Surfactant Protein A Polymorphism Is Associated with Susceptibility to Chronic Obstructive Pulmonary Disease in Chinese Uighur Population / 华中科技大学学报（医学）（英德文版）

This study investigated the correlation between surfactant protein-A (SP-A) polymorphism and the susceptibility of chronic obstructive pulmonary disease (COPD) in Xinjiang Uighurs.Genomic DNA was extracted from peripheral blood of 194 COPD smokers and 201 healthy smokers of Uighur who were hospitalized in or paid a visit to one of the four Xinjiang-based hospitals involved in the study,from March 2009 to December 2010.Single nucleotide polymorphisms (SNPs) were studied at aa62 (CCA/CCG rs 1136451) and aa219 (CGG/rGG,rs4253527) in SP-A.Genotypes were determined by using the TaqMan polymerase chain reaction (PCR).Our results showed that genotype frequencies were different between the COPD and normal smokers in aa62 (x2=6.852,P=0.033).There were also significant differences in allele genotype frequencies between the COPD and the control and allele G might decrease the risk COPD (x2=6.545,P=0.011; OR=0.663; 95％ CI:0.484-0.909).The result suggested that polymorphism of aa62 (CCA/CCG,rs1136451) of SP-A may be associated with the susceptibility to COPD in Xinjiang Uighurs.

Comparative Study on the Efficacy of Tiotropium Bromide Inhalation and Oral Doxofylline Treatment of Moderate to Severe Stable Chronic Obstructive Pulmonary Disease / 华中科技大学学报（医学）（英德文版）

This study compared the efficacy and safety of tiotropium bromide inhalation powder (spiriva) and doxofylline oral tablet (doxofylline) in the treatment of chronic obstructive pulmonary disease (COPD).A multi-center,randomized,double-blind,double-dummy,parallel-controlled study involved 127 eligible stable moderate to severe COPD patients treated with inhaled tiotropium dry powder (18 μg/day) or oral doxofylline tablets (0.2 g/time,2 times a day) for 12 and 24 weeks.Before and after treatment for 12 weeks and 24 weeks,respectively,pulmonary function,6-min walking distance and dyspnea index were recorded.The results showed that in both tiotropium group and doxofylline groups,after 12-week treatment,FEV1,FEV1/FVC％ and 6-min walk distance were significantly higher than those before the medication,while dyspnea index decreased as compared with that before treatment.After 24-week treatment,a slight improvement in the measures was observed as compared with that of 12-weeks treatment,but the difference was not statistically significant.With both 12-week and 24-week treatment,the effect of tiotropium was slightly better than that of doxofylline tablets,with the difference being statistically insignificant.The major adverse events in the tiotropium group and doxofylline group were observed in 9 cases (9.9％) and 12 cases (12.9％),respectively,and no statistically significant difference was found between them.We are led to conclude that both tiotropium at 18 μg a day and doxofylline tablets at 0.2 g/day (two times a day) are effective and safe for the treatment of COPD.

Changes of Protein Kinase Cα and Cyclin D1 Expressions in Pulmonary Arteries from Smokers with and without Chronic Obstructive Pulmonary Disease / 华中科技大学学报（医学）（英德文版）

The purpose of this study was to investigate the changes of protein kinase Cα(PKCα)and cyclin D1 expressions in pulmonary arteries from smokers with normal lung function and smokers with mild to moderate chronic obstructive pulmonary disease(COPD).The peripheral lung tissues were obtained from 10 non-smokers with normal lung function(non-smoker group),14 smokers with normal lung function(smoker group),11 smokers with mild to moderate COPD(COPD group).The morphological changes of pulmonary arteries were observed by HE-staining.The expressions of α-smooth muscle actin(α-SMA),proliferating cell nuclear antigen(PCNA),PKCα and cyclin D1 proteins in pulmonary artery smooth muscle cells(PASMCs)were immunohistochemically determined.The percentages of PCNA-positive cells were taken as the smooth muscle cells proliferation index(PI).The mRNA expressions of PKCα and cyclin D1 in PASMCs were evaluated by real-time fluorescence PCR.Morphometrical analysis showed that the ratio of pulmonary artery wall area to total area(WA%)in smoker group and COPD group was significantly greater than that in non-smoker group(P<0.01).The PASMCs proliferation index in smoker group and COPD group was significantly higher than that in nonsmoker group(P<0.01).The protein levels of PKCα and cyclin D1 in PASMCs were significantly increased in smoker group and COPD group as compared with non-smoker group(P<0.01).The mRNA expressions of PKCa and cyclin D1 in PASMCs were significantly elevated in smoker group and COPD group as compared with non-smoker group(P<0.01).Significant correlations were found between PKCα protein and WA% or PI(P<0.01).Correlations between cyclin D1 protein and WA% or PI also existed(P<0.01).The expression of PKCα was positively correlated with the expression of cyclin D1 at both protein and mRNA levels(P<0.01).In conclusion,increased expressions of PKCα and cyclin D1 might be involved in the pathogenesis of abnormal proliferation of PASMCs in smokers with normal lung function and smokers with mild to moderate COPD.