A randomized, controlled, multicenter clinical trial to evaluate the efficacy and safety of oral sitafloxacin versus moxifloxacin in adult patients with community-acquired pneumonia.

OBJECTIVES: To evaluate the efficacy and safety of oral sitafloxacin versus oral moxifloxacin in the treatment of Chinese adults with community-acquired pneumonia (CAP). PATIENTS AND METHODS: 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). RESULTS: A total of 343 patients were randomized (sitafloxacin 100 mg qd, n = 117; sitafloxacin 100 mg bid, n = 116; moxifloxacin, n = 110), 291 patients were included in the PPS (sitafloxacin 100 mg qd, n = 96; sitafloxacin 100 mg bid, n = 94; moxifloxacin, n = 101). The clinical cure rate was 94.8% in the sitafloxacin 100 mg qd group, 96.8% in the sitafloxacin 100 mg bid group and 95.0% in the moxifloxacin group. At the TOC visit, the microbiological success rate was 97.0% (32/33) in the sitafloxacin 100 mg qd group, 97.1% (34/35) in the sitafloxacin 100 mg bid group and 94.9% (37/39) in the moxifloxacin group in the microbiological evaluable set (MES). The incidence of study-drug-related adverse events (AEs) was 23.3% (27/116) in the sitafloxacin 100 mg qd group, 29.8% (34/114) in the sitafloxacin 100 mg bid group and 28.2% (31/110) in the moxifloxacin group (p > .05). The common AEs related to study drug were dizziness, nausea, diarrhea, increased platelet count and alanine transaminase (ALT) elevation. All the AEs resolved completely after discontinuation of study drug. CONCLUSION: 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.

Anti-angiogenic effect of arsenic trioxide in lung cancer via inhibition of endothelial cell migration, proliferation and tube formation.

Arsenic trioxide (As2O3) exhibits a remarkable effect on leukemia treatment; however, its effect on solid tumors remains poorly explored. The present study demonstrated the inhibitory effect of As2O3 on lung cancer and explored its possible mechanism. It was observed that As2O3 significantly inhibited the growth of lung cancer xenografts and tumor angiogenesis in vivo. The inhibitory effect of As2O3 on cell proliferation in vitro was more remarkable in vascular endothelial cells than in lung cancer cells. It was also observed that As2O3 inhibited the migration of vascular endothelial cells and disrupted vascular tube formation on Matrigel assays. In addition, a series of key signaling factors involved in multiple stages of angiogenesis, including matrix metalloproteinase (MMP)-2, MMP-9, platelet-derived growth factor (PDGF)-BB/PDGF receptor-ß, vascular endothelial growth factor (VEGF)-A/VEGF receptor-2, basic fibroblast growth factor (FGF)/FGF receptor-1 and delta like canonical Notch ligand 4/Notch-1, were regulated by As2O3. These findings suggested that anti-angiogenesis may be an underlying mechanism of As2O3 anticancer activity in lung cancer.

A randomized, double-blind, multicenter Phase II study comparing the efficacy and safety of oral nemonoxacin with oral levofloxacin in the treatment of community-acquired pneumonia.

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 7-10 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 7-10 days demonstrated high clinical and bacteriological success rates in Chinese adult patients with CAP. Nemonoxacin at 500 mg once daily for 7-10 days is recommended for future Phase III clinical trials. ClinicalTrials.gov identifier: NCT01537250.

B and T Lymphocyte Attenuator is a Target of miR-155 during Naïve CD4+ T Cell Activation.

BACKGROUND: MicroRNA-155 (miR-155) is upregulated during T cell activation, but the exact mechanisms by which it influences CD4+ T cell activation remain unclear. OBJECTIVE: To examine whether the B and T lymphocyte attenuator (BTLA) is a target of miR-155 during naïve CD4+ T cell activation. METHODS: Firefly luciferase reporter plasmids pEZX-MT01-wild-type-BTLA and pEZX-MT01-mutant-BTLA were constructed. Lymphocytes were nucleofected with miR-155 inhibitor or negative control (NC). Then, naïve CD4+ CD62L+ helper T cells purified from lymphocytes were stimulated with immobilized antibody to CD3 and soluble antibody to CD28. miR-155 and BTLA expression were examined by real-time RT-PCR. Cell surface CD69 expression and IL-2 secretion were measured by ELISA and flowcytometry, respectively. RESULTS: Luciferase reporter assay showed that miR-155 targeted the BTLA 3'UTR region. Compared with non-stimulated condition, both miR-155 and BTLA mRNA expression were upregulated after T cell activation. Similar results were observed for BLTA protein expression. Compared with NC, the miR-155 inhibitor decreased miR-155 by about 45%, but did not influence BTLA mRNA expression. Compared with NC, the miR-155 inhibitor decreased the surface BTLA expression by about 60%. Upregulation of BTLA in miR-155 knockdown CD4+ T cells did not influence the cell surface expression of CD69, an early activation marker (p=0.523). Similarly, IL-2 production was not changed. CONCLUSION: miR-155 is involved in the inhibition of BTLA during CD4+ T cell activation. These results might serve as a basis for an eventual therapeutic manipulation of this pathway to treat inflammatory and autoimmune diseases.

Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer.

BACKGROUND: Extensive-disease small-cell lung cancer (ED-SCLC) is characterized by rapid progression and relapse, despite high initial response rates to chemotherapy. The primary objective of this trial was to demonstrate the non-inferiority of amrubicin and cisplatin (AP) combination therapy compared with the standard first-line regimen of etoposide and cisplatin (EP) for previously untreated ED-SCLC in a Chinese population. When non-inferiority was verified, the objective was switched from non-inferiority to superiority. METHODS: From June 2008 to July 2010, 300 patients were enrolled and randomly assigned at a 1:1 ratio to AP and EP groups. AP-treated patients received cisplatin (60 mg/m(2), day 1) and amrubicin (40 mg/m(2), days 1-3) once every 21 days. EP-treated patients received cisplatin (80 mg/m(2), day 1) and etoposide (100 mg/m(2), days 1-3) once every 21 days. Treatment was continued for four to six cycles, except in cases of progressive disease or toxicity, and patient refusal. RESULTS: Median overall survival (OS) for AP vs. EP treatment was 11.8 vs. 10.3 months (p = 0.08), respectively, demonstrating non-inferiority of AP to EP (AP group: 95% confidence interval for hazard ratio 0.63-1.03 months). Median progression-free survival and overall response rates for AP vs. EP groups were 6.8 vs. 5.7 months (p = 0.35) and 69.8% vs. 57.3%, respectively. Drug-related adverse events in both groups were similar, with neutropenia being the most frequent (AP 54.4%; EP 44.0%). Leukopenia, pyrexia, and fatigue were more prevalent in the AP group, but all were clinically reversible and manageable. CONCLUSIONS: AP therapy demonstrated non-inferiority to EP therapy, prolonging OS for 1.5 months, but this difference was not statistically significant; thus we propose AP as a promising treatment option for ED-SCLC in China. TRIAL REGISTRATION: This trial was registered on 10 April 2008 (ClinicalTrials.gov NCT00660504).

Real-life effectiveness of budesonide/formoterol therapy in asthma: A subanalysis of the SMARTASIA study.

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).

Effect of X-ray repair cross complementing group 1 polymorphisms on the efficacy of platinum-based chemotherapy in patients with nonsmall cell lung cancer.

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.

Efficacy and Safety of OM-85 in Patients with Chronic Bronchitis and/or Chronic Obstructive Pulmonary Disease.

BACKGROUND: Recurrent acute exacerbations are generally associated with accelerated decline of lung function and characterized by reduced physical activity and worsening of clinical status in patients with chronic obstructive pulmonary disease (COPD). Effective practices and therapies aimed at preventing acute exacerbations are continuously under investigation by healthcare providers. This double-blind, placebo-control, randomized clinical trial sought to evaluate the preventive effect of a bacterial lysate (OM-85) on acute exacerbations in patients with COPD or chronic bronchitis in China. METHODS: A total of 428 patients were randomly assigned either to OM-85 treatment or to placebo. Patients received study drug or placebo for 10 days per month over 3 consecutive months, with a 10-week follow-up. Three hundred and eighty-four (384) patients completed the study (192 in the OM-85 group and 192 in the placebo group) and were included in the full analysis set (FAS). Thirty (30) patients, 21 in the OM-85 and 9 in the placebo groups, were excluded due to protocol violations and drop-outs, and the remaining 354 patients (171 in the OM-85 and 183 in the placebo groups) were included in the per protocol set (PPS). RESULTS: The proportion of patients with recurrent acute exacerbations in the OM-85 group was significantly lower than in the placebo group at the end of the treatment period, both, in the FAS (23.4 % vs. 33.3 %, p = 0.0311) and in the PPS (17.0 % vs. 31.2 %, p < 0.05). Throughout the entire 22-week study period, the proportion of patients with recurrent acute exacerbations in the OM-85 group was lower than in the placebo group in the FAS (32.8 % vs. 38.0 %, p = 0.277), while the difference is statistically significant in the PPS (26.3 % vs. 36.1 %, p < 0.05). CONCLUSION: OM-85 significantly reduced the proportion of patients with acute exacerbation after 12 weeks of therapy and the benefit appeared to be maintained up to 22 weeks, and showed a favorable tolerability profile.

Overexpression of stathmin 1 is a poor prognostic biomarker in non-small cell lung cancer.

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<0.001). In addition, increased STMN1 expression was correlated with poor tumor differentiation (P<0.001), large tumor size (P=0.022), advanced N stage (P=0.033), and advanced TNM stage (P<0.001). Kaplan-Meier analysis indicates that NSCLC patients with higher STMN1 expression showed significantly worse survival. Moreover, multivariate analysis indicates that higher STMN1 protein expression was an independent prognostic factor of disease-specific survival (HR 2.247, 95%CI 1.320-3.825, P=0.003). Finally, the knockdown of STMN1 in lung cancer cells resulted in a decrease in cellular proliferation and invasion. Our findings suggest that STMN1 may have an important role in NSCLC progression and could serve as a potential prognostic marker for patients with NSCLC.

A randomized controlled clinical trial of levofloxacin 750 mg versus 500 mg intravenous infusion in the treatment of community-acquired pneumonia.

The objective of this study was to compare the efficacy and safety of levofloxacin 750 mg for 5 days versus 500 mg for 7-14 days intravenous (IV) in the treatment of community-acquired pneumonia (CAP). This clinical trial was the first of its kind conducted in Chinese people and also in Asian population. A total of 241 were enrolled and randomized to 750 mg group (n = 121) or 500 mg (n = 120) group from 10 study centers. The median treatment duration was 5.0 days in 750 mg and 9.0 days in 500 mg group. The median total dose was 3750 mg in 750 mg and 4500 mg in 500 mg group. The bacterial eradication rate was 100% in both groups. The overall efficacy rate in 750 mg group was 86.2% (94/109), and 84.7% (94/111), in 500 mg group of full analysis set visit 4, 95% confidence interval of 1.6% (-7.8-10.9%); the statistical results showed that 750 mg group was non-inferior to 500 mg group. The most common clinical adverse drug reactions were injection site adverse reactions in both 750 mg group and 500 mg group; the other common adverse drug reactions were insomnia, nausea, skin rash, etc. The most common drug-related laboratory abnormalities were neutrophil percentage decreased, decreased white blood cell count, alanine aminotransferase, and aspartate aminotransferase elevation in both 750 mg group and 500 mg group. Most of adverse drug reactions were mild in severity and well-tolerated. In summary, the regimen of levofloxacin 750 mg IV for 5 days was at least as effective and well tolerated as 500 mg IV for 7-14 days for the treatment of CAP.

BAT3 rs1052486 and rs3117582 polymorphisms are associated with lung cancer risk: a meta-analysis.

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 < 0.00001). This polymorphism was also significantly associated with squamous carcinoma risk (OR = 1.30; 95 % CI, 1.11-1.52; P = 0.001) and lung cancer risk in smokers (OR = 1.23; 95 % CI, 1.10-1.38; P = 0.0005). This meta-analysis suggested that BAT3 polymorphisms contributed the development of lung cancer.

Obesity survival paradox in pneumonia: a meta-analysis.

BACKGROUND: It is unclear whether an 'obesity survival paradox' exists for pneumonia. Therefore, we conducted a meta-analysis to assess the associations between increased body mass index (BMI), pneumonia risk, and mortality risk. METHODS: Cohort studies were identified from the PubMed and Embase databases. Summary relative risks (RRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random effects model. RESULTS: Thirteen cohort studies on pneumonia risk (n = 1,536,623), and ten cohort studies on mortality (n = 1,375,482) were included. Overweight and obese individuals were significantly associated with an increased risk of pneumonia (RR = 1.33, 95% CI 1.04 to 1.71, P = 0.02, I(2) = 87%). In the dose-response analysis, the estimated summary RR of pneumonia per 5 kg/m(2) increase in BMI was 1.04 (95% CI 1.01 to 1.07, P = 0.01, I(2) = 84%). Inversely, overweight and obese subjects were significantly associated with reduced risk of pneumonia mortality (RR = 0.83, 95% CI 0.77 to 0.91, P < 0.01, I(2) = 34%). The estimated summary RR of mortality per 5 kg/m(2) increase in BMI was 0.95 (95% CI 0.93 to 0.98, P < 0.01, I(2) = 77%). CONCLUSIONS: This meta-analysis suggests that an 'obesity survival paradox' exists for pneumonia. Because this meta-analysis is based on observational studies, more studies are required to confirm the results.

ß-Lactam/macrolide dual therapy versus ß-lactam monotherapy for the treatment of community-acquired pneumonia in adults: a systematic review and meta-analysis.

OBJECTIVES: Several studies have compared the clinical effect of ß-lactam/macrolide (BLM) dual therapy versus ß-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 < 0.001, I(2) = 3%). Subsequent subgroup analyses confirmed that BLM dual therapy was statistically superior to BL monotherapy in reduction of mortality. Sensitivity analyses strengthened the validity of the results. CONCLUSIONS: In comparison with BL monotherapy, BLM dual therapy might reduce mortality risk in patients with CAP. Because this finding is based on observational studies, randomized controlled trials are required to demonstrate the usefulness of BLM dual therapy in the treatment of CAP.

TERT rs2736100 polymorphism contributes to lung cancer risk: a meta-analysis including 49,869 cases and 73,464 controls.

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<0.00001). This polymorphism was also significantly associated with LC risk in Asians (OR=1.27, 95 % CI 1.22-1.33, P<0.00001), Caucasians (OR=1.14, 95 % CI 1.10-1.18, P<0.00001), female patients (OR=1.37, 95 % CI 1.24-1.51, P<0.00001), male patients (OR=1.23, 95 % CI 1.15-1.31, P<0.00001), adenocarcinoma patients (OR=1.35, 95 % CI 1.28-1.41, P<0.00001), squamous cell carcinoma patients (OR=1.13, 95 % CI 1.04-1.21, P=0.002), small cell lung cancer patients (OR=1.09, 95 % CI 1.03-1.16, P=0.004), current smokers (OR=1.22, 95 % CI 1.17-1.27, P<0.00001), former smokers (OR=1.14, 95 % CI 1.08-1.21, P<0.0001), and never smokers (OR=1.37, 95 % CI 1.31-1.43, P<0.00001), respectively. This meta-analysis suggested that TERT rs2736100 polymorphism was a risk factor for LC.

Angiotensin-converting enzyme I/D polymorphism is associated with pneumonia risk: a meta-analysis.

BACKGROUND: Previous studies examined the association between angiotensin-converting enzyme (ACE) I/D polymorphism and pneumonia, but their results were inconsistent. Thus, a meta-analysis was performed to clarify the effect of ACE I/D polymorphism on pneumonia risk and pneumonia-related mortality. METHODS: The PubMed, Embase, and Chinese National Knowledge Infrastructure (CNKI) databases were searched for relevant studies published up to 27 April 2013. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS: Pooled analysis of 12 case-control studies (1431 cases and 3600 controls) showed that there was a significant association between ACE I/D polymorphism and pneumonia risk in a recessive genetic model (OR = 1.53, 95% CI 1.30-1.80, p < 0.00001). No significant association between ACE I/D polymorphism and mortality was observed (OR = 2.68, 95% CI 0.80-8.90, p = 0.11). CONCLUSIONS: Our meta-analysis confirmed that ACE I/D polymorphism was associated with pneumonia risk. However, ACE I/D polymorphism was not associated with pneumonia mortality.

Nicotine gum or patch treatment for smoking cessation and smoking reduction: a multi-centre study in Chinese physicians.

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.

Clinical aspects and cytokine response in adults with seasonal influenza infection.

Cytokine responses play an important role in the pathogenesis of influenza infection. Previous studies found that cytokine expressions in patients infected with the novel A (H1N1) influenza virus (nvA (H1N1)) could reflect the severity of the disease. But the patterns of cytokine response in patients infected with seasonal influenza virus and the correlations between cytokine responses and clinical data are still unknown. Seventy-two outpatients for laboratory-confirmed seasonal influenza infection were studied: twenty-four seasonal influenza A patients and forty-eight seasonal influenza B patients. Thirty healthy volunteers were enrolled as a control group. Serum samples from influenza patients obtained on the admission day and 6 days later were measured for eight cytokines using enzyme-linked immunosorbent assay (ELISA). The clinical variables were recorded prospectively. The levels of interleukin (IL)-6, IL-33 and tumor necrosis factor (TNF)-α were significantly higher in influenza A patients than those in the control group while IL-6, IL-17A, IL-29, interferon (IFN)-γ and interferon gamma-induced protein (IP)-10 were significantly higher in influenza B patients than those in the control group. Furthermore, IL-17A, IL-29 and IP-10 were increased in seasonal influenza B patients when comparing with those in the seasonal influenza A patients. A positive correlation of IL-29 levels with fever (Spearman's rho, P-values < 0.05) and a negative correlation of IFN-γ and IP-10 levels with lymphocyte count (Spearman's rho, P-values < 0.05) were found in seasonal influenza infection. While a hyperactivated proinflammatory cytokine responses were found in seasonal influenza infection, a higher elevation of cytokines (IL-17A, IL-29 and IP-10) were found in seasonal influenza B infection versus influenza A. IL-29, IFN-γ and IP-10 were important hallmarks in seasonal influenza infection, which can help clinicians make timely treatment decision for severe patients.

Association between interleukin-4 receptor α chain (IL4RA) I50V and Q551R polymorphisms and asthma risk: an update meta-analysis.

BACKGROUND: The associations between the interleukin-4 receptor α chain (IL4RA) I50V and Q551R polymorphisms and asthma risk remained controversial. METHODS: We searched the Pubmed, Embase, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases for studies published before February 2013. The strengths of the associations were calculated using odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of 50 studies were included in this meta-analysis. There was a significant association between the IL4RA I50V polymorphism and asthma risk in a dominant genetic model (OR = 1.13, 95% CI 1.04-1.23, P = 0.005). The IL4RA Q551R polymorphism was associated with a significantly elevated asthma risk in a recessive genetic model (OR = 1.46, 95% CI 1.22-1.75, P<0.0001). Subgroup analyses found that the IL4RA I50V polymorphism was significantly associated with asthma risk in Asians (OR = 1.72, 95% CI 1.31-2.25, P<0.0001), pediatric asthma risk (OR = 1.50, 95% CI 1.13-1.99, P = 0.005), and atopic asthma risk (OR = 1.88, 95% CI 1.27-2.79, P = 0.002). CONCLUSIONS: The results of this meta-analysis suggested that the IL4RA I50V and Q551R polymorphisms may be risk factors for developing asthma.

Secretoglobin 1A member 1 (SCGB1A1) +38A/G polymorphism is associated with asthma risk: a meta-analysis.

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.

Interleukin-13 +1923C/T polymorphism is associated with asthma risk: a meta-analysis.

There are controversies on the association between interleukin-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 between IL-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 that IL-13 +1923C/T polymorphism was a risk factor of asthma.