KIF18B as a regulator in microtubule movement accelerates tumor progression and triggers poor outcome in lung adenocarcinoma.

KIF18B is involved in several tumor progression and exerts critical effects on microtubule growth during mitosis, but its role in lung adenocarcinoma still remains rare. Hence, we attempted to explore the biological function of KIF18B in lung adenocarcinoma. We first analyzed the expressional pattern of KIF18B in lung adenocarcinoma, and detected the correlation between KIF18B expression and clinical characteristics in lung adenocarcinoma based on The Cancer Genome Atlas (TCGA) database and Oncomine dataset. Subsequently, cell counting kit-8 (CCK-8) assay, wound-healing analysis, and transwell method were performed to assess the effects of KIF18B in lung adenocarcinoma cells. Quantitative real-time reverse transcription-PCR (qRT-PCR) and western blotting were utilized to measure the mRNA and protein expression levels. Our results illustrated that KIF18B expression was significantly up-regulated in lung adenocarcinoma samples compared to normal specimens. High levels of KIF18B were associated with unfavorable prognosis of lung adenocarcinoma patients. Down-regulation of KIF18B in lung adenocarcinoma cells inhibited cell prolifartion, migration, and invasion. Western blot assay demonstrated that KIF18B knockdown markedly decreased Rac1-GTP expression, an important marker of migration and invasion in tumors. Moreover, the phosphorylation of AKT and mTOR expression levels were attenuated after KIF18B knockdown. Taken together, these data enhanced the point that KIF18B might promote lung adenocarcinoma cell proliferation, migration, and invasion by activating Rac1 and mediating the AKT/mTOR signaling pathway.

[The prevalence and risk factors of bronchiectasis in residents aged 40 years old and above in seven cities in China].

OBJECTIVE: To investigate the prevalence and risk factors of bronchiectasis in urban city of China. METHODS: A cross-sectional survey was conducted in 17 urban areas in Beijing, Shanghai, Tianjin, Chongqing cities, and Guangdong, Liaoning, Shanxi provinces. In this study, urban population-based cluster samples were randomly selected from each city/province. In the selected city communities, all residents at least 40 years old were recruited, interviewed with questionnaires and tested with spirometry. Each participant was asked whether he/she was ever diagnosed as bronchiectasis by physician, whether had symptoms of respiratory diseases and possible risk factors, etc. RESULT: Data of 10 811 participants was enrolled for analysis, with a response rate of 75.4% (10 811/14 337). The overall prevalence of physician-diagnosed bronchiectasis was 1.2% (135/10 811), with 1.5% (65/4382) in male and 1.1% (70/6429) in female, without statistical difference in gender (χ² = 3.289, P = 0.070). Prevalence of bronchiectasis increased with age (χ² = 31.029, P < 0.001). There were no statistical significances in crude prevalences of bronchiectasis among cities (χ² = 10.572, P = 0.103), while there was a significant difference among cities after adjustment with confounders (Wald value = 22.116, P = 0.001), by using logistic regression analysis. Logistic regression analysis showed, bronchiectasis was significantly associated with elder ( ≥ 70 years vs 40-49 years; OR = 4.11, 95% CI 2.29-7.36), the family history of respiratory diseases (having two subjects with respiratory diseases in family vs no suffered relatives; OR = 2.04, 95% CI 1.06-3.94), respiratory infection during childhood (suffering two kinds of respiratory diseases vs never; OR = 4.89, 95% CI 2.03-11.81), exposure to coal (OR = 2.30, 95% CI 1.17-4.52), chronic pharyngitis (OR = 3.96, 95% CI 1.38-11.40) and pulmonary tuberculosis (OR = 3.07, 95% CI 1.89-4.98), heart diseases (OR = 1.64, 95% CI 1.11-2.42) and lung cancer(OR = 18.61, 95% CI 7.67-45.18). CONCLUSION: The prevalence of bronchiectasis in population aged 40 years old and above in urban area in China is high and associated with multiple factors such as age, family history of respiratory diseases, respiratory infection during childhood, exposure to coal, chronic pharyngitis, pulmonary tuberculosis, heart diseases, lung cancer and so on.

Asymptomatic patients of chronic obstructive pulmonary disease in China.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has a variable natural history and not all individuals follow the same course. This study aimed to identify the prevalence and characteristics of asymptomatic COPD patients from a population-based survey in China. METHODS: A multistage cluster sampling strategy was used in a population from seven different provinces/cities. All residents (over 40 years old) were interviewed with a standardized questionnaire and spirometry. Post-bronchodilator forced expiratory volume in 1 second (FEV(1))/forced vital capacity (FVC) of less than 70% was defined as the diagnostic criterion of COPD. All COPD patients screened were divided into symptomatic group and asymptomatic group according to the presence or absence of chronic respiratory symptoms. Socio-demographic, personal and exposure variables were collected and analyzed. RESULTS: Among the 1668 patients who were diagnosed with COPD from the 25 627 sampling subjects, 589 (35.3%) were asymptomatic. The age, sex, body mass index (BMI), rural and urban distributions, smoking habit and education levels were similar in the two groups. A total of 64.7% of the asymptomatic patients had no comorbidities. Cardiovascular diseases and lung cancer were more common among symptomatic COPD patients than asymptomatic group. Asymptomatic COPD group were less likely to present with poor ventilation in the kitchen, a family history of respiratory disease and recurrent childhood cough. Asymptomatic COPD patients had significantly higher FEV(1) (73.1% vs. 61.0%), FVC (91.9% vs. 82.0%), and a higher ratio of FEV(1)/FVC (62.9% vs. 58.7%) (all P < 0.001) than symptomatic group. More asymptomatic patients were underdiagnosed (91.9% vs. 54.3%, P < 0.001) than symptomatic patients. CONCLUSIONS: This large population-based survey confirmed a high prevalence of asymptomatic COPD patients in China. More use of spirometry screening test may be important to the early detection of COPD.

[Current status of prevention and management of chronic obstructive pulmonary disease in rural area in China].

OBJECTIVE: To investigate the current status of prevalence, prevention and management of chronic obstructive pulmonary disease (COPD) in rural area in China. METHODS: A cross-sectional survey of COPD was conducted in Beijing city, Shanghai city, Guangdong province, Liaoning province, Tianjin city, Chongqing province and Shanxi province. A population-based cluster sample was randomly selected from each rural area. In the selected community, all residents at least 40 years old were recruited, and interviewed with a modified standardized questionnaire from the international burden of obstructive lung diseases (BOLD) study. All participants were tested with spirometry. Those with airflow limitation were performed on post-bronchodilator spirometry. The post-bronchodilator a ratio of forced expiratory volume in one second to forced vital capacity (FEV1/FVC) less than 70% was defined as the diagnostic criteria of COPD. RESULTS: (1) Data of 9434 participants was valid for analysis, with a valid response rate of 83.6%; the prevalence of COPD in rural was 8.8% (830/9434), 12.8% in male and 5.4% in female. (2) The percentage of smoking and the exposure to biomass smoke in rural was 43.0% (4059/9434) and 83.1% (7835/9434) respectively; cigarettes cessation rate was 17.5%; only 12.4% (502/4059) of smokers had received advice to quit smoking. (3) Among COPD patients, only 30.0% (249/830) had ever been diagnosed as COPD, bronchitis, emphysema, or asthma, 2.4% (20/830) had ever received spirometric tests, and 74.5% were current smokers; only 7.9% (50/634) COPD patients in stage two or over had received regular drug treatment. CONCLUSION: There was high prevalence and poor prevention and management for COPD in rural areas. Therefore, an enforced prevention and management for COPD are urgent.

[The quality of life of patients with chronic obstructive pulmonary disease and correlated factors].

OBJECTIVE: To evaluate the quality of life (QOL) of patients with chronic obstructive pulmonary disease (COPD) and correlated factors. METHODS: Data of 20 245 patients with COPD were collected from the cross-sectional survey of COPD, which was conducted between 2002 and 2004 in urban and rural areas of Beijing, Shanghai, Guangdong, Liaoning, Tianjin, Chongqing and Shanxi for residents aged over 40 years old. The recruited populations were interviewed with questionnaire and tested for spirometry. The quality of life was assessed with 12-item short-form health survey questionnaire (SF-12). Those with less than 70% of post-bronchodilator FEV(1)/FVC were identified as having COPD. The differences between groups in SF-12 scores converted by rank were compared using general linear model. Stepwise multiple linear regressions were conducted to study the main determinants of QOL. RESULTS: Compared to subjects without COPD, those with COPD had impaired QOL (56 +/- 7 vs. 57 +/- 6 in mental component scores, F = 4.442, P < 0.05; 46 +/- 9 vs. 50 +/- 6 in physical component scores, F = 453.960, P < 0.05). Among COPD patients, the mental component score was associated with scores of dyspnea, BMI, comorbidities, sex and living areas, while the physical component score was associated with scores of dyspnea, severity of COPD, comorbidities, exposure to dusts/gases/fumes, sex, age, educational level and previous diagnosis of respiratory diseases (all P < 0.05). CONCLUSIONS: The QOL in patients with COPD was impaired and associated with scores of dyspnea, severity of COPD, comorbidities and BMI. Improvement of dyspnea, nutritional support, prevention of comorbidities and keeping away from risk factors may improve the QOL in COPD patients.

[A study on the correlation of body mass index with chronic obstructive pulmonary disease and quality of life].

OBJECTIVE: To investigate the correlation between body mass index (BMI) and chronic obstructive pulmonary disease (COPD), based on a cross-sectional COPD survey conducted in Beijing, Shanghai, Guangdong, Liaoning, Tianjin, Chongqing and Shaanxi of China between 2002-2004. METHODS: A multi-stage stratification cluster sampling strategy was used in this cross-sectional survey, and 20,245 subjects (8705 males and 11,540 females) aged 40 years or older were recruited, interviewed with a questionnaire, measured for height and weight, and tested with spirometry. 1668 subjects with post-bronchodilator FEV1/FVC less than 70% were identified as having COPD after other known causes of airflow limitation were excluded. Analysis on relationship between COPD and BMI was performed in 1668 COPD and 18 577 non-COPD subjects. RESULTS: Compared with non-COPD subjects, BMI was significantly lower in COPD patients [(22.7+/-3.5) vs (24.1+/-3.4) kg/m2, F=158.31, P<0.01]; BMI was also significantly lower in smokers than in non-smokers [(23.6+/-3.4) vs (24.2+/-3.5) kg/m2, F=49.10, P<0.01]. And an addictive interaction to BMI between COPD and smoking was observed (F=6.03, P<0.05). BMI decreased with the increase of the stage of COPD (F=45.6, P<0.01), with a negative relationship (r=-0.08, P<0.01). Lower BMI was significantly associated with increased risk of COPD (chi2=102.68, P<0.01). Compared with subjects with normal BMI (BMI=24.0-27.9 kg/m2), those with lower BMI (BMI<18.5 kg/m2) were more likely to have COPD [adjusted OR=2.12 (95% CI 1.73-2.59)], while those with higher BMI (BMI=24.0-27.9 kg/m2) and obesity (BMI>or=28.0 kg/m2) were less likely to have COPD [adjusted OR=0.67 (95% CI 0.59-0.76); and 0.60 [(95% CI 0.49-0.73), respectively]. Moreover, there was an interaction to COPD between smoking and BMI (chi2=4.73, P<0.05). Compared with COPD patients with normal BMI, the quality of life in those with lower BMI was impaired (55+/-8 vs 57+/-6 in mental scores of SF-12, F=2.96, P<0.05; 42+/-10 vs 46+/-9 in physical scores of SF-12, F=4.21, P<0.01), and their dyspnea scores were higher (1.4+/-1.5 vs 1.1+/-1.3, chi2=14.32, P<0.01). CONCLUSION: Lower BMI was strongly associated with COPD, possibly as a risk factor for COPD independent of smoking, and a potential predictor for COPD severity.

[The risk factors for chronic obstructive pulmonary disease in females in Chinese rural areas].

OBJECTIVE: To explore the risk factors for chronic obstructive pulmonary disease (COPD) in females in Chinese rural areas. METHODS: Based on a national multi-center, population-based and cross-sectional survey on prevalence of COPD in seven provinces/cities of China, an analysis on the risk factors for the rural females was conducted in six areas, e.g. Beijing, Shanghai, Guangdong, Liaoning, Tianjin and Shanxi. In the national survey, for each area, one rural and one urban cluster samples were randomly selected using a multi-stage strategy. Residents who were 40 years old or older were interviewed with questionnaires and tested with spirometry. The post-bronchodilators forced expired volume in one second to forced vital capacity ratio (FEV(1)/FVC) x 100% < 70% was used as diagnostic criteria of COPD. RESULTS: The average prevalence of COPD in females in the six Chinese rural areas was 5.4%. The prevalence varied with risk factor exposure among different areas, and the prevalence in Guangdong province was the highest among all areas. Logistic regression model was conducted, and statistical association of COPD was found with a family history of respiratory diseases (OR = 2.46, 95% CI = 1.86 - 3.26), frequent coughing during childhood (frequent coughing vs never coughing: OR = 3.93, 95% CI = 2.02 - 7.63), lower body mass index (lower body mass index vs normal body mass index: OR = 2.20, 95% CI = 1.47 - 3.29), age (70 years or older vs 40 - 49 years: OR = 8.98, 95% CI = 5.90 - 13.67), smoking (OR = 1.68, 95% CI = 1.20 - 2.35), exposure to occupational dusts (OR = 1.45, 95% CI = 1.07 - 1.96), worse ventilation in kitchen room (OR = 1.47, 95% CI = 1.06 - 2.03) and lower educational level (OR = 2.19, 95% CI = 1.38 - 3.46). CONCLUSION: The prevalence of COPD in females in rural areas was associated with multiple factors and prevention of COPD for Chinese women in rural areas is warranted.

[Cost analysis of Shenqi Fuzheng injection on reducing adverse effects during chemotherapy].

OBJECTIVE: The goals of this work was to analyse the cost of Shenqi Fuzheng injection-an extraction of a Chinese traditional herbs on reducing adverse effects in lung cancer patients during chemotherapy. METHODS: In a randomized cross-over trial, each patient completed two identical cisplatin-based chemotherapy cycles, one with Shenqi Fuzheng injection, another without Shenqi Fuzheng injection. Adverse effects and change scores of quality of life (QOL) during chemotherapy were compared in tow cycles. The direct cost dealing with adverse effect and cost-effectiveness analysis were taken. RESULTS: One hundred and thirty were enrolled with 123 of whom were evaluable. The patient characteristics were well balanced between the two groups. The chemotherapy cycles with Shenqi Fuzheng injection spent 220.5 more Chinese yuan, but the adverse effect of leukopenia, thrombocytopenia and vomiting were slight different and the change of score of several QOL domains showed significant better as compared to those in another cycle. CONCLUSION: Shenqi Fuzheng injection could reduce the severity of toxicity related to chemotherapy and improve the QOL of patients and had some benefits in terms of cost-effectiveness.

[Purification and characterization of the fusion protein TGF-betaR II/Fc].

AIM: To express the fusion protein TGF-betaR II/Fc in large amounts by using recombinant Bac-TR II baculovirus expression system constructed by our laboratory and to purify and characterize it. Then, to verify whether the fusion protein TGF-betaR II/Fc can be able to block the biological activity of cytokine TGF-beta1. METHODS: The viral titer was determined by plaque forming test. The recombinant baculovirus was amplified by infecting sf9 cells. The fusion protein was purified by FPLC using protein G column. The purified product was analyzed by SDS-PAGE and the amount of target protein calculated by gray scanning. Western blot and sandwich ELISA were used to affirm the expression of the fusion protein. MTT colorimetry was used to test whether the fusion protein can block the inhibition effect of cytokine TGF-beta1 on the growth of L929 cells. It was to verify whether the fusion protein can reduce the fibronectin production in L929 cells accelerated by TGF-beta1 by western blot. RESULTS: The titer of recombinant Bac-TR II baculavirus in the primary culture fluid was 2x10(12) pfu/L. After electrophoresis, gray scanning analysis showed that the target protein accounted for 10 percent of the total protein. Western blot analysis and sandwich ELISA detection proved that the target protein has been expressed. The fusion protein could block the inhibitive effect of cytokine TGF-beta1 on the growth of L929 cells and fibronectin production in L929 cells. CONCLUSION: The fusion protein TGF-betaR II/Fc can inhibit the biological activity of TGF-beta1 in-vitro. This study will be helpful to the mass production of the fusion protein, and will facilitate its further use in the therapy of pulmonary fibrosis.