The influence of the NRG1/ERBB4 signaling pathway on pulmonary artery endothelial cells.

This study aimed to examine the influence of the Neuregulin-1 (NRG1)/ERBB4 signaling pathway on the function of human pulmonary artery endothelial cells (HPAECs) and investigate the underlying mechanisms. Enzyme-linked immunosorbent assay indicated that ERBB4 levels in the serum of patients with pulmonary embolism (PE) were significantly higher than those of healthy controls (p < 0.05). In cellular studies, thrombin stimulation for 6 h led to a significant decrease in cell viability and overexpression of ERBB4 compared to control (p < 0.05). In the NRG1 group, apoptosis of HPAECs was reduced (p < 0.05), accompanied by a decrease in ERBB4 expression and an increase in p-ERBB4, phosphorylated serine/threonine kinase proteins (Akt) (p-Akt), and p-phosphoinositide 3-kinase (PI3K) expression (p < 0.05). In the AG1478 group, there was a significant increase in HPAEC apoptosis and a significant decrease in p-ERBB4 and ERBB4 expression compared to the Con group (p < 0.05). In the AG1478 + NRG1 group, there was an increase in the apoptosis rate and a significant decrease in the expression of p-ERBB4, ERBB4, p-Akt, and phosphorylated PI3K compared to the NRG1 group (p < 0.05). In animal studies, the PE group showed an increase in the expression of ERBB4 and p-ERBB4 compared to the Con group (p < 0.05). NRG1 treatment led to a significant reduction in embolism severity with decreased ERBB4 expression and increased p-ERBB4 expression (p < 0.05). Gene set enrichment analysis identified five pathways that were significantly associated with high ERBB4 expression, including CHOLESTEROL HOMEOSTASIS, OXIDATIVE PHOSPHORYLATION, and FATTY ACID METABOLISM (p < 0.05). Therefore, NRG1 inhibits apoptosis of HPAECs, accompanied by a decrease in ERBB4 and an increase in p-ERBB4. NRG1 inhibition in HPAECs apoptosis can be partially reversed by inhibiting ERBB4 expression with AG1478. ERBB4 has the potential to be a novel biological marker of PE.

The prognostic value of pulmonary embolism severity index in acute pulmonary embolism: a meta-analysis.

BACKGROUND: Prognostic assessment is important for the management of patients with acute pulmonary embolism (APE). Pulmonary Embolism Severity Index (PESI) and simple PESI (sPESI) are new emerged prognostic assessment tools for APE. The aim of this meta-analysis is to assess the accuracy of the PESI and the sPESI to predict prognostic outcomes (all-cause and PE-related mortality, serious adverse events) in APE patients, and compare between these two PESIs. METHODS: MEDLINE and EMBASE database were searched up to June 2012 using the terms "Pulmonary Embolism Severity Index" and "pulmonary embolism". Summary odds ratio (OR) with 95% confidence intervals (CIs) for prognostic outcomes in low risk PESI versus high risk PESI were calculated. Summary receiver operating characteristic curve (SROC) used to estimate overall predicting accuracies of prognostic outcomes. RESULTS: Twenty-one studies were included in this meta-analysis. The results showed low-risk PESI was significantly associated with lower all-cause mortality (OR 0.13; 95% CI 0.12 to 0.15), PE-related mortality (OR 0.09; 95% CI 0.05 to 0.17) and serious adverse events (OR 0.34; 95% CI 0.29 to 0.41), with no homogeneity across studies. In sPESI subgroup, the OR of all-cause mortality, PE-related mortality, and serious adverse events was 0.10 (95% CI 0.08 to 0.14), 0.09 (95% CI 0.03 to 0.26) and 0.40 (95% CI 0.31 to 0.51), respectively; while in PESI subgroup, the OR was 0.14 (95% CI 0.13 to 0.16), 0.09 (95% CI 0.04 to 0.21), and 0.30 (95% CI 0.23 to 0.38), respectively. For accuracy analysis, the pooled sensitivity, the pooled specificity, and the overall weighted AUC for PESI predicting all-cause mortality was 0.909 (95% CI: 0.900 to 0.916), 0.411 (95% CI: 0.407 to 0.415), and 0.7853±0.0058, respectively; for PE-related mortality, it was 0.953 (95% CI: 0.913 to 0.978), 0.374 (95% CI: 0.360 to 0.388), and 0.8218±0.0349, respectively; for serious adverse events, it was 0.821 (95% CI: 0.795 to 0.845), 0.389 (95% CI: 0.384 to 0.394), and 0.6809±0.0208, respectively. In sPESI subgroup, the AUC for predicting all-cause mortality, PE-related mortality, and serious adverse events was 0.7920±0.0117, 0.8317±0.0547, and 0.6454±0.0197, respectively. In PESI subgroup, the AUC was 0.7856±0.0075, 0.8158±0.0451, and 0.6609±0.0252, respectively. CONCLUSIONS: PESI has discriminative power to predict the short-term death and adverse outcome events in patients with acute pulmonary embolism, the PESI and the sPESI have similar accuracy, while sPESI is easier to use. However, the calibration for predicting prognosis can't be calculated from this meta-analysis, some prospective studies for accessing PESI predicting calibration can be recommended.

The dynamic changes of LDH isoenzyme 3 and D-dimer following pulmonary thromboembolism in canine.

INTRODUCTION: To investigate the time course of changes of lactic acid dehydrogenase (LDH), LDH isoenzymes and D-dimer levels following acute pulmonary thromboembolism (PTE). MATERIALS AND METHODS: Eighteen dogs were randomly divided into three groups. Acute PTE was induced by injection of preformed blood clots into pulmonary artery through femoral vein. Thrombin and human fibrinogen were delivered into blood clots in embolism group I. Only thrombin was delivered into blood clots in embolism group II. The control group received normal saline and human fibrinogen in the same manner. Series of blood samples were collected pre-embolism and post-embolism. LDH isoenzymes proportion and D-dimer levels were measured. RESULTS: At 30 min, 1 h, 2 h, 4 h, 24 h post-embolism, the plasma D-dimer levels from embolism group I were significantly higher than pre-embolism and those from control group at the same intervals (p<0.05). The peak appeared at 2 h post-embolism (2.336+/-0.326 vs. 0.016+/-0.013, p<0.05). At 4 h, 24 h and 48 h post-embolism, total serum LDH activity and LDH-3 proportion from two embolism groups were significantly higher than pre-embolism (p<0.05). The peak of LDH-3 proportion in two embolism groups both appeared at 24 h post-embolism (0.225+/-0.021 vs. 0.108+/-0.030, 0.214+/-0.011 vs. 0.096+/-0.031, respectively. p<0.05). CONCLUSIONS: The LDH-3 and D-dimer levels were changed dynamically with a relative specificity manner during the course of acute massive PTE. Combination the D-dimer assay with LDH-3 may have a potential value in diagnosing acute massive PTE.

Hyponatremia and short-term prognosis of patients with acute pulmonary embolism: A meta-analysis.

OBJECTIVES: The aim of this study was to assess the relationship between hyponatremia and the short-term prognosis of patients with acute pulmonary embolism (PE). METHODS: Searches of MEDLINE (1966-) and ISI Databases (1965-) were performed for English language studies. Odds ratio (OR) and adjusted hazard ratio (HR) for short-term prognosis were calculated for PE patients with or without hyponatremia. Meta-analysis was carried out following Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. RESULTS: Eight studies with 18,616 patients were included in this meta-analysis. The mean in-hospital mortality was 12.9% in hyponatremia group, compared with 2.3% in normonatremia group. Meta-analysis showed the summary OR was 5.586 (95% CI 3.424 to 9.112). The mean 30-day mortality was 15.9% in hyponatremia group, compared with 7.4% in normonatremia group. The summary OR was 3.091 (95% CI 1.650 to 5.788). No significant publication bias was found for the meta-analysis. Sensitivity analyses by only pooled the adjusted HRs showed the summary HR was 0.924 (95% CI 0.897 to 0.951), which indicted the mortality risk will be decrease to 0.924 times for per-1mmol/L sodium increase in hyponatremia patients. CONCLUSIONS: Our meta-analysis indicates that hyponatremia was related with poor short-term prognosis in patients with acute PE. Hyponatremia is a simple, cheap, powerful marker of mortality, which should be used routinely tested in the PE prognostic assessment.

Red cell distribution width in predicting 30-day mortality in patients with pulmonary embolism.

PURPOSE: The aim of the study was to investigate red cell distribution width (RDW) in predicting 30-day mortality in patients with pulmonary embolism (PE). METHODS: A single-center, retrospective study design was used between January 1, 2014, and February 1, 2016. The primary end point was 30-day mortality after admission. The RDW predicting value was assessed by receiver operating characteristic curves and area under the curve. RESULTS: A total of 309 patients with PE were included. The 30-day mortality was 14.9% (46/309). The mean RDW level was 13.9%±0.6% (range, 10.7%-21.9%) at admission. The 30-day mortality was higher in the high-RDW-level group compared with the normal-RDW-level group (12.5% vs 23.5%, χ2=5.140, P=.023), with an odds ratio of 2.164 (95% confidence interval [CI], 1.019-4.450). Logistic regression showed that presence of shock, RDW level, and simplified pulmonary embolism severity index (sPESI) were independent risk factors for 30-day mortality in patients with PE. After adjustment by these risk factors, the adjusted odds ratio was 1.439 (95% CI, 1.024-2.116). The area under the curve for RDW predicting the 30-day mortality was 0.6646 (95% CI, 0.5585-0.7518). The cutoff was 16%. The Youden index for RDW and sPESI was 0.400 and 0.453, respectively. When adding RDW into sPESI, the modified sPESI showed highest prediction accuracy, with Youden index 0.499. CONCLUSIONS: Our results suggested that the RDW is a simple and useful indicator in predicting 30-day mortality in patients with PE. However, this conclusion showed be confirmed by prospective study with large sample.

Pollutional haze and COPD: etiology, epidemiology, pathogenesis, pathology, biological markers and therapy.

In recent years, serious pollutional haze occurs in the mainland of China thanks to the development of urbanization and industrialization. There is a close relationship between air pollution and the occurrence and development of chronic obstructive pulmonary disease (COPD), but there are some new characteristics in some aspects of COPD associated with pollutional haze compared with COPD induced by traditional physical and chemical factors. This article attempts to summarize the new progress from these new features of COPD related to pollutional haze, focus on etiology, epidemiology, pathogenesis, pathology, biological markers and therapy.

A comparison of APACHE II and CPIS scores for the prediction of 30-day mortality in patients with ventilator-associated pneumonia.

OBJECTIVE: The aim of this study was to compare the Acute Physiology and Chronic Health Evaluation II (APACHE II) score and the Clinical Pulmonary Infection Score (CPIS) for the prediction of 30-day mortality in patients with ventilator-associated pneumonia (VAP). METHODS: A single-center, prospective cohort study design was employed between January 1, 2010 and January 1, 2014. APACHE II and CPIS scores were determined on the day of VAP diagnosis. Discrimination was tested using receiver-operating characteristic (ROC) curves and the areas under the curve (AUC). Calibration was tested using the Hosmer-Lemeshow statistic. RESULTS: Of 135 patients with VAP, 39 died; the 30-day mortality was 28.9%. APACHE II and CPIS scores were significantly higher in non-survivors compared to survivors (23.1±4.8 vs. 16.7±4.6, p<0.001; 6.8±1.3 vs. 6.2±1.3, p=0.016). APACHE II had excellent discrimination for predicting 30-day mortality in patients with VAP, with AUC 0.808 (95% confidence interval (CI) 0.704-0.912, p<0.001). However, the CPIS score did not have discrimination power for predicting mortality, with AUC 0.612 (95% CI 0.485-0.739, p=0.083). The Hosmer-Lemeshow statistic showed good goodness-of-fit for observed 30-day mortality and APACHE II expected mortality (Chi-square=1.099, p=0.785). However, CPIS expected 30-day mortality did not fit the observed mortality (Chi-square=6.72, p=0.004). CONCLUSIONS: These data suggest that APACHE II is useful for predicting 30-day mortality in patients with VAP, but that the CPIS does not have good discrimination and calibration for predicting mortality.

Ovalbumin enhances YKL-40, IL-5, GM-CSF, and eotaxin expression simultaneously in primarily cultured mouse tracheal epithelial cells.

Epithelial inflammation and eosinophil infiltration are crucial for the pathogenesis of asthma. Many inflammatory mediators, such as YKL-40, interleukin -5 (IL-5), granulocyte-macrophage colony-stimulating factor (GM-CSF), and eotaxin, are important for the development of allergic airway inflammation. This study is aimed at investigating the impact of treatment with ovalbumin (OVA) on the levels of those inflammatory mediators in primarily cultured mouse tracheal epithelial cells. Mouse tracheal epithelial cells were isolated and identified by immunofluorescent staining; the isolated mouse tracheal epithelial cells expressed cytokeratins. Treatment with OVA for 24 or 48 h significantly increased the relative levels of YKL-40, IL-5, GM-CSF, and eotaxin mRNA transcripts and YKL-40, IL-5, GM-CSF, and eotaxin proteins secreted in the supernatants of cultured cells, as compared with that in the untreated control cells (P < 0.01, P < 0.05, respectively). The levels of YKL-40 expression were correlated positively with the levels of IL-5, GM-CSF, and eotaxin expression in the OVA-treated cells. These data indicated that treatment with OVA simultaneously enhanced YKL-40, IL-5, GM-CSF, and eotaxin expression in the cultured mouse tracheal epithelial cells in vitro. These inflammatory mediators may synergistically contribute to the pathogenesis of allergic inflammation, and this study may help to understand the role of YKL-40 in the pathogenesis of asthma.