Background Chronic Obstructive Pulmonary Disease (COPD) is characterized by high morbidity, disability, and mortality rates worldwide. RNA-binding proteins (RBPs) might regulate genes involved in oxidative stress and inflammation in COPD patients. Single-cell transcriptome sequencing (scRNA-seq) offers an accurate tool for identifying intercellular heterogeneity and the diversity of immune cells. However, the role of RBPs in the regulation of various cells, especially AT2 cells, remains elusive. Materials and methods A scRNA-seq dataset (GSE173896) and a bulk RNA-seq dataset acquired from airway tissues (GSE124180) were employed for data mining. Next, RNA-seq analysis was performed in both COPD and control patients. Differentially expressed genes (DEGs) were identified using criteria of fold change (FC ≥ 1.5 or ≤ 1.5) and P value ≤ 0.05. Lastly, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and alternative splicing identification analyses were carried out. Results RBP genes exhibited specific expression patterns across different cell groups and participated in cell proliferation and mitochondrial dysfunction in AT2 cells. As an RBP, AZGP1 expression was upregulated in both the scRNA-seq and RNA-seq datasets. It might potentially be a candidate immune biomarker that regulates COPD progression by modulating AT2 cell proliferation and adhesion by regulating the expression of SAMD5, DNER, DPYSL3, GBP5, GBP3, and KCNJ2. Moreover, AZGP1 regulated alternative splicing events in COPD, particularly DDAH1 and SFRP1, holding significant implications in COPD. Conclusion RBP gene AZGP1 inhibits epithelial cell proliferation by regulating genes participating in alternative splicing in COPD.

肌少症是以多系统衰退为特征的老年综合征,主要反映在骨骼肌功能障碍上.骨骼肌功能障碍普遍存在于慢性阻塞性肺疾病(COPD)的所有阶段,并对患者的重要临床结果产生负面影响.近年来,多种因素被提出影响COPD患者的骨骼肌功能障碍,包括蛋白质合成和分解代谢失衡、全身炎症反应、氧化应激、低氧、高碳酸血症、激素代谢水平异常、活动减少、营养不良、维生素D缺乏等,导致肌肉工作能力下降.本文就COPD合并肌少症可能的发病机制的研究进展进行综述.

目的 探究雌激素通过调控miR-148a-3p/SMAD对慢性阻塞性肺疾病(COPD)中Th17 反应的影响.方法噻唑蓝(MTT)检测人肺支气管上皮(HBE)细胞增殖活力;酶联免疫吸附试验(ELISA)检测白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α、IL-17A及IL-22 水平;实时荧光定量聚合酶链反应(RT-qPCR)检测miR-148a-3p及维甲酸孤儿核受体(RoR)γT mRNA表达情况;Western印迹检测SMAD通路相关蛋白表达量;流式细胞仪检测Th17 细胞比例.结果 雌激素显著促进CSE诱导的HBE细胞活力下降和炎症反应(均P＜0.05);雌激素显著上调miR-148a-3p表达,显著激活SMAD通路(均P＜0.05);雌激素通过上调miR-148a-3p的表达显著促进CSE诱导的Th17 分化(P＜0.05);过表达miR-148a-3p可显著激活SMAD通路(P＜0.05),敲降miR-148a-3p可显著抑制SMAD通路激活(P＜0.05);雌激素通过激活SMAD通路显著促进CSE诱导的Th17 分化(P＜0.05).结论 雌激素通过上调miR-148a-3p的表达,进一步激活SMAD通路,促进COPD中致病性Th17 反应.

目的 探究在慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)中,雌激素通过调控miR?21/SMAD信号通路对香烟烟雾诱导的肺上皮间质转化(epithelial mesenchymal transition,EMT)的影响.方法 RT?qPCR、Western blot、MTT检测miR?21及E?cadherin、α?SMA、Vimentin mRNA水平、SMAD相关蛋白表达、HBE增殖活力.结果 雌激素促进香烟烟雾(CSE)诱导的人肺支气管上皮细胞(HBE)EMT和活力下降;上调miR?21,激活SMAD通路;促进CSE诱导的EMT和细胞活力下降;过表达miR?21,激活SMAD通路;雌激素通过激活SMAD促进CSE诱导的EMT和细胞活力下降.结论 雌激素通过上调miR?21,激活SMDA通路,抑制HBE增殖,促进HBE发生EMT,促进COPD发展进程.

Background:A previous study identified miR-451b as a potential biomarker in smoker with or without chronic obstructive pulmonary disease (COPD). However, the function and molecular mechanisms of miR-451b in the pathogenesis of COPD remain elusive.Methods:Macrophages and lung fibroblasts were exposed to 10% cigarette smoke extract (CSE) solution for 24 h. Expression miR-451b and its potential transcription factor p300 were detected. The association between p300 and miR-451b, miR-451b and RhoA was validated by luciferase reporter assay. The release of IL-12 and TNF-αby macrophages was measured by ELISA assay, and Transwell assay was performed to analyze its migration and invasion. Collagen protein of fibroblasts was detected by Western blotting.Results:Results showed that p300 and miR-451b was downregulated, while RhoA was upregulated in CSE-induced macrophages and lung fibroblasts. The stimulation of CSE promoted the degradation of p300 by ubiquitination, and RhoA was confirmed as the target gene of miR-451b. MiR-451b overexpression significantly decreased the release of IL-12 and TNF-α, downregulated the expression of RhoA, ROCK2, and p65, and suppressed cell migration and invasion in CES-induced macrophages. In addition, miR-451b overexpression decreased the expression of RhoA, ROCK2, COL1A1, and COL2A1 in lung fibroblasts.Conclusions:Our data suggest that p300/miR-451b protects against CSE-induced cell stress possibly through downregulating RhoA/ROCK2 pathway.

目的 探讨血清白介素17(IL-17)、呼出气一氧化氮(FeNO)在支气管哮喘+慢性阻塞性肺疾病(哮喘+慢阻肺)患者的水平及其鉴别诊断价值.方法 以我院在2019年1月至10月收治的23例哮喘患者(哮喘组)、28例慢阻肺患者(慢阻肺组)和21例哮喘+慢阻肺患者(哮喘+慢阻肺组),以及20例健康不吸烟者(健康对照组)为研究对象.检测各组IL-17、FeNO,比较分析二者与肺功能、血常规部分指标之间的相关性;利用受试者工作特征曲线(ROC)分析比较IL-17与FeNO对哮喘+慢阻肺的诊断价值.结果 哮喘+慢阻肺组和哮喘组血清IL-17、FeNO均高于慢阻肺组和健康对照组,哮喘+慢阻肺组FeNO低于哮喘组,差异有统计学意义(P<0.05).各组血清IL-17与FEV1/pred均呈负相关(P<0.05),各组FeNO与肺功能无明显相关性.试验组血清IL-17与FeNO呈正相关(P<0.05).分别以IL-17>184.85pg/ml或FeNO>33.5ppb鉴别哮喘+慢阻肺和慢阻肺,以及FeNO<44.0ppb鉴别哮喘+慢阻肺和哮喘有一定参考价值.结论 血清IL-17与哮喘、慢阻肺、哮喘+慢阻肺气流受限有关,血清IL-17和FeNO水平有助于鉴别哮喘、慢阻肺和哮喘+慢阻肺患者.

Background Multiple gene expression studies have been performed to investigate the biomarkers of chronic obstructive pulmonary disease (COPD). However, few studies have related COPD to macrophage cells. Methods The gene expression levels of clinical samples of COPD smokers (COPD; n=6), healthy smokers (Smoke; n=11), and never smokers (Never; n=4) were downloaded from the Gene Expression Omnibus (GEO) repository of GSE124180. The expression levels of messenger RNAs (mRNAs) and microRNAs (miRNAs) in macrophage cells of M0 (n=7), M1 (n=7), and M2 (n=7) were downloaded from the GEO repository of GSE46903 and GSE51307. Differentially expressed (DE) mRNAs (DEmRNAs) were identified by edgeR and GEO2R, with an adjusted P value <0.05 and |log2fold change (FC)| ≥1 chosen as the cut-off threshold. The potential target genes of miRNA were identified using miRanda (v3.3a) and TargetScan (v6.0) with default settings. Gene Ontology (GO) and Reactome pathway analyses were performed. Results The composition of macrophages was quite different between COPD, Never, and Smoke samples. The proportion of M1 cells was lower than that of M0 and M2 cells in Smokers and COPD samples. Most of the genes specifically up-regulated in M1 are related to inflammation/immunity. The expression levels of miR-30a-5p, miR-200c-3p, miR-20b-5p, miR-199b-5p, and miR-301b-3p in M1 macrophages were all lower than that of M0. Their expression levels in M2 macrophages compared with M1 varied, with higher expression in miR-30a-5p, miR-20b-5p, and lower expression in miR-200c-3p, and miR-301b-3p. The mRNAs of the fms related receptor tyrosine kinase 1 (FLT1), cardiotrophin like cytokine factor 1 (CLCF1), phosphodiesterase 4D (PDE4D), coagulation factor III, and tissue factor (F3) were dysregulated in COPD and macrophage cells. Conclusions The present study mined the miRNA-mRNA signature which might play an essential role in COPD and macrophage polarization.

Background:Chronic obstructive pulmonary disease (COPD) is characterized by irreversible expiratory airflow obstruction, and its chronic course is worsened by recurrent acute exacerbations. Our previous microarray assay identified microRNA (miR)-301a-5p as being associated with progression of acute exacerbation of COPD (AE-COPD); however, the mechanism underlying COPD pathogenesis remains unknown.Methods:Samples of serum and peripheral blood mononuclear cells (PBMCs) were isolated from healthy control subjects and patients with stable COPD (R-COPD) or with an acute exacerbation of COPD (AE-COPD). Human HULEC-5a and human bronchial epithelial (HBE) cells were transfected with methyl-CpG-binding domain protein 2 (MBD2), sh-MBD2, miR-301a-5p mimics or an inhibitor, and then stimulated with cigarette smoke extract (CSE). Conditioned medium co-culture assays were performed by adding the supernatant of medium derived from HULEC-5a cells transfected with miR-301a-5p mimics or inhibitor into wells containing si-c-x-c motif chemokine receptor 4 (CXCR4)-transfected-lung fibroblasts or human leukemic THP-1 cell line macrophages. Transwell assays were performed to analyze cell migration.Results:Our analysis of clinical samples showed that decreased miR-301a-5p levels in patients with AE-COPD were positively correlated with levels of MBD2 expression, but negatively correlated with levels of chemokine ligand C-X-C motif chemokine ligand 12 (CXCL12) expression. MBD2 overexpression significantly promoted miR-301a-5p production, but suppressed CXCL12 production in HULEC-5a and HBE cells. CXCL12 was confirmed to be a direct target of miR-301a-5p. CXCR4 knockdown significantly enhanced the suppressive effect of miR-301a-5p mimics and attenuated the promotional effects of the miR-301a-5p inhibitor on the migration of circulating fibroblasts and macrophages, as well as the expression levels of phospho-mitogen-activated protein kinase (p-MEK) and phospho-protein kinase B (p-AKT).Conclusion:In summary, the MBD2/miR-301a-5p/CXCL12/CXCR4 pathway was shown to affect the migration of lung fibroblasts and monocyte-derived macrophages, which may play an important role during COPD exacerbations.

支气管哮喘(哮喘)和慢性阻塞性肺疾病(慢阻肺)是具有不同病理生理学和炎症表型的异质性疾病. 哮喘以慢性气道炎症、气道高反应、多变可逆的气流受限以及随病程延长而出现的气道重构为主要特征,慢阻肺则以持续的呼吸道症状和气流受限为特征. 在临床上,两种疾病的临床特点可在同一病人同一时期出现.

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by irreversible expiratory airflow obstruction and its chronic course is worsened by recurrent acute exacerbations. Our previous microarray identified miR-301a-5p was associated with the progression of AE-COPD, but its regulatory mechanism underlying COPD pathogenesis remains uncovered.Methods Serum and peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls and patients with COPD in remission (R-COPD) and acute exacerbation (AE-COPD). Human HULEC-5a and HBE cells were transfected with MBD2, sh-MBD2, miR-301a-5p mimics or inhibitor, followed by stimulated with cigarette smoke extract (CSE). The co-culture assays were performed by the addition of the supernatant of medium derived from HULEC-5a cells transfected with miR-301a-5p mimics or inhibitor into si-CXCR4-transfected-lung fibroblast or THP-1 macrophages. Transwell assay was used to analyze cell migration.Results Clinical samples showed that decreased miR-301a-5p level in AE-COPD was significantly positively correlated with the expression level of MBD2, but negatively correlated with CXCL12 expression level. MBD2 overexpression significantly promoted miR-301a-5p, while suppressed CXCL12 in HULEC-5a and HBE cells. CXCL12 was confirmed as a direct target of miR-301a-5p. CXCR4 knockdown significantly the suppressive effect of miR-301a-5p mimics and attenuated the promotional effects of miR-301a-5p inhibitor on the migration of circulating fibroblasts and macrophages, as well as the expression levels of P-MEK and P-AKT.Conclusion In summary, MBD2/miR-301a-5p/CXCL12/CXCR4 appears to be involved in such recruitments of circulating fibroblasts and macrophages during COPD exacerbations.

慢性阻塞性肺疾病(COPD)是一种以进行性、不完全可逆气流受限为特征的慢性炎症性呼吸系统疾病.目前认为COPD的发病与吸烟、大气颗粒污染物吸入等因素有关,但仍有一些尚未明确的因素.近年来研究发现幽门螺旋杆菌(HP)感染可能使COPD发病率上升,并且COPD患者HP感染率较高,HP感染与呼吸道炎症性疾病的发生存在一定联系.文章对近年COPD患者与HP感染相关性研究进行综述.

发热伴肺部阴影患者临床常见,可由多种病因引起,临床鉴别病因往往需要一定时间,初治主要依赖经验,早期识别、纠正、预防此类患者初始经验性治疗影响因素,有助于提高初治成功率,现围绕发热伴肺部阴影初治失败的定义及影响因素作一综述.

慢性阻塞性肺疾病( chronic obstructive pulmo-nary disease,COPD)是一种常见的、发病率和死亡率较高的呼吸系统疾病,预计到2020年将成为死亡原因占第3位的重大疾病. 我国COPD的发病率居高不下, 2013年我国就有910809人死于COPD,占世界COPD死亡总人数的31. 1％ [1]. COPD是一种异质性疾病,2010年Han等[2]根据COPD异质性的特点,提出了 COPD表型的定义,2013年西班牙COPD临床指南根据COPD的异质性将COPD患者分为4种表型:A型:具有慢支或肺气肿的非频繁急性加重患者;B型:慢阻肺-哮喘患者.

嗜酸性粒细胞性肺炎(Eosinophilic Pneumonia,EP)发病率低,易被误诊为感染性疾病而延误治疗,近年随着对EP认识的加深,EP的诊断和治疗取得了明显进展.文章回顾性总结了EP的诊断方法与治疗策略的进展.

Interactions between angiotensin-converting enzyme-2 (ACE2) gene polymorphisms and high salt intake increase the risk of hypertension (HTN); however, this association is not well-established in the Chinese Wa population. In this study, we investigated the prevalence and associated factors of HTN in the Chinese Wa ethnic minority in Yunnan Province, China. In addition, we assessed the associations of single nucleotide polymorphisms (SNPs) in ACE2 with blood pressure and environmental factors. Among a total of 838 Wa individuals, the overall prevalence, awareness, treatment and control rates of HTN were 31.03%, 32.81%, 10.77%, and 0.70%, respectively. In addition, 260 hypertensive patients and 290 normotensive individuals were randomly selected for investigations of salt intake and ACE2 SNPs. The levels of e24-h salt intake in female hypertensive patients were significantly higher that those in normotensive individuals. The ACE2 rs2285666 T allele or TT genotype and rs714205 G allele or GG genotype were identified as risk factors for the development of HTN in female Wa individuals. The CGTG haplotype was a risk factor in hypertensive patients. Moreover, high salt intake increased the occurrence of hypertension among ACE2 rs2285666 TT and rs714205 GG individuals. In this study, we not only identified an association between ACE2 gene polymorphism and HTN in the Chinese Wa population, but also a possible link interaction between ACE2 polymorphism type and high salt intake in increasing the risk of HTN in this population.

Objective To investigate the STAT4 mRNA expression levels,the serum levels of IL-12 and IFN-γ in peripheral blood of patients and normal individuals,and to explore its possible role in the pathogenesis of SLE.Methods STAT4 expression of SLE patients and normal controls were analyzed with QPCR technique.ELISA was applied to determine the serum levels of IFN-γ and IL-12.The data were analyzed with the Plink 1.06 software and spss 16.0.Results 1.The expression levels of STAT4 mRNA of SLE patients were significantly higher than those of control groups(P0.01).There was a correlation between STAT4 and SLEDAI(r=0.385,P 0.05).2.The G-allele of rs10181656 increased the expression of STAT4 mRNA.3.The serum levels of IFN-γ and IL-12 of SLE patients were significantly higher than those of normal controls(P0.01).The serum levels of IFN-γ and IL-12 were positively correlated to SLEDAI(P0.05).4.The expression levels of STAT4mRNA showed a positive correlation with IFN-r(r=0.335,P=0.009) and IL-12(r=0.401,P=0.002),and showed a positive correlation with serositis,hematological,kidney damage and butterfly rash(P 0.05).Conclusions 1.The expression levels of STAT4 mRNA of SLE increase and correlate with SLEDAI,so the expression levels of STAT4 might be used as a referential indicator,suggesting STAT4 may play a role in development of SLE and correlate with the severity of SLE.2.The serum levels of IFN-r and IL-12 increase,and show a positive correlation with SLEDAI,suggesting that IFN-r,IL-12 may be as parameters of SLE activity.According to the mRNA expression levels of STAT4 associated with IFN-r and IL-12,we conclude that STAT4 may have active effect on IFN-r and IL-12 in the gene level.STAT4 may regulate IFN-r,IL-12 and enhance the mRNA expression of the two cytokines.

Objective To investigate the association between single nucleotide polymorphism(SNP) in the signal transducer and activator of transcription(STAT4)gene and the susceptibility of systemic lupus erythematosus(SLE)in Chinese Han population of Yunnan.Methods The Sequenom MassArray system was used to conduct the genotype in 20 SNPs of the STAT4 genes(rs10168266,rs10181656,rs11889341,rs13017460,rs1551443,rs16833249,rs2459611,rs3024879,rs3024886,rs3024894,rs3024895,rs3024933,rs3821236,rs4555370,rs6712821,rs7568275,rs7574865,rs7599504,rs8179673,rs932169)in 378 cases with SLE and 389 cases of normal control.Results Six SNPs of STAT4 gene tested here were significantly associated with SLE,particularly rs10181656(P=5.41E-09),and the association with SLE was significantly higher than that of European.When patients were assigned in subgroup according to the arthritis,butterfly rash,kidney damage,oral ulcers,anti-dsDNA,ANA,hematological and serositis,the G-allele frequencies of SNP rs10181656 was significant differences between SLE patients and controls(P0.01).Conclusion It suggested that polymorphism of STAT4 gene may be related to susceptibility of SLE in Chinese Han population of Yunnan.The G-allele of rs10181656 increased the risk of SLE patients with arthritis,butterfly rash,kidney damage,oronasal ulcers,anti-dsDNA,ANA,hematological and serositis.

Objective To study clinical factors and treatment about thrombosis in drug-eluting stent.Methods A cohort of coronary heart disease patients treated with percutaneous coronary intervention were selected from Jul 2009 to Jul 2012.The clinical data,characteristics of coronary lesion and intervention procedure,as well as antiplatelet therapy of the patients with thrombosis were recorded,and the reasons and treatment of stent thrombosis were analyzed.Results Altogether 703 CHD patients were enrolled into the study.Nine cases(1.28%)of stent thrombosis occurred in 7 patients.10 target lesions developed stent thrombosis within 20 hours to 7 months after PCI.Conclusions Stent thrombosis probably correlates with the following factors:coronary heart disease risk factors including smoking,hyperlipidemia,hypertension and high uric acid levels,multiple stent implantation,the stent malappositiont,mix different types of stents,without high pressure postdilation,long lesions,bifurcation lesions,and imcomplete treatment of antithrombus.Moreover,thrombolysis and emergency percutaneous coronary intervention is the effective treatment for stent thrombosis.