A multicentre, randomised, double-blind, double-dummy, parallel-controlled, phase 3 clinical trial assessing the efficacy and safety of intravenous nemonoxacin malate versus levofloxacin for community-acquired pneumonia in adult patients.

BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3 multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin versus levofloxacin for treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: The eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at test of cure (TOC) visit in the modified intent-to-treat (mITT) population. The efficacy and safety were also compared between nemonoxacin and levofloxacin in terms of secondary efficacy and safety endpoints. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n=349) or levofloxacin (n=176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P> 0.05). The clinical efficacy of nemonoxacin was noninferior to levofloxacin in treatment of CAP. Nemonoxacin achieved microbiological success rate of 88.8% (95/107), while levofloxacin achieved 87.8% (43/49) (P > 0.05) at TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in nemonoxacin group and 22.2% in levofloxacin group, mostly local reactions at the infusion site, nausea, elevated ALT/AST, and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and noninferior to levofloxacin for treating CAP in adult patients.

Serum SOD1 level predicts the severity and prognosis of community-acquired pneumonia patients.

BACKGROUND: Superoxide dismutase 1 (SOD1) is one of the most important participants of antioxidant enzyme system in biological system. Previous studies have found that SOD1 is associated with many inflammatory diseases. The goal of this study was to assess the associations of serum SOD1 with the severity and prognosis in community-acquired pneumonia (CAP) patients by a prospective cohort study. METHODS: CAP patients were enrolled from the Second Affiliated Hospital of Anhui Medical University. Peripheral blood samples were gathered. The level of serum SOD1 was detected through enzyme linked immunosorbent assay (ELISA). Clinical characteristics and demographic information were analyzed. RESULTS: The level of serum SOD1 was gradually upregulated with elevated CAP severity scores. Spearman correlation coefficient or Pearson rank correlation analyses indicated that serum SOD1 was strongly connected with many clinical parameters among CAP patients. Further linear and logistic regression analyses found that the level of serum SOD1 was positively associated with CRB-65, CURB-65, SMART-COP, and CURXO scores among CAP patients. Moreover, serum higher SOD1 at admission substantially increased the risks of ICU admission, mechanical ventilation, vasoactive agent usage, death, and longer hospital stays during hospitalization. Serum SOD1 level combination with CAP severity scores elevated the predictive abilities for severity and death compared with alone serum SOD1 and CAP severity scores in CAP patients during hospitalization. CONCLUSION: The level of serum SOD1 is positively associated with the severity and poor prognosis in CAP patients, suggesting that SOD1 is implicated in the initiation and progression of CAP. Serum SOD1 may be regarded as a biomarker to appraise the severity and prognosis for CAP patients.

Rethinking the Selection of Pathological T-Classification for Non-Small-Cell Lung Cancer in Varying Degrees of Visceral Pleural Invasion: A SEER-Based Study.

Background: The T classification of non-small-cell lung cancer (NSCLC) was upgraded from T1 to T2 when accompanied by visceral pleural invasion (VPI). However, the association between VPI and prognostic outcomes was obscure in NSCLC patients with ≤3 cm tumor size (TS), which leaded the controversy of selection of T classification. The goal was to evaluate the effect of VPI on the prognosis of NSCLC with ≤ 3cm TS and present a modified T classification. Methods: A total of 14,934 NSCLC patients without distant metastasis were recruited through a retrospective study in the SEER database. The effect of VPI on lung cancer specific survival (LCSS) was evaluated using survival curve and COX regression analysis in NSCLC patients with ≤3 cm TS. Results: Although there was no difference of the LCSS of PL0 and PL1 patients with ≤2 cm TS in patients without lymph node (LN) metastasis, the LCSS was lower in PL2 patients than those in PL0 (T1a: p < 0.001; T1b: p = 0.001). Moreover, the LCSS was decreased in PL1 and PL2 patients with 2-3 cm TS compared with PL0 (T1c: PL1, p < 0.001; PL2, p = 0.009) of patients without LN metastasis. No difference of LCSS was observed in patients with LN metastasis between PL0 with PL1 and PL2. Conclusion: In NSCLC patients without LN metastasis and TS ≤ 2 cm, tumor with PL1 should remain defined as T1, tumor with PL2 should be defined as T2. However, 2-3 cm TS patients with PL1 or PL2 should both defined as T2. Meanwhile, ≤3 cm TS patients with LN metastasis can be regarded as T1, whether NSCLC patients accompanied with PL1 or PL2.

Ceramide induces the apoptosis of non­small cell lung cancer cells through the Txnip/Trx1 complex.

Ceramide is a biologically active sphingomyelin that inhibits cell growth and proliferation. In previous studies, it was demonstrated that the use of lipopolysaccharides induces acid sphingomyelinases to produce ceramide, promoting lung cancer cell apoptosis; however, the specific mechanisms of this action remain unclear. Thioredoxin­interacting protein (Txnip) plays an important role in the signal transmission of redox reactions inside and outside the cell. Thus, it was hypothesized that ceramide induces apoptosis in lung adenocarcinoma cells (A549 and PC9) by modulating the Txnip/Trx1 complex. In the present study, the Cell Counting kit­8 method was used to detect cell activity and the drug concentration. Hoechst 33258 staining and flow cytometry were used to detect cell apoptosis, and the positional association between Txnip and Trx1 upregulated by ceramide was observed by immunofluorescence confocal microscopy. Reverse transcription­quantitative polymerase chain reaction and western blot analysis were used to detect the changes in related gene, mRNA and protein expression levels. The results revealed that ceramide treatment resulted in the upregulation of Txnip and in the reduction of Trx1 activities. However, the Txnip inhibitor, verapamil, reversed these changes. The analysis of mRNA expression further verified the changes observed in the protein expression of Txnip, Trx1 and apoptosis­related proteins. On the whole, the present study demonstrates that ceramide induces the apoptosis of lung cancer cells by regulating the Txnip/Trx1 complex.

Role of ASM/Cer/TXNIP signaling module in the NLRP3 inflammasome activation.

BACKGROUND: This study aimed to explore the effects of ceramide (Cer) on NLRP3 inflammasome activation and their underlying mechanisms. METHODS: Lipopolysaccharide (LPS)/adenosine triphosphate (ATP)-induced NLRP3 inflammasome activation in J774A.1 cells and THP-1 macrophages was used as an in vitro model of inflammation. Western blotting and real-time PCR (RT-PCR) were used to detect the protein and mRNA levels, respectively. IL-1ß and IL-18 levels were measured by ELISA. ASM assay kit and immunofluorescence were used to detect ASM activity and Cer content. RESULTS: Imipramine, a well-known inhibitor of ASM, significantly inhibited LPS/ATP-induced activity of ASM and the consequent accumulation of Cer. Additionally, imipramine suppressed the LPS/ATP-induced expression of thioredoxin interacting protein (TXNIP), NLRP3, caspase-1, IL-1ß, and IL-18 at the protein and mRNA level. Interestingly verapamil, a TXNIP inhibitor, suppressed LPS/ATP-induced activation of TXNIP/NLRP3 inflammasome but did not affect LPS/ATP-induced ASM activation and Cer formation. TXNIP siRNA and verapamil inhibited C2-Cer-induced upregulation of TXNIP and activation of the NLRP3 inflammasome. In addition, the pretreatment of cells with sulfo-N-succinimidyl oleate (SSO), an irreversible inhibitor of the scavenger receptor CD36, blocked Cer-induced upregulation of nuclear factor-κB (NF-κB) activity, TXNIP expression, and NLRP3 inflammasome activation. Inhibition of NF-κB activation by SN50 prevented Cer-induced upregulation of TXNIP and activation of the NLRP3 inflammasome but did not affect CD36 expression. CONCLUSION: This study demonstrated that the ASM/Cer/TXNIP signaling pathway is involved in NLRP3 inflammasome activation. The results documented that the CD36-dependent NF-κB-TXNIP signaling pathway plays an essential role in the Cer-induced activation of NLRP3 inflammasomes in macrophages.

Head-to-head comparison of the diagnostic accuracy of Xpert MTB/RIF and Xpert MTB/RIF Ultra for tuberculosis: a meta-analysis.

BACKGROUND: Tuberculosis (TB) diagnosis has significantly improved since the introduction of the automated molecular test Xpert MTB/RIF (Xpert) and the new version Xpert MTB/RIF Ultra (Ultra) that detect Mycobacterium tuberculosis. Due to the rapidly widespread use of Xpert and Ultra, we conducted a meta-analysis to compare the performances of Xpert and Ultra in diagnosing TB and discuss the advantages and limitations of these two tests. METHODS: Web of Science, Medline (via PubMed), Embase (via OvidSP), the Cochrane Central Register of Controlled Trials and Google Scholar (up to April 2020) were searched for relevant studies. The diagnostic performance of Xpert and Ultra for TB was determined using a bivariate random-effects regression model. The sources of heterogeneity were explored via meta-regression and subgroup analyses. RESULTS: Of 19 studies that examined a total of 5855 samples, the pooled sensitivity and specificity of Xpert in TB diagnosis were 0.69 (95% CI: 0.57-0.78) and 0.99 (95% CI: 0.98-0.99), respectively. However, the pooled sensitivity and specificity of Ultra in TB diagnosis were 0.84 (95% CI: 0.76-0.90) and 0.97 (95% CI: 0.96-0.98), respectively. Regardless of whether the comparisons were indirect or direct, Ultra was consistently found to be more sensitive, but with slightly lower specificity than Xpert in diagnosing TB. CONCLUSIONS: Compared with Xpert, Ultra had higher sensitivity but slightly lower specificity for the diagnosis of TB disease. The excellent upgrade in sensitivity of the Ultra test was particularly relevant in subjects with paucibacillary TB including tuberculous pleurisy, tuberculous meningitis and paediatric TB.

Salvianolic acid B exerts a protective effect in acute liver injury by regulating the Nrf2/HO-1 signaling pathway.

Salvianolic acid B (Sal B) exerts strong antioxidant activity and eliminates the free radical effect. However, how it affects the antioxidant pathway is not very clear. The objective of this study was to investigate the underlying mechanism of Sal B in CCl4-induced acute liver injury, especially its effect on the Nrf2/HO-1 signaling pathway. For the in vivo experiment, an acute liver injury model was induced using CCl4 and treated with Sal B. For the in vitro experiment, an oxidative damage model was established followed by Sal B treatment. Serum biochemical indicators and reactive oxygen species activity were detected using corresponding kits. Oxidant/antioxidant status was determined based on the levels of malondialdehyde, glutathione, and superoxide dismutase. Nrf2 and HO-1 levels were analyzed by Western blotting and immunohistochemical staining. Sal B treatment improved liver histology, decreased the aminotransferase levels, and attenuated oxidative stress in the acute liver injury model. Nrf2 and HO-1 levels were increased both in vivo and in vitro. Sal B suppresses acute liver injury and Nrf2/HO-1 signaling plays a key role in this process.

Role of qSOFA in predicting mortality of pneumonia: A systematic review and meta-analysis.

BACKGROUND: The concept of sepsis was redefined recently, and a new screening system termed the quick Sequential Organ Failure Assessment (qSOFA) was recommended for identifying infected patients at high risk for death. However, the predictive value of qSOFA for mortality in patients with pneumonia remains unclear. Thus, we performed a meta-analysis with the aim of determining the prognostic value of qSOFA in predicting mortality in patients with pneumonia. METHODS: Embase, Google Scholar, and PubMed (up to March 2018) were searched for related articles. We constructed a 2 × 2 contingency table according to mortality and qSOFA scores (<2 and ≥2) in patients with pneumonia. Two investigators independently extracted data and assessed study eligibility. A bivariate meta-analysis model was used to determine the prognostic value of qSOFA in predicting mortality. I index and Q-test were used to assess heterogeneity. RESULTS: Six studies with 17,868 patients were included. A qSOFA score ≥2 was related to a higher risk for death in patients with pneumonia, with a pooled risk ratio (RR) was 3.35 (95% CI, 2.24-5.01) using a random-effects model (I = 89.4%). The pooled sensitivity and specificity of a qSOFA score ≥2 to predict mortality in patients with pneumonia were 0.43 (95% CI, 0.33-0.53) and 0.86 (95% CI, 0.76-0.92), respectively. The diagnostic OR was 4 (95% CI, 3-6). The area under the summary receiver operator characteristic (SROC) curve was 0.67 (95% CI, 0.63-0.71). When we calculated the community-acquired pneumonia (CAP) subgroup, the pooled sensitivity and specificity were 0.36 (95% CI, 0.26-0.48) and 0.91 (95% CI, 0.84-0.95), respectively. The area under the SROC curve was 0.70 (95% CI, 0.66-0.74). CONCLUSIONS: A qSOFA score ≥2 is strongly associated with mortality in patients with pneumonia, but the poor sensitivity of qSOFA may have limitations in the early identification of mortality in patients with pneumonia.

Head-to-head comparison of qSOFA and SIRS criteria in predicting the mortality of infected patients in the emergency department: a meta-analysis.

BACKGROUND: Recently, the concept of sepsis was redefined by an international task force. This international task force of experts recommended using the quick Sequential Organ Failure Assessment (qSOFA) criteria instead of the systemic inflammatory response syndrome (SIRS) criteria to classify patients at high risk for death. However, the added value of these new criteria in the emergency department (ED) remains unclear. Thus, we performed this meta-analysis to determine the diagnostic accuracy of the qSOFA criteria in predicting mortality in ED patients with infections and compared the performance with that of the SIRS criteria. METHODS: PubMed, EMBASE and Google Scholar (up to April 2018) were searched for related articles. A 2 × 2 contingency table was constructed according to mortality and qSOFA score (< 2 and ≥ 2) or SIRS score (< 2 and ≥ 2) in ED patients with infections. Two investigators independently assessed study eligibility and extracted data. We used a bivariate meta-analysis model to determine the prognostic value of qSOFA and SIRS in predicting mortality. We used the I2 index to test heterogeneity. The bivariate random-effects regression model was used to pool the individual sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR). The summary receiver operating characteristic curve (SROC) was constructed to assess the overall diagnostic accuracy. RESULTS: Eight studies with a total of 52,849 patients were included. A qSOFA score ≥ 2 was associated with a higher risk of mortality in ED patients with infections, with a pooled risk ratio (RR) of 4.55 (95% CI, 3.38-6.14) using a random-effects model (I2 = 91.1%). A SIRS score ≥ 2 was a prognostic marker of mortality in ED patients with infections, with a pooled RR of 2.75 (95% CI, 1.96-3.86) using a random-effects model (I2 = 89%). When comparing the performance of qSOFA and SIRS in predicting mortality, a qSOFA score ≥ 2 was more specific; however a SIRS score ≥ 2 was more sensitive. The initial qSOFA values were of limited prognostic value in ED patients with infections. CONCLUSIONS: A qSOFA score ≥ 2 and SIRS score ≥ 2 are strongly associated with mortality in ED patients with infections. However, it is also clear that qSOFA and SIRS have limitations as risk stratification tools for ED patients with infections.

C2-ceramide influences alveolar epithelial barrier function by downregulating Zo-1, occludin and claudin-4 expression.

Noncardiogenic lung edema is a key factor affecting the prognosis of acute lung injury (ALI). Previous studies have been focused on regulatory roles of ceramide on lung vascular endothelial barrier functions and had already identified ceramide as mediator involved in the formation of lung edema. However, the effects of ceramide on lung epithelial barrier were still unknown. This study aimed to investigate the effects of ceramide on the barrier function of alveolar epithelial cells. Primary mouse alveolar type II epithelial cells (AECII) were grown on Transwell polyester membranes to construct monolayer, and stimulated with different concentrations of ceramide. Transepithelial resistance (TER) was measured to assess the epithelial cell permeability. Western blotting and real-time quantitative polymerase chain reaction were used to detect the mRNA and protein levels of tight junction, respectively. After incubation with different concentrations of c2-ceramide, TER of AECII monolayer decreased significantly in a dose-dependent manner. Moreover, expressions of ZO-1, occludin and claudin-4 were significantly reduced by c2-ceramide in the study. This study demonstrated that ceramide could increase alveolar epithelial cell monolayer permeability by downregulation of tight junction proteins. Therefore, modulation of ceramide expression may serve as a new therapeutic approach to treat acute lung injury.

Efficacy and Safety of Adjunctive Corticosteroids Therapy for Severe Community-Acquired Pneumonia in Adults: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: Adjunctive corticosteroids therapy is an attractive option for community-acquired pneumonia (CAP) treatment. However, the effectiveness of adjunctive corticosteroids on mortality of CAP remains inconsistent, especially in severe CAP. We performed a meta-analysis to evaluate the efficacy and safety of adjunctive corticosteroids in severe CAP patients. METHODS: Three databases of PubMed, EMBASE and Cochrane Library were searched for related studies published in English up to December, 2015. Randomized controlled trials (RCTs) of corticosteroids in hospitalized adults with severe CAP were included. Meta-analysis was performed by a random-effect model with STATA 11.0 software. We estimated the summary risk ratios (RRs) or effect size (ES) with its corresponding 95% confidence interval (95%CI) to assess the outcomes. RESULTS: We included 8 RCTs enrolling 528 severe CAP patients. Adjunctive corticosteroids significantly reduced all-cause mortality (RR = 0.46, 95%CI: 0.28 to 0.77, p = 0.003), risk of adult respiratory distress syndrome (ARDS) (RR = 0.23, 95%CI: 0.07 to 0.80, p = 0.02) and need for mechanical ventilation (RR = 0.50, 95%CI: 0.27 to 0.92, p = 0.026). Adjunctive corticosteroids did not increase frequency of hyperglycemia requiring treatment (RR = 1.03, 95%CI: 0.61 to 1.72, p = 0.91) or gastrointestinal hemorrhage (RR = 0.66, 95%CI: 0.19 to 2.31, p = 0.52). In subgroup analysis by duration of corticosteroids, we found that prolonged corticosteroids therapy significantly reduced all-cause mortality (RR = 0.41, 95%CI: 0.20 to 0.83, p = 0.01) and length of hospital stay (-4.76 days, 95% CI:-8.13 to -1.40, p = 0.006). CONCLUSIONS: Results from this meta-analysis suggested that adjunctive corticosteroids therapy was safe and beneficial for severe CAP. In addition, prolonged corticosteroids therapy was more effective. These results should be confirmed by adequately powered studies in the future.

A randomized, controlled multicentric study of inhaled budesonide and intravenous methylprednisolone in the treatment on acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND: Almost all international guidelines recommend corticosteroids for management of exacerbations of chronic obstructive pulmonary disease (COPD), because it leads to improved outcomes of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Nevertheless, due to its side effects, there are still concerns regarding the use of systemic corticosteroid (SC). Inhaled corticosteroids (IC) can be used as an alternative to SC, while reducing the risk of occurrence of side effects. PURPOSE: To measure the clinical efficacy and side effects of nebulized budesonide and systemic methylprednisolone in AECOPD. METHODS: Valid data from 410 AECOPD patients in 10 hospitals was collected. Patients were randomly divided into 2 groups; budesonide group, treated with nebulized budesonide (2 mg 3 times/day); and methylprednisolone group, treated with intravenously injected methylprednisolone (40 mg/day). COPD assessment test (CAT), arterial blood gas analysis, hospitalization days, adverse effects, fasting blood glucose, serum creatinine, alanine aminotransferase levels, and blood drug were measured and analyzed in both groups. RESULTS: Symptoms, pulmonary function and arterial blood gas analysis were significantly improved after treatment in both groups (P < 0.05), with no significant differences between them (P > 0.05), while incidence of adverse events in the budesonide group was lower (P < 0.05). No significant differences in CAT score, days of admission, blood gas analysis results and physiological and biochemical indexes were found between the two groups. Patients treated with methylprednisolone showed a higher degree of PaO2 level improvement. CONCLUSION: Results show that inhalation of budesonide (2 mg 3 times/day) and systemic methylprednisolone (40 mg/day) had similar clinical outcome in AECOPD. In conclusion, inhaled budesonide is an alternative to systemic corticosteroids in AECOPD treatment.

MiR-541-3p reverses cancer progression by directly targeting TGIF2 in non-small cell lung cancer.

Lung cancer remains a leading cause of cancer-associated mortality worldwide, and non-small lung cancer (NSCLC) is responsible for over 80 % of lung cancer-related deaths. Identifying novel molecular biomarker that can inhibit the progression of lung cancer will facilitate the development of new treatment strategies. Herein, we demonstrated that miR-541-3p is a tumor-suppressor microRNA (miRNA) in NSCLC progression. We found that expression of miR-541-3p was decreased obviously in NSCLC tissues and plasma. Down-regulation of miR-541-3p was associated with TNM stage and postoperative survival. Overexpression of miR-541-3p inhibited the growth and metastasis of NSCLC cells. The TGIF2 was a direct target of miR-541-3p and promoted the growth and metastasis of NSCLC cells. Further study showed that TGIF2 could reverse the inhibitory effect of miR-541-3p on growth and metastasis of NSCLC cells. Taken together, our data highlight the pivotal role of miR-541-3p in the progression of NSCLC. Thus, miR-541-3p may be a potential prognostic marker and of treatment relevance for NSCLC progression intervention.

The association between osteopontin and survival in non-small-cell lung cancer patients: a meta-analysis of 13 cohorts.

In the last decade, osteopontin (OPN) was identified as one of the important proteins that promote the metastasis of tumor. However, the association between OPN overexpression and clinical outcome of non-small-cell lung cancer (NSCLC) was unclear. The purpose of this study is to investigate the role of OPN in NSCLC patients. A total of 13 studies are included to explore the relationship between the OPN elevation and the overall survival (OS) and disease-free survival (DFS) in NSCLC patients. We searched for related articles in PubMed, Web of Science, Google Scholar, and Cochrane Library databases, which were published before January 31, 2015. Hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI) in the high OPN expression group compared with the low OPN expression group were calculated and analyzed. Primary results were summarized by using a fixed-effects model or a random-effects model. The stratified analyses in subgroups were also performed. Thirteen cohort studies, which involved 1,630 patients, were included. Subgroup analyses were performed by area and test method of OPN. We found that OPN was significantly associated with poor OS (HR =2.20, 95% CI 1.71-2.83, P<0.001) and DFS (HR =2.11, 95% CI 1.62-2.74, P<0.001) in NSCLC patients. OPN overexpression tended to be associated with the presence of advanced tumor TNM stage (III and IV) (OR =2.57, 95% CI 1.61-4.11, P<0.001). The Egger's test suggested that there was no publication bias in OS studies (P=0.062) and DFS studies (P=0.740). These data indicate that OPN seems to have a significant predictive potential in estimating survival in NSCLC.

[Effect of C8-ceramide on apoptosis of alveolar type II epithelial cells].

OBJECTIVE: To investigate the effects of exogenous C8-ceramide on primary alveolar type II epithelial cells (AECII). METHODS: AECII were isolated from 18 day gestational age ICR mice, and cultured in Dulbecco's Modified Eagle Medium with 95% air and 5% CO2at 37 °C. The cells were treated with different concentrations (0, 20, 40 and 80 µmol/L) of C8-ceramide for 24 h and treated with 80 µmol/L of C8-ceramide for different time (3, 6, 12, and 24 h) to observe the viability of cells by MTT assay. Then, the annexin V externalization assay and TUNEL assay were performed to determine apoptosis after the cells were treated with different concentrations (0, 20, 40, and 80 µmol/L) of C8-ceramide for different time (12 and 24 h). RESULTS: The results of MTT assay showed that cell viability decreased in a dose- and time- dependent manner. In Annexin V externalization assay, the cells showed a distribution of (20.63 ± 0.86)%, (22.67 ± 1.72)%, (42.03 ± 1.34)%, (50.40 ± 1.30)% and (20.93 ± 2.51)%, (28.93 ± 3.19)%, (47.00 ± 1.08)%, (57.77 ± 3.04)% cells in apoptosis after treated with 0, 20, 40, 80 µmol/L of C8-ceramide for 12 and 24 h (It is significant difference from untreated cells except for 20 µmol/L at 12 h point, all P<0.05). In TUNEL assay, the cells showed a distribution of (5.51 ± 1.41)%, (13.24 ± 2.62)%, (35.10 ± 4.59)%, (75.07 ± 4.37)% and (5.56 ± 1.36)%, (21.34 ± 2.09)%, (37.12 ± 2.11)%, (91.33 ± 0.72)% cells in apoptosis after treated with 0, 20, 40, 80 µmol/L of C8-ceramide for 12 and 24 h (It is significant difference from untreated cells at the same time point, all P<0.05). CONCLUSION: The results demonstrate that C8-ceramide can decrease the viability of AECII and induce apoptosis.

Association between ubiquitin carboxy-terminal hydrolase-L1 S18Y variant and risk of Parkinson's disease: the impact of ethnicity and onset age.

The Ubiquitin carboxy-terminal hydrolase-L1 (UCHL1) is a candidate risk gene for Parkinson' disease (PD), and a function SNP (rs5030732) in the coding region of this gene has been studied for the association with the disease extensively among worldwide populations, but the results were inconsistent and controversial. Here, to estimate the association between UCHL1 S18Y polymorphism and risk of PD in general population, we conducted a systematic meta-analysis by combining all available case-control subjects in Asian, European, and American populations, with a total of 7742 PD cases and 8850 healthy controls, and the pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for UCHL1 S18Y polymorphism and PD were calculated using the Mantel-Haenszel method with a fixed- or random-effects model. Subgroup analysis was also performed in different onset age-matched groups. Among high-quality studies, UCHL1 S18Y polymorphism was moderately associated with the risk of PD (allele contrasts, OR = 1.063, 95% CI 1.008-1.122; p = 0.024; regressive genetic model, OR = 1.078, 95% CI 1.005-1.157; p = 0.035). When stratifying for ethnicity, none association were observed in subgroups. Analysis of early-onset PD (EOPD) and late-onset PD (LOPD) revealed that the polymorphism was not associated with the risk of PD. In conclusion, our meta-analysis suggests that UCHL1 S18Y polymorphism is moderately associated with susceptibility to PD, and more studies are needed to confirm our conclusion.

Recombinant tissue plasminogen activator for hemodynamically stable patients experiencing an acute pulmonary embolism: a meta-analysis.

BACKGROUND: The role of thrombolytic therapy for the initial treatment of hemodynamically stable patients experiencing an acute pulmonary embolism remains controversial. METHODS AND RESULTS: We performed a meta-analysis of randomized trials comparing between administration of recombinant tissue plasminogen activator (rt-PA) and heparin in hemodynamically stable patients experiencing an acute pulmonary embolism. Seven trials, involving 594 patients, were included in this meta-analysis. Compared with heparin, rt-PA was associated with a non-significant reduction in death (2.75% versus 3.96%; RR 0.69, 95% CI 0.31-1.52, P for heterogeneity=0.520) and recurrent pulmonary embolism (2.13% versus 3.34%; RR 0.70, 95% CI 0.28-1.73), and a non-significant increase in major bleeding (5.15% versus 4.29%; RR 1.06, 95% CI 0.520-2.150). Similar results were found based on a subgroup analysis of patients displaying echocardiographic evidence of right ventricular dysfunction (RVD). In contrast, rt-PA treatment was associated with a significant reduction in escalation of care in trials that also enrolled patients displaying RVD compared with heparin treatment (6.56% versus 19.7%; RR 0.34, 95% CI 0.20-0.65). CONCLUSION: The currently available data provide no evidence for a benefit of administration of rt-PA compared with heparin for the initial treatment of hemodynamically stable patients experiencing an acute pulmonary embolism. However, rt-PA is partially beneficial specifically among patients displaying RVD.

The association between the C-509T and T869C polymorphisms of TGF-ß1 gene and the risk of asthma: a meta-analysis.

Asthma is a complex multigenic disease in which gene-environment interactions play a critical role in disease onset and progression. Transforming growth factor-ß1 (TGF-ß1) is one of several candidate locus for the pathogenesis of asthma, and is highly polymorphic. To derive a more precise estimation of the relationship between the T869C and C-509T polymorphisms of the TGF-ß1 gene and asthma, a meta-analysis of 24 published case-control studies was conducted. 20 studies for C-509T polymorphism and 8 studies for T869C polymorphism were included. The pooled odds ratios were calculated respectively for allele contrasts, additive genetic model, dominant genetic model and recessive genetic model. Subgroup analyses were also performed by ethnicity, age, atopic status and asthma severity for two gene polymorphisms. In regard to T869C polymorphism, significant associations with asthma were observed in recessive (OR 1.23, 95%CI 1.00-1.51 and P=0.047), additive and allele models. In the subgroup analysis by age, significant risks were also found in the recessive model for adults (OR 1.31, 95%CI 1.02-1.69 and P=0.032), atopic asthma (OR 1.63, 95%CI 1.07-2.49 and P=0.023). With respect to C-509T polymorphism, significant associations with asthma were demonstrated in the overall analysis and subgroup analyses in the dominant model for Asian (OR 1.37, 95%CI 1.04-1.81 and P=0.025), Adults (OR 1.26, 95%CI 1.02-1.56 and P=0.035), Children (OR 1.19, 95%CI 1.01-1.40 and P=0.034). Potentially functional TGF-ß1 C-509T and T869C polymorphisms may be risk factors for asthma susceptibility.