Background Non-small cell lung cancer (NSCLC) is a major histological subtype of lung cancer with high mortality and morbidity. A substantial amount of evidence demonstrates long non-coding RNAs (lncRNA) as critical regulators in tumorigeneis and malignant progression of human cancers. The oncogenic role of BBOX1 anti-sense RNA 1 (BBOX1-AS1) has been reported in several tumors. As yet, the potential functions and mechanisms of BBOX1-AS1 in NSCLC are obscure. Methods The gene and protein expression was detected by qRT-PCR and western blot. Cell function was determined by CCK-8, colony forming, would healing and transwell assays. Bioinformatics tools, ChIP assays, dual luciferase reporters system and RNA pull-down experiments were used to examine the interaction between molecules. Subcutaneous tumor models in nude mice were established to investigate in vivo NSCLC cell behavior. Results BBOX1-AS1 was highly expressed in NSCLC tissues and cells. High BBOX1-AS1 expression was associated with worse clinical parameters and poor prognosis. BBOX1-AS1 up-regulation was induced by transcription factor KLF5. BBOX1-AS1 deficiency resulted in an inhibition of cell proliferation, migration, invasion and EMT in vitro. Also, knockdown of BBOX1-AS1 suppressed NSCLC xenograft tumor growth in mice in vivo. Mechanistically, BBOX1-AS1 acted act as a competetive “sponge” of miR-27a-5p to promote maternal embryonic leucine zipper kinase (MELK) expression and activate FAK signaling. miR-27a-5p was confirmed as a tumor suppressor in NSCLC. Moreover, BBOX1-AS1-induced increase of cell proliferation, migration, invasion and EMT was greatly reversed due to the overexpression of miR-27a-5p. In addition, the suppressive effect of NSCLC progression owing to BBOX1-AS1 depletion was abated by the up-regulation of MELK. Consistently, BBOX1-AS1-mediated carcinogenicity was attenuated in NSCLC after treatment with a specific MELK inhibitor OTSSP167. Conclusions KLF5-induced BBOX1-AS1 exerts tumor-promotive roles in NSCLC via sponging miR-27a-5p to activate MELK/FAK signaling, providing the possibility of employing BBOX1-AS1 as a therapeutic target for NSCLC patients.

目的 探讨中性粒细胞淋巴细胞比率(NLR)在慢性阻塞性肺疾病急性加重期的变化及其临床价值.方法 收集2017年1月一2018年5月期间于郑州大学第一附属医院就诊的共135名慢性阻塞性肺疾病(COPD)患者,其中稳定期(SCOPD组)75人,加重期(AECOPD组)60人,对照组为同期体检的34名健康人员,均于清晨空腹状态下采集病例组与对照组的血常规及C-反应蛋白(CRP),比较三组中性粒细胞计数(N)、淋巴细胞计数(L)、中性粒细胞比率(N％)、淋巴细胞比率(L％)、中性粒细胞淋巴细胞比率(NLR)及CRP水平,运用相关分析探讨COPD组患者NLR与CRP的相关性,以受试者工作(ROC)曲线分析NLR及CRP预测慢性阻塞性肺疾病急性加重的最佳切点.结果 AECOPD组NLR(6.21 土2.83)高于SCOPD组(2.08 ±0.89)及对照组(1.71 士0.65),差异有统计学意义(F = 106.96,P= 0.00);AECOPD 组N(6.39 ±3.02) x 109/L、N％ (74.6 ±9.59)％、CRP 水平(50.6 ±7.06)mg/L 高于SCOPD 组N(3.60 ±1.15) x 109/L、N％ (54.9 ±10.2)％、CRP 水平(2.63 ±0.34)mg/L 和对照组N(3.39±1.03) x 109/L、N％ (55.0 ±7.86)％、CRP 水平(1.81 ±0.18)mg/L,差异有统计学意义(P均＜ 0.001);AECOPD 组L( 1.13 ±0.39) x 109/L、L％ (14.8 土7.38)％ 均低于SCOPD 组L(1.92 ±0.69) x 109/L、L％ (30.0±7.83)％和对照组 L(2.07 ±0.46) x 109/L、L％ (34.5 ±7.13)％,差异有统计学意义(P均＜0.001);Pearson 相关分析示,AECOPD 组NLR 与CRP 成正相关(r = 0.555 P ＜0.001),SCOPD 组NLR与CRP成正相关(r =0.365 P=0.001);ROC曲线示,NLR曲线下面积为0.948,CRP曲线下面积为0.996(P＜0.001),NLR预测AECOPD的最佳切点为3.53,CRP最佳切点为9.147 mg/L.结论 NLR与慢性阻塞性肺疾病的急性加重相关,可以作为慢性阻塞性肺疾病急性加重的炎性标志物.

目的:探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者发生胰岛素抵抗(IR)的危险因素.方法:选择行多导睡眠监测(PSG)的患者390例,其中确诊为OSAHS者365例,单纯鼾症者25例,依据HOMA-IR将OS-AHS患者分为IR组(175例)和非IR组(190例),分析两组间一般资料及PSG监测结果的差异.结果:OSAHS患者的IR发生率(47.9％)高于单纯鼾症者(16.0％)(P=0.002).与非IR组相比,IR组OSAHS患者的体重、体质指数、腰围、ESS评分、高血压病发病率、呼吸暂停低通气指数、血氧饱和度低于90％所占的时间比(CT90％)、氧减指数(ODI)、微觉醒指数、总呼吸暂停时间均升高,年龄、最低血氧饱和度、平均血氧饱和度均降低(P<0.05);logis-tic回归分析显示总呼吸暂停时间、CT90％、ODI、高血压病史是IR的危险因素,OR(95％CI)分别为1.037(1.023～1.052)、1.014(1.002～1.027)、1.007(1.004～1.011)、10.236(5.946～17.623).结论:OSAHS与IR关系密切;总呼吸暂停时间、CT90％、ODI、高血压病史可能是OSAHS患者IR的危险因素.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a serious respiratory disease, the mechanism is unclear. This paper revealed the mechanism of ganoderic acid B (BB) on lipopolysaccharide-induced pneumonia in mice. Pneumonia model was induced by LPS in mice and A549 cells. Lung dry/wet weight (W/D) and myeloperoxidase (MPO) activity in lung were examined. Lung histopathological changes was observed by HE staining. Superoxide dismutase (SOD), malondialdehyde (MDA) and proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in mice and A549 cells were detected. Rho/NF-κB pathway in mice and A549 cells were examined by Western Blot. BB significantly reduced W/D and MPO activity, restored lung histopathological changes. BB also increased SOD, decreased MDA, TNF-α, IL-1β and IL-6 in mice and A549 cells. In addition, BB inhibited Rho/NF-κB pathway in mice and A549 cells. BB has protective effect on LPS-induced pneumonia in mice, and its mechanism is related to the regulation of Rho/NF-κB signaling pathway.

AIM:This study aims to evaluate the role of the EPHA5 mutation in the migration and invasion of non-small cell lung cancer (NSCLC) cells and in modulating the killing effect of natural killer (NK) cells to NSCLC cells.METHODS:EPHA5-wt (wild type) and EPHA5-mut (mutation) plasmids were constructed. EPHA5 was silenced using si-EPHA5. NSCLC cell migration and invasion were determined using Transwell assays. NK cell proliferation and apoptosis were determined using CCK-8 assay and flow cytometry, respectively. The killing effect of NK cells to NSCLC cells was also examined.RESULTS:EPHA5 mutation significantly promoted migration and invasion in NSCLC cells. Furthermore, EPHA5 mutation notably impaired the cytotoxicity of NK cells against NSCLC cells. In contrast, EPHA5-wt overexpression and EPHA5 silencing exerted the opposite effect.CONCLUSION:EPHA5 mutation impairs the NK cell-mediated cytotoxicity against NSCLC cells and promotes migration and invasion in NSCLC cells.