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Relationship between reduced nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox gene polymorphism and obstructive sleep apnea-hypopnea syndrome in the Chinese Han population

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Chinese Medical Journal 2009年第12期122卷 1369-1374页

作者： LIU Hui-guo LIU Kui ZHOU Yan-ning xu yong-jian Department of Respiratory Medicine Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Key Laboratory of Respiratory Disease Ministry of Health Wuhan Hubei 430030 China

Background Increased production of reactive oxygen species （ROS） is thought to play a major role in the pathogenesis of obstructive sleep apnea-hypopnea syndrome （OSAHS）. The reduced nicotinamide adenine dinucleotide phosphate （NADPH） oxidase complex is an important source of ROS. The p22phox subunit is polymorphic with a C242T variant that changes histidine-72 for a tyrosine in the potential heme binding site. This study aimed to investigate the relationship between NADPH oxidase subunit p22phox gene polymorphism and OSAHS. Methods The genotypes of p22phox polymorphism were determined by polymerase chain reaction-restriction fragment length polymorphisms （PCR-RFLP） assay in 176 unrelated subjects of the Han population in southern region of China （including 107 OSAHS subjects and 69 non-OSAHS subjects）, while the plasma concentration of superoxide dismutase （SOD） was detected in the two groups, and p22phox mRNA expression in peripheral blood mononuclear cell （PBMC） was determined with reverse transcription polymerase chain reaction （RT-PCR）. Results The phagocyte NADPH oxidase subunit p22phox mRNA expression was significantly increased in the OSAHS group than that in the non-OSAHS group （P 〈0.01）. Compared with the non-OSAHS control group （（85.31±9.23） U/ml）, the levels of SOD were lower in patients with OSAHS （（59.65±11.61） U/ml （P 〈0.01）. There were significant differences in genotypes distribution in p22phox polymorphism between the two groups （P=0.02）. Compared with the non-OSAHS control group, the OSAHS group had a significantly higher T allele frequency in p22phox polymorphism （P=0.03）. There were independent effects of p22phox polymorphism on body mass index （BMI）, neck circumference （NC）, waist-to-hip ratio （WHR） in the OSAHS group, and the carriers of the T allele of p22phox polymorphism had greater NC, WHR, systolic blood pressure （SBP）, diastolic blood pressure （DBP） and apnea-hypopnea index （AHI）（P 〈0.05）, but the carriers of the T allele had lower SOD

关键词： obstructive sleep apnea syndrome reduced nicotinamide adenine dinucleotide phosphate oxidase p22phox gene polymorphism

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Effect of intramuscular injection of hepatocyte growth factor plasmid DNA with electroporation on bleomycin-induced lung fibrosis in rats

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Chinese Medical Journal 2007年第16期120卷 1432-1437页

作者： LONG Xiang XIONG Sheng-dao XIONG Wei-ning xu yong-jian Institute of Pulmonary Disease Tongji Hospital Huazhong University of Science and Technology Wuhan 430030 China

Background So far, there is no efficient treatment for pulmonary fibrosis. The objective of this study was to determine whether intramuscular injection of the hepatocyte growth factor （HGF） pfasmid DNA by in vivo electroporation could prevent bleomycin-induced pulmonary fibrosis in rats, and to investigate the possible mechanisms. Methods Twenty male Wistar rats were randomly divided into four groups： control group （group C）, model group （group M）, early intervention group （group Ⅰ ） and late intervention group （groupⅡ）. Groups M, Ⅰ and Ⅱ were intratracheally infused with bleomycin, then injected the plasmid pcDNA3.1-hHGF to group Ⅰ on day 7, 14 and 21. Group Ⅱ received the same treatment like Group Ⅰ on day 14 and 21. All the rats were killed on day 28 after bleomycin injection. We detected Homo HGF expression in the rats with ELISA method and estimated the pathological fibrosis score of lung tissue using hematoxylin eosin （HE） and Massion staining. The mRNA expression of transforming growth factor-β1 （TGF-β1）, cycloxygenase-2 （COX-2）, and rat HGF in rat pulmonary parenchyma were evaluated by RT-PCR. Immunohistochemistry and Western blotting were performed to determine the protein expression of transforming TGF-β1 and COX-2 in lung parenchyma. Results The plasmid pcDNA3.1-hHGF could express hHGF in NIH3T3 cells and the hHGF protein is secreted into the culture medium. The expression of hHGF protein could be monitored in quadriceps muscle, plasma and lung in Groups Ⅰ and Ⅱ. Pulmonary fibrosis levels of Groups Ⅰ and Ⅱ were obviously lower than that of group M （P〈0.05）. Expression of TGF-β1 protein and mRNA in lung tissue was markedly decreased in Groups Ⅰ and Ⅱ compared with Group M （P〈0.05）. The level of expression of HGF and COX-2 mRNA was higher in Groups Ⅰ and Ⅱ than in Group M （P〈0.05）. Conclusions Injection of the plasmid pcDNA3.1-hHGF into skeletal muscle with electroporation has a potential role in the treatment of bleomycin-induced lung fibrosis. Exog

关键词： pulmonary fibrosis hepatocyte growth factor electroporation gene therapy

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Cigarette smoke extract promotes human pulmonary artery smooth muscle cells proliferation through protein kinase C alpha-dependent induction of cyclin D1

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Chinese Medical Journal 2010年第24期123卷 3663-3670页

作者： XIANG Min xu yong-jian LIU Xian-sheng ZENG Da-xiong Department of Respiratory Medicine Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430030 Chin Department of Respiratory Medicine Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430030 China

Background Exposure to cigarette smoke stimulates the proliferation of human pulmonary artery smooth muscle cells （HPASMCs） in vivo and in vitro. However, the molecular mechanism remains unclear. This study aimed at investigating the role of signaling pathways involving protein kinase C alpha （PKCα） and cyclin D1 in the cigarette smoke extract （CSE）-induced HPASMCs *** Synchronized HPASMCs were treated with different concentrations of CSE. Cell proliferation was evaluated by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyttetrazolium bromide （MTT） assay and cell counting. Cell cycle was analyzed by flow cytometry with propidium iodide staining. Activation of PKCα was measured by detecting the expression of PKCαprotein in the cytosolic and membrane fractions using Western blotting analysis. Small interfering RNA （siRNA） was used to knockdown PKCα and cyclin D1. The cyclin D1 mRNA was assessed by real-time RT-PCR. The PKCα and cyclin D1protein levels were detected by Western *** Low concentrations of CSE （1%-10%） stimulated proliferation of HPASMCs, with its maximal effect at 5%.CSE （5%） led to PKCα activation. Inhibition of PKCα activity using G（o） 6976 or siRNA-mediated knockdown of PKCα significantly attenuated CSE-induced cell proliferation and G1/S transition. Cyclin D1, one of key regulators of G1/S transition, was found to be upregulated by 5% CSE at both the mRNA and protein levels. CSE-stimulated cellproliferation and G1/S transition was abolished by cyclin D1 siRNA. Moreover, G（o） 6976 or PKCα siRNA significantlysuppressed CSE-induced upregulation of cyclin D1 at both the mRNA and protein *** PKCα-cyclin D1 pathway at least partially mediates the CSE-induced proliferation in HPASMCs.

关键词： cell proliferation cell cycle protein kinase C cyclin D1

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Cigarette smoke extract promotes proliferation of airway smooth muscle cells in asthmatic rats via regulating cyclin D1 expression

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Chinese Medical Journal 2010年第13期123卷 1709-1714页

作者： ZHANG Xiao-yu xu yong-jian LIU Xian-sheng ZHANG Zhen-xiang Department of Respiratory Medicine Tongji Hospital Affiliated to Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430030 China Department of Respiratory Medicine Henan Provincial People's Hospital Zhengzhou Henan 450003 China

Background Increased proliferation of airway smooth muscle cells （ASMCs） are observed in asthmatic patients and smoking can accelerate proliferation of ASMCs in asthma. To elucidate the molecular mechanisms leading to these changes, we studied in vitro the effect of cigarette smoke extract （CSE） on the proliferation of ASMCs and the expression of cyclin D1, an important regulatory protein implicated in cell cycle. Methods ASMCs cultured from 8 asthmatic Brown Norway rats were studied. Cells between passage 3 and 6 were used in the study and were divided into control group, pcDNA3.1 group, pcDNA3.1-antisense cyclin D1 （ascyclin D1） group, CSE group, CSE＋pcDNA3.1 group and CSE＋pcDNA3.1-ascyclin D1 group based on the conditions for intervention. The proliferation of ASMCs was examined with cell cycle analysis, MTT colorimetric assay and proliferating cell nuclear antigen （PCNA） immunocytochemical staining. The expression of cyclin D1 was detected by reverse transcriptase-PCR （RT-PCR） and Western blotting. Results （1） The percentage of S＋G2M phase, absorbance value at 490 nm wavelength （A490） and the expression rate of PCNA protein in CSE group were （31.22±1.17）%, 0.782±0.221, （90.2±7.0）% respectively, which were significantly increased compared with those of control group （18.36±1.02）%, 0.521±0.109, and （54.1±3.5）%, respectively）（P 〈0.01）. After the transfection with antisense cyclin D1 plasmid for 30 hours, the percentage of S＋G2M phase, A490 and the expression rate of PCNA protein in ASMCs were much lower than in untreated cells （P 〈0.01）. （2） The ratios of A490 of cyclin D1 mRNA in CSE group was 0.288±0.034, which was significantly increased compared with that of control group （0.158±0.006）（P 〈0.01）. After the transfection with antisense cyclin D1 plasmid for 30 hours, the ratios of A49o of cyclin D1 mRNA in ASMCs was much lower than in untreated cells （P 〈0.01）. （3） The ratios of A490 of cyclin D1 protein expression in CSE group was 0.375±0.008, which was signifi

关键词： cigarette smoke extract asthma airway smooth muscle cells proliferation cyclin D1

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Analysis of the Cooling Water Temperature Rise of Accelerating Electrodes in EAST Neutral Beam Injector Beam Extraction

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Chinese Physics Letters 2013年第3期30卷 44-46页

作者： xu yong-jian HU Chun-Dong XIE Yuan-Lai LI Jun LIU Sheng XIE Ya-Hong YU Ling NBI Group Institute of Plasma Physics Chinese Academy of SciencesHefei 230031

Neutral beam injection is recognized as one of the most effective means of plasma *** preliminary data of beam power deposition in different electrodes during beam extraction are obtained on the EAST neutral beam injector test *** measurement of the cooling water temperature rise of accelerating electrodes is *** data given can guide the optimization of beam extraction parameters and decrease the damage to the accelerating electrodes following long pulse beam extraction.

关键词： injection damage neutral

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hOGG1 Ser326Cys and XRCC1 Arg399Gln polymorphisms associated with chronic obstructive pulmonary disease

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Chinese Medical Journal 2009年第8期122卷 960-966页

作者： YANG Shi-fang xu yong-jian XIE Jun-gang ZHANG Zhen-xiang Department of Respiratory Medicine Tongji Hospital Affiliated to Tongji Medical College Huazhong University of Science and Technology the State Key Laboratory Research on Respiratory Diseases Wuhan Hubei 430030 China

Background Cigarette-smoke induced DNA damage can cause airway cell apoptosis and death, which may be associated with the development of chronic obstructive pulmonary disease （COPD）. However, only 20%-30% of smokers develop COPD, suggesting that different degrees of DNA repair produce different outcomes in smokers, i.e., part of them develop COPD. We investigated the association between polymorphisms in DNA repair genes hOGG1 （Ser326Cys） and XRCC1 （Arg399GIn）, alone or in combination, and susceptibility of COPD. Methods Altogether 201 COPD patients and 309 controls were recruited and frequency-matched on age and sex. hOGG1 and XRCC1 genotypes were determined by PCR-restriction fragment length polymorphism analysis. Results The risk of COPD was not significantly different among individuals with Ser/Cys and Cys/Cys genotypes compared with those with hOGG1 Ser/Ser genotype. The risk of COPD was not significantly different among individuals with Gin/Gin genotype compared with those with XRCC1 Arg/Arg genotype, but it was significantly elevated among individuals with Arg/GIn genotype （adjusted odds ratios （OR）=1.55, 95% confidence intervals （CI） 1.05-2.29, P=0.029）. Assessment of smoking status in current smokers compared with those with hOGG1 Ser/Ser genotype revealed that the risk of COPD was significantly elevated among individuals with Cys/Cys genotype （adjusted OR=5.07, 95% CI 1.84-13.95, P=0.002）. Compared with those with XRCC1 Arg/Arg genotype, the risk of COPD was significantly elevated among individuals with Arg/GIn genotype （adjusted OR=2.77, 95% CI 1.52-5.07, P=-0.001）. Assessment of smoking exposure in light smokers compared with those with hOGG1 Ser/Ser genotype showed that the risk of COPD was significantly elevated among individuals with Cys/Cys genotype （adjusted OR=4.02, 95% CI 1.05-16.80, P=0.042）. Compared with those with XRCC1 Arg/Arg genotype, the risk of COPD was significantly elevated among individuals with Gin/Gin genotype （adjusted OR=4.48, 95% C

关键词： chronic obstructive pulmonary disease cigarette smoke DNA damage 8-oxoG DNA glycosylase 1 X-ray repair cross-complementing group 1

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Expression of Nitric Oxide Synthase Isoenzyme in Lung Tissue of Smokers with and without Chronic Obstructive Pulmonary Disease

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Chinese Medical Journal 2015年第12期128卷 1584-1589页

作者： Wen-Ting jiang Xian-Sheng Liu yong-jian xu Wang Ni Shi-Xin Chen Department of Respiratory Medicine Tongji Hospital Affiliated to Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei 430030 China

Background：It has been demonstrated that only 10%-20% cigarette smokers finally suffer chronic obstructive pulmonary disease （COPD）.The underlying mechanism of development remains uncertain so *** oxide （NO） has been found to be closely associated with the pathogenesis of COPD,the alteration of NO synthase （NOS） expression need to be *** study aimed to investigate the alterations of NOS isoforms expressions between smokers with and without COPD,which might be helpful for identifying the susceptibility of smokers developing into ***：Peripheral lung tissues were obtained from 10 nonsmoker control subjects,15 non-COPD smokers,and 15 smokers with *** NOS （nNOS）,inducible NOS （iNOS）,and endothelial NOS （eNOS） mRNA and protein levels were measured in each sample by using real-time polymerase chain reaction and Westem ***：INOS mRNA was significantly increased in patients with COPD compared with nonsmokers and smokers with normal lung function （P 〈 0.001,P =0.001,respectively）.iNOS protein was also higher in COPD patients than nonsmokers and smokers with normal lung function （P 〈 0.01 and P =0.01,respectively）.However,expressions ofnNOS and eNOS did not differ among nonsmokers,smokers with and without ***,there was a negative correlation between iNOS protein level and lung function parameters forced expiratory volume in 1 s （FEV1）（% predicted）（r =-0.549,P =0.001） and FEV1/forced vital capacity （%,r =-0.535,P =0.001）.Conclusions：The expression of iNOS significantly increased in smokers with COPD compared with that in nonsmokers or smokers without *** results suggest that iNOS might be involved in the pathogenesis of COPD,and may be a potential marker to identify the smokers who have more liability to suffer COPD.

关键词： Chronic Obstructive Pulmonary Disease Nitric Oxide Synthase Smoking

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Sex, age, and annual incidence of primary total knee arthroplasty： a university affiliated hospital survey of 3118 Chinese patients

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Chinese Medical Journal 2012年第22期125卷 3952-3955页

作者： YANG Bo YU Jia-kuo GONG Xi CHEN Lian-xu WANG yong-jian WANG jian MA Dong Peking Univ Hosp 3 Inst Sports Med Beijing 100191 Peoples R China

Background In recent years, the number of patients undergoing primary total knee arthroplasty in China has rapidly increased. However, the incidence of primary total knee arthroplasty is unknown. The purpose of this study was to investigate the sex, age and, annual incidence of primary total knee arthroplasty based on 3118 Chinese patients who underwent the procedure during the period of 2000-2011. Methods Total knee arthroplasties were performed on 511 males and 2607 females in our hospital during the period of 2000-2011. The sex, age, and annual incidence of primary total knee arthroplasty were evaluated. Results The annual incidence of primary total knee arthroplasty increased from 35 knees in 2000 to 681 knees in 2011. The average annual percentage increase in incidence was 33.2%. Females accounted for 83.2% of the patients who underwent primary total knee arthroplasty. In both males and females, the highest incidence was observed in the group aged 65-74 years. Conclusions This study demonstrated a rapid increase in the incidence of primary total knee arthroplasty in our Chinese study population. The sex and age incidence of primary total knee arthroplasty in our study population differed from those reported in Western populations.

关键词： total knee arthroplasty osteoarthritis epidemiology," incidence," sex

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加强对吸烟人群慢性阻塞性肺疾病易患性差异及其原因的研究

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中华结核和呼吸杂志 2010年第4期33卷 243-244页

作者：徐永健华中科技大学同济医学院附属同济医院呼吸内科武汉430030

大量的研究结果充分证明吸烟是导致COPD最重要的环境因素，但并非所有的长期吸烟者最终都会罹患COPD，吸烟人群中不同个体的COPD易患性存在着明显的差异。Fletcher和Peto于30年前就已指出，吸烟人群中对烟草效应敏感者才出现肺功能加速... 详细信息

大量的研究结果充分证明吸烟是导致COPD最重要的环境因素，但并非所有的长期吸烟者最终都会罹患COPD，吸烟人群中不同个体的COPD易患性存在着明显的差异。Fletcher和Peto于30年前就已指出，吸烟人群中对烟草效应敏感者才出现肺功能加速下降的现象，而不敏感者则肺功能下降速率与不吸烟者并无差异。关于吸烟人群COPD易患性差异的研究工作至少具有两方面的重要意义：（1）有助于进一步阐明COPD的病因和发病机制；

关键词：疾病易患性吸烟人群肺功能慢性阻塞性 COPD 长期吸烟者环境因素不吸烟者

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Role of extracellular signal-regulated kinase in regulating expression of interleukin 13 in lymphocytes from an asthmatic rat model

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Chinese Medical Journal 2010年第13期123卷 1715-1719页

作者： LI Yuan-yuan LIU Xian-sheng LIU Chang xu yong-jian XIONG Wei-ning Department of Respiratory Medicine Tongji Hospital Tongii Medical College Huazhong University of Science and Technology Wuhan Hubei 430030 China

Background The extracellular signal-regulated kinase （ERK） is widely expressed in mammal cells and involved in airway proliferation and remodeling in asthma. In this study, we intend to explore the role of ERK in the expression of the Th2 cytokine, interleukin 13 （IL-13） in lymphocytes in asthma. Methods Forty Sprague-Dawley rats were randomly divided into two groups： normal control and asthmatic groups. Peripheral blood lymphocytes were isolated and purified from the blood of each rat and divided into five groups： control, asthmatic lymphocytes, asthmatic cells stimulated with ERK activator epidermal growth factor （EGF）, or with ERK inhibitor PD98059, or with EGF and PD98059 together. The expression of phosphorylated-ERK （p-ERK） was observed by immunocytochemical staining, the expression of ERK mRNA was determined by reverse transcriptase-PCR, IL-13 protein in supernatants was measured by ELISA. Results （1） The ERK mRNA level and the percentage of cells with p-ERK in lymphocytes from asthmatic rats were significantly higher than those in normal controls, and were significantly increased by EGF administration. This effect of EGF was significantly inhibited by PD98059 pretreatment. （2） IL-13 protein in supernatants of asthmatic lymphocytes was higher than that produced by normal control lymphocytes, and was significantly increased by EGF treatment. This EGF effect was partly blocked by PD98059 pretreatment. （3） There was a significant positive correlation between the percentage of cells with p-ERK in peripheral blood lymphocytes and IL-13 protein in supernatants of lymphocytes from asthmatic rats. Conclusions In asthma the ERK expression and activation levels were increased, as was the protein level of IL-13. The ERK signaling pathway may be involved in the increased expression of the Th2 cytokine IL-13 in asthma.

关键词： asthma interleukin 13 lymphocytes extraceUular signal-regulated MAP kinases

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