目的 利用GEPIA数据库,包括TCGA数据库和GTEX数据库,探讨二氢丹参酮I通过氧化应激治疗胃癌的潜在靶点。方法 在数据库中检索二氢丹参酮I在胃癌中潜在靶点的文献,利用GEPIA数据库工具分析二氢丹参酮I在胃癌中的潜在作用机制,分析潜在靶基因与表达关键抗氧化应激蛋白基因的相关性;二氢丹参酮I对胃癌潜在靶基因表达水平的分析;二氢丹参酮I对胃癌潜在靶基因的预后分析。结果 二氢丹参酮I对潜在靶基因的主要靶向基因(蛋白)为缺氧诱导因子-1(hif-1)和瓜氨酸组蛋白h3(cith3),其基因分别为HIF1 A和NOS2;GEPIA数据库显示HIF1 A与CAT(P=e-04,r=0.18)、GPX1(P=0.033,r=0.11)或NFE2L2呈正相关。(P=0,r=0.41),而NOS2与SOD1仅呈正相关(P=0.21,r=0.18),与其它三个基因均无相关性;HIF1 A和NOS2在胃癌组织中的表达水平高于正常胃旁组织;HIF1 A的高表达降低了胃癌患者的总生存率。结论 二氢丹参酮I可通过活性氧介导的氧化应激诱导AGS细胞凋亡,抑制HIF1 A和NOS2的表达,从而抑制AGS细胞的抗氧化应激,提高胃癌患者的总生存率。

Objective In this study, GEPIA database, including TCGA database and GTEx database, were used to explore the potential targets of dihydrotanshinone I on gastric cancer through oxidative stress. Methods Literatures on potential targets of dihydrotanshinone I in gastric cancer were searched in the database;GEPIA database tool was used to analyze the potential mechanism of dihydrotanshinone I on gastric cancer;taking analysis of the correlation between potential target genes and genes expressing key antioxidant stress proteins;We had analysis of expression level of dihydrotanshinone I on potential target genes in gastric cancer patients;and prognostic analysis of dihydrotanshinone I on potential target genes in gastric cancer patients. Results The main targeting genes(proteins) of dihydrotanshinone I on potential target genes were hypoxia inducible factor-1(hif-1) and citrulline histone H3(CITH3), whose genes were HIF1 A and NOS2, respectively;GEPIA database showed that there was a positive correlation between HIF1 A and CAT(P=2e-04, R=0.18), GPX1(P=0.033, R=0.11), or NFE2L2(P=0, R=0.41), while NOS2 only had a positive correlation with SOD1(P=0.21, R=0.18), and no correlation with other three genes. The expression levels of HIF1 A and NOS2 in gastric cancer tissues were higher than those in normal adjacent gastric tissues. The overall survival rate of patients with gastric cancer decreased with the high expression of HIF1 A. Conclusion Dihydrotanshinone I may induce apoptosis of AGS cells through reactive oxygen species mediated oxidative stress, and inhibit the expression of HIF1 A and NOS2, thus inhibit their antioxidative stress, which may improve the overall survival rate of gastric cancer patients.

目的 探讨二氢丹参酮Ⅰ在胃癌细胞中的抗癌作用。方法 采用 3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐法(MTT法)测定细胞活力。流式细胞术检测细胞内活性氧(ROS)水平。荧光法测定Caspase活性。裸鼠胃癌模型验证DHTS的抗癌活性。结果 MTT实验结果表明,DHTS对HCG27和AGS细胞活力具有明显的剂量依赖性和时间依赖性。在DHTS处理的HCG27和AGS细胞中,细胞内ROS水平升高,凋亡细胞增多。 在DHTS处理的HCG27和AGS细胞中发现caspase-3和caspase-8活性增高,caspase-9活性不变。用N -乙酰半胱氨酸阻断ROS生成可显著逆转DHTS诱导的细胞凋亡。DHTS显著抑制小鼠肿瘤瘤体体积的增加。结论 所有的研究结果都有力的说明,DHTS可以在HCG27和AGS人胃癌细胞中启动活性氧生成,诱导氧化应激和细胞凋亡,值得作为抗癌药物进一步开发。

Objective To evaluate the anticancer actions of dihydrotanshinone Ⅰ(DHTS)in gastric cancer cells. Methods Cell viability was determined using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)assay. Intracellular reactive oxygen species (ROS)levels were determined using flow cytometry. Caspase activities were measured with fluorometric assay. The anticancer activity of DHTS in nude mouse gastric cancer model was verified. Results MTT assay showed that DHTS greatly inhibited HCG27 or AGS cell viability in dose- and time-dependent manners. Elevated intracellular ROS levels and increased apoptotic cells were observed in DHTS-treated HCG27 or AGS cells. In addition, activation of caspase-3 and caspase-8, rather than caspase-9, were noticed in DHTS-treated HCG27 or AGS cells. Furthermore, blocking ROS generation with N-acetylcysteine markedly reversed DHTS-induced cell apoptosis. DHTS inhibited the increase of tumor volume in mice. Conclusion All the findings strongly suggest that DHTS may initiate ROS generation and induce oxidative stress and cell apoptosis in HCG27 or AGS human gastric cancer cells, which deserves to be further developed as an anticancer agent.

目的 研究对比胃癌患者术前胃镜活检病理与外科术后病理的异同并进行观察。方法 选取我院消化科于2016年7月—2017年12月收治的64例胃癌患者作为此次研究对象,术前均展开胃镜活检,术后展开外科病理检查,判断两种诊断方法的异同。结果 胃癌确诊率对比,术前胃镜活检后确诊胃癌患者占比85.9%(55/64),疑似胃癌患者占比10.9%(7/64),排除胃癌患者占比3.1%(2/64),术前胃镜活检确诊率85.9%,低于术后病理诊断95.3%,组间比较差异无统计学意义(P>0.05);胃镜活检病理结果对比,术前胃镜检查黏液腺癌占比35.9%,乳头状腺癌占比51.6%,均高于术后病理检查的25.0%、28.1%,组间比较差异具有统计学意义(P＜0.05);胃镜活检分化程度结果对比,胃镜病理与术后病理检查结果对比有明显差异,具有统计学意义(P＜0.05)。结论 对胃癌进行诊断时,尽管术前胃镜活检病理检查与外科术后病理检查结果存在差异,但术前胃镜活检对胃癌确诊率较为理想,可作为术前诊断参考,外科术后病理检查对全面评估胃癌病情具有较高应用价值,值得在临床中应用。

目的 探讨血清胃蛋白酶原在胃癌筛查中的价值。方法 用ELISA方法对1102名患者血清PG水平进行检测,并行内镜病理组织学检查,采用ROC曲线确定PG筛查胃癌的最佳界定值。结果 与对照组、萎缩性胃炎组、胃良性溃疡组相比,早期胃癌组、进展期胃癌组PGI、PGR下降(P＜0.05),进展期胃癌组PGI、PGR较早期胃癌组下降(P＜0.05)。与对照组相比,早期胃癌组、进展期胃癌组、胃良性溃疡组PGII升高(P＜0.05)。PGI及PGR在ROC曲线下面积为0.920和0.831,对胃癌的诊断价值较高。PGI≤71.50 μg/L或PGR≤4.50作为筛查标准时,对胃癌高危人群筛查的灵敏度为83.33%,特异度为82.25%。结论 血清PGI、PGR在不同胃部病变中的表达水平不一致,对胃癌的早期筛查和早期诊断具有重要价值。PGI≤71.50 μg/L或PGR≤4.50是东莞地区筛查胃癌较合适的界定值。

Objective To investigate the value of serum pepsinogen PG detection for screening of gastric cancer. Methods PG was detected by ELISA of 1102 people, gastrointestinal endoscopy and biopsy pathology were also carried on. Using ROC curve to establish the PG screening standard, and verified its' value at high risk population of gastric cancer. Results Compared with control group, atrophic gastritis group and benign gastric ulcer group, serum PGI and PGR in early gastric cancer group and advanced gastric cancer group decreased significantly(P＜0.05). Serum PGI and PGR in advanced gastric cancer group were lower than early gastric cancer group(P＜0.05). Serum PGII in early gastric cancer group, advanced gastric cancer group and benign gastric ulcer group were higher than control group(P＜0.05). The area under ROC curve of PGI and PGII was 0.920 and 0.831 respectively, both of them showed high value for the diagnosis of gastric cancer. Took PGI≤71.50μg/L or PGR≤4.50 as the diagnosis criteria, the sensitivity was 83.33% and specificity was 82.25% at high risk population of gastric cancer. Conclusion Serum PGI and PGR were inconsistent in different gastric disease, which showed high sensitivity and specificity in the screening of gastric cancer,and have important value in early screening and early diagnosis of gastric cancer. PGI≤71.50μg/L or PGR≤4.50 were established as the appropriate standard for PG screening.

目的 观察miR-9在胃癌组织中的表达水平及其与临床病理的相关性。方法 采用实时荧光定量PCR方法分别检测28例胃癌及正常胃组织中miR-9的表达水平,并分析其表达情况与临床病理资料的关系。结果 胃癌组织miR-9的表达水平[0.0078(0.0031~0.0142)]显著低于相应正常胃组织[0.0177(0.0084~0.0311), P<0.05],尤其是伴淋巴结转移者[0.0021(0.0006～0.0685)]miR-9表达水平明显降低。结论 胃癌组织中miR-9低表达,且与胃癌淋巴结转移有关。

Objective To investigate the correlation between the level of miR-9 expression and clinicopathology in gastric carcinoma. Methods The expression of miR-9 in 28 cases of gastric carcinoma tissues and normal gastric tissues were detected by quantitative real-time PCR, and the relationship between the expression and clinicopathology was analyzed. Results The expression of miR-9 expression in gastric carcinoma tissues [0.0078(0.0031~0.0142)] was significantly lower compared with the corresponding normal gastric tissues [0.0177(0.0084~0.0311), P<0.05], especially in lymph node-invasive carcinoma [0.0021(0.0006～0.0685)]. Conclusion miR-9 was down regulated in gastric cancer tissues, which was significantly associated with lymph node metastasis.

目的 探讨胃癌组织中刺猬信号通路(Hedgehog signaling pathway, Hh)中的音猬因子(Sonic hedgehog, Shh)和胶质瘤相关癌基因同源物-1(Glioma-associated oncogene homolog -1, Gli-1)与金属基质蛋白酶-2(Matrix metalloproteinase-2, MMP-2)的表达和临床意义。方法 采用免疫组织化学方法检测40例人胃癌组织、人胃息肉组织和40例正常胃黏膜组织中音猬因子、胶质瘤相关癌基因同源物-1、金属基质蛋白酶-2蛋白的表达。结果 胃癌组织中音猬因子、胶质瘤相关癌基因同源物-1、金属基质蛋白酶-2的阳性表达率分别为62.5%、67.5%、72.5%,高于胃息肉组织(阳性表达率分别为27.5%、37.5%、32.5%)和正常胃黏膜组织(阳性表达率分别为22.5%、17.5%、12.5%)(P<0.05);以上三者的表达与患者性别、年龄、组织学类型无关(P>0.05);而与分化程度、浸润深度、淋巴结转移相关(P<0.05);音猬因子、胶质瘤相关癌基因同源物-1、金属基质蛋白酶-2表达呈正相关。结论 刺猬信号通路可能通过某些机制可上调金属基质蛋白酶-2的表达,从而增强胃癌的侵袭性。联合检测胃癌组织中音猬因子、胶质瘤相关癌基因同源物-1、金属基质蛋白酶-2的表达水平在一定程度上可以作为胃癌预后的客观参考指标。

Objective To investigate the expression and clinical significance of Sonic hedgehog(Shh), Glioma-associated oncogene homolog -1(Gli-1) and Matrix metalloproteinase-2(MMP-2) in gastric cancer.Shh and Gli-1 are the molecules of Hedgehog(Hh) signaling pathway. MMP-2 is the member of matrix metalloproteinase family. Methods The expression of Shh,Gli-1 and MMP-2 proteins was examined by immunohistochemistry in the human gastric cancer tissues and the human gastric polyp and the normal gastric mucosa tissues of 40 cases. Results The positive expression rates of Shh,Gli-1 and MMP-2 in gastric cancer were 62.5%,67.5% and 72.5% respectively, which were significantly higher than those in the gastric polyp tissues (the positive expression rates were 27.5%,37.5% and 32.5% respectively) and normal gastric mucosa tissues (the positive expression rates were 22.5%,17.5% and 12.5% respectively),P<0.05.The expression of Shh,Gli-1 and MMP-2 was not correlated with the sex,age or histological type(P>0.05),but was correlated with depth of invasion,differentiation level and lymphonode metastasis in gastric cancer(P<0.05). The expression of Shh and Gli-1 was positive correlated with MMP-2. Conclusion Hedgehog(Hh)signaling pathway may have great effects on enhancing the invasive ability of gastric cancer by upregulating MMP-2 protein through some unknown mechanisms.The combined detection of the expression level of Shh,Gli-1 and MMP-2 in gastric cancer tissues might be used as an Objective references for assessing the prognosis of gastric cancer.