miR-206在肺癌中的作用及机制研究进展

肺癌是现今全世界死亡率和发病率最高的恶性肿瘤,严重危及人类健康,其中超过85%的患者为非小细胞肺癌,5年预计生存期不超过16%。微小RNA(microRNA,mi RNA)是一类在基因组转录出来后直接在RNA水平上行使生物学功能的非编码RNA,大小约20～25个核苷酸组成,广泛存在于真核生物中。mi RNA可通过对癌基因或抑癌基因进行转录后调控而发挥类似于癌基因或抑癌基因的作用。MicroRNA-206(mi R-206)定位于人类第6号染色体上,最早从骨骼肌中发现,它参与人体中一系列的生物学过程例如细胞增殖,组织器官的生长及肿瘤的发生等。最近大量研究显示mi R-206在肿瘤细胞中表达失调,在肿瘤的生长、增殖、凋亡及侵袭、转移、耐药中发挥重要作用。本文就mi R-206在肺癌中的作用及其机制的研究进展作一综述。     

补肺通络解毒汤联合培美曲塞治疗肺癌的效果及对患者趋化因子受体的影响

目的:探讨补肺通络解毒汤联合培美曲塞治疗肺癌的效果及对患者趋化因子受体的影响。方法:选取2016年4月-2018年5月期间我院收治的肺癌患者78例,依据不同的治疗方法随即分为对照组和研究组,对照组采用培美曲塞+顺铂治疗,研究组在其基础上联合应用补肺通络解毒汤治疗,统计对比两组患者的治疗效果及不良反应的发生情况,对比两组患者治疗前后的生活质量,对比两组患者治疗后癌组织中CCR7和CXCR4的表达情况。结果:治疗过程中,研究组患者的头晕头痛、呕吐恶心、肝损伤的发生率低于对照组(P0.05);治疗前两组患者的生活质量没有明显的差异(P0.05),治疗后均得到提高,研究组患者的躯体、生理、心理和社会等功能评分明显高于对照组(P0.05);治疗后,研究组和对照组患者的缓解率分别为51.28%、28.21%,研究组高于对照组(P0.05);研究组患者癌组织中趋化因子受体CCR7和CXCR4的阳性表达率低于对照组(P0.05)。结论:采用补肺通络解毒汤联合培美曲塞+顺铂治疗肺癌,可以有效减少患者在治疗过程中发生的不良反应,提高生活质量,改善趋化因子受体的表达,控制和缓解病情。     

香鳞毛蕨苷提取物E对人肺癌A549细胞增殖及凋亡的影响

目的:研究香鳞毛蕨苷提取物E(Fragranoside E)对人肺癌A549细胞增殖及凋亡的影响。方法:将体外培养的人肺癌A549细胞分为对照组(0.1%DMSO、100 nM紫杉醇)和实验组,通过CCK-8实验、克隆形成实验检测细胞增殖情况;检测乳酸脱氢酶(LDH)水平以探讨Fragranoside E的细胞毒性;透射电镜及流式细胞术检测A549细胞的凋亡情况。进一步采用5mM N-乙酰半胱氨酸(N-acetylcysteine,NAC)预处理A549细胞2 h后,采用荧光显微镜观察细胞内ROS的释放情况。结果:CCK8及克隆形成实验结果提示Fragranoside E呈浓度和时间依赖性抑制A549细胞增殖(P0.05);≤40μM Fragranoside E处理A549细胞对其LDH的释放无显著影响(P0.05);而40μM Fragranoside E可诱导A549细胞凋亡,细胞内ROS升高,NAC(5 m M)预处理2 h后,细胞内ROS(112.6%±12.3%)较Fragranoside E处理组显著降低(P0.05)。结论:Fragranoside E能够抑制A549细胞增殖,诱导其凋亡,其抗肿瘤活性可能与细胞内ROS释放有关。     

支气管肺泡灌洗术用于重症支气管哮喘的疗效评价及对肺功能、炎症因子水平的影响

目的:探讨支气管肺泡灌洗术用于重症支气管哮喘的疗效及对肺功能、炎症因子水平的影响。方法:选择我院2015年3月～2018年3月收治的150例重症支气管哮喘患者,均接受支气管肺泡灌洗术治疗,分析其临床疗效,临床症状改善状况,治疗前后肺功能、炎症因子、血气指标的变化情况和不良反应的发生情况。结果:治疗后,150例患者中,临床控制70例,好转60例,无效20例,总有效率为86.67%(130/150),哮鸣音消失时间为(5.17±0.64)d、ACT评分(27.85±3.86)分、住院时间为(5.73±0.75)d。治疗后,患者用力肺活量(FVC)、1s用力呼气容积(FEV1)、呼气峰流速(PEF)、血氧分压(PaO_2)、血氧饱和度(SaO_2)均显著高于治疗前(P0.05),嗜酸性粒细胞(EOS)、干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)及二氧化碳分压(PaCO_2)低于治疗前(P0.05)。150例患者中,发生支气管痉挛2例,咽喉部疼痛3例,无猝死、大咯血、气胸等严重并发症发生。结论:支气管肺泡灌洗术用于重症支气管哮喘的疗效肯定,可有效改善患者肺功能,并减轻炎症反应。     

3D打印技术在周围型肺癌手术规划中的应用

目的:通过比较计算机断层扫描,三维重建图像和3D打印在手术中显示肺动脉分支的能力,探讨3D打印技术在周围型肺癌手术规划中的应用价值。方法:2018年1月-2018年12月,同一胸外科治疗组中接受电视胸腔镜择期右肺上叶切除手术的周围型肺癌患者30例。随机分为3组,每组10例,分别通过计算机断层扫描,三维重建图像和3D打印进行术前手术规划。分别记录每组手术规划中的右肺上叶动脉分支数目,然后将这些记录与术中实际所见进行比较。结果:各组间患者一般资料无统计学差异。所有患者均有完整的CT扫描、三维重建、3D打印和术中动脉分支数据,且都接受了VATS解剖性右肺上叶切除术,术中进行顺利,无中转开胸,无术中大出血,术后无明显并发症和围手术期死亡,皆顺利出院。CT组的右肺上叶动脉分支数量为1.5±0.52,3DI组为2.1±0.57,3DP组为2.2±0.63。CT组、3DI组和3DP组分别与手术中所见比较,CT组存在统计学差异(P=0.025),其他两组无统计学意义。结论:3D打印技术在周围型肺癌手术规划中的效果优于计算机断层扫描,比三维重建图像更加直观,建议推广。     

肺保护性通气对单肺通气患者呼吸动力学、炎性因子及认知功能的影响

目的:探讨肺保护性通气对单肺通气(OLV)患者呼吸动力学、炎性因子及认知功能的影响。方法:选取2017年7月～2018年5月期间我院收治的择期行肺部手术的患者215例为研究对象。根据OLV方式的不同将患者分为传统OLV组(n=107)和保护性OLV组(n=108),比较两组OLV0.5 h(T1)、OLV1h(T2)等时间点的胸肺顺应性(CT)、气道阻力(Raw)、气道峰压(Ppeak)等指标情况,比较两组T1、T2、拔管后2 h(T3)白介素-6(IL-6)、白介素-8(IL-8)水平,比较两组术前、术后10 d第一秒用力呼气容积(FEV1)、一氧化碳弥散量(DLCO)、25%用力呼气流量(FEF25),比较两组术前、术后10 d、术后1个月简易精神状态量表(MMSE)评分,记录两组患者术后认知功能障碍发生率。结果:两组患者T2时间点CT均较T1时间点下降,但保护性OLV组高于传统OLV组(P0.05);两组患者T2时间点Raw、Ppeak较T1时间点升高,但保护性OLV组低于传统OLV组(P0.05)。两组患者T2、T3时间点IL-6、IL-8均较T1时间点升高,且T3时间点高于T2时间点(P0.05);保护性OLV组T2、T3时间点均低于传统OLV组(P0.05)。两组患者术前、术后1个月MMSE评分比较差异无统计学意义(P0.05);术后10 d,传统OLV组MMSE评分较术前、术后1个月降低,且术后10 d,保护性OLV组MMSE评分高于传统OLV组(P0.05);保护性OLV组术后认知功能障碍发生率显著低于传统OLV组(P0.05)。结论:OLV患者采用肺保护性通气的方式有助于改善患者呼吸动力学、肺功能以及认知功能,同时可以减轻机体炎性反应。     

苹果酸-天冬氨酸穿梭关键酶和肺腺癌临床特征的相关性

目的:探讨苹果酸-天冬氨酸穿梭途径中的关键酶和肺腺癌临床特征的相关性。方法:首先从GEO数据库、TCGA平台中获取肺腺癌的转录组数据和相应的临床信息,通过非参数检验分析苹果酸脱氢酶1/2和天冬氨酸氨基转移酶1/2这四种关键酶在肿瘤组织和正常组织之间的表达差别,再进一步分析其和肺腺癌患者总生存期、人口学特征、TNM参数以及肿瘤恶性生物学标志物之间的关系。结果:肺腺癌中苹果酸脱氢酶1/2和天冬氨酸氨基转移酶1/2均呈高表达;天冬氨酸氨基转移酶2 (Glutamic-oxaloacetic transaminase 2,GOT2)和肺腺癌的生存概率有关,高表达GOT2的病人往往具有较短的总生存期;GOT2的表达和肺腺癌的人口学特征、TNM参数、临床分期均无明显统计学关联,与肿瘤恶性标志物PCNA呈显著正相关(r=0.2,P0.05)。结论:肺腺癌组织中苹果酸-天冬氨酸穿梭途径中关键酶GOT2呈高表达,并可能促进肺腺癌的发生和恶性进展。     

Keratinocyte Growth Factor Administration Attenuates Murine Pulmonary Mycobacterium tuberculosis Infection through Granulocyte-Macrophage Colony-stimulating Factor (GM-CSF)-dependent Macrophage Activation and Phagolysosome Fusion

Augmentation of innate immune defenses is an appealing adjunctive strategy for treatment of pulmonary Mycobacterium tuberculosis infections, especially those caused by drug-resistant strains. The effect of intranasal administration of keratinocyte growth factor (KGF), an epithelial mitogen and differentiation factor, on M. tuberculosis infection in mice was tested in prophylaxis, treatment, and rescue scenarios. Infection of C57BL6 mice with M. tuberculosis resulted in inoculum size-dependent weight loss and mortality. A single dose of KGF given 1 day prior to infection with 10⁵ M. tuberculosis bacilli prevented weight loss and enhanced pulmonary mycobacterial clearance (compared with saline-pretreated mice) for up to 28 days. Similar effects were seen when KGF was delivered intranasally every third day for 15 days, but weight loss and bacillary growth resumed when KGF was withdrawn. For mice with a well established M. tuberculosis infection, KGF given every 3 days beginning on day 15 postinoculation was associated with reversal of weight loss and an increase in M. tuberculosis clearance. In in vitro co-culture experiments, M. tuberculosis-infected macrophages exposed to conditioned medium from KGF-treated alveolar type II cell (MLE-15) monolayers exhibited enhanced GM-CSF-dependent killing through mechanisms that included promotion of phagolysosome fusion and induction of nitric oxide. Alveolar macrophages from KGF-treated mice also exhibited enhanced GM-CSF-dependent phagolysosomal fusion. These results provide evidence that administration of KGF promotes M. tuberculosis clearance through GM-CSF-dependent mechanisms and enhances host defense against M. tuberculosis infection.     

NLRP3 Protein Deficiency Exacerbates Hyperoxia-induced Lethality through Stat3 Protein Signaling Independent of Interleukin-1β

Supplemental oxygen inhalation is frequently used to treat severe respiratory failure; however, prolonged exposure to hyperoxia causes hyperoxic acute lung injury (HALI), which induces acute respiratory distress syndrome and leads to high mortality rates. Recent investigations suggest the possible role of NLRP3 inflammasomes, which regulate IL-1β production and lead to inflammatory responses, in the pathophysiology of HALI; however, their role is not fully understood. In this study, we investigated the role of NLRP3 inflammasomes in mice with HALI. Under hyperoxic conditions, NLRP3^−/− mice died at a higher rate compared with wild-type and IL-1β^−/− mice, and there was no difference in IL-1β production in their lungs. Under hyperoxic conditions, the lungs of NLRP3^−/− mice exhibited reduced inflammatory responses, such as inflammatory cell infiltration and cytokine expression, as well as increased and decreased expression of MMP-9 and Bcl-2, respectively. NLRP3^−/− mice exhibited diminished expression and activation of Stat3, which regulates MMP-9 and Bcl-2, in addition to increased numbers of apoptotic alveolar epithelial cells. In vitro experiments revealed that alveolar macrophages and neutrophils promoted Stat3 activation in alveolar epithelial cells. Furthermore, NLRP3 deficiency impaired the migration of neutrophils and chemokine expression by macrophages. These findings demonstrate that NLRP3 regulates Stat3 signaling in alveolar epithelial cells by affecting macrophage and neutrophil function independent of IL-1β production and contributes to the pathophysiology of HALI.     

Oxidative stress,redox signaling pathways,and autophagy in cachectic muscles of male patients with advanced COPD and lung cancer

Muscle dysfunction and wasting are predictors of mortality in advanced COPD and malignancies. Redox imbalance and enhanced protein catabolism are underlying mechanisms in COPD. We hypothesized that the expression profile of several biological markers share similarities in patients with cachexia associated with either COPD or lung cancer (LC). In vastus lateralis of cachectic patients with either LC (n=10) or advanced COPD (n=16) and healthy controls (n=10), markers of redox balance, inflammation, proteolysis, autophagy, signaling pathways, mitochondrial function, muscle structure, and sarcomere damage were measured using laboratory and light and electron microscopy techniques. Systemic redox balance and inflammation were also determined. All subjects were clinically evaluated. Compared to controls, in both cachectic groups of patients, a similar expression profile of different biological markers was observed in their muscles: increased levels of muscle protein oxidation and ubiquitination (p<0.05, both), which positively correlated (r=0.888), redox-sensitive signaling pathways (NF-κB and FoxO) were activated (p<0.05, all), fast-twitch fiber sizes were atrophied, muscle structural abnormalities and sarcomere disruptions were significantly greater (p<0.05, both). Structural and functional protein levels were lower in muscles of both cachectic patient groups than in controls (p<0.05, all). However, levels of autophagy markers including ultrastructural autophagosome counts were increased only in muscles of cachectic COPD patients (p<0.05). Systemic oxidative stress and inflammation levels were also increased in both patient groups compared to controls (p<0.005, both). Oxidative stress and redox-sensitive signaling pathways are likely to contribute to the etiology of muscle wasting and sarcomere disruption in patients with respiratory cachexia: LC and COPD.