基于生物信息学分析构建预后相关的预测模型，探讨铜死亡相关LncRNA与胃癌（GC）在免疫和预后方面的关系。从癌症基因组图谱（TCGA）数据库下载胃癌患者的RNA测序和临床数据，基于共表达分析筛选出铜死亡相关LncRNA，通过LASSO 回归和多因素Cox 回归分析构建出与胃癌预后密切相关的铜死亡相关LncRNA风险预测模型，并计算所有胃癌患者样本的风险评分。通过Kaplan-Meier 生存分析、回归分析和受试者工作特征（ROC）曲线等证实模型的预后预测性能，并分析风险评分与通路富集分析、免疫浸润细胞、免疫检查点基因、体细胞基因突变及抗癌药物敏感性的相关性。差异表达分析结果表明，LncRNA HAGLR在肿瘤组织中的表达上调。通过实时荧光定量PCR（qRT-PCR）检测LncRNA HAGLR在69例行根治性手术胃癌患者的癌组织及癌旁组织的表达。结果表明，相比于癌旁组织，胃癌组织中HAGLR表达上调，且与肿瘤大小、浸润深度、肿瘤TNM分期、分化程度及淋巴结转移成明显相关性（P<0.05）。本研究构建的铜死亡相关LncRNA预后模型具有较高的预测价值，并且与免疫细胞浸润异质性明显相关，在预测患者免疫治疗效果及指导化疗药物选择方面具有一定的临床价值。

本文提出了一种能够与胃镜相匹配的光纤拉曼光谱系统和积分能量比相结合来快速诊断胃癌的方法。首先, 采用光纤拉曼光谱系统对来自 17例胃正常粘膜, 12例胃腺癌粘膜的活检组织进行拉曼光谱检测 (激发光波长 785 nm, 功率 50 mW, CCD温度-80 ℃, 采集时间 1 s)。然后, 采用降低基线、快速傅里叶转化 (FFT)平滑对拉曼原始光谱进行预处理。最后, 根据拉曼谱图特征, 分析了拉曼特征峰的归属, 比较了胃正常和胃腺癌粘膜的拉曼光谱差异和连续频带内(1500 cm-1～1700 cm-1)和非连续频带 (1100 cm-1～1200 cm-1)积分能量比。结果表明, 胃腺癌粘膜位于 1002 cm-1、 1073 cm-1、1450 cm-1、1655 cm-1归属于苯丙氨酸和蛋白质的拉曼峰强度比正常粘膜相对增高, 胃正常和胃腺癌粘膜在连续频带内和非连续频带积分能量差异明显(独立样本 t检验, P<0.05), 并以积分能量的比值来作为诊断指标, 获得的准确度达到 97.5%～98.5%, 敏感度达到 91.7%和特异度达到 100.0%。

The detection of early gastric cancer that often develops asymptomatically is crucial for improving patient survival. The photodynamic diagnosis (PDD) of gastric cancer using 5-aminolevulinic acid/protoporphyrin IX (5-ALA/PpIX) has been reported in several studies. However, the selectivity of PDD of gastric tumor is poor with often false-positive results that require the development of new methods to improve PDD for early gastric cancer. Therefore, a measure of the complexity of gastric microcirculation (multi-scale entropy, MSE) and the detrended fluctuation analysis (DFA) were applied as additional tools to detect early gastric cancer in rats.In this experimental study, we used our original model of metastatic adenocarcinoma in the stomach of a rat. To induce a gastric tumor, we used a long-term combination (for 9 months, which is 1/2 of the life of rats) of two natural factors, such as chronic stress (overpopulation being typical for modern cities) and the daily presence of nitrites in food and drinks, which are common ingredients added to processed meat and fish to help preserve food. Our results clearly show that both methods, namely, PDD using 5-ALA/PpIX and complexity/correlation analysis, can detect early gastric cancer, which was confirmed by histological analysis. Pre-cancerous areas in the stomach were detected as an intermediate fluorescent signal or MSE level between normal and malignant lesions of the stomach. However, in some cases, PDD with 5-ALA/PpIX produced a false-positive fluorescence of exogenous fluorophores due to its accumulation in benign and inflammatory areas of the mucosa. This fact indicates that the PDD itself is not sufficient for the correct diagnosis of gastric cancer, and the use of additional characteristics, e.g., complexity measures or scaling exponents, can significantly improve the diagnostic accuracy of PDD of gastric cancer that should be confirmed in further clinical studies and applications.

This study aimed to explore the application of surface-enhanced Raman scattering (SERS) in the rapid diagnosis of gastric cancer. The SERS spectra of 68 serum samples from gastric cancer patients and healthy volunteers were acquired. The characteristic ratio method (CRM) and principal component analysis (PCA) were used to differentiate gastric cancer serum from normal serum. Compared with healthy volunteers, the serum SERS intensity of gastric cancer patients was relatively high at 722cm-1, while it was relatively low at 588, 644, 861, 1008, 1235, 1397, 1445 and 1586cm-1. These results indicated that the relative content of nucleic acids in the serum of gastric cancer patients rises while the relative content of amino acids and carbohydrates decreases. In PCA, the sensitivity and specificity of discriminating gastric cancer were 94.1% and 94.1%, respectively, with the accuracy of 94.1%. Based on the intensity ratios of four characteristic peaks at 722, 861, 1008 and 1397cm-1, CRM presented the diagnostic sensitivity and specificity of 100% and 97.4%, respectively, and the accuracy of 98.5%. Therefore, the three peak intensity ratios of I722/I861, I722/I1008 and I722/I1397 can be considered as biological fingerprint information for gastric cancer diagnosis and can rapidly and directly reflect the physiological and pathological changes associated with gastric cancer development. This study provides an important basis and standards for the early diagnosis of gastric cancer.

为满足大规模胃癌早期筛查对胃蛋白酶原I(PGI)检测高灵敏度、高效率、操作简单、样品量少的需求, 本文构建了一种PGI抗体功能化薄膜型Lamb波生物传感器。对传感器检测腔薄膜进行PGI抗体自组装修饰, 传感器检测腔表面修饰的PGI抗体将样品中PGI抗原特异性的捕获并固定在检测腔薄膜表面, Lamb波传感器薄膜表面质量增加导致其A0模式中心频率发生移动, 且频率移动量与检测腔表面吸附物质质量增加量正相关, 实现对样本中PGI抗原浓度的检测。实验结果表明: PGI抗体功能化薄膜Lamb波生物传感器对PGI抗原实测灵敏度约为102.114 Hz/ng/mL, 理论最低检测限(LOD)为0.176 ng/mL, 单个样本检测时间为40 min, 与现有基于光学检测法PGI检测技术相比, 具有检测系统简单、操作简单、不需要专业人员操作等显著优势, 且比多数光学检测法LOD更低, 比电化学法PGI检测技术LOD低两个数量级。结果表明, 本文提出的PGI抗体免疫功能化薄膜型Lamb波生物传感器对PGI检测且具有检测下限低、灵敏度高、检测效率高、操作简单、无需样品预处理等特点, 满足大规模早期胃癌筛查的基本需求。

探讨白介素17A基因多态性与胃癌预后的关系。129例研究对象纳入生存分析, 分成死亡和存活两组, 用基因测序的方法检测血液样本IL-17A基因SNP位点rs3748067、rs17880588基因型分布。rs3748067位点有3种基因型T/T、C/T、C/C, rs17880588位点有2种基因型A/G、G/G。比较存活组和死亡组之间的基因型分布频率和单点等位基因分布频率, 发现rs3748067的基因型C/T在死亡组的分布频率较存活组高, 基因型T/T和C/C在死亡组的分布频率低于存活组, 两组之间分布频率差异有统计学意义(P<005)。杂合型C/T基因型在存活组分布低于死亡组(OR=2051, CI=0016～1420), 该位点基因型杂合可能为胃癌预后的一种危险因素。rs17880588的两种基因型A/G、G/G在存活组和死亡组的分布频率差异无统计学意义(P>005)。结论: IL-17A基因rs3748067位点SNP与胃癌预后可能有相关性。

目的：研究正常胃粘膜和胃癌组织在拉曼光谱指纹区（800-1 800 cm-1）和高波数区（2 800-3 000 cm-1）的光谱特征,并将其联合使用建立胃癌诊断模型。方法：收集38例正常胃粘膜和37例胃癌组织活检标本,采用785 nm激发光拉曼光谱仪进行拉曼光谱采集。比较正常胃粘膜和胃癌组织在指纹区和高波数区的拉曼光谱异同,使用偏最小二乘判别分析（PLS-DA）结合留一法交叉验证建立诊断模型。结果：1）胃癌组织在853 cm-1,879 cm-1,1 003 cm-1,1 047 cm-1,1 173 cm-1,1 304 cm-1,1 319 cm-1,1 338 cm-1,1 374 cm-1、2 932 cm-1谱峰处与正常胃粘膜的拉曼峰强度差异有统计学意义（P＜0.05）2）将拉曼光谱指纹区和高波数区联合,利用PLS-DA建立胃癌诊断模型的敏感性为94.59%（35/37）,特异性为86.84（33/38）,正确率为90.6%(68/75)。结论：正常胃粘膜和胃癌组织在拉曼光谱指纹区和高波数区均有显著差异,将上述两区联合使用建立模型诊断胃癌能取得良好的诊断效果。

胃癌患者能够得到早期诊断对其治疗具有十分重要的意义, 疾病状态下的血红蛋白拉曼光谱检测在血液代用品的高铁血红蛋白含量检测中以及血氧饱和定量测定中占很大优势。 本实验采用微波加热法制备银胶体粒子, 依次对20例胃癌患者和11例健康人的血红蛋白进行表面增强拉曼光谱分析。 采用SERS谱峰归属分析结果显示胃癌患者血红蛋白中的酪氨酸、 苯丙氨酸和吡咯环的含量均低于正常人。 本文还讨论了血红素的分子结构, 在血红蛋白和氧气结合的前后, Fe2+分别处于高低自旋态, 离子半径也随着与氧结合缩小了0.075 nm从而滑落入卟啉环平面中央的孔隙之中。 这种空间的拉伸变化会牵动与铁相连的F8His, 使得珠蛋白中两股螺旋之间空隙缩小, 导致将HC2酪氨酸排挤出空隙。 利用这一机理, 对血红蛋白1 560 cm-1的吸收峰进行研究, 证实了胃癌患者酪氨酸含量确实低于正常人。 为了能得到更加明显的诊断区分, 利用降维的思想, 采用主成分分析(PCA)的方法对所有的拉曼光谱进行多元统计分析, 得出三维的诊断散点图。 为了更加精确的得出诊断准确率, 用判别分析得出诊断的灵敏度和特异性分别为90.0%和90.9%, 总判别正确率为90.3%。 此项研究表明: 对氧合血红蛋白的表面增强拉曼光谱诊断分析有希望成为一项新型的胃癌诊断技术应用于医学领域。