PURPOSE:Kinase interacting with stathmin (KIS) is a serine/threonine kinase involved in RNA processing and protein phosphorylation. Increasing evidence has suggested its involvement in cancer progression. The aim of this study was to investigate the role of KIS in the development of lung adenocarcinoma (LUAD). Dual luciferase assay was used to explore the relationship between KIS and SOX4, and its effect on ID1/β-catenin pathway. METHODS:Real-time qPCR and western blot were used to assess the levels of KIS and other factors. Cell proliferation, migration, and invasion were monitored, and xenograft animal model were established to investigate the biological functions of KIS in vitro and in vivo. RESULTS:In the present study, KIS was found to be highly expressed in LUAD tissues and cell lines. KIS accelerated the proliferative, migratory and invasive abilities of LUAD cells in vitro, and promoted the growth of LUAD in a mouse tumor xenograft model in vivo. Mechanistically, KIS activated the β-catenin signaling pathway by modulating the inhibitor of DNA binding 1 (ID1) and was transcriptionally regulated by SOX4 in LUAD cells. CONCLUSION:KIS, a target of SOX4, regulates the ID1-mediated enhancement of β-catenin to facilitate LUAD cell invasion and metastasis.

Background 8-Oxoguanine DNA glycosylase (OGG1), a well-known DNA repair enzyme, has been demonstrated to promote lung fibrosis, while the specific regulatory mechanism of OGG1 during pulmonary fibrosis remains unclarified.Methods A bleomycin (BLM)-induced mouse pulmonary fibrosis model was established, and TH5487 (the small molecule OGG1 inhibitor) and Mitochondrial division inhibitor 1 (Mdivi-1) were used for administration. Histopathological injury of the lung tissues was assessed. The profibrotic factors and oxidative stress-related factors were examined using the commercial kits. Western blot was used to examine protein expression and immunofluorescence analysis was conducted to assess macrophages polarization and autophagy. The conditional medium from M2 macrophages was harvested and added to HFL-1 cells for culture to simulate the immune microenvironment around fibroblasts during pulmonary fibrosis. Subsequently, the loss- and gain-of function experiments were conducted to further confirm the molecular mechanism of OGG1/PINK1.Results In BLM-induced pulmonary fibrosis, OGG1 was upregulated while PINK1/Parkin was downregulated. Macrophages were activated and polarized to M2 phenotype. TH5487 administration effectively mitigated pulmonary fibrosis, M2 macrophage polarization, oxidative stress and mitochondrial dysfunction while promoted PINK1/Parkin-mediated mitophagy in lung tissues of BLM-induced mice, which was partly hindered by Mdivi-1. PINK1 overexpression restricted M2 macrophages-induced oxidative stress, mitochondrial dysfunction and mitophagy inactivation in lung fibroblast cells, and OGG1 knockdown could promote PINK1/Parkin expression and alleviate M2 macrophages-induced mitochondrial dysfunction in HFL-1 cells.Conclusion OGG1 inhibition protects against pulmonary fibrosis, which is partly via activating PINK1/Parkin-mediated mitophagy and retarding M2 macrophage polarization, providing a therapeutic target for pulmonary fibrosis.

目的:探讨柴胡皂苷d对卵清蛋白(OVA)诱导的过敏性哮喘小鼠p38丝裂原活化蛋白激酶/核因子κB(p38 MAPK/NF-κB)信号通路及气道炎症的影响.方法:60只BALBc小鼠随机分为正常组、模型组、柴胡皂苷d低(25mg/kg)、中(50mg/kg)、高剂量组(100mg/kg)、阳性对照组(地塞米松,10mg/kg),每组10只.蛋白免疫印迹法检测小鼠肺组织中p38 MAPK/NF-κB通路相关蛋白的表达.结果:与模型组相比,柴胡皂苷d低、中、高剂量组、阳性对照组小鼠气道阻力参数Penh值、肺泡灌洗液中炎性因子水平、炎性细胞数量、肺组织炎症细胞浸润、肺组织中p38 MAPK/NF-κB通路相关蛋白表达降低(P＜0.05).结论:柴胡皂苷d可减轻OVA诱导的过敏性哮喘小鼠的气道炎症反应,其机制可能与抑制p38 MAPK/NF-κB通路有关.

目的 探讨抗黑色素瘤分化相关基因5(MDA5)抗体阳性皮肌炎(DM)合并快速进展型间质性肺疾病(RP-ILD)的临床特点及预后危险因素.方法 回顾性分析2017年6月至2021年6月郑州大学第一附属医院收治的新确诊的抗MDA5阳性DM患者146例,并进行为期1 a的随访.根据是否发生RP-ILD分为两组,其中非RP-ILD组90例,RP-ILD组56例.收集两组患者的一般资料、入院时的临床特征、实验室数据、影像学检查及临床结局,分析其临床特征及预后不良的因素.结果 在RP-ILD组中,患者红细胞沉降率、C反应蛋白水平、Ro-52抗体阳性率、病初出现呼吸衰竭发生率、以呼吸困难为主诉发生率及病死率均高于非RP-ILD组,而血清白蛋白水平低于非RP-ILD组(P<0.05).病初出现呼吸衰竭、Ro-52抗体阳性是发生RP-ILD的危险因素(P<0.05).二元logistic回归分析提示,病初出现呼吸衰竭、Ro-52抗体阳性也是MDA5阳性DM死亡的危险因素(P<0.05).结论 抗MDA5抗体阳性DM常与RP-ILD并存,病死率高,Ro-52抗体阳性及病初出现呼吸衰竭是MDA5阳性DM患者出现RP-ILD及死亡的危险因素.

目的 研究慢性阻塞性肺疾病(COPD)患者外周血中长链非编码RNA MEG3及微小RNA-15a-5p的表达水平及临床意义.方法 用qRT-PCR的方法检测43例慢阻肺患者,其中急性加重组28例,稳定期组15例,以及26例对照组患者外周静脉血中LncRNA MEG3和miR-15a-5p的表达水平.结果 ①慢阻肺患者LncRNA MEG3表达水平高于对照组,并且急性加重组高于稳定期组,miR-15a-5p表达水平显著低于对照组.②慢阻肺患者LncRNA MEG3的表达与miR-15a-5p成负相关(r=-0.396,P=0.02),与CAT评分及C反应蛋白成正相关(r分别为0.478,0.508,P分别为0.002,0.003).③分别应用LncRNA MEG3及miR-15a-5p识别慢阻肺的受试者工作特征(ROC)曲线下面积(AUC)分别为0.661、0.66,敏感度分别为76.92％、50％,特异度分别为60％、77.27％.应用LncRNA MEG3联合miR-15a-5p识别慢阻肺的受试者工作特征(ROC)曲线下面积(AUC)为0.721,敏感度为81.82％,特异度为55％.进一步通过多因素Logistic回归分析显示miR-15a-5p为慢阻肺发生的保护性因素(OR=0.029,95％CI 1.140～9.718,P=0.002).结论 Ln-cRNA MEG3在慢阻肺患者中高表达,miR-15a-5p低表达,并且与疾病的严重程度相关,LncRNA MEG3联合miR-15a-5p对慢阻肺有较好的诊断价值,我们猜测LncRNA MEG3可能通过负向调节miR-15a-5p介导慢性阻塞性肺疾病的发展.

目的 探讨血清生长分化因子-15(GDF-15)水平在慢性阻塞性肺疾病(COPD)患者中的临床意义.方法 选取2020年8-10月该院COPD急性加重期(AECOPD)患者28例为AECOPD组,稳定期COPD患者15例为稳定期COPD组和体检健康者26例为对照组.采用酶联免疫吸附试验检测GDF-15水平,并对AECOPD患者进行为期1年的随访.采用受试者工作特征(ROC)曲线评估GDF-15水平对AECOPD患者再次入院的诊断价值.结果 与对照组比较,稳定期COPD组和AECOPD组患者GDF-15水平升高(P<0.05),且AECOPD组患者GDF-15水平高于稳定期COPD组(P<0.05).COPD患者GDF-15水平与COPD评估测试问卷(CAT)评分、C-反应蛋白、降钙素原均呈正相关(P<0.05).AECOPD患者GDF-15水平与住院时长呈正相关(P<0.05).ROC曲线结果表明,GDF-15诊断AECOPD患者再次入院的最佳临界值为51.34 pg/mL,曲线下面积为0.718,灵敏度和特异度分别为69.23％、86.67％.再次入院患者GDF-15水平明显高于未再次入院者(P<0.05).结论 GDF-15水平与COPD的严重程度和全身炎症反应有关.此外,GDF-15对AECOPD患者再次入院具有一定的诊断价值.

Objective:To understand the efficacy, prognosis and survival rate of patients with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) with bronchiectasis on initial induction of AAV.Methods:A retrospective analysis was performed in 486 patients diagnosed with AAV who underwent chest high-resolution CT (HRCT) examination at the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2017.Based on imaging examinations, the patients were divided into two groups: and non bronchiectasis group ( n=449 cases, n=37 cases). The organ involvement, clinical characteristics and laboratory indicators of two groups were compared with imaging characteristics.The efficacy of immune induction therapy in bronchiectasis was evaluated.The survival rates of patients two groups were compared. Results:The incidence of bronchiectasis was 7.6%(37/486), females more over males (67.6% vs49.9%, P=0.04), and peripheral nerve involvement of females more common (18.9% vs7.8%, P=0.02). Thirty patients with bronchiectasis underwent imaging examination after three months of induction therapy, and 3 cases (10.0%) showed improvement in imaging.The follow-up was observed in 419 patients (86.2%), with a median follow-up time of 35 months.There was no significant difference in the fatality rate between patients with vasculitis and without bronchiectasis.The fatality rate of the vasculitis with interstitial lung was higher than that with non-bronchodilated and/or non-interstitial lung and with vasculitis with bronchiectasis ( P<0.05). Conclusions:The initial treatment improved the imaging of patients with vasculitis and bronchiectasis.Vasculitis combined with bronchiectasis did not increase the risk in the death of patients′.However, but the patients complicated with interstitial lung vasculitis had a greater risk of death.

Objective:To study the application value of health education based on self-efficacy theory in the management of patients with chronic obstructive pulmonary disease (COPD) outside the hospital.Methods:Using the convenient sampling method, a total of 66 COPD patients who were treated and discharged from the First Affiliated Hospital of Zhengzhou University from March to November 2018 were selected as the routine group, and 67 COPD patients who were treated and discharged from December 2018 to August 2019 were selected as the study group. The routine group adopted routine follow-up nursing, while the study group adopted health education based on self-efficacy theory on the basis of routine follow-up nursing. The rehabilitation compliance score and self-efficacy score of the two groups before the intervention, after the intervention and 6 months after the intervention were compared. The readmission rate from the beginning of the intervention to 6 months after the intervention were compared between the two groups.Results:After the intervention, the rehabilitation compliance score of the study group was (39.94±4.91) , which was higher than (33.29±4.60) of the routine group. At 6 months after intervention, the rehabilitation compliance score of the study group was (38.87±4.76) , which was higher than (31.75±4.10) of the conventional group. Repeated measurement analysis of variance showed that there was an interaction between the two groups in rehabilitation compliance score ( Ftime=84.532, Fgroups=10.241, Finteraction=9.785; P<0.05) . After intervention, the self-efficacy score of the study group was (141.36±20.76) , higher than (118.26±15.47) of the control group. On 6 months after the intervention, the self-efficacy score of the study group was (139.21±16.95) , which was higher than (108.51±15.01) of the routine group. Repeated measurement analysis of variance showed that there was an interaction between the two groups in self-efficacy scores ( Ftime=87.541, Fgroups=12.254, Finteraction=13.697; P<0.05) . At 6 months after intervention, the readmission rate of the study group was 16.42%, which was lower than 33.33% of the routine group, and the difference was statistically significant ( χ2=5.099, P=0.024) . Conclusions:The application of health education based on self-efficacy theory in the management of COPD patients outside the hospital can improve rehabilitation compliance and self-efficacy of patients and reduce the frequency of readmissions.

目的:探讨三联雾化吸入疗法在重症哮喘急性发作治疗中的应用效果.方法:选取郑州大学第一附属医院在2017年9月至2020年9月收治的90例重症哮喘急性发作患者,随机分为对照组和观察组,每组45例.对照组给予常规治疗,观察组在此基础上实施三联雾化吸入疗法,比较两组患者的治疗效果.结果:经治疗,观察组治疗总有效率达到了 93.33％,显著高于对照组的77.78％,差异具有统计学意义(P＜0.05).观察组患者的喘息、胸闷、咳嗽、气促和肺部哮鸣音消失时间均短于对照组患者,差异具有统计学意义(P＜0.05).在不良反应发生率方面,两组比较,差异无统计学意义(P＞0.05).结论:三联雾化吸入疗法对成人重症哮喘急性发作的疗效确切,可促进患者临床症状的早期缓解,同时也具有较高的安全性.

目的 探讨呼出气一氧化氮(FeNO)联合血清基质细胞衍生因子-1(SDF-1)水平对支气管哮喘患者气道高反应的预测价值.方法 选取2017年6月-2020年6月于本院就诊的支气管哮喘患者103例为观察组,同期选取健康人群103例为对照组.采用纳库仑呼气分析仪测定FeNO水平;采用酶联免疫吸附(ELISA)法检测所有研究对象SDF-1水平,并以支气管激发试验检测气道高反应性[以比气道传导率下降35％的乙酰甲胆碱浓度(PC35sGaW)表示];采用Pearson分析支气管哮喘患者FeNO、血清SDF-1水平与PC35sGaW的相关性;采用Logistic回归分析影响支气管哮喘患者气道高反应发生的相关因素;采用ROC曲线分析FeNO、SDF-1对支气管哮喘患者气道高反应的预测价值.结果 观察组FeNO、血清SDF-1水平均显著高于对照组(JP＜0.05),PC35sGaW显著低于对照组(P＜0.05);Pearson相关性分析结果显示,支气管哮喘患者FeNO、血清SDF-1水平均与PC35sGaW呈负相关(P＜0.05);Logistic回归分析结果显示,FeNO、SDF-1升高均为影响支气管哮喘患者发生气道高反应的独立危险因素(P＜0.05);ROC曲线分析结果显示,FeNO、血清SDF-1预测支气管哮喘患者气道高反应的曲线下面积分别为0.660、0.785 (P ＜0.001),截断值分别为29.203 ppb、403.574 ng/L,敏感度分别为70.9％、55.3％,特异度分别为55.3％、89.3％;FeNO联合血清SDF-1预测支气管哮喘患者气道高反应的曲线下面积分别为0.813 (P＜0.001),敏感度为61.2％,特异度为89.3％.结论 支气管哮喘患者FeNO、血清SDF-1水平显著升高,均与患者气道高反应性密切相关,对支气管哮喘患者气道高反应具有一定的预测价值,且二者联合价值更高.

目的 探究金雀异黄酮对幼龄哮喘大鼠气道重塑及转化生长因子-β(TGF-β)/核因子E2(NF-E2)相关因子2(Nrf2)/血红素加氧酶-1(HO-1)信号通路的影响.方法 将72只SD幼龄大鼠随机分成六组:模型组、对照组、金雀异黄酮低剂量组、金雀异黄酮中剂量组、金雀异黄酮高剂量组和地塞米松组,每组12只.除对照组外,其余各组幼龄大鼠均采用卵清蛋白(OVA)激发,制备哮喘模型.每次激发完成后1 h,给对照组和模型组幼鼠腹腔注射生理盐水,金雀异黄酮低、中、高剂量组分别腹腔注射4.5、9、18 mg/kg的金雀异黄酮,地塞米松组腹腔注射地塞米松0.2 mg/kg,注射体积10 mL/kg.检测各组大鼠气道反应性(Penh值);ELISA法检测血清中白介素-6(IL-6)、白介素-1β(IL-1β)、肿瘤坏死因子α(TNF-α)含量;HE染色观察肺组织病理学变化,并对气道形态学参数分析;ELISA法测定肺组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)含量;Western blot法检测肺组织中TGF-β、Nrf2、HO-1蛋白的相对表达水平.结果 与对照组相比,模型组大鼠肺组织结构损伤严重,平滑肌基底膜增厚,炎性细胞浸润明显,气管腔内可见黏液附着,Penh值、Wam/Pbm值[(26.45±2.12)vs.(9.26±1.67)]、Wai/Pbm值[(27.32±1.57)vs.(12.28±1.39)]、MDA 含量[(1.47±0.18)nmol/mg vs.(0.52±0.14)nmol/mg]、IL-6[(61.37±2.59)pg/mL vs.(11.83±0.92)pg/mL]、IL-1β[(71.85±3.53)pg/mL vs.(12.48±1.97)pg/mL]、TNF-α[(312.54±9.28)pg/mL vs.(82.19±8.04)pg/mL]含量及TGF-β蛋白水平[(1.24±0.14)vs.(0.16±0.05)]显著升高,差异有统计学意义(P＜0.05),SOD[(18.42±1.85)U/mg vs.(53.86±3.16)U/mg]、GSH 含量[(3.87±0.41)nmol/mg vs.(7.69±0.83)nmol/mg]及 Nrf2[(0.25±0.06)vs.(1.26±0.18)]、HO-1 蛋白水平[(0.26±0.05)vs.(1.28±0.16)]显著降低,差异有统计学意义(P＜0.05).与模型组相比,金雀异黄酮各处理组和地塞米松组大鼠Penh值、Wam/Pbm值、Wai/Pbm值、MDA含量、IL-6、IL-1 β、TNF-α含量及TGF-β蛋白水平显著降低,差异有统计学意义(P＜0.05),SOD、GSH含量及Nrf2、HO-1蛋白水平显著升高,差异有统计学意义(P＜0.05).金雀异黄酮高剂量组和地塞米松组差异无统计学意义(P＞0.05).结论 金雀异黄酮能有效减轻幼龄哮喘大鼠的炎症反应和氧化应激反应,抑制气道重塑,其机制可能与减轻TGF-β蛋白表达,上调Nrf2/HO-1抗氧化通路有关.

miR-363-3p is downregulated in lung adenocarcinoma and can inhibit tumor growth. Here, we aimed to investigate the effect of miR-363-3p on non-small-cell lung cancer (NSCLC) metastasis. In our study, miR-363-3p overexpression inhibited cell migration and invasion via epithelial-mesenchymal transition inhibition, while miR-363-3p knockdown exhibited the opposite effects. Further studies demonstrated that miR-363-3p bound to 3 '-untranslated regions of NEDD9 and SOX4, and negatively regulated their levels. Interestingly, NEDD9 or SOX4 knockdown rescued the metastasis-promoting effects of antagomiR-363-3p. The inhibitory effects of agomiR-363-3p were also blocked by NEDD9 or SOX4 overexpression. Moreover, lentivirus particles carrying pre-miR-363 (LV-pre-miR-363) significantly decreased, while LV-miR-363-3p inhibitor increased metastatic nodule numbers and the levels of NEDD9 and SOX4 in lungs. In conclusion, tumor suppressor miR-363-3p may be a potential target in NSCLC therapy.

目的 探讨血清胱抑素C(CysC)、血管内皮生长因子(VEGF)、白细胞介素17(IL-17)、激活素A(ACTA)在老年慢性阻塞性肺疾病(COPD)伴严重呼吸衰竭患者中的表达.方法 选取2016年3月至2019年3月本院224例老年COPD患者,根据有无发生严重呼吸衰竭分组观察组(n=78)、轻症组(n=146),另选取同期健康体检者86例为对照组.比较3组不同预后患者血清CysC、VEGF、IL-17、ACTA水平,分析血清指标对老年COPD伴严重呼吸衰竭的诊断价值及血清指标间相关性,并分析血清指标与APACHEⅡ评分相关性及预后预测价值.结果 3组血清CysC、VEGF、IL-17、ACTA水平,差异有统计学意义(P＜0.05);VEGF与Cys C、IL-17、ACTA水平呈负相关,CysC、IL-17、ACTA间水平呈正相关(P＜0.05);死亡患者血清CysC、IL-17、ACTA水平、APACHEⅡ评分高于存活患者,VEGF水平低于存活患者(P＜0.05);VEGF水平与APACHEⅡ评分呈负相关,CysC、IL-17、ACTA水平与APACHEⅡ评分呈正相关(P＜0.05);血清CysC、VEGF、IL-17、ACTA水平联合对预测老年COPD伴严重呼吸衰竭预后的AUC(0.864)大于单一血清指标,敏感性为92.86％,特异性为70.00％.结论 血清CysC、VEGF、IL-17、ACTA水平在老年COPD伴严重呼吸衰竭患者中呈异常表达,并与病情密切相关,联合检测有望成为老年COPD伴严重呼吸衰竭诊断及预后判断的有效手段.

Objective:To explore the effect of non-invasive ventilation in patients with chronic obstructive pulmonary disease (COPD) managed by general practitioners and specialists.Methods:A total of 64 patients with COPD and respiratory failure in stable period in the Fifth Affiliated Hospital of Zhengzhou University from December 2017 to December 2018 were selected and randomly divided into two groups by computer blind selection method: the family non-invasive ventilator ventilation group (observation group) and the natural course control group (control group), with 32 cases in each group. The patients were followed up by general practitioners and respiratory specialists once every three months and understood the situation of patients, discussed the parameters of ventilator, guided the application of ventilator, and monitored the pulmonary function indexes dynamically such as forced expiratory volume per second (FEV1% pred), blood gas analysis indexes such as blood gas analysis indicators (pH value, pulse oxygen saturation (SpO 2), arterial oxygen sub-pressure (PaO 2), arterial blood carbon dioxide sub-pressure (PaCO 2), modified British Medical Research Council (mMRC) dyspnea scales, and the number of acute exacerbations within 1 year. Results:After 1 year of treatment, SpO 2, PaO 2 and mMRC scales were improved compared with the control group, with statistically significant differences ( P<0.05), and the number of acute seizures decreased compared with the control group, and the difference was statistically significant ( P<0.05), but there was no significant difference in FEV1% pred, PaCO 2 and pH value( P>0.05). Conclusions:The combination of general practitioners and specialists in the management of noninvasive ventilation at home can significantly improve the arterial oxygen partial pressure of COPD patients, improve the degree of dyspnea and reduce the number of acute cases.

Here, we aimed to investigate the role of Xanthatin in asthma and its underlying mechanism. BALB/c mice were treated with ovalbumin (OVA) to establis a mouse model of asthma. Our results showed that OVA injection significantly increased inflammatory cell infiltration and goblet cell hyperplasia in lung issues, while Xanthatin treatment and STAT3 inhibitor C188-9 administration relieved these symptoms. Moreover, OVA-induced OVA-specific immunoglobulin E level in serum and the number of total cell, macrophages, lymphocytes, neutrophils, and eosinophils in bronchoalveolar lavage fluid (BALF) were markedly reduced by Xanthatin treatment and signal transducer and activator of transcription 3 (STAT3) inhibition. Additionally, Xanthatin treatment and STAT3 inhibition was also significantly decreased the levels of inflammatory cytokines in BALF in asthmatic mice. We further demonstrated that the STAT3/nuclear factor-kappaB (NF-κB) pathway was blocked by Xanthatin in asthmatic mice. Overall, we conclude that Xanthatin attenuates airway inflammation in asthmatic mice through blocking the STAT3/NFκB signaling pathway, indicating the potential of Xanthatin as a useful therapeutic agent for asthma.

目的 探讨抗MDA5抗体在皮肌炎相关性间质性肺病(DM-ILD)严重程度及预后评估中的意义.方法 收集2018年3月至2019年7月在郑州大学第一附属医院就诊的140例皮肌炎(DM)患者的临床资料.将101例抗MDA5抗体阴性的患者纳入A组,将39例抗MDA5抗体阳性的患者纳入B组.根据患者是否合并ILD,将A组患者分为A1组(抗MDA5抗体阴性不合并ILD,54例)和A2组(抗MDA5抗体阴性合并ILD,47例),将B组患者分为B1组(抗MDA5抗体阳性不合并ILD,2例)和B2组(抗MDA5抗体阳性合并ILD,37例).比较各组一般资料、血清涎液化糖链抗原-6(KL-6)、一氧化碳弥散量(DLCO)及胸部高分辨率CT(HRCT)评分.结果 B组仅存在皮疹的患者比例高于A组,差异有统计学意义(P<0.05).B2组女性所占比例低于A2组,且仅存在皮疹的患者比例高于A2组,差异有统计学意义(均P<0.05).B组KL-6水平高于A组,DLCO水平低于A组,差异有统计学意义(均P<0.05).B2组与B1组抗MDA5抗体滴度比较,差异无统计学意义(P>0.05).B2组KL-6水平高于B1组和A2组,B2组DLCO水平低于B1组和A2组,差异有统计学意义(均P<0.05).DLCO与KL-6呈负相关(r=-0.573,P<0.05),与抗MDA5抗体滴度无关(r=0.245,P>0.05).B2组HRCT评分高于A2组,差异有统计学意义(P<0.05).HRCT评分与抗MDA5抗体滴度水平呈正相关(r=0.356,P<0.05),与KL-6水平呈正相关(r=0.638,P<0.05),与DLCO呈负相关(r=-0.326,P<0.05).B组累积生存率低于A组,差异有统计学意义(P<0.05).结论 抗MDA5抗体阳性的DM-ILD患者的KL-6水平高,肺部病变严重,生存率低.

Lung cancer continues to be the leading cause of cancer-related deaths worldwide due to its high incidence, malignant behaviour and lack of major advancements in treatment strategy. The occurrence and development of lung cancer is closely related to inflammation. Thus, we conducted the present study to investigate the effects of IL-38 (interleukin-38), a newly identified anti-inflammatory factor, on non-small cell lung cancer (NSCLC), which accounts for about 85% of all lung cancers. We first evaluated the IL-38 expression in 384 pairs of NSCLC samples and their adjacent normal mucosa by real-time PCR, ELISA (enzyme-linked immunoassay) and tissue microarrays. Then the role of IL-38 on patient survival rates, cancer progression and their sensitivity to chemotherapy drugs was assessed. IL-38 was barely expressed in the NSCLC tissues but highly expressed in the adjacent normal tissues. The downregulation of IL-38 was significantly correlated with the results of the American Joint Committee on Cancer stage and degree of differentiation, and it was also shown to be an independent prognostic indicator of disease-free survival and overall survival for patients with NSCLC. Overexpression of IL-38 in NSCLC cells suppressed cell migration, invasion, proliferation and colony formation through suppressing β-catenin. IL-38 inhibited NSCLC formation in a mice model and sensitized the cancer cells to chemotherapy drugs. Our results show that IL-38 plays an inhibitory role in NSCLC development and functions as a novel prognostic indicator and a potential therapeutic target.

Objective: The aim of present study was to investigate the influence of genetic variation of programmed death-ligand 1 (PD-L1) on the prognosis of patients with non-small cell lung cancer (NSCLC) who received platinum-based adjuvant chemotherapy. Methods: This study was designed as a retrospective analysis, and a total of 278 patients with postoperative NSCLC who received platinum-based adjuvant chemotherapy from January 2012 to December 2018 in the Department of Respiratory Medicine of the First affiliated Hospital of Zhengzhou University were included in this study. Biological specimens of the patients were collected during hospitalization. Recurrence status and adverse reactions were evaluated in the hospital during adjuvant chemotherapy. Survival data of the patients were obtained through telephone follow-up after completing the fixed cycle of adjuvant chemotherapy. DNA extracted from the collected hematological specimens was genotyped for PD-L1 gene polymorphism. Additionally, postoperative cancer tissue specimens from 68 patients were collected for RNA extraction in order to perform the PD-L1 mRNA expression analysis. The univariate analysis of genotypes and prognosis was carried out by Kaplan-Meier survival analysis. Results: Prognostic results indicated that the median disease-free survival (DFS) of the 278 patients with NSCLC was 3.2 years and the median overall survival (OS) was 4.9 years. The prevalence of -1813G>C polymorphism were: GG genotype 173 cases (62.23%), GC genotype 92 cases (33.09%), CC genotype 13 cases (4.68%), the minor allele frequency was 0.21, the distribution of the three genotypes was in accordance with Hardy-Weinberg Equilibrium (P=0.864). In view of the rare frequency of CC genotype, GC and CC genotype were merged in the following analysis. The survival analysis results of the two genotype groups suggested that the median DFS of patients with GG and GC/CC genotype was 2.7 and 4.0 years, which was statistically significant (P=0.013). Furthermore, the median OS of patients with GG and GC/CC was 4.0 and 5.4 years respectively, which was statistically significant as well (P=0.009). However, the safety analysis failed to find the significant association between the polymorphism and adverse events (P>0.05). Interestingly, expression analysis of RNA extracted from cancer tissues specimens indicated that the PD-L1 mRNA expression of the patients with GG genotype were significantly higher than those of the GC/CC genotype (3.67±0.65 vs 2.69±0.78, P<0.001). Conclusion: The prognosis of patients with postoperative non-small cell lung cancer who received platinum-based adjuvant chemotherapy is influenced by -1813G>C polymorphism of PD-L1 gene.

Non-small cell lung cancer (NSCLC) is one of the most frequent cancers worldwide. The abnormal expression of long non-coding RNAs (lncRNAs) has been reported to be closely associated with the progression of human cancers, including NSCLC. Here, we demonstrated that differentiation antagonizing noncoding RNA (DANCR) was overexpressed in NSCLC tissues. Upregulation of DANCR expression was significantly associated with larger tumor size, advanced TNM stage and lymph node metastasis, and also predicted poor prognoses of patients with NSCLC. Functional experiments showed that DANCR enhanced NSCLC growth and metastasis both in vitro and in vivo. Further investigation revealed that DANCR could compete with the Sox4 mRNA to bind with miR-138, thus affecting Sox4 expression. In addition, we found that Sox4 bound to the promoter regions of DANCR gene to activate DANCR expression, suggesting a positive feedback loop of DANCR/miR-138/Sox4 in NSCLC. Taken together, these results provide a comprehensive analysis of the roles of DANCR as a competing endogenous RNA (ceRNA) in NSCLC progression.

BACKGROUND:MicroRNAs (miRNAs) have been reported to play crucial role in the airway inflammatory diseases. However, the involvement of miR-206 in airway inflammatory diseases is still uninvestigated. The study aimed to explore the effect of miR-206 on lipopolysaccharide (LPS)-induced inflammation injury in MRC-5 cells, and point out a potential relevance for chronic obstructive pulmonary disease (COPD).METHODS:LPS was utilized to expose MRC-5 cells, then cell viability, cell migration, apoptosis, apoptosis-associated factors, as well as the concentrations and protein levels of IL-6 and IL-8 were explored. After transfected with miR-206 mimic and inhibitor, above parameters were reassessed in LPS-injured cells. Expression level of IRAK1 was examined in miR-206 mimic/inhibitor transfected cells by using RT-qPCR. The effect of IRAK1 on LPS-induced inflammation injury was investigated in MRC-5 cells after transfection with pc-IRAK1 and sh-IRAK1. The effects of miR-206 and IRAK1 on MEK/ERK and JNK pathways were determined by western blot assay.RESULTS:LPS significantly triggered inflammation injury in MRC-5 cells by inhibiting cell viability, suppressing the healing of scratches, inducing cell apoptosis, down-regulating Bcl-2 expression and up-regulating Bax, cleaved-Caspase-3 and cleaved-Caspase-9 expression, and concurrently increasing the concentrations and the protein levels of IL-6 and IL-8. MiR-206 overexpression aggravated LPS-induced inflammation injury in MRC-5 cells. Up-regulation of IRAK1 was observed in miR-206 mimic-transfected cells. Moreover, IRAK1 overexpression promoted LPS-induced inflammation injury in MRC-5 cells. MiR-206 activated MEK/ERK and JNK pathways by regulating IRAK1.CONCLUSIONS:MiR-206 promotes LPS-induced inflammation injury through regulation of IRAK1 in MRC-5 cells.