Songshi Ni

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

BackgroundPrognostic 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.MethodsMEDLINE 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.ResultsTwenty-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.ConclusionsPESI 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.

Circulating endothelial microparticles involved in lung function decline in a rat exposed in cigarette smoke maybe from apoptotic pulmonary capillary endothelial cells.

BACKGROUND Plasma levels of endothelial microparticles (EMPs), small membrane vesicles, shed from activated or apoptotic endothelial cells are elevated in patients with COPD and in smokers with normal lung function. Whether plasma EMPs levels are elevated in a rat exposed in cigarette smoke, whether the elevated EMPs derived from pulmonary endothelial cell apoptosis, and the relationship between EMP and lung function are obscure. METHODS All 60 wister rats were divided into six groups, three groups of ten rats were exposed to cigarette smoke of ten non-filter cigarettes per day, 5 days a week, using a standard smoking machine (Beijing BeiLanBo Company, China) for a period of 2, 4 and 6 months (n=10, respectively). Age-matched three control groups were sham-smoked. Pulmonary function parameters, including the ratio of forced expiratory volume in 0.3 second over forced vital capacity (FEV0.3/FVC) and dynamic compliance (Cdyn), were tested at the end of each period (2, 4, 6 months). Blood samples were collected and platelet-free plasma was isolated. Then CD42b-/CD31+ EMPs were analysed by flow cytometry. In parallel, lungs were removed and Colocalization with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), Hoeschts and CD31 was performed to evaluate pulmonary capillaries-specific apoptosis and identify the origins of the EMPs. RESULTS At 2, 4 and 6 months, in comparison with control groups, rats in cigarette smoke exposed groups had a significant increase in CD42b-/CD31+ EMPs (P<0.001, P<0.001, P<0.001, respectively), and Pulmonary function indicated that FEV0.3/FVC (P<0.05, P<0.01, P<0.01, respectively) and Cdyn (P<0.01, P<0.001, P<0.001 respectively) decreased. At the same time, CD42b-/CD31+ EMP counts were negatively correlated with Cdyn (P<0.05). Moreover, in vivo, TUNEL-positive cells co-localized with CD31 in whole lung tissue demonstrated a sequence of apoptosis signal in the cigarette smoke exposed groups. CONCLUSIONS CD42b-/CD31+ EMPs may be a potential biomarker for indicating the severity of impairment of pulmonary function in the rats exposed cigarette smoke. The increased EMPs may derive from pulmonary capillaries-specific apoptosis.

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.

Transplantation of umbilical cord mesenchymal stem cells alleviates pneumonitis of MRL/lpr mice.

OBJECTIVE To investigate whether the umbilical cord mesenchymal stem cells (UC-MSCs) transplantation in the MRL/lpr mice has effect or not on their pneumonitis and the possible mechanisms underlying this treatment. METHODS Twenty four 18-week-old MRL/lpr female mice were divided into three groups as following: the group 2 (UC-MSCT group) have been transplanted with 1×10(6) UC-MSCs through caudal vein, the group 3 (multi-UC-MSCT Group) have been transplanted with 1×10(6) UC-MSCs three times and the group 1 (control group) have been treated with 0.5 mL phosphate buffer saline (PBS) as control. The histopathology of the lung was observed. The pulmonary expression of high mobility group box protein-1 (HMGB-1) was measured by western blot and detected by quantitation real time polymerase chain reaction (PCR). Immunohistochemistry method was used to detect HMGB-1 expressions in pulmo. RESULTS In comparision to control ground mice, UC-MSCs significantly reduced interstitial pneumonitis in the MRL/lpr mice. The lung peribronchiolar lesion index of UC-MSCT group (1.40±0.24) and multi-UC-MSCT group (1.02±0.29) were significantly decreased as compared to control group (1.95±0.35) (P<0.01). The perivascular lesion index of UC-MSCT group (1.20±0.18) and multi-UC-MSCT group (1.08±0.16) were also significantly reduced as compared to control group (1.56±0.32) (P=0.018, 0.002) and the lung alveolar areas lesion index of control group (1.72±0.34) was significantly increased as compared to UC-MSCT group (1.30±0.21) and multi-UC-MSCT group (1.05±0.15) (P=0.011, 0.000). The lung HMGB-1 protein in UC-MSCT group (0.32±0.04) and in multi-UC-MSCT group (0.28±0.06) were both significantly decreased as compared to that in control group (0.80±0.21) (P<0.05). The level of HMGB-1 mRNA in UC-MSCT group (4.68±0.37) and in multi-UC-MSCT group (4.35±0.10) lung were both significantly decreased as compared to those in control group (16.29±3.84) (P<0.05). In immunohistochemical staining lung sections, high expression of HMGB-1 was found mainly located in the cytoplasm and extracellular matrix of MRL/lpr mice pulmonary epithelial cells, the expression of HMGB-1 in UC-MSCT group and multi-UC-MSCT group was significantly decreased as compared to that in the control group. CONCLUSIONS These findings indicate that UC-MSCs have a therapeutic effect on systemic lupus erythematosus (SLE) pneumonitis, possibly by inhibiting HMGB-1 expression, which suggests a potential application of UC-MSCs in the treatment of human lupus.

CXCL6 promotes non-small cell lung cancer cell survival and metastasis via down-regulation of miR-515-5p

Chemokine plays an important role in lung cancer and CXCL6 is one of chemokine, however, its effect on miRNAs profile and its roles in non-small cell lung cancer cell (NSCLC) is not elucidated. This study is purposed to explore the influence of CXCL6 on miRNA expression profile and found that CXCL6 could reduce the expression of miR-515-5p in NSCLC cells. MiR-515-5p in NSCLC cells could inhibit NSCLC survival and metastasis. MiR-515-5p acted as a tumor suppressor by targeting CXCL6 in NSCLC cells. These data highlighted a novel molecular interaction between miR-515-5p and CXCL6. MiR-515-5p may constitute a potential therapy target for NSCLC.

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.

Rosuvastatin improves myocardial Hypertrophy after hemodynamic Pressure overload via regulating the Crosstalk of Nrf2/ARE and TGF-β/ Smads Pathways in Rat Heart

ABSTRACT Left ventricular hypertrophy is more commonly associated with hemodynamic overload imposed by hypertension or volume overload. Transforming growth factor &bgr; (TGF‐&bgr;) is involved in the cardiac hypertrophy and fibrosis of the left ventricle. The fact that TGF‐&bgr;1 and the nuclear factor erythroid 2‐related factor 2 (Nrf2) both become up‐regulated upon persistent vessel overload suggests that these two factors may virtually impact on their signaling pathways. In this research, 40 rats were divided into sham group, model group, rosuvastatin low and high dose group. Rat models were established by incomplete constriction of abdominal aorta. After five weeks treatment, blood pressure, heart mass index (HMI), hemodynamic parameters and the average diameter of myocardium cell and collagen volume fraction (CVF) improved significantly in rosuvastatin groups, compared with the model group. Both rosuvastatin groups, increased in expression of Smad7, Nrf2, NAD (P) H dehydrogenase [quinone] 1 (Nqo1) and heme oxygenase 1(Ho1),and decreased in expression of TGF‐&bgr;l, Smad3 compared with the model group. Results from co‐immunoprecipitation and GST pull down showed that Nrf2 interacts with Smad7. Our results revealed the crosstalk between TGF‐&bgr;1/Smads and Nrf2/ antioxidant response elements (ARE) pathways in myocardial remodeling through the interaction between Smad7 and Nrf2. Rosuvastatin can improve cardiac function and hypertrophy by regulating the crosstalk of the two signaling pathways.

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.

Lentivirus vector-mediated Rho guanine nucleotide dissociation inhibitor 2 overexpression induces beta-2 adrenergic receptor desensitization in airway smooth muscle cells

BACKGROUND Beta-2 adrenergic receptor (β2AR) downregulation is critical to asthma rescue therapy; however, tolerance, also known as β2AR or bronchodilator desensitization, mechanisms potentially resulting in life-threatening rescue treatment failure remain poorly understood. METHODS Airway smooth muscle cells (ASMCs) from BALB/c mice were primarily cultured. The full-length Rho guanine nucleotide dissociation inhibitor 2 (RhoGDI2) gene from ASMCs was amplified by RT-PCR, and RhoGDI2 gene was subcloned into the digested PWPXL plasmid. The recombinant lentivirus PWPXL-RhoGDI2 expression plasmid was packaged into mature lentivirus by 293T cells and used to infect ASMCs. Fluorescent quantitation RT-PCR and Western Blot were used to detect the level of mRNA and protein expression of RhoGDI2, β2AR, guanine nucleotide exchange factor (GEF), GTPase-activating protein (GAP) and G protein-coupled receptor kinases (GRKs) in overexpression RhoGDI2-ASMCs group, negative GFP control ASMCs group and normal control ASMCs group. Membrane receptor numbers of β2AR was observed by radioligand receptor binding assay in overexpression RhoGDI2-ASMCs group, negative GFP control ASMCs group and normal control ASMCs group. RESULTS RhoGDI2 vector successfully transfected ASMCs, with infection efficiency (the percentage of GFP-positive cells) >80%. RhoGDI2, GEF and G-protein-coupled receptor kinase 2 (GRK2) expressions significantly increased in the RhoGDI2 overexpression group compared to control and negative control groups (all P<0.05). Conversely, β2AR and GAP expressions were significantly lower in the RhoGDI2 overexpression group (both P<0.05), exhibiting an inverse correlation with RhoGDI2 expression. Control and negative control groups exhibiting β2AR density more than 2-fold higher than that observed in the RhoGDI2 overexpression group. CONCLUSIONS RhoGDI2 reduces β2AR density, potentially by reducing β2AR and GAP expressions and increase GEF and GRK2 expressions. Thus, RhoGDI2 is central in cellular β2AR desensitization, though this full mechanism and intermediates merit further investigation.

Identification of proteasome subunit beta type 3 involved in the potential mechanism of corticosteroid protective effectiveness on beta-2 adrenoceptor desensitization by a proteomics approach

BACKGROUND Asthma is a chronic inflammatory disease characterized by airway inflammation with mucus hypersecretion and hyperresponsiveness to various nonspecific stimuli. Corticosteroids are usually used to prevent β2 adrenoceptor (β2AR) desensitization in clinical and experimental practice. But the exact mechanism of corticosteroid effectiveness on β2AR desensitization is unclear. OBJECTIVES To find the potential mechanisms related to the protective effects of corticosteroid on salbutamol induced β2AR desensitization by a proteomics approach. METHODS Thirty-two BALB/c (6-8 weeks old) mice were divided into four groups: group A, control group, phosphate buffered saline (PBS)-treated group; group B, asthmatic group, treated by ovalbumin (OVA); group C, β2AR desensitized asthmatic group, treated by OVA and salbutamol (SBT) and group D, corticosteroid-treated β2AR desensitized asthmatic group, treated with OVA, SBT and Dexamethasone (DEX). After administrated with those drugs, their serum total IgE, bronchoalveolar lavage fluid (BALF) cytokine concentration, airway resistance and membrane receptor number of β2AR were evaluated. After then, the mice of group C and D were sacrificed, their protein from lung tissue were extracted and then seperated by two-dimensional gel electrophoresis (2DE). Then, the isolated protein spots were analyzed by ImageMaster software and mass spectrometry. Bioinformatic tools were used to search these protein spots and find interesting protein spots associated with corticosteroid protective effect on β2AR desensitization. Finally, these protein spots were confirmed by Western blotting. RESULTS With inflammatory cell count, cytokine concentration of BALF, pathological sections, total serum IgE, airway resistance, membrane receptor number and β2AR total amount changes, asthmatic mouse model and β2AR desensitization asthmatic mouse model were successfully established. Seventeen protein spots were found different expression between group C and group D, 4 protein spots were down-regulated and 13 protein spots were up-regulated compared to group C. Proteasome subunit beta type 3 was down-regulated. CONCLUSIONS Increased proteasome subunit beta type 3 expression may be responsible for salbutamol-induced β2AR desensitization in asthmatic disease, and DEX possibly render the β2AR resensitization partially by decreasing the content of proteasome.