Case report: Resection of a giant right ventricular myxoma.

Myxoma constitutes the main subtype of all benign cardiac tumors, tending to be more common in women and occurring mostly in the left and right atria. Its classic clinical presentations are intracardiac obstruction, embolization, and systemic or constitutional symptoms, such as fever, in decreasing order. Several imaging techniques such as echocardiography, computed tomography, and angiocardiography contribute to the diagnosis of myxoma, ruling out significant coronary diseases, and assessment of myocardial invasion and tumor involvement of adjacent structures. Surgical resection is the only effective therapeutic option for patients with cardiac myxoma. Here, we report a unique case of a middle-aged man who presented with a giant myxoma and a 3-day history of chest tightness and shortness of breath after physical activity. Subsequently, transthoracic echocardiography revealed a mass of solid echodensity located within the right ventricle, complicated by abnormal hemodynamics. A cardiac computed tomographic angiography showed a large homogeneous density filling defect consuming most parts of the right ventricle and protruding from beat to beat. A surgical resection and histological study later successfully confirmed the diagnosis, and the patient's postoperative recovery course was found to be uneventful.

A pharmacogenetics study of platinum-based chemotherapy in lung cancer: ABCG2 polymorphism and its genetic interaction with SLC31A1 are associated with response and survival.

Objective: The expression and function of platinum transporters affect drug tissue concentration and therapeutic effects. We had previously characterized functional variant of platinum intake transporter SLC31A1 gene. We aimed to investigate the association of platinum efflux transporter gene ABCG2 polymorphism and combined ABCG2 and SLC31A1 polymorphisms with clinical outcomes of NSCLC patients receiving platinum-based chemotherapy. Methods: We genotyped thirteen tagging and functional SNPs of ABCG2 in 1004 patients, and assessed their association with response, toxicity and survival using unconditional logistic regression and Cox proportional hazards regression analyses respectively. Results: Nonsynonymous rs2231142 (odds ratio [OR] 2.07; 95 % confidence interval [CI] 1.26-3.63), rs1871744 (OR 0.60; 95 % CI 0.42-0.87) and their haplotype and diplotype were associated with objective response. Rs4148157 was associated with shorter overall survival (Log-rank P = 0.002; hazard ratio [HR] 1.22; 95 % CI 1.05-1.42). Furthermore, the combined SLC31A1 rs2233914 and ABCG2 rs1871744 genotype was significantly associated with poor response (OR 0.31; 95 % CI 0.17-0.56; P interaction = 0.003). And the combined genotypes of the functional rs10759637 of SLC31A1 and the nonsynonymous rs2231142 (Log-rank P = 5.20×10-5; HR 1.47; 95 % CI 1.19-1.81; P interaction = 0.007) or linked rs4148157 of ABCG2 were significantly associated with poor survival. Conclusion: This study reveals divergent association of ABCG2 polymorphism with response and survival of NSCLC patients receiving platinum-based chemotherapy, demonstrates the combined effects of functional variants of ABCG2 and SLC31A1 on clinical outcomes, and highlights pharmacogenetic relevance of platinum transporter genes interaction.

Right mini-thoracotomy approach reduces hospital stay and transfusion of mitral or tricuspid valve reoperation with non-inferior efficacy: evidence from propensity-matched study.

BACKGROUND: There is limited evidence about the efficacy and cost difference between minimally invasive and conventional valve reoperation. This study intended to compare the short-term efficacy and cost between right mini-thoracotomy approach and median sternotomy approach in valve reoperation. METHODS: From Feb 2011 to Sep 2017, 156 patients underwent valve reoperation including 68 cases of minimally invasive approach and 88 cases of traditional median sternotomy approach in our hospital. A propensity scoring was used to match patients with similar demographic characteristics. A total of 42 pairs of patients were left and divided into the conventional sternotomy group (CS group) and the right mini-thoracotomy group (RT group). A retrospective study of efficacy and cost was conducted between two groups. RESULTS: There was no statistical difference between two groups in demographical characteristics after propensity-scoring match (P>0.05). In-hospital mortality was 11.9% (5/42) for CS group and 7.1% (3/42) for the RT group (P=0.687). No significant disparity was found in the incidence of complications between two groups (P>0.05). CPB time (P=0.012), bypass time (P=0.006) and operation time (P=0.003) of CS group were significantly higher than RT group. Blood loss (P=0.014) and transfusion volume (P=0.003) of RT group was less than CS group. Shorter ICU and hospital stay was seen in RT group compared with CS group (P<0.001). Though the materials cost of RT group was higher than CS group (P<0.001), no significant disparity was found in total cost between CS group and RT group (P=0.790). CONCLUSIONS: The right mini-thoracotomy approach can achieve equivalent efficacy with conventional median approach, and doesn't necessarily increase the total cost. Moreover, the minimally invasive approach can decrease the operation time, hospital stay and blood product transfusion.

YKL-40 is highly expressed in the epicardial adipose tissue of patients with atrial fibrillation and associated with atrial fibrosis.

BACKGROUND: YKL-40 (CHI3L1) is a novel biomarker for inflammation, tissue remodeling, and fibrosis, as well as cardiovascular diseases. We investigated the association between YKL-40 expression in epicardial adipose tissue (EAT) and atrial fibrosis in patients with atrial fibrillation (AF). METHODS: Blood samples, subcutaneous adipose tissue (SAT), paracardial adipose tissue (PAT), EAT, and adjacent atrial myocardium were acquired from patients receiving coronary artery bypass grafts. The patients were divided into the AF group (n = 28) and the sinus rhythm (SR) group (n = 36). RESULTS: We did not detect a significant difference in the serum YKL-40 levels in the SR and AF groups (P = 0.145). Quantitative real-time PCR showed that YKL-40 (CHI3L1) mRNA levels in the EAT were significantly higher than in the SAT or PAT of AF patients, or the EAT of SR patients (All P < 0.001). We found similar results for YKL-40 protein levels by immunohistochemistry. Masson staining showed significantly more fibrosis in AF patients than in SR patients (P < 0.001). Western blotting indicated that AF patients had significantly higher expression of collagen I (P = 0.039). We found a linear relationship between YKL-40 mRNA expression and the collagen volume fraction of the atrial myocardium (y = 3.576x + 26.205, P < 0.001). Multivariate linear regression analysis revealed that body mass index is an independent risk factor for YKL-40 expression in EAT (ß = 0.328, P = 0.011). CONCLUSIONS: YKL-40, which is highly expressed in the EAT of patients with AF, is affected by body mass index and associated with atrial fibrosis, which may contribute to the development of AF.

Hypoxic-stabilized EPAS1 proteins transactivate DNMT1 and cause promoter hypermethylation and transcription inhibition of EPAS1 in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality globally. Although cigarette smoking is by far the most important risk factor for lung cancer, the aberrant expression of oncogenes and tumor suppressor genes contributes a great deal to tumorigenesis. Here, we reveal that aberrant expression of endothelial PAS domain-containing protein 1 ( EPAS1) gene, which encodes hypoxia inducible factor 2α, has a critical role in NSCLC. Our results showed EPAS1 mRNA was down-regulated in 82.5% of NSCLC tissues, and a new region of EPAS1 promoter was found to be highly methylated in lung cancer cell lines and NSCLC tissues. Moreover, the methylation rates were negatively correlated to EPAS1 mRNA expression in lung tissues. Further, demethylation analysis demonstrated EPAS1 was regulated by DNA methyltransferases (DNMTs) in NSCLC. In contrast, DNMT1 was verified as an EPAS1 target gene by chromatin immunoprecipitation assay and could be transactivated by stabilized EPAS1 proteins in hypoxic lung cells, thereby decreasing EPAS1 mRNA expression by methylation regulation. Collectively, our study suggests there might be a mechanism of negative-feedback regulation for EPAS1 in NSCLC. That is, hypoxic-stabilized EPAS1 proteins transactivated DNMT1, which further promoted the hypermethylation of EPAS1 promoter and decreased EPAS1 mRNA expression levels in NSCLC.-Xu, X.-H., Bao, Y., Wang, X., Yan, F., Guo, S., Ma, Y., Xu, D., Jin, L., Xu, J., Wang, J. Hypoxic-stabilized EPAS1 proteins transactivate DNMT1 and cause promoter hypermethylation and transcription inhibition of EPAS1 in non-small cell lung cancer.

Genetic polymorphism of SLC31A1 is associated with clinical outcomes of platinum-based chemotherapy in non-small-cell lung cancer patients through modulating microRNA-mediated regulation.

SLC31A1 is the major transporter for platinum drug intake, its expression correlates with drug disposition and response. In 1004 Chinese NSCLC patients with platinum-based chemotherapy, we investigated the association between SLC31A1 polymorphisms and clinical outcomes. Heterozygotes of rs10759637 at 3'UTR was associated with severe thrombocytopenia (odds ratio [OR]: 2.69; P = 0.012) and shorter overall survival (hazard ratio [HR]: 1.24; P = 0.005). Variant homozygote of rs2233914 was correlated with longer overall survival (hazard ratio [HR]: 0.73; P = 0.008). Haplotype and diplotype of these linked SNPs were associated with hematologic toxicities. In stratification analyses, rs10759637 and rs2233914 consistently correlated with overall survival in specific subgroups such as men, smoker, patients older than 58 years, or with ECOG PS 0-1, or with squamous cell carcinoma. rs10759637 could change the local structure of 3'UTR harboring putative binding sites for hsa-miR-29, whose transfection into 16HBE cells resulted in remarkable suppression of gene expression. The rs10759637 variant significantly correlated with lowered luciferase activity in reporter assays and decreased expression of SLC31A1 transcript in tumorous tissues. The study thereby identified functional polymorphism of SLC31A1 that modulates miRNA-3'UTR interaction and gene expression as potential pharmacogenetic biomarker for clinical outcomes of platinum-based chemotherapy in NSCLC patients.

Continuous administration of recombinant human B-type natriuretic peptide can improve heart and renal function in patients after cardiopulmonary bypass surgery.

BACKGROUND: Any cardiac surgery under cardiopulmonary bypass (CPB) will induce ischemia-reperfusion injury and systematic inflammatory response, which may lead to exacerbation. Conventional therapy strategy is to use inotropes, diuretics and vasodilator drugs, yet, the therapeutic effects of which need to be improved. Recombinant human B-type natriuretic peptide (rhBNP) has been shown to be efficacious in the treatment of acute decompensated heart failure and acute myocardial infarction. However, the effects of rhBNP on patients carried out CPB surgery is unknown. METHODS: We retrospect 357 patients carried out CPB surgery between Jan 1st 2014 and Dec 31st 2015 of our department. And according the use of rhBNP, these patients were divided into two groups: rhBNP group and control group. Patients in rhBNP group were received continuous intravenous rhBNP (0.0075-0.01 µg/kg/min) in 6 hours after CPB surgery, for a period of 72 h. Hemodynamic parameters were measured immediately after CPB surgery, and then at 2, 4, 8, 12 and 24 h after surgery. Blood samples were obtained immediately after surgery and thereafter once a day at 6:00 AM within the first 3 days after surgery. The daily urine volume as well as the time of tracheal intubation, ICU stay and chest drainage were also recorded. RESULTS: The baseline characteristics and heart functions were well balanced between two groups, and no patient died in the surgery. It showed significant differences in time-dependent changes in both groups of MAP (P<0.0001, within groups), MPAP (P<0.0001, within groups), PAWP (P<0.0001, within groups), CI (P<0.0001, within groups), SVRI (P<0.0001, within groups), serum BNP (P<0.0001, within groups), CK-MB (P<0.0001, within groups), troponin (P<0.0001, within groups) and creatinine (P<0.0001, within groups). It also showed significant differences in time-dependent changes between the two groups of MAP (P=0.04, between groups), PAWP (P=0.04, between groups), serum troponin (P<0.0001, between groups), serum creatinine (P<0.0001, between groups) and urine volume (P<0.0001, between groups). Interestingly, our results showed that patients in rhBNP group tended to wean off the respirator half a day later than those in control group (P=0.05), while no significant difference showed in both the length of chest drainage time and intensive care unit stay between the two groups. CONCLUSIONS: The administration of rhBNP can improve heart and renal function in patients underwent CPB surgery as well as accelerating the recovery from myocardial injury. But the prognosis of the patients who were administrated rhBNP did not improve in our study.

An Adjusted Calculation Model of Reduced Heparin Doses in Cardiopulmonary Bypass Surgery in a Chinese Population.

OBJECTIVE: To investigate the safety and efficacy of an adjusted regimen of heparin infusion in cardiopulmonary bypass (CPB) surgery in a Chinese population. DESIGN: Prospective, single-center, observational study. SETTING: University teaching hospital. PARTICIPANTS: Patients having cardiac surgery with CPB were selected for this study using the following criteria: 18 to 75 years of age, undergoing first-time cardiac surgery with conventional median sternotomy, aortic clamping time between 40 and 120 minutes, and preoperative routine blood tests showing normal liver, renal, and coagulation functions. The exclusion criteria include salvage cases, a history of coagulopathy in the family, and long-term use of anticoagulation or antiplatelet drugs. INTERVENTIONS: Sixty patients were divided randomly into a control group (n = 30) receiving a traditional heparin regimen and an experimental group (n = 30) receiving an adjusted regimen. MEASUREMENTS AND MAIN RESULTS: Activated coagulation time (ACT) was monitored at different time points, ACT>480 seconds was set as the safety threshold of CPB. Heparin doses (initial dose, added dose, and total dose), protamine doses (initial dose, added dose, and total dose), CPB time, aortic clamping time, assisted circulation time, sternal closure time, blood transfusion volume, and drainage volume 24 hours after surgery were recorded. There was no significant difference in achieving target ACT after the initial dose of heparin between the 2 groups; CPB time, aortic clamping time, assisted circulation time, postoperative complication rate, and drainage volume between the 2 groups were not significantly different (p>0.05). However, initial and total dosage of heparin, initial and total dosage of protamine, sternal closure time, and intraoperative blood transfusion volume in the experimental group were significantly lower (p< 0.05). CONCLUSIONS: Adjusted regimen of heparin infusion could be used safely and effectively in Chinese CPB patients, which might reduce the initial and total dosage of heparin and protamine as well as sternal closure time and intraoperative blood transfusion volume.

Effects of MIAVS on Early Postoperative ELWI and Respiratory Mechanics.

BACKGROUND: The effects of minimally invasive aortic valve surgery (MIAVS) on the early postoperative extravascular lung water index (ELWI) and respiratory mechanics have rarely been studied. MATERIAL/METHODS: A total of 90 patients were divided into 3 groups: a conventional full sternotomy (CS) group (n=30), an upper ministernotomy (US) group (n=30), and a right anterior thoracotomy (RT) group (n=30). Hemodynamic and respiratory mechanics parameters were recorded at perioperative time points, including before skin incision (T(-1)); at sternum closing (T0); and 4 h (T4), 8 h (T8), 12 h (T12), and 24 h (T24) after the operation. The ventilator support time, ICU length of stay, and postoperative hospitalization time, as well as the thoracic drainage volume and blood transfusion volume, were recorded. RESULTS: The ELWI and pulmonary vascular permeability index (PVPI) increased at T4, and the values were significantly lower in the US group than in the RT group and CS group (P<0.05). At T8, the ELWI and PVPI in the US group and RT group were significantly lower than in the CS group. At T12, there were no significant differences among the 3 groups. In addition, at T4 static lung compliance decreased, plateau airway pressure increased, and airway resistance changed non-significantly. There were no significant differences between the US group and the RT group, but both groups showed better results than the CS group did. CONCLUSIONS: The ELWI and PVPI may transiently increase after aortic valve surgery with cardiopulmonary bypass. Compared with the 12 h required to recover from a conventional sternotomy operation, it may only take 8 h to recover from MIAVS.

DACH1 inhibits the proliferation and invasion of lung adenocarcinoma through the downregulation of peroxiredoxin 3.

In this study, we found the expression of Dachshund 1 (DACH1) is downregulated while peroxiredoxin 3 (PRX3) upregulated in both lung adenocarcinoma tissues and cells. Transfection of DACH1 can significantly downregulate PRX3 expression in targeting lung adenocarcinoma cells. Further experimental results demonstrated the evidence that overexpression of DACH1 resulted in significant retardation of in vitro proliferation and invasion of lung adenocarcinoma cells. Direct upregulation of PRX3 by co-transfection of PRX3 messenger RNA (mRNA) can prevent the above alteration caused by DACH1 transfection. Besides, lower DACH1 expression significantly correlated with tumor diameter and tumor invasion in all the 36 patients diagnosed with lung adenocarcinoma in our hospital during the past months. In conclusion, DACH1 can inhibit the proliferation and invasion of lung adenocarcinoma through the downregulation of PRX3. Decreased expression of DACH1 is involved in the initiation and development of lung cancer, which might be an adverse prognostic factor of lung adenocarcinoma.

Hydrogen Sulfide Attenuates Myocardial Hypoxia-Reoxygenation Injury by Inhibiting Autophagy via mTOR Activation.

BACKGROUND: Autophagy plays a significant role in myocardial ischemia reperfusion (IR) injury. Hydrogen sulfide (H2S) has been demonstrated to protect cardiomyocytes against IR injury, while whether it has anti-autophagy effect has not been known. The aim of this study was to investigate whether H2S regulates autophagy during IR injury and its possible mechanism. METHODS AND RESULTS: The cardiomyocytes of neonatal rats were randomized into Con, hypoxia-reoxygenation (HR) and H2S protection groups. The severity of cell injury was evaluated by cell vitality (MTT) and lactate dehydrogenase (LDH) release assays, and autophagy level was evaluated by flow cytometry and the assessment of autophagy-related gene (Atg) expression, such as that of Beclin1 and LC3-II. In response to H2S, Beclin1 and LC3-II protein were found to be down-regulated and p-mTOR protein was found to be up-regulated, together with an increase in cell vitality and a decrease in LDH. Furthermore, to find out whether mTOR was involved in the protective effect of H2S, rapamycin, inhibiter of mTOR, was used with or without applying NaHS and HR. It was found that rapamycin attenuated the myocardiocyte protective effect of H2S. To demonstrate the effect of autophagy during HR injury, the cardiomyocytes were pre-treated with 3-MA, which is an autophagy inhibitor, cell injury was attenuated by 3-MA. CONCLUSIONS: H2S plays a myocardial protective role against IR injury by regulating autophagy via mTOR activation.

Identification and validation of the methylation biomarkers of non-small cell lung cancer (NSCLC).

BACKGROUND: DNA methylation was suggested as the promising biomarker for lung cancer diagnosis. However, it is a great challenge to search for the optimal combination of methylation biomarkers to obtain maximum diagnostic performance. RESULTS: In this study, we developed a panel of DNA methylation biomarkers and validated their diagnostic efficiency for non-small cell lung cancer (NSCLC) in a large Chinese Han NSCLC retrospective cohort. Three high-throughput DNA methylation microarray datasets (458 samples) were collected in the discovery stage. After normalization, batch effect elimination and integration, significantly differentially methylated genes and the best combination of the biomarkers were determined by the leave-one-out SVM (support vector machine) feature selection procedure. Then, candidate promoters were examined by the methylation status determined single nucleotide primer extension technique (MSD-SNuPET) in an independent set of 150 pairwise NSCLC/normal tissues. Four statistical models with fivefold cross-validation were used to evaluate the performance of the discriminatory algorithms. The sensitivity, specificity and accuracy were 86.3%, 95.7% and 91%, respectively, in Bayes tree model. The logistic regression model incorporated five gene methylation signatures at AGTR1, GALR1, SLC5A8, ZMYND10 and NTSR1, adjusted for age, sex and smoking, showed robust performances in which the sensitivity, specificity, accuracy, and area under the curve (AUC) were 78%, 97%, 87%, and 0.91, respectively. CONCLUSIONS: In summary, a high-throughput DNA methylation microarray dataset followed by batch effect elimination can be a good strategy to discover optimal DNA methylation diagnostic panels. Methylation profiles of AGTR1, GALR1, SLC5A8, ZMYND10 and NTSR1, could be an effective methylation-based assay for NSCLC diagnosis.

Pulmonary expression of CYP2A13 and ABCB1 is regulated by FOXA2, and their genetic interaction is associated with lung cancer.

Inhaled xenobiotics such as tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone are mainly metabolized by phase I oxidase cytochrome P450, family 2, subfamily A, polypeptide 13 (CYP2A13), phase II conjugate UDP glucuronosyltransferase 2 family, polypeptide B17 (UGT2B17), and phase III transporter ATP-binding cassette, subfamily B (MDR/TAP), member 1 (ABCB1), with genetic polymorphisms implicated in lung cancer. Their genetic interaction and pulmonary expression regulation are largely unknown. We analyzed joint association for CYP2A13 and ABCB1 polymorphisms in 2 independent lung cancer case populations (669 and 566 patients) and 1 common control population (749 subjects), and characterized the trans-acting function of the lung development-related transcription factor forkhead box A2 (FOXA2). We undertook FOXA2 overexpression and down-regulation in lung epithelial cell lines, analyzed functional impact on the transactivation of CYP2A13, UGT2B17, and ABCB1, and measured correlation for their expressions in lung tissues. We found a substantial reduction in cancer risk (OR 0.39; 95% CI 0.25-0.61; Pinteraction = 0.029) associated with combined genotypes for CYP2A13 R257C and a functionary regulatory variant in the cis element of ABCB1 synergistically targeted by GATA binding protein 6 and FOXA2. Genetic manipulation of FOXA2 consistently influenced its binding to and transactivation of the promoters of CYP2A13, UGT2B17, and ABCB1, whose mRNA and protein expressions were all consistently correlated with those of FOXA2 in both tumorous and normal lung tissues. We therefore establish FOXA2 as a core transcriptional modulator for pulmonary xenobiotic metabolic pathways and uncover an etiologically relevant interaction between CYP2A13 and ABCB1, furthering our understanding of expression and function of the xenobiotic metabolism system.

BRG1 overexpression in smooth muscle cells promotes the development of thoracic aortic dissection.

BACKGROUND: Here we investigated Brahma-related gene 1 (BRG1) expression in aortic smooth muscle cells (SMCs) and its role in the regulation of the pathological changes in aortic SMCs of thoracic arotic dissection (TAD). METHODS: BRG1, matrix metalloproteinase 2 (MMP2), and MMP9 mRNA and protein expression in human aortic specimens were examined by qPCR and western blot, respectively. The percentage of apoptotic and contractile SMCs in aortic specimens were determined by TUNEL assay and α-SMA immunohistochemical staining, respectively. The role of BRG1 in MMP2 and MMP9 expression, cell apoptosis, and phenotype transition in aortic SMCs were investigated using a human aortic SMC line via adenovirus mediated gene transfer. MMPs mRNA and protein levels were analyzed by qPCR and western blot, respectively. The percentage of apoptotic and contractile cells were determined through flow cytometry analysis. RESULTS: The expression level of BRG1 in the aortic walls (adventitia-removed) was significantly higher in the TAD than the normal group. BRG1 expression was positively correlated to expression of MMP2 and MMP9 and SMC apoptosis, but was negatively correlated to the percentage of contractile aortic SMCs in TAD specimens. In human aortic SMC line, BRG1 transfection led to significant upregulation of MMP2 and MMP9 expression and a concomitant increase in SMC apoptosis as well as a decrease in the percentage of contractile phenotype of cells. CONCLUSIONS: BRG1 is significantly upregulated in the aortic SMCs of TAD, and its overexpression might promote the development of TAD by increasing MMP2 and MMP9 expression, inducing SMC apoptosis and the transition from contractile to synthetic phenotype.

Quantitative assessment of the diagnostic role of APC promoter methylation in non-small cell lung cancer.

BACKGROUND: Adenomatous polyposis coli (APC) has been reported to be a candidate tumor suppressor in many cancers. However, the diagnostic role of APC promoter methylation in non-small cell lung cancer (NSCLC) remains unclear. We systematically integrated published articles and DNA methylation microarray data to investigate the diagnostic performance of the APC methylation test for NSCLC. Two thousand two hundred and fifty-nine NSCLC tumor samples and 1,039 controls were collected from 17 published studies and TCGA NSCLC data. The association between APC promoter methylation and NSCLC was evaluated in a meta-analysis. An independent DNA methylation microarray dataset from TCGA project, in which five CpG sites located in the promoter region of APC were involved, was used to validate the results of the meta-analysis. RESULTS: A significant association was observed between APC promoter hypermethylation and NSCLC, with an aggregated odds ratio (OR) of 3.79 (95% CI: 2.22 to 6.45) in a random effects model. Pooled sensitivity and specificity were 0.548 (95% CI: 0.42 to 0.67, P < 0.0001) and 0.776 (95% CI: 0.62 to 0.88, P < 0.0001), respectively. Each of the five CpG sites was much better in prediction (area under the curve, AUC: 0.71 to 0.73) in lung adenocarcinoma (Ad) than in lung squamous cell carcinoma (Sc) (AUC: 0.45 to 0.61). The AUCs of the logistic prediction model based on these five CpGs were 0.73 and 0.60 for Ad and Sc, respectively. Integrated analysis indicated that CpG site location, heterogeneous or autogenous controls, and the proportion of adenocarcinoma in samples were the most significant heterogeneity sources. CONCLUSIONS: The methylation status of APC promoter was strongly associated with NSCLC, especially adenocarcinoma. The APC methylation test could be applied in the clinical diagnosis of lung adenocarcinoma.

The use of intra-aortic balloon pump in patients undergoing heart valve replacement: outcome and risk analysis.

BACKGROUND AND AIM OF THE STUDY: Intra-aortic balloon pump (IABP) in heart valve surgical patients is associated with a higher mortality than coronary artery bypass grafting (CABG). The study aim was to analyze the early outcome of heart valve surgical patients requiring IABP support, and to assess the risk factors for early mortality. METHODS: Among a cohort of 5,786 patients undergoing heart valve replacement without CABG, 81 (1.4%) required IABP support. Data from these latter patients were collected and analyzed retrospectively, and univariate and multivariate logistic regression were applied to identify risk factors for early mortality in patients requiring IABP support. RESULTS: IABP was inserted in 30 patients intraoperatively, and in 51 patients postoperatively. The overall mortality was 50.6%. Mortality in the intraoperative IABP subgroup was significantly lower than in the postoperative IABP subgroup (26.7% versus 64.7%, p = 0.001). The independent risk factors for early mortality were: age increasing by 10 years (OR 1.906, 95% CI: 1.165-3.116, p = 0.010) and pulmonary hypertension (OR 4.153, 95% CI: 1.380-12.499, p = 0.011). Intraoperative IABP insertion (OR 0.297, 95% CI: 0.100-0.876, p = 0.028) was identified as a protective factor compared to postoperative insertion. CONCLUSION: The mortality of patients requiring IABP support after heart valve replacement was high. The efficacy of intraoperative IABP insertion was better than a postoperative mandatory use. Clearly, more attention should be paid to older patients or those with pulmonary hypertension, who may benefit less from IABP.

Hypermethylation reduces expression of tumor-suppressor PLZF and regulates proliferation and apoptosis in non-small-cell lung cancers.

Deregulation of promyelocytic leukemia zinc finger protein (PLZF), a tumor suppressor gene, was reported in different types of solid tumors. This study for the first time explored the reduced expression of PLZF and its effects in non-small-cell lung cancer (NSCLC) carcinogenesis. PLZF was found to be down-regulated by 62.8% in 87.1% of 154 paired NSCLC samples by quantitative real-time PCR, and its expression was found to be associated with the sex of the patient (P=0.02). Further analysis showed that down-regulation of PLZF in 35.6% NSCLC samples (31 out of 87) was triggered by hypermethylation in the promoter region. This was validated by demethylation analysis using the A549 cell line. Dual-luciferase reporter assay indicated that CTCF binding to the promoter region could activate PLZF transcription. Overexpression of PLZF in both A549 and LTEP lung cancer cell lines was found to inhibit proliferation and increase apoptosis. Therefore, reduced expression of PLZF was found to be common in NSCLC. PLZF down-regulation was partially correlated with hypermethylation in the promoter region. Decreased levels of PLZF expression may contribute to the pathogenesis of NSCLC by promoting cell survival. Therefore, the restoration of PLZF expression may serve as a new strategy for NSCLC therapy.

Comparison of six risk scores for in-hospital mortality in Chinese patients undergoing heart valve surgery.

BACKGROUND: To compare six risk scores with regard to their validity to predict in-hospital mortality after heart valve surgery in a single-centre patient population of China. METHODS: From January 2006 to December 2011, 3479 consecutive patients who underwent heart valve surgery at our centre were collected and scored according to the EuroSCORE II, VA risk score, NNE risk score, Ambler risk score, NYC risk score, and STS risk score. Calibration of the six risk scores was assessed by the Hosmer-Lemeshow (H-L) test. Discrimination was tested by calculating the area under the receiver operating characteristic (ROC) curve. RESULTS: Observed mortality was 3.32% overall. The STS score showed good calibration in predicting in-hospital mortality (H-L: P = 0.126). The EuroSCORE II, VA score, NNE score, and NYC score underpredicted observed mortality (H-L: P < 0.0001, P < 0.0001, P = 0.001, and P < 0.0001, respectively) and the Ambler score overpredicted observed mortality (H-L: P = 0.005). The discriminative power (i.e. the area under the ROC curve) for in-hospital mortality was highest for the STS score (0.706), followed by the EuroSCORE II model (0.693), NNE score (0.684), NYC score (0.682), Ambler score (0.677) and VA score (0.643). CONCLUSION: Compared with the EuroSCORE II, VA score, NNE score, NYC score, and the Ambler score, the STS score gives an accurate prediction for individual operative risk in patients undergoing heart valve surgery at our centre. Therefore, the use of the STS score for risk evaluation maybe suitable in patients undergoing heart valve surgery at our centre in the future.

Risk model of prolonged intensive care unit stay in Chinese patients undergoing heart valve surgery.

BACKGROUND: The aim of this study was to develop a preoperative risk prediction model and an scorecard for prolonged intensive care unit length of stay (PrlICULOS) in adult patients undergoing heart valve surgery. METHODS: This is a retrospective observational study of collected data on 3925 consecutive patients older than 18 years, who had undergone heart valve surgery between January 2000 and December 2010. Data were randomly split into a development dataset (n=2401) and a validation dataset (n=1524). A multivariate logistic regression analysis was undertaken using the development dataset to identify independent risk factors for PrlICULOS. Performance of the model was then assessed by observed and expected rates of PrlICULOS on the development and validation dataset. Model calibration and discriminatory ability were analysed by the Hosmer-Lemeshow goodness-of-fit statistic and the area under the receiver operating characteristic (ROC) curve, respectively. RESULTS: There were 491 patients that required PrlICULOS (12.5%). Preoperative independent predictors of PrlICULOS are shown with odds ratio as follows: (1) age, 1.4; (2) chronic obstructive pulmonary disease (COPD), 1.8; (3) atrial fibrillation, 1.4; (4) left bundle branch block, 2.7; (5) ejection fraction, 1.4; (6) left ventricle weight, 1.5; (7) New York Heart Association class III-IV, 1.8; (8) critical preoperative state, 2.0; (9) perivalvular leakage, 6.4; (10) tricuspid valve replacement, 3.8; (11) concurrent CABG, 2.8; and (12) concurrent other cardiac surgery, 1.8. The Hosmer-Lemeshow goodness-of-fit statistic was not statistically significant in both development and validation dataset (P=0.365 vs P=0.310). The ROC curve for the prediction of PrlICULOS in development and validation dataset was 0.717 and 0.700, respectively. CONCLUSION: We developed and validated a local risk prediction model for PrlICULOS after adult heart valve surgery. This model can be used to calculate patient-specific risk with an equivalent predicted risk at our centre in future clinical practice.

Supraannular aortic replacement for severe valve detachment attributable to Behçet's disease.

The occurrence of aortic regurgitation (AR) attributable to Behçet's disease is rare, but it brings extraordinary complexity to surgical intervention due to the high risk of postoperative morbidity as the result of valve dehiscence or pseudoaneurysms caused by fragile aortic structures and inflamed tissue. The high rate of prosthetic valve detachment after aortic valve replacement is one of the most serious consequences of aortic regurgitation in Behçet's disease, which results in severe aortic annular destruction, presenting a big challenge to cardiac surgeons. Under this condition, a conventional surgical technique is necessary to be modified for improving postoperative prognosis of patients. In this paper, we described the surgical treatment of 5 patients with Behçet's aortitis and report their long-term outcomes.