Lv Wang

Performance of EuroSCORE II in patients who have undergone heart valve surgery: a multicentre study in a Chinese population

OBJECTIVES The EuroSCORE II is an updated version of the EuroSCORE. This multicentre study validated the EuroSCORE II and logistic EuroSCORE in Chinese patients who underwent heart valve surgery. METHODS A total of 11 170 adult patients underwent heart valve surgery from January 2008 to December 2011. Model discrimination and calibration were assessed for both EuroSCORE II and logistic EuroSCORE. The patients were divided into three subgroups according to the weight of the procedures, and the performance of EuroSCORE II for each group was assessed. A correlation analysis was performed for operative complications and EuroSCORE II. RESULTS The in-hospital mortality of this series was 2.02% (226 of 11 170), and the predicted mortality rate was 2.62±5.75% by EuroSCORE II and 2.55±6.51% by logistic EuroSCORE (LES). The C-statistics of EuroSCORE II and LES were 0.72 [95% confidence interval (CI) 0.69-0.75] and 0.67 (95% CI 0.63-0.70), respectively. Both models failed the Hosmer-Lemeshow goodness-of-fit test, with a P<0.05. According to the weight of the procedure, the isolated non-CABG subgroup had the best discrimination (C-statistics: 0.76 in the non-CABG group, 0.67 in the 2 procedures group and 0.73 in the 3+ procedures group). The complication ratio was strongly related to the EuroSCORE II-predicted mortality (Pearson correlation coefficient: 0.90 for ARDS, 0.97 for acute renal failure, 0.97 for prolonged ventilation and 0.94 for a prolonged ICU stay). CONCLUSIONS EuroSCORE II was an improvement upon its original logistic model for Chinese patients who underwent heart valve surgery, particularly for a single-valve procedure. The EuroSCORE II-predicted mortality correlated with the operative complications.

Validation of EuroSCORE II in Chinese Patients Undergoing Heart Valve Surgery

BACKGROUND 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. 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 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. RESULTS 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: P < 0.0001). 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: P < 0.0001). 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). CONCLUSION 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 Effect of Rhubarb Pre-Treatment on Intestinal Microcirculation in Septic Rats

The intestine plays a vital role in the pathophysiology of sepsis development. The objective of the present study was to explore the effects of rhubarb on intestinal microcirculation in septic rats. We used moorFLPI laser speckle imaging to detect the blood flow of the intestinal mucosa and wall. Using an ELISA, we assayed the concentration of lactate (L) and pyruvic acid (P) in the intestinal tissue to calculate the ratio of lactate to pyruvic acid (L/P ratio). To observe the intestinal mucosal capillaries, gelatin and ink were perfused into the intestine and subsequently stained with hematoxylin and eosin (HE) to measure the ratio of the vessel area. We then used immunohistochemistry to measure CD31 expression. Using an MTT assay, the effect of the rhubarb extract on the proliferation of human umbilical vein endothelial cells (HUVECs) was analyzed. The blood flow in the intestinal wall and mucosa of the control, sham and rhubarb-treated groups was significantly higher, while the sepsis group had relatively low blood flow. The L/P ratio in the intestinal tissue was larger in the sepsis group than in the other three groups. The microvascular area (MVA) in the sepsis group was smaller than in the control group, sham group or rhubarb group. Positive expression for CD31 was observed in the cytoplasm of vascular endothelial cells. The intestinal mucosal capillaries were reduced in septic rats as compared to the other three groups. HUVEC proliferation was enhanced by the rhubarb extract monomers at 1 μmol/L, but suppressed at higher concentrations of 10 to 100 μmol/L. These results suggest that pre-treatment with rhubarb prior to sepsis induction promotes the expansion of the intestinal mucosal capillaries, protects intestinal mucosal capillary endothelial cells and increases the number of functional intestinal capillaries.

CRISPLD2 Is Expressed at Low Levels during Septic Shock and Is Associated with Procalcitonin

Introduction Previous studies have shown that cysteine-rich secretory protein containing LCCL domain 2 (CRISPLD2) is a novel lipopolysaccharide (LPS)-binding protein, and the upregulation of CRISPLD2 expression protects mice against LPS-induced lethality. The aim of this study was to examine the expression of CRISPLD2 in patients with sepsis and characterize the association of this protein with procalcitonin. Methods The expression of CRISPLD2 was determined in100 healthy volunteers and 119 septic patients. According to the definition of sepsis, patients were divided into three groups sepsis, severe sepsis, and septic shock. The relationship between CRISPLD2 levels and procalcitonin was also examined and statistically analyzed. Results The CRISPLD2 levels in healthy individuals were 219.3±69.1 µg/ml. Patients with sepsis exhibited higher CRISPLD2 levels than observed in healthy individuals (p = 0.001), but CRISPLD2 expression was not upregulated in patients with septic shock. No significant differences were observed between the levels of CRISPLD2 in surviving and non-surviving spesis patients. CRISPLD2 levels were negatively correlated with procalcitonin levels(r = −0.334, p<0.001). Conclusions The present study is the first to demonstrate the decreased expression of CRISPLD2 in septic shock and its association with PCT in sepsis. Further studies are needed to clarify the potential association between CRISPLD2 expression and clinical outcomes to determine if it could be used as a novel sepsis biomarker.

Targeting programmed cell death 4 (PDCD4) with biogenic compounds in ARDS by Gaussian process‐based QSAR virtual screening

The programmed cell death 4 (PDCD4) has recently been recognized as a new and attractive target of acute respiratory distress syndrome. Here, we attempted to discover new and potent PDCD4 mediator ligands from biogenic compounds using a synthetic strategy of statistical virtual screening and experimental affinity assay. In the procedure, a Gaussian process‐based quantitative structure‐activity relationship regression predictor was developed and validated statistically based on a curated panel of structure‐based protein‐ligand affinity data. The predictor was integrated with pharmacokinetics analysis, chemical redundancy reduction, and flexible molecular docking to perform high‐throughput virtual screening against a distinct library of chemically diverse, drug‐like biogenic compounds. Consequently, 6 hits with top scores were selected, and their binding affinities to the recumbent protein of human PDCD4 were identified, 3 out of which were determined to have high or moderate affinity with Kd at micromolar level. Structural analysis of protein‐ligand complexes revealed that hydrophobic interactions and van der Waals contacts are the primary chemical forces to stabilize the complex architecture of PDCD4 with these mediator ligands, while few hydrogen bonds, salt bridges, and/or π‐π stacking at the complex interfaces confer selectivity and specificity for the protein‐ligand recognition. It is suggested that the statistical Gaussian process‐based quantitative structure‐activity relationship screening strategy can be successfully applied to rational discovery of biologically active compounds. The newly identified molecular entities targeting PDCD4 are considered as promising lead scaffolds to develop novel chemical therapeutics for acute respiratory distress syndrome.

Society of Thoracic Surgeons 2008 cardiac risk models predict in-hospital mortality of heart valve surgery in a Chinese population: A multicenter study

OBJECTIVES The Society of Thoracic Surgeons 2008 cardiac surgery risk models have been developed for heart valve surgery with and without coronary artery bypass grafting. The aim of our study was to evaluate the performance of Society of Thoracic Surgeons 2008 cardiac risk models in Chinese patients undergoing single valve surgery and the predicted mortality rates of those undergoing multiple valve surgery derived from the Society of Thoracic Surgeons 2008 risk models. METHODS A total of 12,170 patients underwent heart valve surgery from January 2008 to December 2011. Combined congenital heart surgery and aortal surgery cases were excluded. A relatively small number of valve surgery combinations were excluded. The final research population included the following isolated heart valve surgery types: aortic valve replacement, mitral valve replacement, and mitral valve repair. The following combined valve surgery types were included: mitral valve replacement plus tricuspid valve repair, mitral valve replacement plus aortic valve replacement, and mitral valve replacement plus aortic valve replacement and tricuspid valve repair. Evaluation was performed by using the Hosmer-Lemeshow test and C-statistics. RESULTS Data from 9846 patients were analyzed. The Society of Thoracic Surgeons 2008 cardiac risk models showed reasonable discrimination and poor calibration (C-statistic, 0.712; P = .00006 in Hosmer-Lemeshow test). Society of Thoracic Surgeons 2008 models had better discrimination (C-statistic, 0.734) and calibration (P = .5805) in patients undergoing isolated valve surgery than in patients undergoing multiple valve surgery (C-statistic, 0.694; P = .00002 in Hosmer-Lemeshow test). Estimates derived from the Society of Thoracic Surgeons 2008 models exceeded the mortality rates of multiple valve surgery (observed/expected ratios of 1.44 for multiple valve surgery and 1.17 for single valve surgery). CONCLUSIONS The Society of Thoracic Surgeons 2008 cardiac surgery risk models performed well when predicting the mortality for Chinese patients undergoing valve surgery. The Society of Thoracic Surgeons 2008 models were suitable for single valve surgery in a Chinese population; estimates of mortality for multiple valve surgery derived from the Society of Thoracic Surgeons 2008 models were less accurate.

NF-κB-Induced MicroRNA-211 Inhibits Interleukin-10 in Macrophages of Rats with Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome

Background/Aims: The present study addressed the potential involvement of microRNAs in acute respiratory distress syndrome (ARDS)-related inflammation and elucidates the underlying molecular mechanism. Methods: ARDS rat model was established by lipopolysaccharide, with compromised gas exchange capacity and lung edema. The inflammatory cells from bronchoalveolar lavage fluid (BALF) were profiled with automatic blood cell analyzer. The relative fluorescence intensity of BALF-derived macrophages was analyzed by flow cytometry. The relative microRNA expression was determined using microarray and Taqman assay. The secretory interleukin (IL)-10 was measured by enzyme-linked immunosorbent assay. Luciferase reporter assay was performed to determine the regulatory effects of miR-211 and NF-κB on IL-10 and miR-211 expressions, respectively. Chromatin immunoprecipitation (ChIP) was conducted to detect the direct binding of NK-κB on miR-211 promoter. The protein level was determined by Western blot. Results: The provoked acute inflammation was characterized with increased total cells, macrophages, neutrophils and lymphocytes. The relative expression of miR-211 was aberrantly up-regulated in BALF-derived macrophages from ARDS rats, which was accompanied with reduction of secretory IL-10. We further demonstrated that miR-211 inhibited IL-10 expression by binding to its 3’-UTR. The expression of miR-211 was modulated by NF-κB. Conclusion: Here we elucidated a crucial role of NF-κB/miR-211/IL-10 signaling axis in ARDS-related inflammation.