Study on TFF1 and PALB2 gene variants associated with gastric carcinoma risk in the Chinese Han population

ObjectiveGastric carcinoma (GC) has received extensive attention due to its complex pathogenesis. Studies have shown that the expression of Trefoil factor 1 (TFF1) and Partner and localiser of BRCA2 (PALB2) genes promotes the occurrence of GC. Therefore, we investigated whether TFF1 and PALB2 gene polymorphisms are associated with GC risk in the Chinese Han population.MethodsA total of 509 GC cases and 505 controls were recruited, and single nucleotide polymorphisms (SNPs) of TFF1 and PALB2 in these subjects were genotyped. The association between each candidate polymorphism and GC risk was assessed by calculating odds ratios (ORs) and 95% confidence intervals (CIs). The visualization of gene-gene interactions and functional enrichment analysis were then performed using Cytoscape software and the R package “cluster profile”.ResultsThe TFF1 rs2156310 polymorphism significantly reduced the predisposition to GC in people under 60 years of age (AA vs. AG - GG, OR = 0.58, 95% CI = 0.35–0.97, p = 0.036). The gender-stratified analysis found that PALB2 rs513313 was significantly associated with the risk of GC in males (CT vs. TT, OR = 1.51, 95% CI = 1.06–2.15, p = 0.022). Besides, PALB2 rs249954 significantly reduced the susceptibility to GC in females (AA vs GG, OR = 0.42, 95% CI = 0.19–0.94, p = 0.034).ConclusionOur results revealed that TFF1 and PALB2 gene polymorphisms were correlated with the genetic susceptibility to GC, providing certain data support for researchers to further study the mechanism of GC.     

三七总皂苷联合顺铂对胃癌大鼠肾损伤的改善作用及机制分析

摘要 目的：探讨三七总皂苷联合顺铂对胃癌大鼠肾损伤的改善作用并分析潜在机制。方法：选择60只健康SD雄性大鼠分为对照组、胃癌模型组、顺铂组及三七总皂苷组,各15只。除对照组外,其余组大鼠采用皮下接种胃癌BGC823细胞悬液法建立胃癌模型。建模成功后,给予对照组和胃癌模型组大鼠生理盐水腹腔注射和灌胃,给予顺铂组大鼠腹腔注射25 mg/kg顺铂注射液并灌胃生理盐水,给予三七总皂苷组大鼠腹腔注射25 mg/kg顺铂注射液并灌胃30 mg/kg三七总皂苷。分别于建模成功时、药物处理28 d时采用酶联免疫吸附法检测血清肌酐（SCr）、尿素氮（BUN）和尿液β-N-乙酰氨基葡萄糖苷酶（NAG）、肾损伤分子1（KIM-1）水平。处死大鼠后取肾脏,分别测定肾脏组织匀浆中超氧化物歧化酶（SOD）、丙二醛（MDA）、过氧化氢酶（CAT）、谷胱甘肽（GSH）水平,制备肾脏组织石蜡切片并行苏木精-伊红染色后观察大鼠肾组织的病理学变化。采用TUNEL染色法检测肾脏组织细胞凋亡情况,采用Western Blotting法检测肾脏组织中LC3、HIF-1α和Beclin1 蛋白表达情况。结果：顺铂组和三七总皂苷组大鼠血清SCr、BUN和尿液NAG、KIM-1水平均显著高于对照组和模型组（P<0.05）,三七总皂苷组大鼠血清SCr、BUN和尿液NAG、KIM-1水平显著高于顺铂组（P<0.05）。三七总皂苷组大鼠肾脏组织SOD、GSH水平显著低于模型组但显著高于顺铂组,MDA显著高于模型组但显著低于顺铂组（P＜0.05）,CAT与模型组无显著差异（P＜0.05）,但显著高于顺铂组（P>0.05）。顺铂组大鼠肾小管明显扩张、管腔狭窄,基底层上皮细胞水肿、坏死并形成空泡,肾小管。三七总皂苷组大鼠肾脏病理学改变程度显著轻于顺铂组。顺铂组和三七总皂苷组大鼠肾脏组织细胞凋亡指数显著增加,三七总皂苷组大鼠肾脏组织细胞凋亡指数显著低于顺铂组（P＜0.05）。顺铂组大鼠肾脏组织中LC3、HIF-1α和Beclin1蛋白水平均显著高于模型组,但显著低于三七总皂苷组（P＜0.05）。结论：三七总皂苷可能通过减轻过氧自由基和过氧化水平、增强线粒体自噬水平减少肾组织细胞凋亡,减轻顺铂引起的胃癌大鼠肾损伤。     

血清CEA、G-17、MK、ProGRP与胃癌根治术患者术后复发风险的关系研究

摘要 目的：探讨血清癌胚抗原（CEA）、胃泌素17（G-17）、中期因子（MK）、胃泌素释放肽前体（ProGRP）与胃癌根治术（RG）患者术后复发风险的关系。方法：选取2018年1月～2020年8月新疆医科大学第一附属医院普外科收治的156例胃癌患者为胃癌组,根据RG后是否复发分为复发组和无复发组,另选取同期我院52名健康体检志愿者为对照组。收集胃癌患者临床资料,采用酶联免疫吸附法检测血清CEA、G-17、MK、ProGRP水平。通过单因素和多因素Logistic回归分析RG患者术后复发的影响因素,受试者工作特征（ROC）曲线分析血清CEA、G-17、MK、ProGRP水平对RG患者术后复发的预测价值。结果：与对照组比较,胃癌组血清CEA、G-17、MK、ProGRP水平升高（P＜0.05）。随访2年,失访2例,154例RG患者术后复发率为28.57%（44/154）。多因素Logistic回归分析显示,CEA、G-17、MK、ProGRP升高、TNM分期Ⅲ期、分化程度为低分化、淋巴结转移为RG患者术后复发的独立危险因素（P＜0.05）。ROC曲线分析显示,血清CEA、G-17、MK、ProGRP水平联合预测RG患者术后复发的曲线下面积（AUC）大于CEA、G-17、MK、ProGRP单独预测。结论：血清CEA、G-17、MK、ProGRP水平升高与RG患者术后复发密切相关,可能成为RG患者术后复发的辅助预测指标,且血清CEA、G-17、MK、ProGRP联合预测RG患者术后复发的价值较高。     

针刺对术后胃肠功能紊乱大鼠胃肠传输功能及脑肠肽的影响

摘要 目的：探讨针刺三里穴、中脘对大鼠胃大部切除术后胃肠传输功能恢复的影响及可能的作用机制。方法：将60只 SD 大鼠随机分为空白组、模型组和针刺组,每组 20 只。造模成功后第3天开始,针刺组进行针刺足三里、中脘,连续治疗14天。于末次针刺结束后,各组记录进食量、体重等;后各组禁食24 h后进行胃残留率和小肠推进率测定,腹主动脉取血测定胃泌素、胃动素、食欲素A及食欲素1型受体。结果：造模前,三组大鼠体重和进食量差异无统计学意义,P>0.05。造模后3天,模型组及针刺组体重和进食量低于空白组,差异有统计学意义,P<0.05。针刺干预后,模型组体重和进食量低于空白组和针刺组,差异有统计学意义,P<0.05。针刺干预后,针刺组大鼠胃残留率、小肠推进率、胃泌素、胃动素、食欲素A及食欲素1型受体高于模型组,差异有统计学意义,P<0.05;模型组胃残留率、小肠推进率、胃泌素、胃动素、食欲素A及食欲素1型受体低于空白组,差异有统计学意义,P<0.05;针刺组与空白组胃残留率、小肠推进率、胃泌素、胃动素、食欲素A及食欲素1型受体差异无统计学意义,P>0.05。结论：针刺胃大部切除术后大鼠足三里穴、中脘穴,改善胃排空和小肠推进功能,促进术后胃肠功能的恢复,其作用机制可能为改变脑肠肽代谢,增加食欲素A水平,激活食欲素1型受体,促进胃泌素、胃动素分泌。     

5’核苷酸酶碱性磷酸酶双重染色法在毛细淋巴管研究中的应用

本文应用5’-N-ALP双重染色法观察了裸鼠皮肤及人胃癌组织内淋巴管的形态和细微分布.在光镜下毛细淋巴管、淋巴管呈5’-N强阳性反应,管壁显示明显的棕色或深棕色,而毛细血管、血管的ALP呈强阳性,管壁呈明显的蓝色.据此可用组化方法将毛细淋巴管和毛细血管区别开来.本法能显示呈褐色的毛细淋巴管,特别是呈实性条索状的毛细淋巴管,因而双重染色比HE染色更能客观、准确地显示毛细淋巴管的分布.     

双功能抗体介导的胃癌杀伤效应

将诱变的αＣＤ３杂交瘤（ＴＫ~－）与ＰＤ４杂交瘤（ＨＧＰＲＴ~－）融合,获得分泌双功能抗体（ＢｓＡｂ）的四体杂交瘤Ｃ３．ＢｓＡｂＣ３可分别与ＣＤ３分子及胃癌相关抗原Ｐ４０反应．体外杀伤试验证实,当效靶比为４０：１,ＢｓＡｂＣ３浓度为１ｍｇ／Ｌ时,其杀伤效应可达７７．６％．该杀伤效应具有明显的特异性,仅Ｐ４０阳性表达的靶细胞可被溶解,体内杀伤试验证实,裸鼠接种胃癌细胞后５ｄ,以ＢｓＡｂＣ３活化的外周血淋巴细胞（ＰＢＬｓ）经局部皮下注射处理,可使移植胃癌完全消退（５／５）．这一明显的治疗作用可能与局部注射途径有关,可供临床应用参考．     

Inhibition of satiety by a cholecystokinin antagonist is independent of gastric emptying

The ability of a cholecystokinin antagonist Proglumide to inhibit satiety induced by intraperitoneal injections of cholecystokinin octapeptide (CCK-OP) and bombesin was examined in rats equipped with chronic gastric cannulae. Both CCK-OP and bombesin significantly suppressed sham feeding. Proglumide administered alone did not alter sham feeding but it abolished the suppression of feeding induced by CCK-OP. In contrast, Proglumide did not inhibit the effect of a low dose of bombesin, but partially inhibited satiety induced by a high dose of bombesin, thus confirming our previous findings. These results indicate that the effect of Proglumide is independent of its recently described effects on gastric emptying in rat.     

Analysis of food stimulation of gastrin release in dogs by a panel of inhibitors

The release of gastrin into the serum of five conscious gastric fistula dogs after a meat meal was monitored for 2 hours. Neither the rate of increase in serum gastrin nor the 2 hour cumulative integrated gastrin response was changed by administration of small doses of somatostatin tetradecapeptide (0.5 microgram/kg.hr IV for 2 hr), 16-16 dimethyl prostaglandin E2 (0.25 microgram/kg.hr IV for 2 hr or 1 microgram/kg intragastrically), or bethanechol (20 micrograms/kg.hr IV for 2 hr). Acidification of the food in the antrum to pH 1.2 to 1.4 eliminated serum gastrin release in response to food. In control studies, serum gastrin levels were not altered by IV administration of saline for 2 hr with no food or when a plate of food was held just out of the dogs' reach (teasing). Food-stimulated gastrin release was contrasted with that stimulated by bombesin under identical laboratory conditions [17]. In each case, antral acidification, somatostatin, prostaglandin E2 and bethanechol affected bombesin-stimulated gastrin release differently from that stimulated by food. We conclude that food and bombesin release gastrin by different pathways.     

The effects of 11-methyl 16,16 dimethyl prostaglandin E2 on gastric acid secretion in man

11-Methyl 16,16 Dimethyl Prostaglandin E₂ (TM-PGE) was administered orally to man in dosages of 2.5, 5, 7.5 and 10 μg/kg. Maximal inhibition of basal secretion was 52 and 78% and submaximal histamine-stimulated secretion 45 and 70% for volume and acid output, respectively. Secretory inhibition was observed for approximately two hours after ingestion of the drug. No effect was observed on serum gastrin levels. Side effects occurred with equal frequency in the placebo and drug groups. TM-PGE is well tolerated and inhibits both basal and submaximal histamine-stimulated acid secretion in man. Further evaluation may prove it to be helpful in the clinical treatment of acid hypersecretory states and peptic ulcer disease.     

Block of acid secretion by amytal and its partial reversal by menadione with ascorbate in the gastric mucosa of the guinea-pig

The effect of amytal on energy metabolism and acid secretion in an isolated gastric mucosa of the guinea-pig were studied. Determination of adenine nucleotides, creatine phosphate, pyruvate and lactate in the gastric mucosa showed that amytal depressed the levels of ATP, creatine phosphate and energy charge with elevation of the AMP and pyruvate levels. This treatment inhibited concomitantly acid secretion and active chloride transport detected by short circuit current. The addition of menadione with ascorbate to the medium in the presence of amytal partially restored ATP and energy charge levels and also induced a partial recovery of acid secretion and active chloride transport. These results suggest that ATP is a direct energy donor for acid secretion in the gastric mucosa of the guinea-pig.