潘生丁增强5-氟脲嘧啶抗肿瘤作用的体外实验研究

通过检测 MKN45人胃癌细胞株3~H-TDR 掺入情况,在体外实验研究潘生丁和抗癌药物5-氟脲嘧啶之间的协同作用。结果表明二者间有显著的协同效应(P<0.01),为下一步的动物实验和临床应用提供了理论依据。     

Effect of gastric dysrhythmias on postcibal motor activity of the stomach

The effect of electrical dysrhythmias on the mechanical activity of the fed stomach was investigated in 5 conscious dogs implanted with Ag-AgCl electrodes and strain gauge force transducers. Each dog was fed 1 can of ALPO^® and electromechanical activities of the stomach were recorded for the next 120 min. The results show that intraarterial boluses of met-enkephalin (75 g/kg), PGE₂ (36 g/kg), and epinephrine (36 g/kg) induced episodes of antral dysrhythmias whereas saline (1 cc) did not. The postcibal antrat motility index for the test period was not altered following saline injection, but it was reduced by 61%, 70%, and 81% following the administration of met-enkephalin, epinephrine, and PGE₂, respectively (p<0.01 vs. baseline period). During periods of normal electrical rhythm, PGE₂ and epinephrine significantly reduced the antral motility index (2.07±0.93 and 3.24±0.79, respectively) vs. saline (7.92±0.44) (p<0.05 for both drugs) whereas met-enkephalin (4.98±0.56) did not. In contrast, during episodes of dysrhythmia, met-enkephalin significantly depressed antral motility (1.70±0.74) (p<0.05 vs. periods with normal electrical rhythm) whereas neither epinephrine nor PGE₂ caused a further reduction in antral motility from what was seen during periods of normal electrical rhythm (1.84±0.72 and 1.34±0.37, respectively). We thus conclude that intraarterial administration of met-enkephalin, PGE₂, or epinephrine induce gastric dysrhythmias postcibally and depress antral contractile activity. The relaxatory effect of met-enkephalin on antral contractions is primarily due to its dysrhythmic effect whereas PGE₂ and epinephrine inhibit antral motility even when the electrical rhythm is undisturbed.This work was supported in part by the USPHS, NIH grants AM26428, AM07198, and AM34988 and the Mayo Foundation.     

基于术前脾脏CT影像组学列线图预测胃癌的浆膜浸润

目的：联合临床检验指标及影像学特征构建一种能够术前识别胃癌浆膜浸润的模型。方法：选取2015年1月至2019年12月温州医科大学附属第一医院经病理证实的656例胃癌患者,采用随机数字表法分为建模组（394例）和验证组（262例）。收集建模组患者的脾脏影像学资料,对收集的数据进行套索回归并选取差异有统计学意义的特征来构建浆膜浸润预测模型。在最大约登指数下取肿瘤浸润风险评分截断值将患者分为高危组（238例）和低危组（418例）,然后与其他浸润相关因素如BMI、年龄、性别、高血压、糖尿病等进行单变量和多变量Logistic回归分析,结合显著的独立影响因素共同建立可视化的浆膜浸润预测列线图。结果：将患者以肿瘤浸润评分≤-0.335分为低危组,＞-0.335为高危组,经验证组验证,建模组和验证组的诊断准确性较为一致（P＜0.001）。经浸润影响因素的单变量和多变量Logistic回归分析发现,影像组学肿瘤浸润评分（OR=2.9,95%CI=2.1～4.2,P＜0.001）、术前低白蛋白（OR=1.3,95%CI=1.2～3.1,P=0.003）、血小板与淋巴细胞比值（OR=1.8,95%CI=1.2～2.7,P=0.004）、肿瘤分化程度（OR=2.6,95%CI= 1.8～3.7,P＜0.001）是浆膜浸润的独立影响因素。基于这4个指标建立的预测模型能够较为准确地预测浆膜浸润风险,其AUC值为0.733。结论：基于脾脏影像的肿瘤浸润评分联合其他临床因素可准确预测胃癌浆膜浸润与否,提高诊断精度。     

阿帕替尼对Her2阴性晚期胃癌患者的治疗效果及毒副作用分析

目的:探究Her2阴性晚期胃癌患者采用阿帕替尼进行治疗的疗效及毒副作用。方法:按照不同治疗方法将本院就诊的Her2阴性晚期胃癌患者分为阿帕替尼组(AP组)和替吉奥组(TI组),各46例,分析比较两组患者的临床疗效、生活质量、毒副作用及远期疗效。结果:治疗后,AP组11例、TI组6例患者出现部分缓解,AP组患者RR、DCR数值明显比TI组高(P<0.05);AP组患者生活质量明显优于TI组(P<0.05)。AP组和TI组患者均出现血小板减少、蛋白尿、肝功能异常等不良反应,但未出现Ⅳ级毒副作用,其中AP组患者高血压、血小板减少的发病率分别为63.52%、76.73%,TI组患者发病率分别为62.45%、78.11%, AP组出现毒副作用的患者人数与TI组比较无明显差异(P>0.05)。随访3年结果显示,AP组患者3年生存率为10.86%,TI组患者为0,AP组患者总生存率明显高于TI组(P<0.05)。结论:阿帕替尼对Her2阴性晚期胃癌患者的临床疗效及远期治疗效果较佳,虽然治疗后也会出现一定的毒副作用,但与替吉奥治疗后出现的毒副作用相近,且患者身体承受程度较佳。阿...     

胃癌术前淋巴结转移评估方法研究进展

胃癌在我国的发病率及病死率较高,目前,手术仍然是胃癌的主要治疗方式。术前诊断淋巴结转移对于胃癌手术方式的选择有着重大意义。目前,临床中对于胃癌术前淋巴结转移的诊断尚没有金标准。本文对胃癌术前淋巴结转移评估方法的研究进展进行综述。     

γ线照射对大鼠胃酸分泌及胃泌素释放的影响

本实验观察了大鼠全身照射不同剂量(4～25Gy)及全腹部照射(10Gy)后胃酸分泌的变化并用RIA方法测定照射后胃窦及血清中胃泌素水平.结果表明,全身8～25Gy照射后第3天,腹部10Gy照射后1～6周,胃酸分泌明显抑制.主现表现为胃液中[H~+]分泌的抑制,致使照射后胃液酸度降低.10Gy以上剂量照射使胃泌素释放增加,表现为血清胃泌素明显升高,胃窦胃泌素明显减少,导致照射引起的"低胃酸、高胃泌素血症".这种表现与人的某些萎缩性胃炎或恶性贫血的状况相似.     

Changes in gut bacterial communities in canaries infected by Macrorhabdus ornithogaster

Macrorhabdus ornithogaster is an opportunistic yeast that colonizes the gastric mucosa of many avian species. Until now, no studies have focused on the influence of a gastric infection on the balance of the intestinal microbiota of birds. In this study, 44 faecal samples from individual canaries, with and without M. ornithogaster infection, were analysed. The detection of the yeast was evaluated by 18S rRNA PCR. In order to evaluate the impact of the Macrorhabdus infection on the bacterial communities, culture-independent methods, by the use of amplicon-based sequencing as well as 16S rRNA-DGGE, were adopted. The different health status of animals affected the relative abundance of the main OTUs, with a greater diversification of the gut microbiota in healthy animals compared to the infected. In particular, Lactococcus, Pseudomonas, Acinetobacter, Lachnospiraceae, Propionibacterium and Weissella were found to be characteristic of uninfected animals (FDR?<?0.05), while Lactobacillus and Candidatus Arthromitus were characteristic of infected animals (FDR?<?0.05). Both these taxa have been reported as immunostimulatory, involved in immunological disorders. In infected animals the inferred metagenome assessed by PICRUST clearly showed a positive correlation between the presence of M. ornithogaster and KEGG genes related to ether lipid metabolism, already reported to be immunostimulatory by activation of macrophages and to play a pathophysiological role in several immunological disorders. Finally, our results show an interaction between infection of the digestive tract and intestinal microbiota of pet birds and provide insight into the changing of the complex enteric bacterial community.

• HIGHLIGHTS

• Macrorabdus ornithogaster is a gastric yeast that colonizes a wide range of birds.

• Differences were found between infected and healthy animals in gut microbiota.

• Candidatus Arthromitus was closely associated with infected birds.

• M. ornithogaster can affect intestinal microbiota composition of canaries.

     

Overexpression of S100A4 is closely related to the aggressiveness of gastric cancer

Elevated levels of the calcium-binding protein S100A4 cause metastasis of benign rat mammary tumor cells. To investigate whether S100A4 plays an important role in the invasion and metastasis of gastric cancers, we examined the gene mutations in the coding regions and expression patterns of the S100A4 in gastric adenocarcinoma in Korea. Moderate to strong expression of S100A4 was found in 53 (68.8%) of the 77 gastric adenocarcinomas, whilst normal gastric epithelium either failed to stain or showed weak staining. Interestingly, S100A4 expression was more frequently observed in gastric cancer patients with advanced gastric cancer (p=0.039), positive lymph node metastasis (p=0.001), and peritoneal dissemination (p=0.022). No gene mutations were found in the analyzed genomic area in 77 gastric adenocarcinomas and 15 gastric cancer cell lines. We found one single nucleotide polymorphism without an amino acid change, A99G, in two cases. These data suggest that the overexpression of S100A4 may be closely related to the aggressiveness of gastric cancer in Korea.     

Expression of CDX2 and MUC2 in Barrett's mucosa

Barrett's mucosa is a risk factor for esophageal adenocarcinoma and should be detected at an early stage. It is defined by the presence of columnar epithelium with goblet cells in the lower esophagus, but histologic diagnosis can be uncertain in the absence of distinct goblet cells. We investigated 55 biopsies from 48 patients with endoscopically plain Barrett's esophagus and performed immunohistochemistry for CDX2 and MUC2. In addition, alcian blue (pH 2,5)/PAS staining was done. In histologically unequivocal Barrett's mucosa, nuclear expression of CDX2 in goblet cells and many columnar cells, as well as cytoplasmic positivity for MUC2 in goblet cells, could be observed. Alcian blue (pH 2,5)/PAS stained acidic mucins in goblet cells and in some non-goblet columnar cells. In six cases, no definite Barrett's mucosa was present, and no expression of MUC2 could be observed. In these biopsies, there was granular cytoplasmic and/or focal nuclear staining for CDX2 in non-goblet columnar epithelial cells, indicating their intestinal differentiation. We suggest that this peculiar mucosa is the precursor of unequivocal Barrett's mucosa and would designate it early Barrett's mucosa. Alcian blue for acidic mucins is inconsistent in this epithelium and does not reliably indicate early intestinal differentiation.     

Lipopolysaccharide Induces CD25-Positive, IL-10-Producing Lymphocytes Without Secretion of Proinflammatory Cytokines in the Human Colon: Low MD-2 mRNA Expression in Colonic Macrophages

Despite the huge number of colonized Gram-negative bacteria in the colon, the normal colon maintains its homeostasis without any excessive immune response. To investigate the potential mechanisms involved, human colonic lamina propria mononuclear cells (LPMCs) obtained from uninflamed mucosa were cultured with lipopolysaccharide (LPS) prepared from Bacteroides vulgatus (BV-LPS) or Bacteroides fragilis (BF-LPS), as representatives of indigenous flora, or pathogenic Salmonella minnesota (SM-LPS). Colonic LPMCs failed to produce inflammatory cytokines in response to any type of LPS. Colonic macrophages barely expressed mRNA for MD-2, an essential association molecule for LPS signaling via Toll-like receptor 4. Further, BV-LPS induced CD25 and Foxp3 expression in lymphocytes and CD4(+)CD25(+) cells expressed IL-10 mRNA. Thus, the low expression of functioning LPS receptor molecules and induction of IL-10-producing CD4(+)CD25(+) lymphocytes by indigenous LPS may play a central role in the maintenance of colonic immunological homeostasis.