Normal lung attenuation distribution and lung volume on computed tomography in a Chinese population.

Backgroud and objectives: Although lung attenuation distribution and lung volume on computed tomography (CT) have been widely used in evaluating COPD and interstitial lung disease, there are only a few studies regarding the normal range of these indices, especially in Chinese subjects. We aimed to describe the normal range of lung attenuation distribution and lung volume based on CT. Methods: Subjects with normal lung function and basically normal chest CT findings (derivation group) at Ruijin Hospital, Shanghai (from January 2010 to June 2014) were included according to inclusion and exclusion criteria. The range of the percentage of lung volume occupied by low attenuation areas (LAA%), percentile of the histogram of attenuation values (Perc n), and total lung volume were analyzed. Relationships of these measures with demographic variables were evaluated. Participants who underwent chest CT examination for disease screening and had basically normal CT findings served as an external validation group. Results: The number of subjects in the derivation group and external validation groups were 564 and 1,787, respectively. Mean total lung volumes were 4,468±1,271 mL and 4,668±1,192 mL, and median LAA%(-950 HU) was 0.19 (0.03-0.43) and 0.17 (0.01-0.41), in the derivation and external validation groups, respectively. Reference equations for lung volume and attenuation distribution (LAA% using -1,000-210 HU, Perc 1 to Perc 98) were generated: Lung volume (mL) = -1.015 *10^4+605.3*Sex (1= male, 0= female)+92.61*Height (cm) -12.99*Weight (kg) ±1766; LAA% (-950 HU)=[0.2027+0.05926*Sex (1= male, 0= female) -4.111*10^-3*Weight (kg) +4.924*10^-3*Height (cm) +8.504*10^-4*Age]^7.341-0.05; Upper limit of normal range: [0.2027+0.05926*Sex-4.111*10^-3*Weight+4.924*10^-3*Height+8.504*10^-4*Age+0.1993]^7.341-0.05. Conclusion: This large population-based retrospective study demonstrated the normal range of LAA%, Perc n, and total lung volume measured on CT scans among subjects with normal lung function and CT findings. Reference equations are provided.

Add-on Tiotropium in Chinese Patients With Moderate Asthma: A Pooled Subgroup Analysis of MezzoTinA-Asthma 1 and 2.

PURPOSE: Asthma affects approximately 30 million patients in China; however, tiotropium data for Chinese patients is limited. This study aimed to assess the efficacy and safety of tiotropium in Chinese patients with moderate symptomatic asthma. METHODS: A post hoc subgroup analysis was conducted on 430 Chinese patients pooled from two 24-week, replicate phase 3 trials (NCT01172808 and NCT01172821), in which they received once-daily tiotropium 2.5 µg (Tio R2.5) or 5 µg (Tio R5) (n = 106 or 109, respectively), twice-daily salmeterol 50 µg (Sal 50) (n = 110), or placebo (n = 105), while maintaining inhaled corticosteroids (ICS). The co-primary endpoints assessed in week 24 were forced expiratory volume in 1 second (FEV1) peak0-3h response, trough FEV1 response, and responder rate as assessed using the Asthma Control Questionnaire (ACQ). RESULTS: For both FEV1 peak0-3h responses and trough FEV1 responses, the mean treatment differences were greater for Tio R2.5, Tio R5, and Sal 50 compared with placebo at 0.249 L, 0.234 L, and 0.284 L, and 0.172 L, 0.180 L, and 0.164 L, respectively (P < 0.001). The ACQ responder rate in placebo, Tio R2.5, Tio R5, and Sal 50 was 58.7%, 62.3%, 59.3%, and 69.1%, respectively. Furthermore, 11 (2.6%) of 430 patients had serious adverse events (Tio R5, n = 4; Tio R2.5, n = 1; Sal 50, n = 1; and placebo, n = 5). CONCLUSIONS: Once-daily tiotropium, as add-on to medium-dose ICS, was effective and well tolerated for Chinese patients with moderate symptomatic asthma, consistent with the main analysis.

Prevalence and risk factors of asthma in mainland China: The CARE study.

BACKGROUND: There are limited population based data on the prevalence of asthma in China. The China Asthma and Risk factors Epidemiologic (CARE) survey was designed to understand the prevalence and risk factors for asthma in mainland China. OBJECTIVES: The CARE survey aims to demonstrate the prevalence and risk factors of asthma in mainland China among adolescents (age >14 years) and adults. METHODS: The survey was performed between February 2010 and August 2012 in eight provinces/cities of seven areas in mainland China. The inhabitants (age, >14 years) recruited in this survey were through multi-stage cluster random sampling. Asthma diagnosis was based on medical history and lung function tests. Multivariable logistic regression was used to analyzed the risk factors for asthma. RESULTS: The study included 164 215 subjects (men, 79 692 [48.53%]; women, 84 523 [51.47%]). 2034 (1.24%) were asthmatic patients. Among all asthmatic patients, 521 (25.61%) were newly diagnosed. Univariable regression analysis showed that risk factors for asthma included smoking, first-degree relatives with asthma, allergic rhinitis, chronic bronchitis, COPD, pollinosis, allergic pneumonia, concomitant allergic diseases, BMI and raising pets. Multivariable logistic regression indicated that asthma risk factors included women, age stratification, smoking, first-degree relatives suffering from asthma or pollinosis, combined with allergic rhinitis, eczema or GERD. CONCLUSIONS: We speculated that the prevalence of asthma is increasing in mainland China among individuals aged >14 years in the past 10 years. A number of risk factors were identified. The risk factors of asthma would be further elucidated in our future work. CLINICAL IMPLICATIONS: Our CARE study highlights that asthma epidemic in mainland China should be paid more attention.

Hedgehog signaling regulates the expression levels of inflammatory mediators in cigarette­induced airway inflammation.

Chronic obstructive pulmonary disease (COPD) is a persistent airway inflammation influenced by cigarette smoke. Previous studies have reported that Hedgehog (Hh) signaling is aberrantly activated by cigarette smoke and dysregulated in COPD. The present study explored the role of the Hh signaling pathway on the expression levels of certain inflammatory mediators in cigarette­induced airway inflammation. Herein, a total of three A549 cell populations were generated: The A0 group as control cells, the A1 group cells treated with nicotine at a concentration of 10 µM for 12, 24 and 48 h, and the A2 group cultured simultaneously with nicotine and cyclopamine for the same duration. The total concentrations of the inflammatory mediators interleukin­6 (IL­6), IL­8 and tumor necrosis factor (TNF)­α, and an anti­inflammatory cytokine, IL­10, were assessed in all of the cells by ELISA and western blotting. The protein levels of sonic hedgehog (Shh), glioma­associated oncoprotein 1 (Gli1) and Smoothened (Smo) in nicotine­induced Hh signaling were also detected. The results indicated that A549 had increased levels of IL­6, IL­8 and TNF­α when cultured with nicotine when compared with the control cells. By contrast, the expression levels of these inflammatory mediators decreased with varying degrees when treated with cyclopamine that blocked the Hh signaling pathway. The IL­10 expression levels exhibited the reverse. The expressions of the Shh, Gli1 and Smo proteins were higher in the A1 group when compared with the control and decreased with cyclpoamine treatment. In conclusion, the Hh signaling pathway may partly have an impact on cigarette­induced airway inflammation via the regulation of inflammatory mediators. Thus, blocking Hh signaling and diminishing the airway inflammation reaction may serve as a potential therapy for COPD.

Critical roles of adenosine A2A receptor in regulating the balance of Treg/Th17 cells in allergic asthma.

INTRODUCTION: Deficiency of Treg cells and hyperactivity of Th17 cells together are involved in the immunological pathogenesis of asthma. The adenosine A2A receptor (A2AR) plays a critical role in the increased Foxp3 expression of Treg cells and the decreased Th17 generation. OBJECTIVE: The study aimed to investigate A2AR expression in peripheral blood and its regulatory effect on balance of Treg/Th17 cells in asthma. METHODS: Thirty-one patients with chronic persistent asthma were recruited and divided into 18 intermittent to mild asthma patients, 13 moderate to severe asthma patients. A2AR, Foxp3, and ROR-γt mRNA expression levels in peripheral blood mononuclear cells (PBMCs) were measured by quantitative polymerase chain reaction (qPCR). TGF-ß, IL-17, and IgE in plasma were detected with enzyme-linked immunosorbent assay (ELISA). Forty-two BALB/c mice were randomly, equally assigned to control group, ovalbumin (OVA) group and OVA + CGS (CGS21680, A2AR agonist) group. The infiltration of lung inflammation cells were evaluated by HE, A2AR, Foxp3, and ROR-γt mRNA in lung tissues measured by qPCR, TGF-ß, IL-17, and IgE in plasma measured with ELISA, and IL-17 and TGF-ß protein in lung tissues analyzed with immunohistochemical. RESULTS: Our results showed that expression A2AR mRNA in PBMCs was associated with asthma severity. Foxp3 mRNA, TGF-ß, and FEV1%pred positively correlated with A2AR mRNA in asthma. ROR-γt mRNA and IL-17 negatively correlated with A2AR mRNA in asthma. CGS could promote Foxp3 mRNA expression, TGF-ß, and improve lung function while inhibit ROR-γt mRNA expression, IL-17, and the infiltration of lung inflammation cells. CONCLUSION: A2AR could regulate the balance of Treg/Th17 cells in asthma.

Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease: a case report and review of the literature.

Invasive pulmonary aspergillosis (IPA) is an infection that often occurs in immunocompromised patients and has a high mortality rate. In recent years, the reported incidence of IPA in the context of chronic obstructive pulmonary disease (COPD) has seemingly increased. The combination of factors such as long-term corticosteroid use, increasing rate of bacterial exacerbations over time, lung immune imbalance, and malnutrition are responsible for the emergence of IPA in COPD patients. A diagnosis of IPA in COPD patients is difficult to make, which explains the delay in antifungal therapy and the high mortality rate. The purpose of this study is to increase the recognition and improve the outcomes associated with this situation through the description of our case. In patients in which IPA is suspected, comprehensive analysis of their clinical manifestations, imaging, microbiology and serological examination results are effective means of increasing the rate of reliable diagnosis. If the patient's condition permits, a pathological specimen should be obtained as soon as possible.

ACE2 overexpression inhibits acquired platinum resistance-induced tumor angiogenesis in NSCLC.

Angiotensin II (AngII) is a multifunctional bioactive peptide in the renin-angiotensin system (RAS). Angiotensin-converting enzyme 2 (ACE2) is a newly identified component of RAS. We previously reported that ACE2 overexpression may inhibit cell growth and vascular endothelial growth factor (VEGF) production in vitro and in vivo. In the present study, we investigated the effect of ACE2 on tumor-associated angiogen-esis after the development of acquired platinum resistance in non-small cell lung cancer (NSCLC). Four NSCLC cell lines, A549, LLC, A549-DDP and LLC-DDP, were used in vitro, while A549 and A549-DDP cells were used in vivo. A549-DDP and LLC-DDP cells were newly established at our institution as acquired platinum-resistant sublines by culturing the former parent cells in cisplatin (CDDP)-containing conditioned medium for 6 months. These platinum-resistant cells showed significantly higher angiotensin II type 1 receptor (AT1R), ACE and VEGF production and lower ACE2 expression than their corresponding parent cells. We showed that ACE2 overexpression inhibited the production of VEGF in vitro and in vivo compared to their corresponding parent cells. We also found that ACE2 overexpression reduced the expression of AT1R and ACE. Additionally, we confirmed that ACE2 overexpres-sion inhibited cell growth and VEGF production while simultaneously suppressing ACE and AT1R expression in human lung cancer xenografts. Our findings indicate that ACE2 overexpression may potentially suppress angiogenesis in NSCLC after the development of acquired platinum resistance.

Impact of Angiotensin I-converting Enzyme Inhibitors and Angiotensin II Type-1 Receptor Blockers on Survival of Patients with NSCLC.

It has been shown that angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) can decrease tumor growth and tumor-associated angiogenesis and inhibit metastasis. Epidermal growth factor receptor (EGFR) mutations are found in approximately 30% of patients with advanced non-small cell lung cancer (NSCLC) in East Asia and in 10-15% of such patients in Western countries. We retrospectively identified 228 patients with histologically confirmed advanced NSCLC and 73 patients with early stage disease; 103 of these patients took antihypertensive drugs, and 112 received treatment with EGFR tyrosine kinase inhibitors (TKIs). There was a significant difference in progression-free survival after first-line therapy (PFS1) between the ACEI/ARB group and the non-ACEI/ARB group. For the patients treated with TKIs, there was a significant difference in PFS but not in overall survival (OS) between the ACEI/ARB group and the non-ACEI/ARB group. For the patients with advanced NSCLC, there was a significant difference in PFS1 between the ACEI/ARB group and the non-ACEI/ARB group. ACEI/ARB in combination with standard chemotherapy or TKIs had a positive effect on PFS1 or OS, regardless of whether the lung cancer was in the early or advanced stage.

Computed tomography manifestation of acute exacerbation of chronic obstructive pulmonary disease: A pilot study.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an acute event characterized by the worsening of a patient's respiratory symptoms. To the best of our knowledge, few studies have investigated the computed tomography (CT) manifestation of AECOPD. Thus, the aim of the present study was to examine the CT manifestations during AECOPD. In total, 40 patients with AECOPD admitted to the emergency department were enrolled. CT images obtained at the time of exacerbation and at the 3-month follow-up were paired. Clinical characteristics and routine blood test results were also recorded. Airway dimensions and attenuation per patient were quantified from the 3rd to the 6th generation of four bronchi by Airway Inspector Slicer 2.8. The emphysema extent was also quantified and lung infiltration was detected, classified and measured. The CT images showed an increased wall area percentage (WA%) and increased mean and peak wall attenuation during the AECOPD; however, the extent of emphysema did not change significantly. In total, 60% of AECOPD patients presented with lung infiltration, compared with those at the follow-up CT scanning. The presence and extent of segmental distribution consolidation was correlated with the neutrophil percentage (N%), with a statistically significant difference observed. The total volume of lung parenchymal infiltration was correlated with the white blood cell (WBC) count and N%; however, no significant correlations were detected between the presence or extent of acinar shadow, air space consolidation with lobular distribution, ground-glass attenuation with lobular distribution, thickening of the interlobular septa and signs of infection (including the number of main symptoms, body temperature, WBC count and N%). The WA%, mean wall attenuation and peak wall attenuation increased during AECOPD, but the emphysema extent was unchanged. Lung infiltration existed frequently; however, only consolidation with segmental distribution appeared to be associated with bacterial infection.

Histone deacetylase inhibitor regulates the balance of Th17/Treg in allergic asthma.

BACKGROUND AND AIMS: The aim of this study is to investigate the expression pattern of histone deacetylase 9 in peripheral blood of patients with allergic asthma and its regulatory effect on the balance of Th17/Treg cells involved in the pathogenesis of asthma. METHODS: flap-Ub promoter-GFP-WRE vector was used to construct the Jurkat-HA-FOXP3 cell line. After histone deacetylase inhibitor-trichostatin A (TSA) treatment, FOXP3 and RORγt expression were detected by real-time-polymerase chain reaction (RT-PCR). BALB/c mice were randomly assigned to control group, TSA treatment and the asthma group. Serum Immunoglobulin E (IgE) was detected with enzyme-linked immunosorbent assay (ELISA), airway inflammation in lung tissue evaluated by haematoxylin/eosin staining, bronchoalveolar lavage fluid (BALF) cell number and differential counted, interleukin (IL)-17A and TGF-ß concentrations in BALF measured with ELISA, and expression of RORγt and FOXP3 messenger RNA (mRNA)measured by RT-PCR. Forty-seven patients with asthma were recruited and assigned to intermittent, mild and moderate-severe group. GATA3, IL-4, histone deacetylases (HDAC) 9 mRNA expression level were measured by RT-PCR. RESULTS: After TSA treatment, FOXP3 mRNA level was upregulated, while RORγt mRNA level was downregulated. FOXP3 protein level was also upregulated by TSA. In vivo, TSA treatment can inhibit IL-17 but promote transforming growth factor-beta production in the BALF of asthma mice, and inhibited the expression of Th17 cells and RORγt mRNA in lung; also can promote Foxp3 mRNA expression. GATA3, IL-4 mRNA expression levels were upregulated in patients with asthma than the healthy control. HDAC9 mRNA expression level was associated with the severity of disease. CONCLUSION: The histone deacetylase inhibitor TSA can regulate the balance of Th17/Treg in asthma by regulating the activity of histone deacetylase.

Critical role of RIG-I-like receptors in inflammation in chronic obstructive pulmonary disease.

INTRODUCTION: Viral infection is a significant cause of chronic obstructive pulmonary disease (COPD) and acute exacerbation of COPD. Retinoic acid inducible gene I (RIG-I)-like receptors (RLRs), including RIG-I and melanoma differentiation associated gene 5 (MDA-5), are important pattern recognition receptors for viral elimination. OBJECTIVE: The study aims to investigate the role of RIG-I and MDA-5 in COPD pathogenesis. METHODS: We examined the expression of RIG-I and MDA-5 by immunohistochemistry, real-time PCR and Western blots in COPD patients and control subjects. RESULTS: Our results showed that MDA-5 expression was upregulated in lung tissues and peripheral blood mononuclear cells of COPD patients and there was a negative correlation between MDA-5 mRNA levels and forced expiratory volume in 1 s %pred. COPD patients had higher interleukin (IL)-1 and IL-8 mRNA expression levels, and these inflammatory cytokines positively correlate with MDA-5 levels. However, there was no difference in the expression of RIG-I between COPD patients and control subjects. CONCLUSION: Our results suggested that MDA-5, but not RIG-I, may play a critical role in airway inflammation in COPD.

A predictive model for the development of chronic obstructive pulmonary disease.

The screening of a person at risk for chronic obstructive pulmonary disease (COPD) and timely treatment may provide opportunities to delay the progressive destruction of lung function. Therefore, a model to predict the disease is required. We hypothesized that demographic and clinical information in combination with genetic markers would aid in the prediction of COPD development, prior to its onset. The aim of the present study was to create a predictive model for COPD development. Demographic, clinical presentation and genetic polymorphisms were recorded in COPD patients and control subjects. Nighty-six single-nucleotide polymorphisms of 46 genes were selected for genotyping in the case-control study. A predictive model was produced using logistic regression with a stepwise model-building approach and was validated. A total of 331 patients and 351 control subjects were included. The logistic regression identified the following predictors: Gender, respiratory infection in early life, low birth weight, smoking history and genotype polymorphisms (rs2070600, rs10947233, rs1800629, rs2241712 and rs1205). The model was established using the following formula: COPD = 1/[1 + exp (-2.4933-1.2197 gender + 1.1842 respiratory infection in early life + 2.4350 low birth weight + 1.8524 smoking - 1.1978 rs2070600 + 2.0270 rs10947233 + 1.1913 rs10947233 + 0.6468 rs1800629 + 0.5272 rs2241712 + 0.4024 rs1205)] (when the value is >0.5). The Hosmer-Lemeshow test showed no significant deviations between the observed and predicted events. Validation of the model in 50 patients showed a modest sensitivity and specificity. Therefore, a predictive model based on demographic, clinical and genetic information may identify COPD prior to its onset.

[An epidemiological survey on management and insights of asthma in China in 2009 to 2010].

OBJECTIVE: Through the analysis of relevant data of China Asthma and Risk factors Epidemiologic investigation (CARE study), we understand the status quo of management and insights of asthma patients in our country. METHODS: Using multi-stage random cluster sampling method, epidemiological survey was performed on the prevalence rate in 8 provinces (cities) of China residents who aged over 14 years from 2009 to 2010. Detailed epidemiological data was collected via face-to-face home visit interview among 2 034 asthmatics who were diagnosed in the last epidemiology survey. Asthma was diagnosed based upon case history, clinical signs and lung function test. The SPSS12.0 software was conducted for statistical analysis and the status of asthma control was investigated. RESULTS: This survey has shown that 22.71% (462/2 034) asthmatics had ever taken a lung functional test in the past year. A total of 294 (14.45%) people had peak flow meters but only 1.62% (33/2 034) regularly used it daily. There were 22.42% (456/2 034) asthmatics aware that bronchial asthma is characterized by chronic airway inflammation. 14.85% (302/2 034) asthmatics understood that the treatment goal of this disease is long-term good control or complete control. This survey has found that 59.64% (1 213/2 034) patients complained that asthma has affected their work, life and entertainment, including 8.90% (181/2 034) asthmatics dependent on instruments in daily life and 4.57% attempting to suicide. This suggested that allergic asthma has seriously decreased the quality of life. CONCLUSION: Therefore it is necessary to educate the asthmatics, guide the patients to the long-term management and standardized therapy and raise the level of disease understanding, thus reducing the burden of disease to society. Gaining better insight of patient's attitude about self-care is critical to the improvement of asthma management.

Associations of three well-characterized polymorphisms in the IL-6 and IL-10 genes with pneumonia: a meta-analysis.

Published data on the associations between three well-characterized polymorphisms in the interleukin 6 and 10 (IL-6 and IL-10) genes and the risk of pneumonia are inconclusive. A meta-analysis was performed to derive a more precise estimate. The electronic databases MEDLINE (Ovid) and PubMed were searched from the earliest possible year to May 2014. A total of 9 articles met the criteria, and these included 3460 patients with pneumonia and 3037 controls. The data were analyzed with RevMan software, and risk estimates are expressed as odds ratios (ORs) and 95% confidence intervals (95% CIs). Analyses of the full data set failed to identify any significant association of pneumonia risk with the IL-6 gene -174C allele (OR = 1.00; 95% CI: 0.98-1.03), the IL-10 gene -592C allele (OR = 1.20; 95% CI: 0.95-1.52), or the IL-10 gene -1082A allele (OR = 1.21; 95% CI: 0.99-1.49). In a subgroup analysis by pneumonia type, ethnicity, sample size and quality score, no significantly increased risk of pneumonia was found for individuals carrying the IL-6 gene -174C allele. There was a low probability of publication bias, as reflected by the fail-safe number. This meta-analysis suggests that there is no significantly increased risk of pneumonia associated with previously reported IL-6 and IL-10 polymorphisms.

[An epidemiological survey of current asthma control status in China].

OBJECTIVE: Base on the China asthma and risk factors epidemiologic investigation (CARE study), we analyzed the current status of asthma control in China. METHODS: With the multi-stage random cluster sampling method, epidemiological survey was performed among Chinese residents who aged over 14 years in 8 provinces (cities) from 2010 to 2011. Detailed clinic data of 2 034 asthma patients were collected via face-to-face home visit . Asthma was diagnosed based upon the history, clinical signs and lung function tests. The SPSS 12.0 was conducted for statistics analysis. RESULTS: This survey found that the prevalence rate of asthma in China was 1.24% (2 034/164 215), including 973 male and 1 061 female patients, with a mean age of (56 ± 18) years old. Consistent with the Global Initiative for Asthma (GINA) guidelines, 40.51% (824/2 034) and 42.58% (866/2 034) of our patients achieved control and partial control, respectively. According to the asthma control test (ACT) estimates, 15.63% (318/2 034) and 49.46% (1 006/2 034) of patients achieved full control (ACT 25) and well control(ACT 20-24), respectively. In the past year, 22.62% (460/2 034) of patients reported hospitalized and 26.99% (549/2 034) of patients reported emergency room visit at least one time due to asthma exacerbation. 61.80% (1 257/2 034) of patients were on daily us of medication. Inhaled corticosteroids (ICS) plus a long-acting ß2 agonist (LABA) or solely ICS were used in 6.39% and 14.75% of patients, respectively. Theophylline treatment accounted for 29.11% (592/2 034). Oral glucocorticoid and oral leukotriene modifier (LTRA) treatment accounted for 9.49% (193/2 034) and 3.10% (63/2 034), respectively. According to the survey, 34.51% (702/2 034) of asthma patients reported a history of smoking . The percentage of asthma control in non smoking patients was higher than in smoking patients [43.24% (576/1 332) and 35.33% (248/702), respectively]. Meanwhile, the rates of both hospitalization and emergency due to asthma exacerbation in smoking asthma patients were significantly higher than nonsmoking asthma patients (27.35% and 31.77%, 20.12% and 24.47%, respectively). CONCLUSIONS: The situation of asthma control has been improved in China. However, compared with GINA guidelines, there is still a considerable gap. Smoking is one of the crucial factors that affect asthma control.

Correlation between group behavior and quorum sensing in Pseudomonas aeruginosa isolated from patients with hospital-acquired pneumonia.

BACKGROUND: This study investigated the correlation between the expression of the Las and Rhl quorum-sensing (QS) systems and the communal behavior (motility, biofilm formation, and pyocyanin production) of Pseudomonas aeruginosa (P. aeruginosa) isolated from patients with hospital-acquired pneumonia. METHODS: We analyzed 138 P. aeruginosa isolates from 48 patients (30 men and 18 women; age 68.18±15.08 years). P. aeruginosa clinical isolates were assessed for Las and Rhl gene expression and bacterial motility, biofilm formation, and pyocyanin production. RESULTS: P. aeruginosa swimming, twitching, and swarming motility positively correlated with the expression of LasI, LasR, and RhlI (P<0.05) but not with that of RhlR (P>0.05). At all analyzed time points, a significant positive correlation was found between biofilm formation and the expression of LasI, LasR (P<0.01), and RhlI (P<0.05 for day 1, P<0.01 for days 7 and 14), whereas RhlR expression positively correlated with biofilm formation only on day 14 (P<0.05). On days 1 and 7, positive correlation was observed between pyocyanin production and the levels of LasI and RhlI (P<0.05). In bacterial clearance cases, the expression of QS-related genes and the group behavior of the pathogen did not correlate (P>0.05). However, in cases of persistent P. aeruginosa infection, the changes in LasI and LasR gene expression were positively correlated with those in bacterial motility (P<0.05), and the changes in LasI, LasR, RhlI, and RhlR expression showed a significant positive association with those in biofilm formation (P<0.01). CONCLUSIONS: In patients with hospital-acquired pneumonia, the expression of the Las and Rhl QS genes was associated with bacterial motility, biofilm formation, and pyocyanin production, suggesting an involvement of the QS genes in the clearance of pathogenic P. aeruginosa in patients.

Clinicopathological and demographical characteristics of non-small cell lung cancer patients with ALK rearrangements: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aimed to comprehensively examine the relationship between the clinicopathological and demographical characteristics and ALK rearrangements in patients with non-small cell lung cancer (NSCLC). METHODS AND MAIN FINDINGS: In total, 62 qualified articles including 1178 ALK rearranged cases from 20541 NSCLC patients were analyzed, and the data were extracted independently by two investigators. NSCLC patients with ALK rearrangements tended to be younger than those without (mean difference: -7.16 years; 95% confidence interval (95% CI): -9.35 to -4.96; P<0.00001), even across subgroups by race. Compared with female NSCLC patients, the odds ratio (OR) of carrying ALK rearrangements was reduced by 28% (95% CI: 0.58-0.90; P = 0.004) in males, and this reduction was potentiated in Asians, yet in opposite direction in Caucasians. Likewise, smokers were less likely to have ALK rearrangements than never-smokers (OR = 0.33; 95% CI: 0.25-0.44; P<0.00001), even in race-stratified subgroups. Moreover, compared with NSCLC patients with tumor stage IV, ALK rearrangements were underrepresented in those with tumor stage I-III (OR = 0.58; 95% CI: 0.44-0.78; P = 0.0002). Patients with lung adenocarcinomas had a significantly higher rate of ALK rearrangements (7.2%) than patients with non-adenocarcinoma (2.0%) (OR = 2.25; 95% CI: 1.54-3.27; P<0.0001). CONCLUSION: Our findings demonstrate that ALK rearrangements tended to be present in NSCLC patients with no smoking habit, younger age and tumor stage IV. Moreover, race, age, gender, smoking status, tumor stage and histology might be potential sources of heterogeneity.

Expression of suppressor of cytokine signaling 1 in the peripheral blood of patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive diffuse parenchymal disease with a poor prognosis. A variety of cytokines and chemokines are involved in its pathophysiology. The aim of this study was to evaluate the clinical features in IPF patients with the expression of suppressor of cytokine signaling 1 (SOCS-1), which acts as a negative regulator of cytokine signaling. METHODS: IPF patients (n = 20) and healthy controls (n = 16) were included in this study. The expression of SOCS-1 was analyzed in peripheral blood mononuclear cells (PBMC) of subjects using RT-PCR. Interleukin 4 (IL-4), transforming growth factor ß1 (TGF-ß1) and type I collagen expression were also analyzed in each individual using enzyme-linked immunosorbent assay (ELISA). The clinical characteristics of IPF patients were delineated. These results were analyzed by SPSS13.0 statistics software. RESULTS: SOCS-1 mRNA expression was significantly decreased in the PBMC of IPF patients compared with healthy controls; serum levels of IL-4 and TGF-ß1 were higher in IPF patients. The patients with lower expression of SOCS-1 developed lower percentage of forced vital capacity (FVC%) and DLCO/VA. A patients' SOCS-1 mRNA level was negatively correlated with serum levels of IL-4, and negatively correlated with their high-resolution computed tomography (HRCT) scores. CONCLUSIONS: SOCS-1 mRNA can be detected in PBMC, and it is down-regulated in IPF patients. The expression of SOCS-1 is associated with the severity of IPF patients' symptoms, so it might be the predictor of disease severity. SOCS-1 might play an important role in IPF by reducing the expression of the T helper type 2 (Th2) cell-related cytokine IL-4.

[Risk factors of bronchial asthma among people aged over 14 years in China].

OBJECTIVE: To survey the risk factors of asthma among the people aged over 14 years in China. METHODS: Home visits for completing epidemiological questionnaires in accordance with stratified cluster random sampling survey were conducted in 8 provinces (cities) of China residents aged over 14 years from February 2010 to August 2011. Asthma was diagnosed based upon case history, clinical signs and lung function test. The SPSS 12.0 software was used for statistic analyses for the epidemiological status of asthma. RESULTS: Sampling population was composed of 180 099 subjects. Among 164 215 valid questionnaires, there were 79 692 males and 84 523 females, 2 034 had asthma. The overall prevalence rate was 1.2% (2 034/164 215). Correlation analyses showed that the risk factors were smoking (OR = 1.697, 95%CI: 1.547-1.861), breast feeding (OR = 0.801, 95%CI: 0.670-0.959), genetics (OR & 95%CI >1, asthma (OR = 10.440, 95%CI: 8.991-12.112)), complications (OR & 95%CI >1), body mass index (compared with normal weight, overweight (OR = 1.360, 95%CI: 1.212-1.531), obesity (OR = 10.631, 95%CI: 9.570-11.801)) and petting (OR & 95%CI >1). CONCLUSION: Among Chinese asthmatics aged over 14, their risk factors include host (genetics & obesity) and environmental (smoking, breastfeeding, complications & pets) factors.

Deubiquitination and stabilization of T-bet by USP10.

The T-box transcriptional factor T-bet is crucial in the development, differentiation and function of Th1 cells. It drives Th1 immune response primarily through promoting expression of Th1 hallmark cytokine IFN-γ. Although T-bet was found associated with many immune-mediated diseases such as asthma and systemic sclerosis, little is known about the regulation of T-bet stability and function. Here we identified USP10, a carboxyl-terminal ubiquitin-processing protease, could interact with T-bet in the nucleus. Overexpression of USP10 directly inhibited T-bet ubiquitination and increased the expression of T-bet. We further confirmed Quercetin, a reported inhibitor of T-bet, could target USP10. Quercetin treatment downregulated USP10 and promoted T-bet degradation in a proteasome dependent way. Moreover, we found USP10 expression was upregulated in asthmatic patient PBMC, suggesting USP10 may maintain high level of T-bet and IFN-γ to fight against Th2-dominated inflammation.