within VSMCs were detected. Rat aortic VSMCs were cultured in serum from rats with hyperlipidemia or DKK-1; Wnt3a, ß-catenin, TCF4, and cyclin D1 expressions, and cell cycle distribution were determined. The findings demonstrated that increased number of VSMCs, lipid droplets, and vacuoles within thoracic aorta in the high-fat-fed group. Compared with controls, VSMCs from high-fat-fed rats showed higher mRNA expressions of wnt3a, ß-catenin, TCF4, and cyclin D1, as well as in VSMCs cultured with hyperlipidemic serum. After 24 h, VSMCs stimulated with hyperlipidemic serum showed significantly increased cell number and S-phase entry compared with cells exposed to normolipidemic serum. These effects were blocked by DKK-1. These results suggest that Wnt/ß-catenin signaling plays an important role in hyperlipidemia-induced VSMC proliferation.

Overexpression of vasostatin-1 protects hypoxia/reoxygenation injuries in cardiomyocytes-endothelial cells transwell co-culture system.

Vasostatin-1 (VS-1) plays important roles in myocardial ischemia/reperfusion injury. We have explored the protective effects of VS-1 on cardiomyocytes using cardiomyocyte-endothelial cells Transwell Co-culture System. Cardiomyocytes and rat aortic endothelial cells (RAECs) were prepared from ventricles and thoraco-abdominal aorta of Sprague-Dawley rats. The experiment used cardiomyocytes alone culture group (C) and cardiomyocytes-RAECs co-culture group (T), each with three subgroups: C-Ad-Null, C-Ad-VS-1, C-Hb (Ad-VS-1 + NO scavenger Hb), or T-Ad-Null, T-Ad-VS-1 transfection, T-Hb. After 48 h incubation, all groups were treated with hypoxia for 60 min and then reoxygenated for 120 min. We also investigated endothelial cells-mediated cardiomyocytes protection. RAECs were treated with hypoxia for 30 min and reoxygenated with normal cardiomyocytes for 120 min. The cardiomyocytes apoptosis rate, aspartate aminotransferase (AST) and creatine kinase isozyme MB (CK-MB) were recorded. As expected, cardiomyocytes apoptosis, AST and CK-MB were significantly increased in the T-Ad-Null group than in the C-Ad-Null group. VS transfection significantly reduced these levels. However, apoptosis, AST and CK-MB levels were increased again after Hb treatment, returning to the similar level of the C-Ad-null group in the C-Hb group, but still significantly lower in the T-Hb group compared with the T-Ad-null group. RAEC injury caused cardiomyocyte injury, and VS-1 transfection of the RAEC decreased apoptosis and the levels of AST and CK-MB. The findings suggest that VS-1 exerts protective effects on the cardiomyocytes directly or indirectly by cardiomyocyte-endothelial cells interaction.

Gene expression analysis in cardiac tissues from infants identifies candidate agents for Tetralogy of Fallot.

Tetralogy of Fallot (TOF) is the most common cyanotic heart defect and the most common cause of blue baby syndrome. Although great progress has been made, the molecular mechanisms of TOF are far from being fully understood, and treatment of this disease remains palliative. In this study, we downloaded gene expression data of TOF subjects with those of normally developing subjects from the Gene Expression Omnibus database and employed computational bioinformatics analyses to compare their gene expression patterns. Furthermore, small molecules that induce inverse gene changes to TOF were identified. A total of 2,274 genes involved in energy metabolism and protein binding were differentially expressed in TOF samples compared with samples from normal controls. Pathways associated with cellular oxygen tension were dysfunctional. In addition, we identified a group of small molecules that may be exploited as adjuvant drug to alleviate some symptoms for TOF patients. These drugs are clearly a direction that warrants additional consideration.

Knockdown of GAS5 Inhibits Atherosclerosis Progression via Reducing EZH2-Mediated ABCA1 Transcription in ApoE-/- Mice.

Atherosclerosis is a disorder occurring in the large arteries and the primary cause of heart diseases. Accumulating evidence has implicated long non-coding RNAs (lncRNAs) in atherosclerosis. This study aims to clarify the potential effects of lncRNA growth arrest-specific 5 (GAS5) on cholesterol reverse-transport and intracellular lipid accumulation in atherosclerosis. GAS5 was mainly localized in the nucleus and highly expressed in the human monocytic leukemia cell line (THP-1) macrophage-derived foam cells in coronary heart disease. Overexpressed GAS5 increased THP-1 macrophage lipid accumulation. Of note, GAS5 can inhibit the expression of ATP-binding cassette transporter A1 (ABCA1) by binding to enhancer of zeste homolog 2 (EZH2). Overexpression of EZH2 reduced cholesterol efflux and ABCA1 expression. EZH2 promoted triple methylation of lysine 27 (H3K27) in the ABCA1 promoter region. Subjected to overexpressed GAS5, overexpressed EZH2, or downregulated ABCA1, the Apolipoprotein E (ApoE)-/- mice with atherosclerosis showed increased total cholesterol (TC), free cholesterol (FC), cholesterol ester (CE), low-density lipoprotein (LDL) levels, aortic plaque, and lipid accumulation, accompanied by reduced high-density lipoprotein (HDL) level and cholesterol outflow. Altogether, knockdown of GAS5 can potentially promote reverse-transportation of cholesterol and inhibit intracellular lipid accumulation, ultimately preventing the progression of atherosclerosis via reducing EZH2-mediated transcriptional inhibition of ABCA1 by histone methylation.

Effects of inhaled nitric oxide for postoperative hypoxemia in acute type A aortic dissection: a retrospective observational study.

BACKGROUND: Postoperative hypoxemia in acute type A aortic dissection (AADA) is a common complication and is associated with negative outcomes. This study aimed to analyze the efficacy of low-dose (5-10 ppm) inhaled nitric oxide (iNO) in the management of hypoxemia after AADA surgery. METHODS: In this retrospective observational study, Medical records of patients who underwent AADA surgery at two institutions between January 2015 and January 2018 were collected. Patients with postoperative hypoxemia were classified as iNO and control groups. Clinical characteristics and outcomes were compared using a propensity score-matched (PSM) analysis. RESULTS: Among 436 patients who underwent surgical repair, 187 (42.9%) had hypoxemia and 43 were treated with low-dose iNO. After PSM, patients were included in the iNO treatment (n = 40) and PSM control (n = 94) groups in a 1:3 ratio. iNO ameliorated hypoxemia at 6, 24, 48, and 72 h after initiation, and shortened the durations of ventilator support (39.0 h (31.3-47.8) vs. 69.0 h (47.8-110.3), p < 0.001) and ICU stay (122.0 h (80.8-155.0) vs 179.5 h (114.0-258.0), p < 0.001). There were no significant between-group differences in mortality, complications, or length of hospital stay. CONCLUSIONS: In this study, we found that low-dose iNO improved oxygenation in patients with hypoxemia after AADA surgery and shortened the durations of mechanical ventilation and ICU stay. No significant side effects or increase in postoperative mortality or morbidities were observed with iNO treatment. These findings warrant a randomized multicenter controlled trial to assess the exact efficiency of iNO for hypoxemia after AADA.

Significance of Jab1 expression in human esophageal squamous cell carcinoma.

GOAL: The aim of the present study was to examine the expression of Jun activation domain-binding protein 1(Jab1) and p27 and to elucidate its clinicopathologic significance in a larger series of squamous cell carcinoma (SCC) of the esophagus. BACKGROUND: Reduced expression of p27 has been associated with poor prognosis in most human cancers, including esophageal SCCs. Jab1 is known as a coactivator of AP-1 transcription factor, which contributes to tumor progression by degrading the p27 protein. STUDY: Immunohistochemical and Western blot analysis were performed in 90 cases of esophageal SCCs and ECA109 cells. Survival analyses were performed by using the Kaplan-Meier method. RESULTS: Immunohistochemical analysis showed that Jab1 expression was negatively associated with p27 level and significantly associated with unfavorable clinicopathologic variables. Overexpression of Jab1 in ECA109 cells resulted in decreased p27 level and this decrease was sensitive to 26S proteasome inhibitors. Subcellular fractionation confirmed Jab1 could lead to nuclear export of p27. Survival analysis revealed that Jab1 overexpression was significantly associated with overall survival (P<0.001). When Jab1 and p27 are combined, patients with Jab1(+)/p27(-) revealed poorer overall survival (P<0.001), what's more, patients with the phenotype of Jab1(+)/lymph node(+) had poorer disease-free and overall survival than others (P<0.001). CONCLUSIONS: These findings suggest that Jab1 is involved in the pathogenesis of esophageal SCC and that elevated levels of Jab1 expression may indicate a poor prognosis for patients with esophageal SCC.

Values of aortic dissection detection risk score combined with ascending aorta diameter >40 mm for the early identification of type A acute aortic dissection.

BACKGROUND: Type A acute aortic dissection (A-AAD), involving the ascending aorta, is a life-threatening disease. To detect A-AAD early and rapidly in patients with acute chest pain, especially in patients with acute myocardial infarction (AMI) secondary to A-AAD, we investigated values of combined use of the risk score and the ascending aorta diameter >40 mm for the early identification of A-AAD. METHODS: Our study retrospectively encompassed 239 patients with acute chest pain on admission to our hospital between July 2010 and December 2016. The risk score was calculated according to the aortic dissection detection (ADD) risk score system, and the ascending aorta diameter was accurately obtained from the transthoracic echocardiography (TTE). RESULTS: A risk score ≥1 had an excellent sensitivity of 94.9% and a fair negative predictive value (NPV) of 77.8%, with a poor specificity of 8.7% and a positive predictive value (PPV) of 33.5% for the diagnosis of A-AAD. A risk score ≥2 had an excellent specificity of 91.3% and a fair NPV of 73.1%, whereas it had a lower sensitivity of 30.8% and a PPV of 63.2%. A risk score ≥1, combined with an ascending aorta diameter >40 mm, had a sensitivity, a specificity, a PPV, and an NPV of 84.6%, 87.6%, 76.7%, and 92.2% for the diagnosis of A-AAD, respectively. The combined use of a risk score ≥2 and an ascending aorta diameter >40 mm had an excellent specificity of 98.1% and a PPV of 86.4%, a fair NPV of 72.8%, and a poor sensitivity of 24.4% for the detection of A-AAD. Moreover, the omission diagnostic rate for A-AAD was significantly decreased from 33.3% to 7.4% using a risk score ≥1 combined with an ascending aorta diameter >40 mm in patients with AMI secondary to A-AAD. CONCLUSIONS: The combined use of an ADD risk score ≥1 and an ascending aorta diameter >40 mm was highly indicative of A-AAD in patients presenting with acute chest pain, especially in patients with AMI secondary to A-AAD, which urgently needed computed tomography angiography (CTA) or magnetic resonance imaging (MRI) to confirm the diagnosis of A-AAD.

Risk factors and short-term prognosis of preoperative renal insufficiency in infective endocarditis.

BACKGROUND: The incidence of postoperative complications and the in-hospital mortality rate of infective endocarditis (IE) complicated with renal insufficiency are relatively high. This study aimed to analyze the clinical features, etiological characteristics, diagnosis and treatment, and prognosis of IE with renal insufficiency and to explore the risk factors for renal damage. METHODS: IE patients undergoing valvular surgery between 2008 and 2017 in two cardiac centers were retrospectively analyzed. They were divided into renal insufficiency (RI) [endogenous creatinine clearance rate (Ccr) <60 mL/min/1.73 m2] and normal renal function (NRF) (Ccr ≥60 mL/min/1.73 m2) groups. The disease conditions at admission, etiology, treatment, and prognosis were compared between the two groups. Multivariate regression analysis was performed for the related factors. RESULTS: A total of 8,055 cases of valvular surgery was performed during the study period. We analyzed 401 IE patients [average age 43.9±15 years; RI, n=56 (14%); NRF, n=345 (86%)], after the exclusion of 2 patients with primary glomerulonephritis. RI patients showed higher perioperative mortality (14.3% vs. 4.5%, P=0.042) and streptococcal infection (71.4% vs. 43.8%, P=0.001) rates. The RI group was also older and had worse heart function, greater decreases in hemoglobin and platelet levels, a higher rate of prosthetic valve involvement, more cases of postoperative dialysis, and worse prognosis (all P<0.05). Binary logistic multivariate regression analysis showed that the incidence of streptococcal infection [odds ratio (OR) =4.271, 95% confidence interval (CI), 1.846-9.884; P=0.001], age ≥51 years (OR =5.138, 95% CI, 2.258-11.694; P<0.001), and New York Heart Association (NYHA) functional class III-IV (OR =10.768, 95% CI, 2.417-47.972; P=0.002) were independent risk factors for preoperative renal insufficiency. CONCLUSIONS: IE patients with preoperative renal insufficiency had a high mortality rate and poor prognosis, with streptococcal infection predisposing to a higher risk of renal insufficiency. Moreover, older the age and worse heart function in IE resulted in a greater risk for renal insufficiency.

A prospective evaluation of apolipoprotein M gene T-778C polymorphism in relation to coronary artery disease in Han Chinese.

OBJECTIVES: Apolipoprotein M (apoM) is important for the formation of pre-beta-high-density lipoprotein (HDL) and cholesterol efflux in macrophages. It is demonstrated that single-nucleotide polymorphism (SNP) T-778C of apoM gene is related to type 2 diabetes in Han Chinese. In the present study, we investigated the possible association of apoM polymorphism in relation to coronary artery disease (CAD) in Han Chinese. DESIGN AND METHODS: This case-controlled study consisted of 118 CAD patients who were diagnosed angiographically to have at least 30% stenosis, and 255 unrelated subjects who were used as control. ApoM gene polymorphism in the proximal promoter region was analyzed by PCR-RFLP and serum lipid levels were also measured. RESULTS: It is indicated that CAD patients had increased frequency of C allele on apoM T-778C compared to the controls (14.8% vs. 6.9%, P=0.0008). Multivariable logistic regression analysis indicated that odds ratios (ORs) for all subjects with apoM CC+CT genotypes and C allele were 1.9 (95% CI=1.1-2.9, P<0.0001) and 1.9 (95% CI=1.3-3.2, P<0.0001), respectively. The plasma total cholesterol (TC) levels were significantly higher in individuals with CC or CT genotype than those with TT genotype in both CAD patients and controls. CONCLUSIONS: The present findings suggest that the C allele at nucleotide -778 in the apoM gene is a risk factor for genetic susceptibility to CAD and is also associated with TC levels in Han Chinese.

Elevated free fatty acid level is a risk factor for early postoperative hypoxemia after on-pump coronary artery bypass grafting: association with endothelial activation.

BACKGROUND: We aimed to investigate the relationship between increased free fatty acid (FFA) level and early postoperative hypoxemia after coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: Ninety-eight consecutive patients undergoing CABG were enrolled. Early postoperative hypoxemia was defined as the lowest of the ratio of arterial oxygen tension (PaO2) to inspired oxygen fraction (FiO2) ≤ 200 mm Hg within 24 h without pleural effusion and pneumothorax. The 26 perioperative factors, serum levels of FFA and inflammatory cytokines between the hypoxemia and non-hypoxemia groups were recorded or detected using autoanalyzer and enzyme-linked immunosorbent assay, respectively. Additionally, the risk factors for early postoperative hypoxemia were evaluated using multiple logistic regression analysis. RESULTS: The incidence rate of early postoperative hypoxemia was 37.8 %. Serum FFA levels were significantly higher in the hypoxemia group than in the non-hypoxemia group (P<0.001). Further, postoperative serum FFA levels were inversely related to the lowest of the ratio of PaO2/FiO2 at 24 h after CABG (r= - 0.367, P<0.001). Multiple logistic regression analysis confirmed that age, body mass index and postoperative serum FFA concentrations were independently associated with early postoperative hypoxemia. Notably, patients with hypoxemia had markedly higher serum intercellular adhesion molecule-1 (ICAM-1) levels than those without (P<0.001). Moreover, serum FFA levels at 2 h after CABG correlated positively with ICAM-1 concentrations (r=0.492, P<0.001). CONCLUSIONS: Elevated FFA concentration is a risk factor for early postoperative hypoxemia after on-pump CABG, which may be closely associated with endothelial activation.

Significance of changes in transforming growth factor-beta mRNA levels in autogenous vein grafts.

BACKGROUND: This study was designed to investigate changes in mRNA levels of transforming growth factor-beta (TGF-beta), collagen I, and collagen III in autogenous vein grafts. METHODS: Twenty-four New Zealand rabbits were randomly divided into 4 groups with 6 rabbits each. The external jugular veins of the New Zealand rabbits were harvested and grafted into the ipsilateral carotid artery. All rabbits were fed with a standard diet. After the operation, the rabbits were sacrificed at 1, 2, 3, or 4 weeks. TGF-beta, collagen I, and collagen III mRNA levels in the venous grafts were measured by semiquantitative methods at every time point. The contralateral external jugular veins were also harvested and analyzed as controls. Glyceraldehyde-3-phosphate dehydrogenase was used as an internal standard to normalize all samples for potential variations in mRNA content. In order to observe the expression of TGF-beta protein, immunohistochemical SABC methods were used. RESULTS: One week postoperation, the mRNA level of TGF-beta was upregulated to 1.73 +/- 0.19 in the vein graft and 1.21 +/- 0.16 in the control vein (P < 0.01). High mRNA levels were maintained until week 4 postoperation. The mRNA levels of collagen I and collagen III were also significantly increased to 2.18 +/- 0.21 versus 1.12 +/- 0.24 and 1.08 +/- 0.13 versus 0.83 +/- 0.12, respectively (P < 0.05). Immunohistochemical staining revealed a higher density of TGF-beta expression in the vein grafts. CONCLUSIONS: An uninterrupted increase in mRNA levels of TGF-beta, collagen I, and collagen III is observed in autogenous vein grafts. This increase may be the major cause of intimal hyperplasia, sclerosis, and even graft failure.

[Mechanism of intimal hyperplasia of venous grafts after coronary artery bypass grafting, an experimental study].

OBJECTIVE: To study the mechanism of intimal hyperplasia after coronary artery bypass grafting (CABG) and to find an effective way for preventing intimal hyperplasia. METHODS: Twenty-four male New Zealand rabbits were randomly divided into two groups of 12 rabbits: operation group and sham-operation (control) group. The external jugular vein was harvested and anastomosed end-to-side to the ipsilateral carotid artery in operation group or grafted in situ in the control group. Six rabbits in each group were killed and their grafted veins were taken 2 weeks and 4 weeks after operation respectively. The mRNA expressions of transforming growth factor beta (TGF-beta), collagen I, collagen III, and angiotension 1 receptor (AT1R) were measured by RT-PCR and electrophoresis. RESULTS: The intimal hyperplasia was much more remarkable in the operation group than in the control group either 2 weeks or 4 weeks after operation. The mRNA expressions of TGF-beta, AT1R, collagen I, and collagen III were significantly higher in the operation group than in the control group, especially 2 weeks after (P < 0.01). Four weeks after the operation, the expressions of TGF-beta, AT1R, collagen I and collagen III were 4.05 +/- 0.49 vs 2.05 +/- 0.26, 18.23 +/- 1.32 vs 4.61 +/- 0.53, 80 +/- 0.17 vs 0.90 +/- 0.18, and 7.05 +/- 0.68 vs 2.80 +/- 0.17 respectively (all P < 0.05). CONCLUSION: TGF-beta and AT1R may have an important role in the intimal hyperplasia of venous graft in CABG. Continuous arterial pressure may be the main factor of increased expression of TGF-beta and AT1R that cause the enormous synthesis and deposit of collagen.

[Establishment of model human stem cell of transplantation into myocardium of chick embryos].

OBJECTIVE: To establish an animal model of human stem cell transplantation into myocardium in chick embryos. METHODS: Hoechsst 33,258 labeled human primordial germ cells (hPGC) were microsurgically injected into the myocardium of 633 chick embryos of 3-4 days development. Ten days after, the hearts were isolated from the 94 surviving chick embryos, embedded, and sliced. In situ hybridization (ISH) with human specific DNA Alu probe was conducted on the sections with fluorescence to detect the existence of transplanted PGC. Immunohistochemistry with human-myocardium-specific antibody cTnT was conducted on the adjacent sections to observe the differentiation of human myocardial cells. RESULTS: ISH showed that PGC were detected in the myocardium of chick embryos 10 days post-operationally. Immunohistochemistry showed that the myocardium added with antibody in adjacent sections was cTnT-positive and the myocardium untreated with antibody was cTNT-negative. Successful cell transplantation occurred in 15.3% +/- 2.4% of chick embryos. CONCLUSION: Establishment of an animal model of cell transplantation of human stem cells into myocardium in chick embryos is feasible.

Effect of antioxidant vitamin supplementation on cardiovascular outcomes: a meta-analysis of randomized controlled trials.

BACKGROUND: Antioxidant vitamin (vitamin E, beta-carotene, and vitamin C) are widely used for preventing major cardiovascular outcomes. However, the effect of antioxidant vitamin on cardiovascular events remains unclear. METHODOLOGY AND PRINCIPAL FINDINGS: We searched PubMed, EmBase, the Cochrane Central Register of Controlled Trials, and the proceedings of major conferences for relevant literature. Eligible studies were randomized controlled trials that reported on the effects of antioxidant vitamin on cardiovascular outcomes as compared to placebo. Outcomes analyzed were major cardiovascular events, myocardial infarction, stroke, cardiac death, total death, and any possible adverse events. We used the I(2) statistic to measure heterogeneity between trials and calculated risk estimates for cardiovascular outcomes with random-effect meta-analysis. Independent extraction was performed by two reviewers and consensus was reached. Of 293 identified studies, we included 15 trials reporting data on 188209 participants. These studies reported 12749 major cardiovascular events, 6699 myocardial infarction, 3749 strokes, 14122 total death, and 5980 cardiac deaths. Overall, antioxidant vitamin supplementation as compared to placebo had no effect on major cardiovascular events (RR, 1.00; 95%CI, 0.96-1.03), myocardial infarction (RR, 0.98; 95%CI, 0.92-1.04), stroke (RR, 0.99; 95%CI, 0.93-1.05), total death (RR, 1.03; 95%CI, 0.98-1.07), cardiac death (RR, 1.02; 95%CI, 0.97-1.07), revascularization (RR, 1.00; 95%CI, 0.95-1.05), total CHD (RR, 0.96; 95%CI, 0.87-1.05), angina (RR, 0.98; 95%CI, 0.90-1.07), and congestive heart failure (RR, 1.07; 95%CI, 0.96 to 1.19). CONCLUSION/SIGNIFICANCE: Antioxidant vitamin supplementation has no effect on the incidence of major cardiovascular events, myocardial infarction, stroke, total death, and cardiac death.

Effect of hormone replacement therapy on cardiovascular outcomes: a meta-analysis of randomized controlled trials.

BACKGROUND: Hormone replacement therapy (HRT) is widely used to controlling menopausal symptoms and prevent adverse cardiovascular events. However, the benefit and risk of HRT on cardiovascular outcomes remains controversial. METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched the PubMed, EmBase, and Cochrane Central Register of Controlled Trials databases for obtaining relevant literature. All eligible trials reported on the effects of HRT on cardiovascular outcomes. We did a random effects meta-analysis to obtain summary effect estimates for the clinical outcomes with use of relative risks calculated from the raw data of included trials. Of 1903 identified studies, we included 10 trials reporting data on 38908 postmenopausal women. Overall, we noted that estrogen combined with medroxyprogesterone acetate therapy as compared to placebo had no effect on coronary events (RR, 1.07; 95%CI: 0.91-1.26; P = 0.41), myocardial infarction (RR, 1.09; 95%CI: 0.85-1.41; P = 0.48), stroke (RR, 1.21; 95%CI: 1.00-1.46; P = 0.06), cardiac death (RR, 1.19; 95%CI: 0.91-1.56; P = 0.21), total death (RR, 1.06; 95%CI: 0.81-1.39; P = 0.66), and revascularization (RR, 0.95; 95%CI: 0.83-1.08; P = 0.43). In addition, estrogen therapy alone had no effect on coronary events (RR, 0.93; 95%CI: 0.80-1.08; P = 0.33), myocardial infarction (RR, 0.95; 95%CI: 0.78-1.15; P = 0.57), cardiac death (RR, 0.86; 95%CI: 0.65-1.13; P = 0.27), total mortality (RR, 1.02; 95%CI: 0.89-1.18; P = 0.73), and revascularization (RR, 0.77; 95%CI: 0.45-1.31; P = 0.34), but associated with a 27% increased risk for incident stroke (RR, 1.27; 95%CI: 1.06-1.53; P = 0.01). CONCLUSION/SIGNIFICANCE: Hormone replacement therapy does not effect on the incidence of coronary events, myocardial infarction, cardiac death, total mortality or revascularization. However, it might contributed an important role on the risk of incident stroke.

Dysfunctional co-expression network analysis of familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is an inherited disorder of blood lipid metabolism characterized by high serum low-density lipoprotein cholesterol levels and premature coronary artery disease. In this study, we used a system biology approach to identify co-expressed gene pairs that were potentially involved in the progression of FH and constructed a conserved co-expression network using these genes. A total of 4232 co-expressed relationships were identified and we verified the significance by random permutation. FH patients showed differences in lipoprotein and cholesterol metabolism in circulating monocytes and lymphocytes compared to healthy controls. We hope our study could aid in understanding of FH and could provide the basis for FH biomarker identification.

Overexpression of vasostatin-1 protects hypoxia/reoxygenation injuries in cardiomyocytes independent of endothelial cells.

INTRODUCTION: Vasostatin-1 (VS-1) has been suggested in protecting hypoxia/reoxygenation (H/R) injuries in isolated hearts. However, the molecular mechanisms remained to be elucidated. METHODS: Cardiomyocytes were treated with recombinant Ad-VS-1 adenoviral vector before H/R. Cell viability was studied using MTT methods and annexin V-FITC flow cytometry. Intracellular oxidative stress was measured by superoxide dismutase (SOD) and malondialdehyde (MDA), and inflammatory reactions by enzyme-linked immunosorbent assay (ELISA). Measurement of myocardial nitrous oxide synthase (NOS) was determined by serum nitric oxide (NO) concentrations using nitrite reductase and endothelial nitric oxide synthase (eNOS) by Western blotting. Inhibitors of the NOS system, including hemoglobin and KT5823, were applied to verify the results. RESULTS: In comparison of the blank group, cardiac myocytes overexpressing VS-1 showed significant decrease in apoptosis, intracellular oxidative stress, and inflammatory reactions (P < 0.05). In addition, serum NO concentrations and expression of eNOS were notably enhanced (P < 0.05). These protective effects of VS-1 were suppressed in the presence of apoptosis-inducing agents. CONCLUSIONS: Overexpression of VS-1 in cardiomyocytes could limit the H/R injuries at molecular levels. The protective effects were independent of endothelial cell function, suggestive of a potential therapeutic target for patients with myocardial ischemia in the future.

Clinical results of tricuspid valve replacement - a 21-case report.

OBJECTIVE: To summarize the clinical experiences of 21 patients treated with tricuspid valve replacement (TVR) and investigate the surgical indications and methods. METHODS: Data from 21 patients who underwent TVR from December 2002 to March 2009 were retrospectively collected and analyzed. The mean age was 48.86±15.37 years (range: 20-72 years). The underlying disease of the patients was classified as rheumatic (n = 10), congenital (n = 8), endocarditis (n = 2) or chest trauma (n = 1). Previous cardiac surgery had been performed in 12 patients (57.14%). RESULTS: In-hospital death occurred in two patients (9.52%). Postoperative morbidities included cardiac failure (n = 2), bleeding related re-operation (n = 1), and plural effusion (n = 2). CONCLUSION: The early outcomes of TVR were acceptable. At the present time TVR can be performed through optimal perioperative management.

Early outcomes of isolated coronary artery bypass grafting in Chinese aged patients with diabetes mellitus.

OBJECTIVE: To compare the early outcomes of coronary artery bypass grafting (CABG) in aged diabetic patients, and evaluate the affection of diabetes on the early outcomes of CABG in aged patients. METHODS: The study took place in the Department of Cardiovascular Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China, between January 2000 and July 2008. Five hundred and ninety-three elderly patients (age > or = 70-years-old), undergoing isolated CABG were retrospectively divided into diabetic group and non-diabetic group. We analyzed the pre-operative, intra-operative, and post-operative variables of the 2 groups. The t-test, Chi-square test, and multivariate logistic regression were used to determine the differences between the 2 groups of patients. RESULTS: There was no statistical difference of pre-operative and intraoperative variables between the 2 groups, except that there were more left main coronary artery diseases in the diabetic group. Values in the post-operative period such as morbidity, complications, and blood infusion had no differences between the 2 groups. Diabetes mellitus and age are not the risk factors for in-hospital mortality. CONCLUSION: Coronary artery bypass grafting in elderly patients is plausible. Furthermore, diabetic patients could get the same surgical results as those non-diabetic patients.