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To evaluate the efficacy and safety of oral sitafloxacin versus oral moxifloxacin in the treatment of Chinese adults with community-acquired pneumonia (CAP).This is a multicenter, randomized, open-label, positive-controlled clinical trial (chinadrugtrials.org.cn identifier: CTR20130046). CAP patients received sitafloxacin tablets 100 mg once daily (qd) or 100 mg twice daily (bid) to compare with moxifloxacin tablets 400 mg qd, for 7-10 days. The primary outcome was non-inferiority of sitafloxacin to moxifloxacin in clinical cure rate at test of cure (TOC) visit in per-protocol set (PPS).A total of 343 patients were randomized (sitafloxacin 100 mg qd,Sitafloxacin 100 mg qd or 100 mg bid for 7-10 days is not inferior to moxifloxacin 400 mg qd for 7-10 days in clinical efficacy for adult CAP patients. Sitafloxacin provides a safety profile comparable to moxifloxacin.

Background/Purpose: To compare the clinical efficacy and safety of nemonoxacin with levofloxacin in treating community-acquired pneumonia (CAP) in a Phase II clinical trial. Methods: One hundred ninety-two patients with CAP were randomized to receive oral nemonoxacin (500 mg or 750 mg) or levofloxacin (500 mg) once daily for 7â10 days. Clinical and bacteriological responses were determined at the test of cure (TOC) visit in the full analysis set (FAS). Results: The clinical cure rate of nemonoxacin (500 mg), nemonoxacin (750 mg), and levofloxacin (500 mg) was 93.3%, 87.3%, and 88.5%, respectively, in the FAS (n = 168), and 93.0%, 93.9%, and 88.9%, respectively in the per protocol set (n = 152). At the TOC visit, nemonoxacin at 500 mg and 750 mg was proven to be noninferior to levofloxacin at 500 mg in the FAS in terms of clinical efficacy. The overall bacteriological success rate was 83.3% in both nemonoxacin groups and 80.0% in the levofloxacin 500 mg group in the bacteriological FAS. The comprehensive efficacy rate was comparable among the three groups (87.5% for the nemonoxacin 500 mg group, 93.8% for the nemonoxacin 750 mg group, and 81.3% for the levofloxacin 500 mg group). Most drug-related adverse events were mild and transient, mainly gastrointestinal symptoms such as nausea and vomiting, transient neutropenia, and elevated liver enzymes. No drug-related serious adverse events occurred. Conclusion: Either 500 mg or 750 mg of oral nemonoxacin taken once daily for 7â10 days demonstrated high clinical and bacteriological success rates in Chinese adult patients with CAP. Nemonoxacin at 500 mg once daily for 7â10 days is recommended for future Phase III clinical trials.ClinicalTrials.gov identifier: NCT01537250. Keywords: clinical trial, community-acquired pneumonia, efficacy, nenomoxacin, safety

BACKGROUND In the Study to Investigate Real Life Effectiveness of Symbicort Maintenance and Reliever Therapy in Asthma Patients Across Asia, the effectiveness of single-inhaler budesonide/formoterol maintenance and reliever therapy was evaluated in patients with poorly controlled asthma. OBJECTIVE To study the effects of this therapy on a Chinese patient subgroup. METHODS In this 12-week, multicenter, open-label therapeutic phase IV study, patients with partially controlled or uncontrolled asthma were switched from their usual asthma treatment to budesonide/formoterol (160/4.5 μg, one inhalation twice daily and as needed) after a 2-week run-in period. Primary and secondary objectives of the study, asthma control and quality of life were assessed by using the five-item Asthma Control Questionnaire and the Standardized Asthma Quality of Life Questionnaire. Asthma symptom scores, study medication use, asthma control and/or symptom-free days, and the number of asthma-related nighttime awakenings were also monitored. RESULTS In total, 478 Chinese patients were enrolled and 407 patients initiated treatment. The patients displayed a significant improvement in mean (standard deviation) five-item Asthma Control Questionnaire (-0.58 ± 0.86; p < 0.0001) and Standardized Asthma Quality of Life Questionnaire (0.69 ± 0.79; p < 0.0001) scores versus the run-in period. Mean (standard deviation) asthma symptom scores were significantly reduced compared with run-in (-0.30 ± 0.55 daytime, -0.31 ± 0.56 nighttime; p < 0.0001 for both), as was as-needed study medication use (-0.24 ± 1.16 daytime, -0.28 ± 0.97 nighttime; p < 0.0001 for both). Patients who received previous treatment with salmeterol/fluticasone propionate also showed improvement in asthma control. CONCLUSIONS In China, asthma control in Chinese patients whose asthma was not fully controlled with previous standard therapy improved during 12 weeks of treatment with budesonide/formoterol maintenance and reliever therapy. Quality of life was improved, and treatment was well tolerated. (Clinical Trials identifier NCT00939341).

Stathmin 1 (STMN1), a major microtubule-depolymerizing protein, is involved in cell cycle progression and cell motility. However, the clinical significance of STMN1 expression in non-small cell lung cancer (NSCLC) has not been determined. The expression pattern of STMN1 mRNA was analyzed by quantitative real-time PCR (qRT-PCR) in 37 cases of NSCLC and in the corresponding non-tumor tissue samples. Furthermore, immunohistochemistry was performed to detect STMN1 protein expression in 113 primary NSCLC tissues. The functional role of STMN1 in lung cancer cell lines was evaluated by small interfering RNA-mediated depletion followed by analyses of cell proliferation and invasion. We found that the STMN1 mRNA and protein levels in NSCLC tissues were significantly higher than those in the corresponding non-tumor tissues (P

Aims: X-ray repair cross complementing group 1 (XRCC1) has been indicated to be correlated with the efficacy of platinum-based chemotherapy. But study results were still debatable. Thus, a meta-analysis was conducted. Materials and Methods: A literature search was performed using the PubMed, EMBASE, CNKI, with the databases being last accessed on November 24, 2014. Odds ratios with 95% confidence intervals were used to assess the strength of the association. Results: In this meta-analysis, we found that XRCC1 Arg194Trp polymorphism was significantly associated with the efficacy of platinum-based chemotherapy. However, XRCC1 Arg399Gln polymorphism showed no impact on the efficacy of platinum-based chemotherapy. Conclusion: This meta-analysis suggested that the XRCC1 Arg194Trp polymorphism may be associated with efficacy of platinum-based chemotherapy. Further studies with a larger sample size are needed to further assess this result.

Background/Purpose: Nemonoxacin is a novel nonfluorinated quinolone with excellent in vitro activity against most pathogens in community-acquired pneumonia (CAP), especially Gram-positive isolates. The purpose of this study was to assess the efficacy and safety of nemonoxacin compared with levofloxacin in patients with CAP. Methods: A phase 3, multicenter, randomized (2:1) controlled trial was conducted in adult CAP patients receiving nemonoxacin 500 mg or levofloxacin 500 mg orally once daily for 7–10 days. Clinical, microbiological response and adverse events were assessed. Non-inferiority was determined in terms of clinical cure rate of nemonoxacin compared with that of levofloxacin in a modified intention-to-treat (mITT) population. NCT registration number: NCT01529476. Results: A total of 527 patients were randomized and treated with nemonoxacin (n = 356) or levofloxacin (n = 171). The clinical cure rate at test-of-cure visit was 94.3% (300/318) for nemonoxacin and 93.5% (143/153) for levofloxacin in the mITT population [difference (95% CI), 0.9% (−3.8%, 5.5%)]. The microbiological success rate was 92.1% (105/114) for nemonoxacin and 91.7% (55/60) for levofloxacin in the bacteriological mITT population [difference (95% CI), 0.4% (−8.1%, 9.0%)]. The incidence of adverse events (AEs) was comparable between nemonoxacin (33.1%, 118/356) and levofloxacin (33.3%, 57/171) (P > 0.05). Conclusion: Nemonoxacin 500 mg once daily for 7–10 days is as effective and safe as levofloxacin for treating adult CAP patients in terms of clinical cure rates, microbiological success rates, and safety profile.ClinicalTrials.gov identifier: NCT01529476. Keywords: Clinical outcome, Community-acquired pneumonia, Levofloxacin, Nemonoxacin, Randomized controlled trial, Safety

Some studies investigated the association of TERT rs2736100 polymorphism with lung cancer (LC). But the results were not consistent. We performed a meta-analysis to examine the association between rs2736100 and LC. Databases including PubMed, EMBASE, Wanfang, and China National Knowledge Infrastructure (CNKI) were searched. Data were extracted, and pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated. A total of 19 studies including 49,869 cases and 73,464 controls were involved in this meta-analysis. Overall, a significant association between TERT rs2736100 polymorphism and LC risk was observed (OR=1.23, 95 % CI 1.18-1.28, P

Background A number of studies assessed the association of − 589C/T polymorphism in the promoter region of interleukin-4 (IL-4) with asthma in different populations. However, the results were contradictory. A meta-analysis was conducted to investigate the association between polymorphism in the IL-4 and asthma susceptibility. Methods Databases including Pubmed, EMBASE, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Results Thirty-four studies involving 7345 cases and 7819 controls were included. Overall, significant association between − 589C/T polymorphism and asthma was observed for TT + CT vs. CC (OR = 1.26; 95% CI 1.12–1.42; P = 0.0001; I2 = 26%). In the subgroup analysis by ethnicity, significant associations were found among Asians (OR = 1.36; 95% CI 1.07–1.73; P = 0.01; I2 = 0%) and Caucasians (OR = 1.30; 95% CI 1.09–1.54; P = 0.004; I2 = 53%) but not among African Americans (OR = 1.20; 95% CI 0.72–2.00; P = 0.48; I2 = 48%). In the subgroup analysis by atopic status, no significant association was found among atopic asthma patients (OR = 1.20; 95% CI 0.92–1.34; P = 0.27; I2 = 6%) and non-atopic asthma patients (OR = 0.97; 95% CI 0.73–1.28; P = 0.81; I2 = 0%). Conclusions This meta-analysis suggested that the IL-4 − 589C/T polymorphism was a risk factor of asthma.

There are controversies on the association betweeninterleukin-13(IL-13) +1923C/T polymorphism (rs1295686) and the risk of asthma. We performed this study to assess the association by the method of meta-analysis. A systematic search current to October 16, 2012, was conducted using PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) and identified ten studies comprising 13698 cases and 38209 controls. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. There was a significant association betweenIL-13+1923C/T polymorphism and asthma risk in codominant model. When stratified by ethnicity,IL-13+1923C/T polymorphism remained significantly associated with higher asthma risk in Asians and Caucasians. In the subgroup analysis by study quality, a significantly increased asthma risk was observed in high quality studies. Sensitivity analysis and cumulative analysis further strengthened the validity of the results. No publication bias was found in this meta-analysis. In conclusion, results from this meta-analysis suggested thatIL-13+1923C/T polymorphism was a risk factor of asthma.

Recently, the serum levels of YKL-40, a chitinase-like glycoprotein, have been shown to be significantly elevated in asthmatics and are associated with asthma severity. Although these studies raise the possibility that YKL-40 may influence asthma, the mechanisms remain unknown. This study firstly investigated the mechanisms involved in YKL-40–mediated inflammation in human bronchial epithelial cells (HBECs) and analyzed the soluble factors secreted by bronchial epithelial cells exposed to YKL-40 that were responsible for increasing proliferation and migration of primary normal human bronchial smooth muscle cells (BSMCs). YKL-40–induced inflammation was assayed in two HBECs (BEAS-2B cell line and primary HBECs). In addition, we treated BEAS-2B cells and HBECs with YKL-40 and added the conditioned culture media to BSMCs. The proliferation and migration of BSMCs were determined by premixed WST-1 cell proliferation reagent (Clontech Laboratories) and QCM chemotaxis migration assay (Millipore), respectively. Bronchial epithelial cells treated with YKL-40 resulted in a significant increase of IL-8 production, which was dependent on MAPK (JNK and ERK) and NF-κB pathways activation. YKL-40–induced IL-8 was found to further stimulate proliferation and migration of BSMCs, and the effects were inhibited after neutralizing IL-8. Through investigating the interaction of airway epithelium and smooth muscle, our findings implicate that YKL-40 may be involved in the inflammation of asthma by induction of IL-8 from epithelium, subsequently contributing to BSMC proliferation and migration. Moreover, inhibition of IL-8 signaling is a potential therapeutic target for YKL-40–induced inflammation and remodeling of asthma.

List of ethics committees. Names of institutional ethics committees at each center. (DOCX 15Â kb)

To investigate the expression pattern of UbcH10 in non-small cell lung cancer (NSCLC) and its correlations with clinicopathological features and prognostic value in NSCLC patients. The UbcH10 expression in NSCLC tissues, SK-MES-1, and A549 lung cancer cell lines was evaluated, and its correlation with clinicopathological features and prognostic value in NSCLC patients was examined by Kaplan–Meier analysis and Cox regression analysis. The biological effects of UbcH10 on the cell proliferation, cell cycle, and chemosensitivity to gemcitabine or paclitaxel in SK-MES-1 cells were examined upon the UbcH10 silencing. UbcH10 is overexpressed in poorly differentiated NSCLC samples than in well-differentiated ones, and its expression level was significantly higher in squamous cell carcinoma than that in adenocarcinoma. Higher UbcH10 expression was associated with a shorter postoperative survival time of NSCLC patients by Kaplan–Meier method and was found to be an independent risk factor that influences the postoperative survival time of NSCLC patients by Cox regression analysis. UbcH10 mRNA and protein expression were significantly upregulated in SK-MES-1 cells compared with A549 and MRC-5 cells. Suppression of UbcH10 expression in SK-MES-1 cells inhibited cell proliferation and increased chemosensitivity to gemcitabine or paclitaxel concomitant with decreased MDR1 gene expression. UbcH10 may play an important role in NSCLC carcinogenesis, and silencing UbcH10 may represent a potential therapeutic strategy for NSCLC.

Summary Background Activating mutations in EGFR are important markers of response to tyrosine kinase inhibitor (TKI) therapy in non-small-cell lung cancer (NSCLC). The OPTIMAL study compared efficacy and tolerability of the TKI erlotinib versus standard chemotherapy in the first-line treatment of patients with advanced EGFR mutation-positive NSCLC. Methods We undertook an open-label, randomised, phase 3 trial at 22 centres in China. Patients older than 18 years with histologically confirmed stage IIIB or IV NSCLC and a confirmed activating mutation of EGFR (exon 19 deletion or exon 21 L858R point mutation) received either oral erlotinib (150 mg/day) until disease progression or unacceptable toxic effects, or up to four cycles of gemcitabine plus carboplatin. Patients were randomly assigned (1:1) with a minimisation procedure and were stratified according to EGFR mutation type, histological subtype (adenocarcinoma vs non-adenocarcinoma), and smoking status. The primary outcome was progression-free survival, analysed in patients with confirmed disease who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov, number NCT00874419, and has completed enrolment; patients are still in follow-up. Findings 83 patients were randomly assigned to receive erlotinib and 82 to receive gemcitabine plus carboplatin; 82 in the erlotinib group and 72 in the chemotherapy group were included in analysis of the primary endpoint. Median progression-free survival was significantly longer in erlotinib-treated patients than in those on chemotherapy (13.1 [95% CI 10.58–16.53] vs 4.6 [4.21–5.42] months; hazard ratio 0.16, 95% CI 0.10–0.26; p vs no patients with either event on erlotinib); the most common grade 3 or 4 toxic effects with erlotinib were increased alanine aminotransferase concentrations (three [4%] of 83 patients) and skin rash (two [2%] patients). Chemotherapy was also associated with increased treatment-related serious adverse events (ten [14%] of 72 patients [decreased platelet count, n=8; decreased neutrophil count, n=1; hepatic dysfunction, n=1] vs two [2%] of 83 patients [both hepatic dysfunction]). Interpretation Compared with standard chemotherapy, erlotinib conferred a significant progression-free survival benefit in patients with advanced EGFR mutation-positive NSCLC and was associated with more favourable tolerability. These findings suggest that erlotinib is important for first-line treatment of patients with advanced EGFR mutation-positive NSCLC. Funding F Hoffmann-La Roche Ltd (China); Science and Technology Commission of Shanghai Municipality.

The chitinase-like protein YKL-40, which binds chitin but lacks chitinase activity, has been found to be either the cause or a biomarker for asthma. The aim of our study was to investigate whether serum YKL-40 levels are increased in Chinese patients with asthma and identify its correlation to acute exacerbation, total serum immunoglobulin (Ig)E, the percentage of peripheral blood eosinophils and lung function. We quantified serum YKL-40 levels, total IgE levels and peripheral blood eosinophil percentages in patients with asthma, as well as in controls from the communities surrounding our hospital. The lung function of asthma subjects was also measured. Our data showed that the serum YKL-40 levels were significantly elevated in patients with asthma compared with controls and, when the asthma subjects were stratified, serum YKL-40 levels in the exacerbation group were higher than those in the stable and control groups. In addition, serum YKL-40 levels correlated positively with total serum IgE levels and the percentage of peripheral blood eosinophils, but correlated inversely with lung functions. Thus, we conclude that YKL-40 is found in increased quantities in the serum of Chinese patients with asthma, and its level correlates with exacerbation attacks, indicating that high levels of serum YKL-40 may be a biological characteristic of the exacerbation of asthma.

Levofloxacin (LVFX), a fluoroquinolone agent, has a broad spectrum that covers Gram-positive and -negative bacteria and atypical pathogens. It demonstrates good clinical efficacy in the treatment of various infections, including lower respiratory tract infections (LRTIs) and urinary tract infections (UTIs). To evaluate the efficacy and safety of oral LVFX 500 mg once daily, a large open-label clinical trial was conducted in 1266 patients (899 with LRTIs and 367 with UTIs) at 32 centers in China. In the per-protocol population, the clinical efficacy rate (cure or improvement) at 7 to 14 days after the end of treatment was 96.4% (666/691) for LRTIs and 95.7% (267/279) for UTIs. In 53 patients diagnosed with atypical pneumonia the treatment was effective. The bacteriological efficacy rate was 96.6% (256/265) for LRTIs and 93.3% (126/135) for UTIs. The eradication rate of the causative pathogens was 100% (33/33) for Haemophilus influenzae and 96.0% (24/25) for Streptococcus pneumoniae in LRTIs, and 94.1% (80/85) for Escherichia coli in UTIs. The overall efficacy rates were 89.3% (617/691) for LRTIs and 87.8% (245/279) for UTIs. The incidence of drug-related adverse events (ADRs) was 17.3% (215/1245), and the incidence of drug-related laboratory abnormalities was 15.7% (191/1213). Common ADRs were dizziness, nausea, and insomnia. Common laboratory abnormalities included "WBC decreased", "alanine aminotransferase (ALT) increased", "aspartate aminotransferase (AST) increased", and "lactate dehydrogenase (LDH) increased". All of these events were mentioned in the package inserts of fluoroquinolones including LVFX, and most events were mild and transient. Thirty-four patients (2.7%) were withdrawn from the study because of the ADRs. No new ADRs were found. This study concluded that the dosage regimen of LVFX 500 mg once daily was effective and tolerable for the treatment of LRTIs and UTIs.

Several studies have examined the associations of polymorphisms in HLA-B-associated transcript 3 (BAT3) with lung cancer risk. However, the results were conflicting. Thus, a meta-analysis was conducted to determine the relationship between BAT3 polymorphisms and lung cancer risk. Databases including PubMed, EMBASE, and Wanfang were searched. Summary odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) were estimated using random effects models or fixed effects models. Nine studies were included in this meta-analysis. BAT3 rs1052486 was associated with a significantly increased lung cancer risk (OR = 1.06, 95 % CI 1.01–1.12, P = 0.03). This polymorphism was also significantly associated with lung cancer risk in Caucasians (OR = 1.07; 95 % CI, 1.01–1.12; P = 0.02). Furthermore, BAT3 rs3117582 increased lung cancer risk (OR = 1.31, 95 % CI, 1.26–1.35, P

OBJECTIVES Several studies have compared the clinical effect of β-lactam/macrolide (BLM) dual therapy versus β-lactam (BL) monotherapy in community-acquired pneumonia (CAP) patients. However, the results remain controversial. Thus, we did this meta-analysis to determine which treatment was more effective. METHODS Databases comprising PubMed, Embase and the Cochrane Register of Controlled Trials were searched to find relevant studies. The primary outcome was mortality. The Newcastle-Ottawa scale was used to evaluate the methodological quality of included studies. Multivariable-adjusted ORs with 95% CIs were pooled in the random effects model. RESULTS Four prospective cohort studies and 12 retrospective cohort studies were included (n = 42 942). Compared with BL monotherapy, BLM dual therapy was significantly associated with reduced mortality (adjusted OR 0.67, 95% CI 0.61-0.73, P

In China, around 23% of physicians (41% male, 3% female) currently smoke. Pharmacotherapy for tobacco dependence is available, but is not widely used in China. The purpose of this study was to estimate the effectiveness and the safety on smoking cessation of nicotine gum and nicotine patch in Chinese healthcare professionals. Three hundred regular smokers motivated to quit were recruited from six hospitals in China. All subjects were accepted nicotine replacement therapy, and they could choose nicotine gum (2 mg or 4 mg, depending on baseline smoking level) or nicotine patch (15 mg/16 h) for 12 weeks, with a 12-week follow-up. Limited behavioural support was provided. At Week 24, the 2-24 weeks continuous abstinence rate (verified by expired carbon monoxide) was 17%, the point prevalence abstinence rate (no smoking since the previous visit) was 35%, and 38% of subjects had continuously reduced their daily cigarette consumption by at least 50% versus baseline. Compliance with treatment was good, particularly with patch. No serious adverse event was reported, and most adverse events were mild or moderate. The most common treatment-related adverse events were gastrointestinal (both gum and patch) and local irritation symptoms. Nicotine patch and gum were well tolerated in Chinese smokers. Abstinence rates were comparable to those previously reported with nicotine replacement therapy, and many smokers who did not quit substantially reduced their cigarette consumption.

Background Epidemiological studies have evaluated the association between Secretoglobin 1A member 1 ( SCGB1A1 ) + 38A/G polymorphism and asthma, but the results remain inconclusive. The aim of this study was to perform a meta-analysis to investigate a more authentic association between SCGB1A1 + 38A/G polymorphism and asthma. Methods Published literature from PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Embase databases were searched for eligible publications. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random or fixed-effect model according the between-study heterogeneity. Results A total of 19 case-control studies in 18 articles were included in the meta-analysis, including 3191 cases and 5182 controls. We found that SCGB1A1 + 38A/G polymorphism was associated with a significantly increased risk of asthma risk when all studies were pooled in a dominant model (OR = 1.29; 95% CI 1.08–1.54; P = 0.005). The cumulative meta-analysis and sensitivity analysis further strengthened the stability of the result. Furthermore, publication bias was not detected. Conclusions This study suggested that SCGB1A1 + 38A/G polymorphism was a risk factor for asthma. Further large and well-designed studies are needed to confirm this association.

Background Associations between interleukin-13 (IL-13) polymorphisms and asthma risk remained controversial and ambiguous. Therefore, we performed a meta-analysis to assess the associations between IL-13 polymorphisms and asthma susceptibility. Methods Pubmed, EMBASE, Chinese National Knowledge Infrastructure (CNKI) and Wangfang databases were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the strength of association in the random-effects model. Results Thirty-four studies were included in this meta-analysis. The results indicated that IL13 -1112C/T polymorphism was significantly associated with asthma risk (OR = 1.20, 95% CI 1.08–1.34, P = 0.0009) in a dominant genetic model. When stratifying for race, IL13 -1112C/T polymorphism exhibited increased asthma risk in Caucasians (OR = 1.30, 95% CI 1.09–1.55, P = 0.003), while no significant association was found in Asians and African Americans. In the subgroup analysis based on atopic status, significant association was observed in atopic patients (OR = 1.25, 95% CI 1.07–1.45, P = 0.004) but not in the non-atopic patients. In addition, a significant association between IL13+2044A/G polymorphism and asthma risk was observed (OR = 1.18, 95% CI 1.08–1.28, P = 0.0002). In the subgroup analysis by ethnicity, there were significant associations between IL13+2044A/G polymorphism and asthma risk in Asians (OR = 1.19, 95% CI 1.04–1.36, P = 0.01) and Caucasians (OR = 1.22, 95% CI 1.06–1.40, P = 0.005) but not in African Americans. In the subgroup analysis stratified by atopic status, a marginal significant association was found in atopic patients (OR = 1.12, 95% CI 1.00–1.26, P = 0.05). Conclusions This meta-analysis suggested that the IL13 -1112C/T and +2044A/G polymorphisms were risk factors for asthma.

BACKGROUND: A number of studies assessed the association of cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) gene polymorphisms with asthma in different populations. However, the results were contradictory. We performed a meta-analysis to examine the association between CTLA-4 polymorphisms and asthma susceptibility. METHODS: Pubmed, EMBASE, HuGE Navigator, and Wanfang Database were searched. Data were extracted independently by two reviewers. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. RESULTS: Seventeen studies involving 6378 cases and 8674 controls were included. Significant association between +49 A/G polymorphism and asthma was observed for AA vs. AG+GG (OR = 1.18, 95% CI 1.01-1.37, P = 0.04). There were no significant associations between -318 C/T, -1147 C/T, CT60 A/G, -1722 C/T, or rs926169 polymorphisms and asthma risk. CONCLUSIONS: This meta-analysis suggested that the +49 A/G polymorphism in CTLA-4 was a risk factor for asthma.

Several studies assessed the associations of interleukin-10 (IL-10) polymorphisms with asthma in different populations. However, the results were inconclusive. The aim of the present study was to further assess the associations by the method of meta-analysis. Pubmed, EMBASE, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched. Data were extracted independently by two authors. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. Seventeen potentially eligible articles were identified (4478 cases and 4803 controls). Significant associations between -1082A/G and -592A/C polymorphisms and asthma were observed. However, there was no significant association between -819T/C polymorphism and asthma risk. In addition, there were significant associations of the IL-10 haplotypes with asthma. In summary, this meta-analysis suggested that IL-10 promoter polymorphisms were associated with asthma risk.

The struggle to control infectious diseases has become increasingly difficult due to resistance to current antibiotics and the co-existence of multiplying and non-multiplying bacteria, which makes it an urgent task to discover new antibiotic targets and to develop new antibiotics. Hydrogenases are found in micro-organisms belonging to the archaea and bacteria domains, which can catalyse the reversible oxidation of hydrogen gas (H2↔2H++2e) and play pleiotropic roles in microbial survival. Studies have shown that H2 is a potent antioxidant and can selectively neutralize OH• (hydroxyl radicals). OH•, however, has been implicated as one of the mechanisms whereby bactericidal antibiotics and professional phagocytes kill bacteria. Thus we have enough reason to speculate that hydrogenases and H2 are conducive to increasing the virulence and antibiotic resistance of bacteria, and hydrogenase inhibitors would help control bacterial infection.

To evaluate the efficacy and safety of budesonide (BUD)/formoterol (FORM) compared with BUD, both administered by way of a dry powder inhaler (Turbuhaler * ). * Turbuhaler is a registered trade name of AstraZeneca, Södertälje, Sweden.This was a 6-month, multicenter, randomized, parallel-group, double-blind, double-dummy design study (NCT 00421122). Patients were randomized to either BUD/FORM 160/4.5 μg, two inhalations twice daily, or BUD 200 μg, two inhalations twice daily. Improvement of lung function, daily symptoms, reliever use and health-related quality-of-life (St George's Respiratory Questionnaire [SGRQ] score) were compared between the two treatment groups.A total of 308 patients with moderate to very severe COPD from 12 centers in China were randomized to BUD/FORM (n = 156) or BUD (n = 152). The primary endpoint, 1-hour post-dose forced expiratory volume in 1 second (FEV1), in the BUD/FORM group improved by 0.18 L (from 0.83 L at baseline to 1.01 L) and this was significantly better (p 0.001) than the small increase (0.03 L) observed in the BUD group after 24 weeks' treatment. Increases in pre-dose and 15-min post-dose FEV(1) together with 1-hour post-dose forced vital capacity were also significantly larger with BUD/FORM than BUD (p 0.001 for all). Compared with BUD alone, BUD/FORM improved COPD total symptom scores (-1.04 ± 0.16 vs. -0.55 ± 0.17; p = 0.03), reduced reliever use (-0.85 ± 0.16 puffs/day vs. -0.31 ± 0.16 puffs/day; p = 0.012) and improved health-related quality-of-life (mean change of total SGRQ score -4.5 points (p = 0.0182). Overall, both treatments were well tolerated.In Chinese patients with moderate to very severe COPD, fixed combination treatment with BUD/FORM resulted in clinically meaningful improvements in lung function, health-related quality-of-life, COPD symptoms and a reduction in reliever use, compared with BUD alone and both treatments were well tolerated. Treatment of BUD/FORM for milder patients with COPD and head to head comparison of Chinese and Caucasians in future studies will be helpful to expand upon the findings of the current clinical trial.

Introduction Treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors or chemotherapy have shown improved survival outcomes in East Asian, never-smoker patients with non-small cell lung cancer (NSCLC). However, treatment sequence has not been optimized in patients with unknown EGFR mutation status. This trial compared first-line chemotherapy with pemetrexed (P)-cisplatin (C), followed by either gefitinib (G) or P maintenance. Methods East Asian, never-smoker, chemo-naive patients with stage IIIB/IV NSCLC, performance status ≤1 and unknown EGFR mutation status were randomized 1:1 to receive 4 cycles of pemetrexed [500mg/m 2 ]+cisplatin [75mg/m 2 ] q3 weeks, followed by maintenance with either gefitinib [250mg/d] (PC/G) or pemetrexed [500mg/m 2 ] q3 weeks and ≤2 optional cycles of cisplatin (PC/P). The primary endpoint, progression-free survival (PFS), was calculated from randomization date. Results Between Feb and Nov 2007, 70 patients from China, Korea, and Taiwan were randomized and treated, among whom 59 patients (84.3%) had non-squamous NSCLC. Forty-nine patients (70.0%) completed the full sequential treatment ( n =25 G; n =24 P). Median PFS was numerically longer for patients on PC/G (9.95 months) than those on PC/P (6.83months; hazard ratio [HR]=0.53, 95% confidence interval [CI]=0.27, 1.04). In contrast, median overall survival was numerically higher for patients on PC/P (HR=2.15, 95% CI=0.83, 5.60), though there was a high censoring rate. Response rate was similar in both arms. Treatment arms were similar for grade 3/4/5 toxicities. Conclusions East Asian never-smoker patients with advanced NSCLC and unknown EGFR mutation status had improved PFS following treatment with first-line PC and sequential G. Irrespective of subsequent maintenance treatment, induction PC was safe and efficacious, leading to prolonged OS in the Asian patient population.

Arsenic trioxide (As2O3) has been established to be an effective agent for treating acute promyleocytic leukemia. Laboratory data suggest that As2O3induces apoptosis of several solid tumor cells including lung cancer cells. Regions of tissue hypoxia often arise in aggressive solid tumors, and hypoxic tumors exhibit augmented invasiveness and metastatic ability in several malignancies. Furthermore, hypoxia may impair the treatment efficiency; therefore, we studied the cytotoxic effect of As2O3on human lung adenocarcinoma cell lines A549 and A549/R (resistant to vincristine, adriamycin and mitomycin etc.) grown under normoxic and hypoxic (1% oxygen) conditions. At both normoxia and hypoxia, 5, 10 and 15 µM As2O3induced evident growth inhibition and apoptosis in A549 cells as well as A549/R cells after 48 hours of exposure. In contrast, the conventional chemotherapeutic drug vincristine showed lowered efficiency in hypoxic A549 cells. As2O3induced G2/M cell cycle arrest in both normoxic and hypoxic A549 cells. As2O3significantly decreased the messenger RNA (mRNA) levels of Cyclin B1and survivin and the protein levels of Cyclin B1, phospho-CDC2(Thr 161) and survivin in both normoxic and hypoxic A549 cells. Together, our findings indicated that As2O3significantly inhibited the proliferation of lung cancer cells via G2/M cell cycle arrest and induction of apoptosis at both normoxia and hypoxia, and the induction of apoptosis was associated with down regulation of survivin.

Rosai-Dorfman disease (RDD) is a benign proliferative histiocytic disorder predominantly of the lymph nodes with extranodal involvement in some cases. However, serous membranes are seldom involved in the extranodal cases, and epicardial involvement is never reported. Most RDD cases show a self-limiting process with good prognosis and corticosteroid treatment in some patients exhibiting good effect. We recently observed a case of RDD primarily manifesting pericardial and bilateral pleural effusion that finally led to death, and corticosteroid treatment showed little effect. Autopsy showed the characteristic S100-positive and CD68-positive histiocytes exhibiting emperipolesis in the lungs, pleura, epicardium, mediastinal lymph nodes, and colon. This case illustrates the importance of RDD in the differential diagnosis of effusion in multiple serous cavities. The failure of corticosteroid therapy in this patient and her death showed the poor prognosis of some patients with RDD. Moreover, to our knowledge, epicardial involvement of RDD has not been reported.

Background Knowledge of predominant microbial patterns in community-acquired pneumonia (CAP) constitutes the basis for initial decisions about empirical antimicrobial treatment, so a prospective study was performed during 2003–2004 among CAP of adult Chinese urban populations. Methods Qualified patients were enrolled and screened for bacterial, atypical, and viral pathogens by sputum and/or blood culturing, and by antibody seroconversion test. Antibiotic treatment and patient outcome were also assessed. Results Non-viral pathogens were found in 324/610 (53.1%) patients among whom M. pneumoniae was the most prevalent (126/610, 20.7%). Atypical pathogens were identified in 62/195 (31.8%) patients carrying bacterial pathogens. Respiratory viruses were identified in 35 (19%) of 184 randomly selected patients with adenovirus being the most common (16/184, 8.7%). The nonsusceptibility of S. pneumoniae to penicillin and azithromycin was 22.2% (Resistance (R): 3.2%, Intermediate (I): 19.0%) and 79.4% (R: 79.4%, I: 0%), respectively. Of patients (312) from whom causative pathogens were identified and antibiotic treatments were recorded, clinical cure rate with β-lactam antibiotics alone and with combination of a β-lactam plus a macrolide or with fluoroquinolones was 63.7% (79/124) and 67%(126/188), respectively. For patients having mixed M. pneumoniae and/or C. pneumoniae infections, a better cure rate was observed with regimens that are active against atypical pathogens (e.g. a β-lactam plus a macrolide, or a fluoroquinolone) than with β-lactam alone (75.8% vs. 42.9%, p = 0.045). Conclusion In Chinese adult CAP patients, M. pneumoniae was the most prevalent with mixed infections containing atypical pathogens being frequently observed. With S. pneumoniae, the prevalence of macrolide resistance was high and penicillin resistance low compared with data reported in other regions.

This case report details the sudden onset of severe dermatomyositis (DM) symptoms followed by rapid progression of adenocarcinoma of the lung and an obvious diminution of the primary tumor with the administration of lung cancer targeted drug therapy alone, followed by nearly complete disappearance of the DM symptoms, with no conspicuous improvement in the DM symptoms when using corticosteroids.

To study the effect of continuous positive airway pressure (CPAP) on sleep physiology of mini pigs with obstructive sleep apnea syndrome (OSAS) induced by altitude hypoxia, 12 adult male mini pigs were randomly assigned into 2 groups, named A and B. The mini pigs in group A were treated with altitude hypoxia 6 h per day for 22 days, and then with CPAP 6 h per day for 30 days. For comparison, the mini pigs in group B were treated with altitude hypoxia only. The test of inspiration pressure of pharyngeal portion and the monitoring of sleeping were performed after the treatments of altitude hypoxia and CPAP. The sleeping monitor recorded the movements of chest and abdomen, respiratory airflow, heart rate, and pulse oxygen saturation (SpO2). The Apnea /Hypopnea Index (AHI), Apnea Index (AI), Hypopnea Index (HI), average SpO2 were all derived from the data of sleeping monitoring. In group A, the AHI and AI decreased after CPAP treatment; in the same time, SpO2 increased; these changes were significant (P0.05). The HI showed no significant change after CPAP treatment. The AHI, AI and HI of group A after CPAP treatment were significantly lower than those of group B after altitude hypoxia treatment only, and the SpO2 of group A was higher than that of group B. The pharyngeal inspiration pressure of group A was significantly decreased after CPAP treatment and was significantly lower than that of group B. All in all, the findings suggested that CPAP treatment could normalize the physiological indices of sleeping.

This study sought to assess the effect of CPAP on the structure and function of upper airway of mini pig with OSAS induced by altitude hypoxia. 12 adult male mini pigs were randomly assigned to 2 groups, named A and B. The mini pigs in group A were treated with altitude hypoxia 6 h per day for 22 days, and then with CPAP 6 h per day for 30 days. The mini pigs in group B were treated with altitude hypoxia only. Pharyngeal CT scanning and respiratory pressure testing were performed after the treatments . At last all mini pigs were sacrificed and their pharyngeal tissue was acquired for pathological examination. Result of pharyngeal CT scanning showed that, in group A, both of transverse diameters of pharyngeal cave in anterior and posterior areas of hyoid bone increased significantly after CPAP treatment (P0.05), while the pharyngeal longitudinal diameters exhibited no significant change (P0.05). The thickness of pharyngeal posterior wall of the anterior areas of hyoid bone increased significantly (P0.05) after CPAP, while the thickness of the lateral wall displayed no significant change. The pharyngeal longitudinal diameters of group A after CPAP were shorter than those of group B, and the transverse diameters were longer than those of group B, but these differences were not statistically significant (P0.05). The pharyngeal posterior walls in soft palate area and anterior area of hyoid bone after CPAP were significantly thicker than those of group B (P0.05), but there were no significant differences between the two groups as far as lateral wall thickness was concerned (P0.05). After CPAP treatment, the pharyngeal inspiration pressure in group A decreased significantly (P0.05), and the pressure was significantly lower than that of group B. Microscopic findings showed that the epithelium was proliferated partly after CPAP treatment. The muscle fibers of group A became fatter and were arranged disorderly with unclear transverse striation. The dropsied and congestive subcutaneous tissues were also infiltrated with inflammatory cells. These pathological changes were more obvious in group B. The results suggested that CPAP treatment could normalize the structure and function of pharyngeal tissue in OSAS mini pigs.

Vanadium, a potent toxic agent and carcinogen, is widely used in industry. Evidences show that exposure to vanadium is associated with an increased risk of lung cancer. But the mechanisms involved are far from fully understood. In this present study, we investigated that exposure of human bronchial epithelial cells (Beas-2B) to vanadium pentoxide resulted in an obvious induction of cyclooxygenase-2 (COX-2) expression and this induction was both dose- and time-dependent. Exposure of Beas-2B cells to vanadium pentoxide also led to significant activation of nuclear factor of activated T-cells (NFAT) on a time- and dose-dependent manner. Furthermore, we found that inhibition of NFAT by dominant negative mutant of NFAT (DN-NFAT) resulted in a dramatic inhibition of COX-2 expression induced by vanadium pentoxide, showing that NFAT activation was required for COX-2 induction by vanadium pentoxide in Beas-2B cells. Moreover, knockdown of COX-2 expression by COX-2-specific small interference RNA and blockage of NFAT pathway by DN-NFAT and NFAT3 small interference RNA showed an increased cell apoptosis in Beas-2B on vanadium exposure. Together, our results demonstrated that COX-2 expression could be induced by vanadium pentoxide in NFAT-dependent way and played an anti-apoptotic role in Beas-2B cells. From the results, we anticipate that the carcinogenesis of vanadium to human bronchial cells may result from anti-apoptosis mediated by the NFAT-dependent induction of COX-2, and we also assume that either pro-apoptotic or anti-apoptotic effect in certain type of cells after vanadium exposure may depend on the level of COX-2 induction.

A mini pig model for study of human obstructive sleep apnea syndrome (OSAS) was established by altitude hypoxia. Eight mini pigs were randomly assigned to 3 groups, named A, B, and C. They were placed in a double-roomed altitude chamber. As control, Groups A lived in Room 2 and there was an altitude of sea level in it. Groups B and C were in Room 1 and the pressure in it was 53.9 KPa with an oxygen concentration of 10.0%-11.2%. All of these mini pigs were in their rooms for 6 hours per day. Pigs in Groups B were in the room for 12 consecutive days and sacrificed on the 13th day. Pigs in Groups A and C were executed on the 23rd day. The pharyngeal CT scanning and the defermination of respiratory pressure in pharynx oralis and saturation of arterial blood oxygen were conducted in all exprimental mini pigs before they were put in chamber and before they were put to death. The pharyngeal tissues of the executed pigs were pathologically examined. CT scanning revealed there was significant (P0.05) increase in mini pigs' posterior pharyngeal wall (8.8 +/- 1.1 vs 6.5 +/- 0.6) and lateral pharyngeal wall (8.1 +/- 0.2 vs 6.3 +/- 0.6) on the 13th day as compared with that before they were put in chamber, and there was also significant (P0.05) increase (9.2 +/- 1.2 vs 6.3 +/- 0.7; 8.9 +/- 0.7 vs 6.4 +/- 0.5) on the 23rd day. There was significant (P0.05) reduction in diameter from left to right at the hyoid bone level (7.6 +/- 1.4 vs 9.7 +/- 1.4) and in the anteroposterior diameter at the soft palace level (3.8+/-1.1 vs 6.5 +/- 1.3) on the 13th day as compared with that before the mini pigs were put in chamber, and there was also sinificant (P0.05) reduction (6.4 +/- 1.6 vs 9.3 +/- 1.5; 4.3 +/- 0.9 vs 5.9 +/- 0.8) on the 23rd day. There was significant reduction (P0.05) in anteroposterior diameter on the posterior area of hyoid bone (3.7 +/- 0.9 vs 6.4 +/- 0.6) on the 23rd day. A significant change (P0.05) was observed in respiratory pressure of pharynx oralis on the 23rd day (0.0755 Mv) when compared with that before the first day (0.0658 Mv) in chamber and no significant change was seen on the 13th day. The saturation of blood oxygen decreased from 96.3% to 87.0% on the 13th day (P0.05) and further descended to 88.5% on the 23rd day (P0.05), compared with that before the first day in chamber. Pathological examination showed. In Group A, the mucosa of pharynx is covered by nonkeratinized-stratified squamous epithelium, and the layer of submucosa is thin; the muscular layer has clear striations and less fat cells among muscular fibers. In Group B, the pharyngeal epithelium is cornified and proliferated. Edema and proliferation of connective tissue occur in submucosa, and the muscular layer is thick with unclear striations; local infiltration of fat cells can be observed among muscular fibers. The pathological changes were more serious in Group C than in Group B. The results suggest that the method of intermittent altitude hypoxia could make the pharyngeal tissue of mini pig remodel and change its muscular biomechanical properties into those similar to the performance of OSAS in human. Living in altitude hypoxia for 22 days, the mini pigs became ill with OSAS, thus the expected animal model has been established in this study and could be used in further researches on OSAS in patients.

7507 Background: Etoposide combined with cisplatin (EP) has been the first-line chemotherapy regimen for small cell lung cancer (SCLC) for >20 years; however, a more effective regimen has been recommended by many clinical oncologists. Thus, we here present our preliminary results of a phase III clinical trial of the novel drug amrubicin in combination with cisplatin (AP) in comparison to EP in patients with previously untreated extensive SCLC (ED-SCLC). Methods: A total of 299 previously untreated ED-SCLC patients were randomized (ratio, 1:1) into two treatment groups: (1) the AP group (n = 149): 4–6 cycles of amrubicin (40 mg/m2/day on days 1–3) and cisplatin (60 mg/m2/day on day 1) and (2) the EP group (n = 150): 4–6 cycles of etoposide (100 mg/m2/day on days 1–3) and cisplatin (80 mg/m2/day on day 1 every 21 days). Patients were evaluated for therapy response and electrocardiography results every 2 cycles. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), overall response rate (ORR), and general safety. Results: Baseline characteristics were similar among the two groups. For AP and EP groups, the median OS was 11.79 and 10.28 months, the median PFS was 7.13 and 6.37 months, and ORR was 69.8% and 57.3%, respectively. The most frequent adverse events (≥grade 3) in AP and EP groups were bone marrow failure (23.5% and 21.3%, respectively), neutropenia (54.4% and 44.0%, respectively), and leukopenia (34.9% and 19.3%, respectively). Conclusions: Our phase III trial demonstrated that for previously untreated ED-SCLC patients, AP therapy was not inferior to EP therapy in terms of OS and offered predictable and manageable toxicities. Clinical trial information: NCT00660504.