LncRNA MEG3靶向miR-181a-5p调控宫颈癌细胞放射敏感性

目的 研究LncRNA MEG3对宫颈癌细胞放射敏感性的影响,并探讨其作用机制。方法 运用qRT-PCR法检测放射抗性和放射敏感性宫颈癌细胞中LncRNA MEG3的表达;将过表达对照组(转染pcDNA 3.1)、过表达LncRNA MEG3组(转染pcDNA 3.1-LncRNA MEG3)、抑制miR-NC组(转染anti-miR-NC)、抑制miR-181a-5p组(转染anti-miR-181a-5p)、过表达LncRNA MEG3+过表达miR-NC组(共转染pcDNA 3.1-LncRNA MEG3和anti-miR-NC)、过表达LncRNA MEG3+过表达miR-181a-5p组(共转染pcDNA 3.1-LncRNA MEG3和anti-miR-181a-5p),均用脂质体法转染至SiHa细胞;克隆形成实验检测细胞的存活分数;流式细胞术检测细胞的凋亡率;双荧光素酶报告基因检测实验检测细胞的荧光活性;Western blot检测细胞中PTEN、p-Akt、Akt的蛋白表达。结果 与放射敏感组相比,放射抗性宫颈癌组织中LncRNA MEG3的表达明显降低(P<0.05),其表达量与宫颈癌细胞的放射敏感性呈正相关;过表达LncRNA MEG3、抑制miR-181a-5p均可显著增强宫颈癌细胞SiHa放射敏感性,促进凋亡(P<0.05);野生型LncRNA MEG3细胞的荧光活性受miR-181a-5p的抑制。过表达miR-181a-5p逆转了LncRNA MEG3对宫颈癌细胞放射增敏和促凋亡作用及对PTEN/Akt信号通路的调控。结论 长链非编码RNA LncRNA MEG3可增强宫颈癌细胞放射敏感性,其机制可能与靶向miR-181a-5p调控PTEN/Akt 信号通路有关,可为提高宫颈癌的预后提供新方向。     

川续断提取物续断皂苷Ⅵ防治骨质疏松症的研究进展

随着我国老年人绝对数量的增长以及老龄化加速,骨质疏松症(osteoporosis,OP)已然成为我国需要面对的公共健康问题。近年来对续断防治OP的基础及临床研究成为热点,研究发现川续断皂苷Ⅵ具有较好的防治OP的功效,可以通过多个细胞层面及生物学通路干预骨代谢,从而发挥治疗OP的作用。笔者从续断皂苷Ⅵ对BMSCs、成骨细胞、破骨细胞及相关生物学信号通路的影响来综述续断皂苷Ⅵ防治骨质疏松的研究概况,以期为续断皂苷Ⅵ的基础研究、临床应用及新药开发等提供参考。     

胃癌组织中WISP1和Ki67的表达及其临床病理意义

目的:探讨胃癌组织中WISP1和Ki67蛋白的表达及其临床病理意义。方法:收集中国医科大学附属第一医院肿瘤外科手术切除的胃癌组织标本87例及其配对非癌（距癌灶边缘>5 cm取材）胃黏膜组织80例，采用免疫组织化学方法检测WISP1和Ki67蛋白在胃癌组织及其配对正常胃黏膜组织中的表达。结果:胃癌组织中WISP1的阳性表达率为81.61%（71/87），显著高于非癌胃黏膜组织阳性表达率12.50%（10/80）。WISP1蛋白表达，在低分化腺癌中的阳性表达较中（P=0.000）、高（P=0.032)分化管状腺癌显著增高，弥漫型胃癌显著高于肠型胃癌（P=0.000），在肿瘤直径>5 cm的胃癌组织中显著高于肿瘤直径≤5 cm的胃癌组织（P=0.010），在伴有淋巴结转移的胃原发灶癌组织中较无淋巴结转移组增高（P=0.025）。Ki67蛋白表达与进展期胃癌患者肿瘤浸润深度（P=0.043）和淋巴结转移（P=0.027）相关。WISP1阳性表达与Ki67表达呈正相关（rk=0.240，P=0.026）。结论:WISP1在胃癌组织中表达显著上调，联合检测胃癌组织中WISP1和Ki67蛋白的表达，可更好的预测淋巴结转移情况，为胃癌患者预后评价提供参考。     

左金丸抗幽门螺杆菌感染的分子网络调控机制研究

目的基于网络药理学和生物信息学方法探究左金丸抗幽门螺杆菌(Hp)感染的分子网络调控机制。方法通过中药系统药理学数据库和分析平台(TCMSP)检索左金丸化学成分,筛选并预测其入血活性成分和作用靶点,检索疾病数据库中与Hp感染相关的作用靶点,构建左金丸成分靶点与疾病靶点的交互网络,获得左金丸抗Hp的特征性基因;通过DAVID6.8数据库对上述特征性基因进行GO功能富集和KEGG通路富集分析;利用Cytohubba筛选出左金丸抗Hp感染的关键靶点。结果通过TCMSP筛选、预测得到左金丸32个入血活性成分和197个作用靶点。GO分析共得到199条富集结果,其中生物过程包含炎症反应、RNA信号转录、信号传导等152条,细胞组分包含细胞核、细胞外基质、蛋白复合物等19条,分子功能包含细胞因子活性、DNA结合、ATP结合等28条。KEGG分析结果显示,Jak-STAT信号通路、T细胞受体信号通路、细胞周期信号通路、Wnt信号通路等65条通路与左金丸抗Hp感染密切相关。经Cytohubba筛选得到CXCL8、IL10、IL4、VEGFA、MMP9等10个关键基因。结论左金丸抗Hp感染具有多成分、多靶点、多通路协同作用的特点,可为其活性成分研究和抗Hp药效及机制研究提供依据。     

<i>Sinomenium</i> Inhibits the Viability of Hepatoma Carcinoma Cells through Activating IFNA2

Hepatocellular carcinoma (HCC) ranks the sixth place of most common cancers. Meanwhile, it is the tertiary mortality cause of cancer. There is no effective therapeutic method to prevent and treat the liver cancer. Sinomenine is a kind of Chinese traditional medicine herbal, it is reported that it can inhibit the viability of several cancer cells. The study is to explore whether sinomenine is also able to inhibit the cell viability of HCC and its potential mechanism. The IC50 of sinomenine in BEL-7402 cells was 5.351 mmol/L, and the IC50 of sinomenine in SMMC-7721 cells was 6.204 mmol/L. The gene expression results showed the relative expression of FGF2, CCND2, DCN, F3, MMP7, NRG1, HMGB1, TRIM29, HAS2, EHF, CTGF, PLK2 were down-regulated, and the relative expression of VEGF A, CITED2, NUPR1, DDX58, IRF9, NAMPT, MMP1, NDRG1, HMGA2, PPARGC1A, IFIT2, PARP9, HEY1, LOX, ETV1, ISG15, BACH, CYLD were up-regulated. Moreover, the IPA analysis results suggested that IFIT3, IFIT1, OAS1, MX1, IRF9, IFI6, IFITM1, ISG15 were up-regulated in BEL-7402 cells treated with sinomenine by activating IFNA2. The findings presented in this study may provide a promising method for the prevention and treatment of liver cancer.     

重症烧伤患者急救期输液及营养的路径护理

目的讨论研究对重症烧伤患者实行急救期输液及营养的路径护理的临床疗效与意义。方法选择医院烧伤科重症烧伤患者100例随机分组委观察组与对照组各50例。对照组给予急救期输液及营养常规护理。观察组提供急救期营养及输液路径护理。比较两组患者不同护理方式后营养状况、不良反应人数及护理满意度。结果治疗后观察组各项营养指标均显著优于对照组(P<0.05);观察组不良反应发生人数较少,护理服务满意程度较高。结论为重症烧伤患者提供急救期输液与营养路径护理可降低不良反应发生率并为患者加强营养支持,增强免疫力,有助于帮助其有效度过危险期,可促进患者后期治疗与恢复,更有助于拉近护患距离,提升医疗护理服务满意度。     

BRCA1-associated protein induced proliferation and migration of gastric cancer cells through MAPK pathway

BRCA1-associated protein (BRAP) was first found to bind to the nuclear localization signal motifs of BRCA1. In this study, we investigated the role of BRAP in gastric cancer. The cancer genome atlas(TCGA) data were obtained from UALCAN. We downregulated and upregulated the level of BRAP in gastric cancer cells by transfection with shRNAs and plasmids. Then, we evaluated the expression of BRAP by qRT-PCR and investigated the expression of important proteins by Western blot analysis. We conducted a microarray analysis to identify the function of BRAP in gastric cancer cells. Then, we investigated the effect of BRAP on proliferation and migration by CCK-8 assays, colony formation assays, wound healing assays and an extreme limiting dilution analysis. The analysis of TCGA data showed that BRAP was significantly overexpressed in gastric cancer tissues compared to that in normal gastric mucosal tissues (P < 0.001). A hybridization-based microarray assay was used to analyze MGC-803 cells and BRAP-downregulated MGC-803 cells. We found 22,199 protein-coding RNAs that were differentially expressed. The genes in the two groups were analyzed with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and both the focal adhesion and MAPK pathways were significantly enriched. The results of Cell Counting Kit-8(CCK-8) assays, colony formation assays, wound healing assays and the extreme limiting dilution analysis showed that the knockdown of BRAP reduced gastric cancer cell proliferation and migration and inhibited the process of epithelial-mesenehymal transition (EMT). The overexpression of BRAP induced gastric cancer cell proliferation, migration and the process of EMT. To verify the function of the mitogen-activated protein kinase (MAPK) signaling pathway, we performed a Western blot analysis. The results showed that the downregulation of BRAP decreased the levels of p-ERK and p-Raf1, thereby decreasing the activity of the MAPK signaling pathway. The use of Honokiol increased the levels of p-ERK and p-Raf1, rescuing the function of BRAP downregulation in the MAPK pathway. Xenograft tumor transplantation experiments in nude mice further confirmed the role of BRAP in gastric cancer progression and metastasis.     

LPS对骨肉瘤细胞迁移、侵袭及TLR4/HOTAIR通路的影响

目的探讨脂多糖(LPS)对骨肉瘤细胞迁移和侵袭的影响及其潜在的作用机制。方法将人MG-63骨肉瘤细胞随机分为2组:对照组和LPS组。LPS组细胞用10 g/ml的LPS干预24 h,对照组用生理盐水干预。ELISA检测干预后培养基中促炎因子的水平,Transwell实验检测细胞迁移和侵袭能力,Western Blot检测相关蛋白的表达。结果与对照组相比,LPS组培养基中促炎因子TNF-α、IL-1和IL-6的释放水平均显著增高(P<0.05),LPS组迁移细胞数和侵袭细胞数均显著增高(P<0.05),LPS组中E-cadherin的表达显著降低(P<0.05),而N-cadherin、α-SMA、波形蛋白、TLR4和HOTAIR的表达均显著增高(P<0.05)。结论LPS诱导的肿瘤微环境可促进骨肉瘤细胞的迁移和侵袭,其机制与TLR4/HOTAIR途径介导的EMT过程的发生有密切关系。     

基于SNP芯片研究PI3K/Akt/mTOR通路上自噬相关基因SNPs与胃癌的关联

目的： 探讨与胃癌发生相关的PI3K/Akt/mTOR通路上新的与自噬相关基因单核苷酸多态性位点（SNPs），为寻找有价值的胃癌发生相关的分子标志物提供新的依据。方法： 采用1：1配对病例-对照研究的方法。通过KEGG pathway网站和Gene Ontology、Ensemble数据库及HaploView、STRING、Cytoscape软件联合SNP芯片筛选目标SNPs，采用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF-MS）对筛检出来的SNPs位点在来自福建省仙游县的622例胃癌患者和622例健康人群基因组中进行验证。结果： SNP芯片及生物信息学分析筛选出IRS1 rs10205233、PIK3CD rs3934934、PIK3R1 rs706711、PIK3R1 rs706714和AKT1 rs35285446为候选位点。扩大样本验证发现IRS1 rs10205233的多态性变异（C > T）显著降低了胃癌的发病风险[共显性模型、显性模型的OR（95% CI）分别为0.761（0.595，0.975）、0.764（0.601，0.973）]。进一步分层分析，该位点显性模型、隐形模型、共显性模型以及等位基因在贲门癌和非贲门癌人群中均未见统计学差异（P > 0.05）。并未见其他位点与患胃癌风险的关联有统计学意义。对PIK3R1基因2个位点（rs706711、rs706714）的单体型分析也未见统计学差异。结论： IRS1 rs10205233位点与福建省胃癌高发区仙游县的胃癌发生存在关联，T等位基因可能是胃癌发生的一个遗传保护因素。