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ObjectiveTricuspid regurgitation (TR) is a common valvular heart disease with unsatisfactory medical therapeutics and high surgical mortality. The present study aims to evaluate the safety and effectiveness of transcatheter tricuspid valve replacement (TTVR) in high-risk patients with severe TR.MethodsThis was a compassionate multicentre study. Between September 2018 and November 2019, 46 patients with TR who were not suitable for surgery received compassionate TTVR under general anaesthesia and the guidance of trans-oesophageal echocardiography and fluoroscopy in four institutions. Access to the tricuspid valve was obtained via a minimally invasive thoracotomy and transatrial approach. Patients’ data at baseline, before discharge, 30 days and 6 months after the procedure were collected.ResultsAll patients had severe TR with vena contracta width of 12.6 (11.0, 14.5) mm. Procedural success (97.8%) was achieved in all but one case with right ventricle perforation. The procedural time was 150.0 (118.8, 180.0) min. Intensive care unit time was 2.0 (1.0, 4.0) days. 6-month mortality was 17.4%. Device migration occurred in one patient (2.4%) during follow-up. Transthoracic echocardiography at 6 months after operation showed TR was significantly reduced (none/trivial in 33, mild in 4 and moderate in 1) and the primary safety end point was achieved in 38 cases (82.6%). Patients suffered from peripheral oedema and ascites decreased from 100.0% and 47.8% at baseline to 2.6% and 0.0% at 6 months.ConclusionsThe present study showed TTVR was feasible, safe and with low complication rates in patients with severe TR.

Background: Data on outcome of Stanford type A aortic dissection (TAAD) in Marfan syndrome (MFS) patients are limited. We investigated the full spectrum of reoperation and survival after initial surgery in MFS patients who suffered TAAD. Methods: Retrospective analysis of 85 consecutive MFS patients in one-single center during the past 15 years. Results: Overall, 85 MFS patients with TAAD underwent surgical repair [74% acute dissections; 80% DeBakey type I; 91% composite valved graft; 70% total arch replacement (TAR); 68% frozen elephant trunk (FET); 7% in-hospital mortality] at Changhai hospital affiliated to the Second Military Medical University over the past 15 years. Five (20.8%) patients in non-TAR group need aortic arch reintervention with resternotomy during follow-up, which is significantly higher than that in TAR group (P=0.001). Freedom from aortic arch reoperation in non-TAR group was all 78.7%±8.5% at 5, 10, and 15 years. No patient required aortic arch reoperation in TAR group (P=0.001). On the other hand, the FET was inserted into false lumen intentionally at initial surgery in 2 cases of chronic TAAD with narrowed true lumen. Scheduled thoracoabdominal aortic replacement was performed 6 months later. Both 2 patients are with well clinical outcomes. At last, we found that Debakey type and TAR at initial surgery were irrelevant to survival and reoperation for descending aorta. Conclusions: TAR combined with FET is recommended in MFS patients when the aortic arch is dissected or enlarged. The FET could be inserted into the false lumen intentionally in selective case for scheduled 2-staged descending aortic repair.

BACKGROUND: Multiple of subsequent procedures may necessary in Marfan syndrome (MFS) patients after initial surgery. The aim of this study was to investigate the full spectrum of secondary distal vascular or valvular interventions encountered after initial surgery. METHODS: Retrospective analysis of 201 consecutive MFS patients between January 2000 and March 2019 who underwent 274 distal aortic reinterventions and 5 mitral valve replacements. RESULTS: Of the enrolled 201 MFS patients (73 female, mean age 37.0±12.8 years), the surgical indication for 93 patients was aortic root aneurysm, and for another 108 patients was dissection. The mean follow-up interval was 8.4±5.5 years. Total arch replacement (TAR) was performed in 68.5% of MFS patients presenting with type A aortic dissection (TAAD) and in 2.2% of patients with aneurysm. Secondary TAR became necessary for 3.4% of patients who failed to receive TAR at initial surgery in aneurysm group during follow-up, while for 33.3% of patients in dissection group (P

// Guanxin Zhang 1, * , Gengxi Jiang 1, * , Chong Wang 1 , Keng Zhong 1 , Jiajun Zhang 1 , Qing Xue 1 , Xin Li 1 , Hai Jin 1 , Bailing Li 1 1 Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China * These authors have contributed equally to this work Correspondence to: Hai Jin, email: projinhai@163.com Bailing Li, email: smmu_libailing@163.com Keywords: non-small cell lung cancer, VDAC1, mRNA-320a, cell proliferation, invasion Received: February 07, 2016 Accepted: May 20, 2016 Published: June 11, 2016 ABSTRACT Accumulating evidence indicates that Voltage Dependent Anion Channel 1 (VDAC1) correlates with the initiation and progression of non-small cell lung cancer (NSCLC). However, the regulatory mechanism of VDAC1 in NSCLC remains unclear. Previous studies have reported that expression of miR-320a was decreased in human primary squamous cell lung carcinoma, which prompted us to investigate whether there is a functional link between decreased miR-320a and a high expression of VDAC1. In the present report, using computational analysis, we first show that miR-320a has a potential binding site on VDAC1 mRNA, and expression of miR-320a was decreased in NSCLC cell lines. Using gain-of-function and rescue experiments, we demonstrate that VDAC1 is a direct target of miR-320a in NSCLC cells, and miR-320a inhibits VDAC1 expression in NSCLC cells. Further we show that MiR-320a was significantly decreased in NSCLC tissues compared with adjacent non-tumor tissues, and MiR-320a level is negatively correlated with VDAC1 in NSCLC tissues by Pearson’s correlation coefficient analysis. Moreover, using cellular ATP assay, we found that suppression of VDAC1 expression may inhibit cell proliferation and invasion of NSCLC by decreasing cell energy and metabolism. Importantly, we showed that ectopic overexpression of miR-320a blocked tumor cell proliferation and invasion, both in vitro and in vivo , through inhibiting VDAC1. Our results suggest that reduced expression of miR-320a facilitates the development of NSCLCs by increasing VDAC1 expression. We identified a novel regulatory mechanism between miR-320a and VDAC1, and miR-320a may serve as a tumor suppressor gene and a promising therapeutic target of NSCLCs.

Introduction Sildenafil (Viagra, Pfizer) is being used to treat pulmonary hypertension (PH). However, there are limited data on the effects of sildenafil on patients with PH after left-sided valvular surgery. The purpose of this study was to determine the optimal dosage and the effects of sildenafil on prognosis of patients with PH after left-sided valvular surgery. Methods This randomised controlled trial, double-blind study enrolled patients with PH undergoing left-sided valvular surgery in our hospital from January to December, 2010. Ninety patients were enrolled. And 0.5 mg/kg sildenafil citrate or placebo was administered through nasogastric tubes, the haemodynamics changes in the 0.5/1/2/4 hours were assessed. The sildenafil citrate/placebo was continued to the discharges and the early prognoses of these patients were compared. Results Compared with placebo, a 0.5 mg/kg dose of sildenafil significantly reduced the time of mechanical ventilation, stay-in-ICU and hospitalisation duration. Conclusions Sildenafil might be beneficial to the early prognosis of patients with PH after left-sided valvular surgery.

Glucagon-like peptide-1 (GLP-1), an insulinotropic peptide released from the intestine after eating, is essential for normal glucose tolerance (GT). To determine whether this effect is mediated directly by GLP-1 receptors (GLP1R) on islet β-cells, we developed mice with β-cell specific knockdown of Glp1r. β-cell Glp1r knockdown mice had impaired GT after intraperitoneal (IP) glucose, and did not secrete insulin in response to IP or intravenous GLP-1. However, they had normal GT after oral glucose, a response that was impaired by a GLP1R antagonist. β-cell Glp1r knockdown mice had blunted responses to a GLP1R agonist, but intact glucose lowering with a DPP-4 inhibitor. Thus, in mice, β-cell Glp1r are required to respond to hyperglycemia and exogenous GLP-1, but other factors compensate for reduced GLP-1 action on the β-cell during meal ingestion. These results support a role for extra-islet GLP1R in oral glucose tolerance and paracrine regulation of β-cells by islet GLP-1.

To assess the efficacy of autologous biological pacing function by autograft of gene-transferred mesenchymal stem cells in a porcine model of complete heart block.Fourteen healthy young male pigs were randomized into active group (n=8) and control group (n=6). Porcine MSCs were transfected with Ad.HCN4 or Ad.Null. The pacemaker function of transfected MSCs was studied by whole-cell patch clamp. The CHB model of porcine was created with transthoracic ablation technique and the transfected MSCs were autografted into the free wall of right ventricle. The pacing function was studied by ECG and ambulatory Holter recording weekly. The adrenergic responsiveness was evaluated by the variation of heart rate after isoprenaline infusion or food provision following an overnight fasting. HCN4-MSCs expressed a robust time-dependent inward current (If) and the current density of If was 4.3±0.6 pA/pF at -105 mV. In week 2 after autograft, the heart rate of active group became significantly higher than control (53±5 bpm vs. 38±4 bpm, P0.05) and the percent of pacing beats in active group was higher than control (69±10% vs. 28±8%, P0.05). By infusion of isoprenaline, the heart rate was increased significantly in both groups. However, there was a significant increase of heart rate when presenting food for active group (P0.05) while not in control.Our findings demonstrated that autografted HCN4-MSCs could increase the heart rate by providing an adrenergic-responsive biological pacing function, indicating a promising approach without immunological or ethical issues for the treatment of complete heart block.

Obesity has a complicated metabolic pathology, and defining the underlying mechanisms of obesity requires integrative studies with molecular end points. Real-time quantitative PCR (RT-qPCR) is a powerful tool that has been widely utilized. However, the importance of using carefully validated reference genes in RT-qPCR seems to have been overlooked in obesity-related research. The objective of this study was to select a set of reference genes with stable expressions to be used for RT-qPCR normalization in rats under fasted vs re-fed and chow vs high-fat diet (HFD) conditions. Male long-Evans rats were treated under four conditions: chow/fasted, chow/re-fed, HFD/fasted and HFD/re-fed. Expression stabilities of 13 candidate reference genes were evaluated in the rat hypothalamus, duodenum, jejunum and ileum using the ReFinder software program. The optimal number of reference genes needed for RT-qPCR analyses was determined using geNorm. Using geNorm analysis, we found that it was sufficient to use the two most stably expressed genes as references in RT-qPCR analyses for each tissue under specific experimental conditions. B2M and RPLP0 in the hypothalamus, RPS18 and HMBS in the duodenum, RPLP2 and RPLP0 in the jejunum and RPS18 and YWHAZ in the ileum were the most suitable pairs for a normalization study when the four aforementioned experimental conditions were considered. Our study demonstrates that gene expression levels of reference genes commonly used in obesity-related studies, such as ACTB or RPS18, are altered by changes in acute or chronic energy status. These findings underline the importance of using reference genes that are stable in expression across experimental conditions when studying the rat hypothalamus and intestine, because these tissues have an integral role in the regulation of energy homeostasis. It is our hope that this study will raise awareness among obesity researchers on the essential need for reference gene validation in gene expression studies.

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.

The peroxisome proliferator-activated receptor-γ (PPAR-γ) is a nuclear receptor that is activated by lipids to induce the expression of genes involved in lipid and glucose metabolism, thereby converting nutritional signals into metabolic consequences. PPAR-γ is the target of the thiazolidinedione (TZD) class of insulin-sensitizing drugs, which have been widely prescribed to treat type 2 diabetes mellitus. A common side effect of treatment with TZDs is weight gain. Here we report a previously unknown role for central nervous system (CNS) PPAR-γ in the regulation of energy balance. We found that both acute and chronic activation of CNS PPAR-γ, by either TZDs or hypothalamic overexpression of a fusion protein consisting of PPAR-γ and the viral transcriptional activator VP16 (VP16-PPAR-γ), led to positive energy balance in rats. Blocking the endogenous activation of CNS PPAR-γ with pharmacological antagonists or reducing its expression with shRNA led to negative energy balance, restored leptin sensitivity in high-fat-diet (HFD)-fed rats and blocked the hyperphagic response to oral TZD treatment. These findings have implications for the widespread clinical use of TZD drugs and for understanding the etiology of diet-induced obesity.

Transgenic (TG) mice expressing a Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibitory peptide targeted to the cardiac myocyte longitudinal sarcoplasmic reticulum (LSR) display reduced phospholamban phosphorylation at Thr17and develop dilated myopathy when stressed by gestation and parturition (Ji Y, Li B, Reed TD, Lorenz JN, Kaetzel MA, and Dedman JR. J Biol Chem 278: 25063–25071, 2003). In the present study, these animals (TG) are evaluated for the effect of inhibition of sarcoplasmic reticulum (SR) CaMKII activity on the contractile characteristics and Ca2+cycling of myocytes. Analysis of isolated work-performing hearts demonstrated moderate decreases in the maximal rates of contraction and relaxation (±dP/d t) in TG mice. The response of the TG hearts to increases in load is reduced. The TG hearts respond to isoproterenol (Iso) in a dose-dependent manner; the contractile properties were reduced in parallel to wild-type hearts. Assessment of isolated cardiomyocytes from TG mice revealed 40–47% decrease in the maximal rates of myocyte shortening and relengthening under both basal and Iso-stimulated conditions. Although twitch Ca2+transient amplitudes were not significantly altered, the rate of twitch intracellular Ca2+concentration decline was reduced by ∼47% in TG myocytes, indicating decreased SR Ca2+uptake function. Caffeine-induced Ca2+transients indicated unaltered SR Ca2+content and Na+/Ca2+exchange function. Phosphorylation assays revealed an ∼30% decrease in the phosphorylation of ryanodine receptor Ser2809. Iso stimulation increased the phosphorylation of both phospholamban Ser16and the ryanodine receptor Ser2809but not phospholamban Thr17in TG mice. This study demonstrates that inhibition of SR CaMKII activity at the LSR results in alterations in cardiac contractility and Ca2+handling in TG hearts.

The importance of pancreatic versus intestinal-derived GLP-1 for glucose homeostasis is controversial. We detected active GLP-1 in the mouse and human pancreas, albeit at extremely low levels relative to glucagon. Accordingly, to elucidate the metabolic importance of intestinal proglucagon-derived peptides (PGDPs), we generated mice with reduction of Gcg expression within the distal (Gcg(DistalGut−/−)) or entire (Gcg(Gut−/−)) gut. Substantial reduction of gut Gcg expression markedly reduced circulating levels of GLP-1, and impaired glucose homeostasis, associated with increased levels of GIP, and accelerated gastric emptying. Gcg(DistalGut−/−) mice similarly exhibited lower circulating GLP-1 and impaired oral glucose tolerance. Nevertheless, plasma levels of insulin remained normal following glucose administration in the absence of gut-derived GLP-1. Collectively, our findings identify the essential importance of gut-derived PGDPs for maintaining levels of circulating GLP-1, control of gastric emptying, and glucose homeostasis.

Hyperglycemia is one of the most important clinical features of burn patients. Previous reports had demonstrated that miRNA was involved in regulating glucose metabolism in various diseases such as diabetes and obesity. Our current study discovered the relationship between miR-194 and hyperglycemia in burn rats via suppressing insulin-like growth factor 1 receptor (IGF-IR). We found that the fasting blood glucose was significantly increased in rats of the burn group, and protein expression of IGF-IR was attenuated in response to burn injury. Similar to the results of animal experiments, miR-194 expression was significantly elevated and IGF-IR protein level was suppressed in L6 cells treated with serum from burn rats compared with those treated by serum from sham rats. However, IGF-IR mRNA level was comparable between burn and sham rats, suggesting that IGF-IR may be downregulated at the translation level. Further experiments revealed that miR-194 was significantly increased in burn rats compared with sham rats using miRNA array and real-time polymerase chain reaction (PCR) assay. And IGF-IR protein expression was reduced in L6 cells transfected with miR-194 plasmid. Insulin-like growth factor 1 receptor expression was also repressed and fasting blood glucose was increased in rats injected with miR-194 plasmid. In general, we have identified a novel function of miR-194 in modulating burn-induced hyperglycemia via suppressing the expression of IGF-IR.

A convincing line of evidence is being developed that the congenital nongoitrous hypothyroidism and dwarfism observed in the WIC-rdw rat may indeed be caused by a primary defect in thyroid hormonogenesis. In support of this hypothesis, several recent reports have shown the presence of elevated molecular chaperone levels in the WIC-rdw thyrocytes, the endoplasmic reticulum of which was markedly dilated, suggesting a defect in intracellular protein transport. Here the studies were undertaken to identify the precise molecular defect in the WIC-rdw rat. First, the genetic linkage analysis revealed that the rdw locus was on rat chromosome 7 and was identical to the thyroglobulin (Tg) gene locus. Moreover, the Tg protein level was reduced in the WIC-rdw thyroid despite a similar level of the Tg gene transcripts that were indistinguishable in their size from the normal. Next, the complete sequencing of the rdw and the normal rat Tg cDNAs revealed a single nucleotide change, G6958C, resulting in a G2320R missense mutation in a highly conserved region of the Tg molecule. Finally, transient expression of the intact Tg cDNA containing the rdw mutation in the COS-7 cells showed no detectable Tg in the secreted media, indicating a severe defect in the export of the mutant Tg. Together, our observations suggest that a missense mutation, G2320R, in the Tg gene is responsible for the rdw mutation in the WIC-rdw rat.

The actions of 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3) are mediated through the nuclear vitamin D receptor (VDR). The regulation of VDR abundance plays an important role in determining the magnitude of the target cell response to 1,25(OH)2D3. The major physiological activity of 1,25(OH)2D3 is the regulation of calcium absorption in the small intestine, and the level of VDR is an important factor in this regulation. However, the characterization of VDR gene expression in the small intestine remains unknown. In the present study, we investigated the regulation of the human VDR (hVDR) gene expression in the small intestine. The 4.0 kb of the 5'-flanking region of the hVDR gene promoter was cloned and characterized by the measurement of luciferase activity and an electrophoretic mobility-shift assay (EMSA). With the EMSA, we found that Cdx-2 (a homeodomain protein-related caudal) binds to the sequence 5'-ATAAAAACTTAT-3' at -3731 to -3720 bp (hVD-SIF1) relative to the transcription start site of the hVDR promoter. This sequence is very similar to the human sucrase-isomaltase footprint 1 (SIF1) element. With a competition analysis and specific antibodies for Cdx-2, we demonstrated that Cdx-2 is able to activate VDR gene transcription by binding to this element. The mutation of the hVD-SIF1 sequence in the hVDR gene promoter markedly suppressed the transactivation of the reporter gene in Caco-2 cells. In addition, the DNA fragment (-3996 to -3286) containing the hVD-SIF1 binding site increased transcription when placed upstream of the herpes simplex virus thymidine kinase promoter. These findings suggest that Cdx-2 plays an important role in the intestine-specific transcription of the hVDR gene.

Overconsumption of a high-fat diet promotes weight gain that can result in obesity and associated comorbidities, including Type 2 diabetes mellitus. Consumption of a high-fat diet also alters gut-brain communication. Glucagon-like peptide 1 (GLP-1) is an important gastrointestinal signal that modulates both short- and long-term energy balance and is integral in maintenance of glucose homeostasis. In the current study, we investigated whether high-fat diets (40% or 81% kcal from fat) modulated the ability of the GLP-1 receptor (GLP-1r) agonists exendin-4 (Ex4) and liraglutide to reduce food intake and body weight. We observed that rats maintained on high-fat diets had a delayed acute anorexic response to peripheral administration of Ex4 or liraglutide compared with low-fat diet-fed rats (17% kcal from fat). However, once suppression of food intake in response to Ex4 or liraglutide started, the effect persisted for a longer time in the high-fat diet-fed rats compared with low-fat diet-fed rats. In contrast, centrally administered Ex4 suppressed food intake similarly between high-fat diet-fed and low-fat diet-fed rats. Chronic consumption of a high-fat diet did not change the pharmacokinetics of Ex4 but increased intestinal Glp1r expression and decreased hindbrain Glp1r expression. Taken together, these findings demonstrate that dietary composition alters the temporal profile of the anorectic response to exogenous GLP-1r agonists.

Glucagon-like peptide 1 (GLP-1) is a peptide hormone that is released from the gut in response to nutrient ingestion and that has a range of metabolic effects, including enhancing insulin secretion and decreasing food intake. Postprandial GLP-1 secretion is greatly enhanced in rats and humans after some bariatric procedures, including vertical sleeve gastrectomy (VSG), and has been widely hypothesized to contribute to reduced intake, weight loss, and the improvements in glucose homeostasis after VSG. We tested this hypothesis using two separate models of GLP-1 receptor deficiency. We found that VSG-operated GLP-1 receptor–deficient mice responded similarly to wild-type controls in terms of body weight and body fat loss, improved glucose tolerance, food intake reduction, and altered food selection. These data demonstrate that GLP-1 receptor activity is not necessary for the metabolic improvements induced by VSG surgery.

Glutathione S-transferases (GSTs) play important roles in the detoxification of electrophilic carcinogens, and GSTM1 null genotype is associated with the dysfunction of GSTs. Previous studies investigating the association between GSTM1 null genotype and risk of esophageal carcinoma in Chinese provided inconsistent findings. To provide a more precise estimation on the association between GSTM1 null genotype and risk of esophageal carcinoma in Chinese population, a meta-analysis was performed. Eligible studies were searched in PubMed, Embase, and China National Knowledge Infrastructure databases. Odds ratio (OR) with the corresponding 95 % confidence interval (95 %CI) was used to assess the association. A total of 18 case–control studies involving 1,947 cases and 3,506 controls were finally included in the meta-analysis. Meta-analysis of those 18 studies showed that GSTM1 null genotype was associated with an increased risk of esophageal carcinoma in Chinese (random effect model OR = 1.49, 95 %CI = 1.11–2.00, P = 0.008). The findings from cumulative meta-analysis showed that the association was more obvious as the data increased by publication year. There was no risk of publication bias in the meta-analysis. Therefore, the findings from our meta-analysis provide a strong evidence for the association between GSTM1 null genotype and risk of esophageal carcinoma in Chinese population, and GSTM1 null genotype contributes to increased risk of esophageal carcinoma in Chinese.

Background:To investigate the correlation between consumption of whole grains and the risk of all-cause, cardiovascular disease (CVD), and diabetes-specific mortality according to a dose–response meta-analysis of prospective cohort studies.Methods:Observational cohort studies, which reported

To assess the performance of the The European System for Cardiac Operative. Risk Evaluation II (EuroSCORE II) in Chinese patients undergoing heart valve surgery at our centre.From January 2006 to December 2011, 3479 consecutive patients who underwent heart valve surgery at our centre were collected and scored according to the original EuroSCORE and EuroSCORE II models. All patients were divided into single valve surgery and multiple valve surgery subgroups. The entire cohort and each subgroup were analysed. Calibration of the original EuroSCORE and EuroSCORE II models was assessed by the Hosmer-Lemeshow (H-L) test. Discrimination was tested by calculating the area under the receiver operating characteristic (ROC) curve.Observed mortality was 3.32% overall, compared to expected mortality 3.84% for the original additive EuroSCORE (H-L: P = 0.013), 3.33% for the original logistic EuroSCORE (H-L: P = 0.08), and 2.52% for the EuroSCORE II (H-L: P0.0001). The EuroSCORE II model showed good calibration in predicting in-hospital mortality for patients undergoing single valve surgery (H-L: P = 0.103) and poor calibration for patients undergoing multiple valve surgery (H-L: P0.0001). The discriminative power of the original EuroSCORE model (area under the ROC curve of 0.684 and 0.673 for the additive and logistic model, respectively) and EuroSCORE II model (area under the ROC curve of 0.685) for the entire cohort was poor. The discriminative power of the EuroSCORE II model was good for the single valve surgery group (area under the ROC curve of 0.792) and was poor for the multiple valve surgery group (area under the ROC curve of 0.605).The EuroSCORE II model gives an accurate prediction for individual operative risk in patients undergoing single valve surgery but an imprecise prediction in patients undergoing multiple valve surgery at our centre. Therefore, the use of the EuroSCORE II model for risk evaluation may be suitable in patients undergoing single valve surgery, and the creation of a new model which accurately predicts outcomes in patients undergoing multiple valve surgery is possibly required at our centre in the future.

The aim of this study was to develop a logistic risk prediction model for prolonged ventilation after adult heart valve surgery.This is a retrospective observational study of collected data on 3965 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 = 2400) and a validation dataset (n = 1565). A multivariate logistic regression analysis was undertaken using the development dataset to identify independent risk factors for prolonged ventilation (defined as ventilation greater than 72 h). Performance of the model was then assessed by observed and expected rates of prolonged ventilation on the development and validation dataset. Model calibration and discriminatory ability were analyzed by the Hosmer-Lemeshow goodness-of-fit statistic and the area under the receiver operating characteristic (ROC) curve, respectively.There were 303 patients that required prolonged ventilation (7.6%). Preoperative independent predictors of prolonged ventilation are shown with odds ratio and P value as follows: (1) age, 1.9, P .0001; (2) hypercholesterolemia, 5.3, P = .001; (3) renal failure, 18.2, P = .004; (4) previous cardiac surgery, 2.4, P = .0002; (5) left bundle branch block, 4.2, P = .011; (6) ejection fraction, 1.4, P = .003; (7) left ventricle weight, 1.5, P = .007; (8) New York Heart Association class III-IV, 1.8, P = .021; (9) critical preoperative state, 4.5, P .0001; (10) tricuspid insufficiency, 1.2, P = .031; (11) concurrent CABG, 2.2, P = .019; and (12) concurrent other cardiac surgery, 2.1, P = .001. The Hosmer-Lemeshow goodness-of-fit statistic was not statistically significant in both development and validation dataset (P = .202 vs P = .291). The ROC curve for the prediction of prolonged ventilation in development and validation dataset was .789 and .710, respectively.We developed and validated a local risk prediction model for prolonged ventilation after adult heart valve surgery. This model can be used to calculate patient-specific risk by the logistic equation with an equivalent predicted risk at our center in future clinical practice.

OBJECTIVE To observe the effects of Xuefu Zhuyu Capsule (XFZYC), a compound traditional Chinese herbal medicine, on endothelin-1 (ET-1) release in myocardium and vascular endothelium and nitric oxide (NO)/nitric oxide synthase (NOS) system of swines after acute myocardial infarction (AMI) and reperfusion, and to explore the action mechanisms of XFZYC in improving the endothelium function. METHODS Forty-five Yorkshire swines were randomized into 3 groups: sham-operated group, untreated group and XFZYC-treated group. A Yorkshire swine model of reperfusion in AMI was established by ligation of left anterior descending coronary artery for 90 min followed by 2 h relaxation. The content of serum ET-1 and NO was measured by radioimmunoassay before and after AMI and after reperfusion, respectively. Twenty-four hours after operation, all Yorkshire swines underwent diagnostic coronary angiography to delineate coronary arteries. The expressions of ET-1 and endothelial nitric oxide synthase (eNOS) in myocardial tissue of ischemic area were quantified with Western blotting. Microvessel density of the implanting sites was assessed by using HE staining. RESULTS Compared with the untreated group, the levels of serum ET-1 after AMI and reperfusion were significantly decreased in XFZYC-treated group (P

Using the mouse Langendorff heart perfusion model, the signaling pathways that regulate cardiac CREB-S133 phosphorylation have been defined. In mouse hearts stimulated with isoproterenol (ISO) (10(-8) M), endothelin-1 (ET-1) (10(-8) M), and phorbol 12-myristate 13-acetate (TPA) (10(-7) M), CREB-S133 phosphorylation was attained only by TPA-treatment. Activation of protein kinase A (PKA) was achieved by ISO. ISO- and ET-1-stimulation activated Ca2+/calmodulin-dependent kinase II (CaMKII). Protein kinase C (PKC) and p90(RSK) were activated with all three stimuli. Inhibition of ERK1/2 with PD98059 (10(-5) M) completely inhibited the activation of p90(RSK), but did not block CREB-S133 phosphorylation in TPA-perfused heart, indicating that PKA, CaMKII, and p90(RSK) do not phosphorylate CREB-S133 in the murine heart. PKC activation is signal specific. Analyses of PKC isoforms suggest that CREB phosphorylation is mediated by PKC epsilon translocating into nucleus only with TPA stimulation. These results, unlike those reported in other tissues, demonstrate that cardiac CREB is not a multi-signal target.

To investigate the role of Ca2+/calmodulin-dependent kinase II in cardiac sarcoplasmic reticulum function, transgenic mice were designed and generated to target the expression of a Ca2+/calmodulin-dependent kinase II inhibitory peptide in cardiac longitudinal sarcoplasmic reticulum using a truncated phospholamban transmembrane domain. The expressed inhibitory peptide was highly concentrated in cardiac sarcoplasmic reticulum. This resulted in a 59.7 and 73.6% decrease in phospholamban phosphorylation at threonine 17 under basal and beta-adrenergic stimulated conditions without changing phospholamban phosphorylation at serine 16. Sarcoplasmic reticulum Ca2+ uptake assays showed that the Vmax was decreased by approximately 30% although the apparent affinity for Ca2+ was unchanged in heterozygous hearts. The in vivo measurement of cardiac function showed no significant reductions in positive and negative dP/dt, but a moderate 18% decrease in dP/dt40, indicative of isovolumic contractility, and a 26.1% increase in the time constant of relaxation (tau) under basal conditions. The changes in these parameters indicate a moderate cardiac dysfunction in transgenic mice. Although the 3 and 4-month-old transgenic mice displayed no overt signs of cardiac disease, when stressed by gestation and parturition, the 7-month-old female mice develop dilated heart failure, suggesting the important role of Ca2+/calmodulin-dependent kinase II pathway in the development of cardiac disease.

Background MicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptional regulate gene expression in a variety of cancers. Increasing evidences indicate that miR-30 expression is down-regulated in numerous human cancers including non-small cell lung cancer (NSCLC) which hypothesizes that miR-30 may play an important role in tumorigenesis. The aim of this study was to investigate the target gene of miR-30 and its roles in tumor growth of NSCLC. Methods Luciferase reporter assays were employed to validate regulation of a putative target of miR-30. The effect of miR-30 on endogenous levels of this target were subsequently confirmed via Western blot (WB). Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed to determine the expression level of miR-30 in NSCLC specimens and adjacent non-tumor tissues. MTT assays were conducted to explore the impact of miR-30 overexpression on the proliferation of human NSCLC cells. Results Both miR-30b and miR-30c (miR-30b/c) were found having target site in same region of Rab18 mRNA. Luciferase assays using a reporter carrying a putative miR-30b/c target site in the coding DNA sequence (CDS) region of Rab18 revealed that miR-30b/c directly targeted Rab18. Overexpression of miR-30b/c led to down-regulation of Rab18 in A549 and H23 cells at protein levels but not mRNA levels. Down-regulation of miR-30b/c and up-regulation of Rab18 protein levels were detected in NSCLC specimens compared with adjacent non-tumor tissues. Overexpression of miR-30b/c suppressed NSCLC cells growth. Knockdown of Rab18 by siRNA significantly inhibited the proliferation of NSCLC cells. Conclusions We demonstrated that miR-30b/c was down-regulated in NSCLC specimens compared with adjacent non-tumor tissues. miR-30b/c directly targeted and down-regulated Rab18 expression and inhibited NSCLC cells proliferation. These data indicated that miR-30b/c could serve as a tumor suppressor gene involved in NSCLC pathogenesis.