Helicobacter pylori induces epithelial-mesenchymal transition in gastric carcinogenesis via the AKT/GSK3β signaling pathway

Helicobacter pylori (H. pylori) is a main risk factor for gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is involved in the development and progression of H. pylori-associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3β signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether H. pylori infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT-associated proteins, including E-cadherin and N-cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E-cadherin, N-cadherin, AKT, phosphorylated (p-)AKT (Ser473), GSK3β and p-GSK3β (Ser9) were further determined in H. pylori-infected Mongolian gerbil gastric tissues and cells co-cultured with H. pylori by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E-cadherin were decreased, whereas the expression levels of the mesenchymal marker N-cadherin were increased during gastric carcinogenesis. Their expression levels were associated with H. pylori infection. Furthermore, H. pylori infection resulted in downregulation of E-cadherin expression and upregulation of N-cadherin expression in Mongolian gerbils and GES-1 cells. In addition, an investigation of the associated mechanism of action revealed that p-AKT (Ser473) and p-GSK3β (Ser9) were activated in GES-1 cells following co-culture with H. pylori. Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E-cadherin, N-cadherin, p-AKT and p-GSK3β did not show significant differences between GES-1 cells that were co-cultured with or without H. pylori. The levels of p-AKT and p-GSK3β were increased in H. pylori-infected Mongolian gerbils. In conclusion, the present study demonstrated that H. pylori infection activated AKT and resulted in the phosphorylation and inactivation of GSK3β, which in turn promoted early stage EMT. These effects were AKT-dependent. This mechanism may serve as a prerequisite for GC development.     

Suppression of PRDX4 inhibits cell proliferation and invasion of ectopic endometrial stromal cells in endometriosis

Abstract

Oxidative stress (OS) has been proposed to play a role in the development of EMs. Peroxiredoxins are a family of antioxidant proteins that exhibit peroxidase activity in a thioredoxin-dependent manner, protecting cells against OS. The Western blotting results showed that the relative expression of PRDX4 was significantly increased in ectopic endometria compared with the normal endometria of EMs-free (p?<?.05). The H₂O₂ concentration was also significantly higher in the ectopic endometrium. PRDX4 siRNA was transfected into primary ectopic endometrial stromal cells (EESCs). The viability of the transfected EESCs was measured by CCK-8 assay, and the results showed significantly decreased cell viability. Furthermore, the apoptosis rate and ROS generation in flow cytometry assays were significantly increased after the knockdown of PRDX4 expression (p?<?.05). Scratch assays and transwell assays revealed that decreased expression of PRDX4 mediated by siRNA inhibited EESC migration and invasion. In conclusion, these findings indicate the potential role of PRDX4 in the development of EMs and PRDX4 as a possible therapeutic target for EMs treatment.     

Association of genetic variants at MYP10 and MYP15 with high myopia in a Han Chinese population

Background: Previous genome-wide association study (GWAS) has revealed the association between MYP10 at 8p23 and MYP15 at 10q21.1 and high myopia (HM) in a French population. This study is managed to discover the connection between some single nucleotide polymorphism (located at MYP10 and MYP15) and Han Chinese HM.

Methods and Results: This case-control association study contained 1673 samples, including 869 ophthalmic patients and 804 controls. Twelve tag SNPs have been selected from the MYP10 and MYP15 loci and genotyped by SNaPshot method. Among 12 SNPs, rs4840437 and rs6989782 in TNKS gene were found significant association with HM. Carriers of rs4840437G allele and rs4840437GG genotype created a low risk of high myopia (P = .036, OR = 0.81, 95%CI = 0.71–0.93; P = .016, OR = 0.73, 95%CI = 0.56–0.96; respectively). Carriers of rs6989782T allele and rs6989782TT+CT genotype also had a decreased risk of high myopia (P = .048, OR = 0.82, 95%CI = 0.71–0.94; P = .006, OR = 0.74, 95%CI = 0.59–0.92; respectively). Other 10 SNPs displaced nonsignificant association with HM. Additionally, the risk haplotype AC and the protective haplotype GT, generated by two SNPs in TNKS, were considerably more likely to be association with HM (for AC, P = .002 and OR = 1.26; for GT, P = .027 and OR = 0.84).

Conclusions: Our results demonstrated that some heritable variants in the TNKS gene are associated with HM in the Han population. The possible functions of TNKS in the development and pathogenesis of hereditary high myopia still require further researches to identify.     

聪耳通窍汤联合耳针对老年神经性耳鸣近远期疗效观察

目的探讨聪耳通窍汤联合耳针治疗老年神经性耳鸣患者的近远期疗效。方法选取耳鼻喉科门诊收治的老年神经性耳鸣患者136例,按随机数字表法分组,对照组68例予以耳针治疗,研究组68例在对照组基础上予以聪耳通窍汤治疗。检测比较两组间近、远期临床疗效、甲襞微循环指标、血液流变学指标以及不良反应发生率。结果治疗后,对照组总有效率为67.64%(46/68)低于研究组总有效率83.82%(57/68),具有统计学意义(P<0.05);随访6个月后,对照组总有效率64.71%(44/68)低于研究组总有效率89.71%(61/68),具有统计学意义(P<0.05);与对照组比较,研究组治疗后甲襞微循环襻周积分、管襻积分、流态积分及总积分较低,治疗后血浆黏度、高切全血黏度、低切全血黏度及红细胞压积较低,差异具有统计学意义(P<0.05);治疗中出现的不良反应为恶心、腹胀、针刺部位疼痛,两组间不良反应发生率无统计学差异(P>0.05)。结论聪耳通窍汤联合耳针治疗老年神经性耳鸣患者的近远期疗效均较好,能明显改善患者微循环状态及血液流变学指标,减轻内耳循环障碍,具有较高安全性。     

呼吸专科护士慢性呼吸疾病管理现状调查

目的调查呼吸专科护士慢性呼吸疾病管理现状,为提高慢性呼吸疾病的管理水平提供参考。方法依据《中国成人慢性呼吸疾病患者护理管理指南》设计调查问卷,对重庆、四川、贵州、陕西、河北、湖北、海南7省市的205名呼吸专科护士进行问卷调查。结果呼吸专科护士慢性呼吸疾病管理总分为(140.72±23.90)分。慢性呼吸疾病管理得分最低的3个条目有评估工具应用、个性化管理计划的实施、慢阻肺随访的次数及指导哮喘患者使用峰流速仪;呼吸专科护士所在单位慢性呼吸疾病管理平台建设均低于50%。结论呼吸专科护士慢性呼吸疾病管理处于中等偏下水平,评估是慢性呼吸疾病管理的薄弱点。需加强呼吸专科护士专业能力培养,规范慢性呼吸疾病全程管理,强化医院平台建设等,提高慢性呼吸疾病的管理水平。     

非活动性结核性胸膜炎与活动性结核性胸膜炎的CT扫描影像特征分析

目的: 探讨非活动性结核性胸膜炎与活动性结核性胸膜炎CT扫描影像表现。方法: 对2012年6月1日至2021年3月30日在首都医科大学附属北京胸科医院就诊的单纯非活动性结核性胸膜炎患者68例和同期活动性结核性胸膜炎44例的CT扫描影像表现进行比较。结果: (1) 68例非活动性结核性胸膜炎患者 CT扫描影像表现中胸膜粘连62例(91.2%),胸膜有钙化者28例(41.2%),叶间裂受累22例(32.4%),胸腔积液12例(17.6%),包裹性胸腔积液8例(11.8%)。(2)44例活动性结核性胸膜炎患者CT扫描影像表现中胸膜粘连30例(68.2%),未见胸膜钙化,叶间裂受累32例(72.7%),胸腔积液43例(97.7%),包裹性胸腔积液26例(59.1%)。(3)非活动性与活动性结核性胸膜炎CT扫描影像比较:胸膜粘连、胸膜钙化发生率高,差异均有统计学意义(χ²=9.630,P=0.002;χ²=23.737,P=0.000);叶间裂受累、胸腔积液、包裹性胸腔积液的发生率低,差异均有统计学意义(χ²=12.692,P=0.000;χ²=68.548,P=0.000;χ²=28.301,P=0.000)。结论: 非活动性结核性胸膜炎的CT扫描影像与活动性结核性胸膜炎比较胸膜粘连、胸膜钙化的发生率高,胸腔积液、包裹性胸腔积液、叶间裂受累的发生率低。识别非活动性和活动性结核性胸膜炎的CT扫描影像特点,对患者临床治疗有指导意义。     

糖尿病肾病内热证与肾功能及炎症因子的相关性研究

目的:观察糖尿病肾病不同分期内热证与肾功能及炎症指标的相关性。方法:收集202例糖尿病肾病患者的临床资料,采用酶联免疫吸附法检测微炎症指标,包括超敏C反应蛋白(high-sensitivity C-reactive protein,HS-CRP)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α),进行统计分析。结果:与非内热证组比较,中期、晚期内热证组24小时尿蛋白定量明显升高;晚期内热证组的血清肌酐明显升高,肾小球滤过率(glomerular filtration rate,GFR)明显降低;炎症因子CRP、IL-6、TNF-α随疾病进展均呈上升趋势;晚期内热证组与非内热证组比较,IL-6、TNF-α升高;中期HS-CRP与内热积分呈正相关,晚期TNF-α与内热积分呈正相关。结论:内热病机贯穿于糖尿病肾病的始终,与糖尿病肾病肾功能以及疾病进展密切相关;同时,内热积分与炎症因子HS-CRP、TNF-α的表达存在一定的相关性,这种相关性在疾病中期、晚期表现更加明显。