阿帕替尼联合CCI-779体外抑制小细胞肺癌细胞株NCI-H446的增殖和迁移

背景与目的肺癌是世界上最常见的恶性肿瘤,其中小细胞肺癌是恶性程度最高的亚型,具有生长迅速、早期转移和高度血管化等特点。阿帕替尼(Apatinib)是我国自主研发的血管内皮生长因子受体2抑制剂,在多种实体瘤中疗效显著。本研究旨在探讨Apatinib对小细胞肺癌细胞株NCI-H446的体外作用以及联合哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)抑制剂CCI-779对小细胞肺癌的体外作用。方法体外培养小细胞肺癌细胞株NCI-H446,CCK8法、细胞凋亡实验、细胞周期实验及Transwell实验检测Apatinib及联合mTOR抑制剂CCI-779对NCI-H446细胞增殖、凋亡、周期及迁移的影响;Western blot实验检测血管内皮生长因子受体和细胞周期相关蛋白的表达。结果CCK8实验结果显示高浓度Apatinib能抑制NCI-H446细胞增殖;细胞凋亡实验结果显示高浓度Apatinib诱导NCI-H446细胞凋亡;Transwell实验结果显示高浓度Apatinib抑制NCI-H446细胞迁移;联合mTOR抑制剂CCI-779后,低浓度Apatinib便能抑制NCI-H446细胞增殖和迁移,诱导细胞凋亡。结论Apatinib对小细胞肺癌细胞株NCI-H446的作用具有浓度依赖性特征,高浓度Apatinib能够抑制NCI-H446细胞增殖和迁移,诱导细胞凋亡,与mTOR抑制剂CCI-779联用能增加NCI-H446细胞对Apatinib的敏感性。

基于TCGA数据库的EGFR突变型与野生型肺腺癌患者免疫微环境的差异性分析

背景与目的肺癌是一种具有高发病率与高死亡率的恶性肿瘤,腺癌是其中一个重要的组织亚型。表皮生长因子受体(epidermal growth factor receptor,EGFR)突变是肺腺癌患者重要的驱动基因。EGFR-酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)对EGFR敏感突变的患者疗效显著。而免疫治疗作为新兴的治疗却不能使EGFR突变患者获益,其中的机制研究尚不明确,并集中于EGFR与程序性死亡受体-配体1(programmed cell death-ligand 1,PD-L1)表达之上,而我们推测与两类患者不同的免疫微环境有关。方法从癌症基因组图谱(TheCancerGenome Atlas,TCGA)数据库收集肺腺癌数据集,下载临床信息资料及基因表达谱资料。通过TIMER2.0计算TCGA数据库中免疫相关淋巴细胞浸润情况。并对EGFR突变型与野生型患者进行基因集富集分析。结果临床特征分析显示EGFR突变更频繁发生于女性以及未吸烟患者中。免疫浸润分析显示EGFR突变患者通常具有更高的肿瘤相关成纤维细胞、普通髓系祖细胞、造血干细胞、效应CD4^(+)T细胞、自然杀伤T细胞浸润;具有更低的记忆B细胞、初始B细胞、浆细胞、浆细胞样树突状细胞、记忆CD4^(+)T细胞、CD4^(+)辅助性T细胞2、CD8^(+)T细胞、中心记忆CD8^(+)T细胞、初始CD8^(+)T细胞浸润。我们发现CD8^(^(+))T细胞、自然杀伤T细胞、记忆B细胞和造血干细胞在肿瘤中浸润的程度越高则患者预后越好(Log-rank检验,P=0.017、0.009,3、0.018和0.016)。同时CD4^(+)辅助性T细胞2在肿瘤中浸润的程度越高则患者预后越差(Log-rank检验,P=0.016)。基因集富集分析的结果显示,相比较EGFR野生型肺腺癌患者而言,EGFR突变患者的自然杀伤细胞介导的对肿瘤细胞的免疫应答的正调控、自然杀伤细胞激活参与免疫反应、在自然杀伤细胞介导的对肿瘤细胞的免疫应答这三条与自然杀伤细胞有关的通路上均处于下调状态,而参与免疫应答的细胞因子分泌的正调节这条通路为上调。结论EGFR突变患者肿瘤微环境缺乏有效的杀伤肿瘤的效应细胞并出现了效应细胞功能失调。这可能是EGFR突变患者免疫治疗疗效差的潜在原因。

The theory of compression–shear coupled composite wave propagation in rock

The wave velocity analysis of rock medium is the main method used to explore the internal compositions in the crust and research seismic.In this paper,a compression–shear coupled nonlinear elastic constitutive relation is established,which is consistent with the mechanical properties of rock and mineral medium under high pressure.On this basis,numerical solutions of the wave equation and plane wave analytical solutions for the primary and secondary wave velocities are obtained.As is indicated by the comparison with the linear elastic constitutive theory,the results reflect the compression–shear coupling characteristics of the rock,including the stress path effect and the compression–shear coupling wave effect.With different parameter values,the velocity of the secondary wave changes from lower than that of the elastic shear wave,to higher than that of the elastic shear wave.The research results are expected to provide meaningful explanations for the physical mechanisms of the supershear wave and sub-Rayleigh wave,and guidance for the detection of rock and soil composition and the observation of seismic waves.

Numerical simulation of liquid falling film on horizontal circular tubes

The objective of this study is to investigate numerically the flow characteristics of falling film on horizontal circular tubes. Numerical simulations are performed using FLUENT for 2D configurations with one and two cylinders. The volume of fluid method is used to track the motion of liquid falling film and the gas-liquid interface. The effect of flow characteristics on heat and transfer coefficient may be remarkable, although it has been neglected in previous studies. The velocity distribution and the film thickness characteristics on the top tube, some special flow characteristics on the bottom tube, intertube flow modes and effect of liquid feeder height on flow characteristics have been studied. Our simulations indicate that 1） the velocity distributions of the upper and lower parts of the tube are not strictly symmetric and non- uniform, 2） the film thickness depends on flow rate and angular distributions, 3） the flow characteristics of the top tube are different from those of the bottom tube, 4） three principal and two intermediate transition modes are distinguished, and 5） the liquid feed height plays an important role on the formation of falling film. The numerical results are in a good agreement with the theoretical values by the Nusselt model and the reported results.

Nano-Fe_(3)O_(4) Encapsulated-Silica Particles Bearing 3-Amino-propyl Group as a Magnetically Separable Catalyst for Efficient Knoevenagel Condensation of Aromatic Aldehydes with Active Methylene Compounds

Knoevenagel condensation of aromatic aldehydes with active methylene compounds such as malononitrile,ethylcyanoacetate,benzimidazol-2-acetonitrile and benzothiazole-2-acetonitrile proceeded very smoothly,catalyzed by nano-Fe_(3)O_(4) encapsulated-silica particles supported primary amine.Both reaction time and yield are satisfying.The advantages of this catalyst are ease of preparation,non-toxicity,low cost,ease of handling and recyclability.