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.     

Bone Metabolism Discrepancy in Type 2 Diabetes Mellitus Patients With and Without Non-Alcoholic Fatty Liver Disease

To explore the distribution of several bone metabolic indicators in type 2 diabetes patients (T2DM) with and without non-alcoholic fatty liver disease (NAFLD) and to preliminarily evaluate the relationship of bone metabolism with NAFLD in patients with T2DM. The hospitalized patients with T2DM were divided into the group of T2DM complicated with NAFLD and the group of T2DM alone according to the results of ultrasonic diagnosis. The general information and laboratory test data such as bone metabolism indexes of these patients were collected and the differences of the indexes between the 2 groups were compared. Furthermore, the independent influencing factors of NAFLD in patients with T2DM were analyzed. A total of 186 patients were included in the study. Compared with patients with T2DM only, patients with T2DM combined with NAFLD were characterized with younger age (p < 0.001), higher BMI (p = 0.016), ALT (p = 0.001), TG (p = 0.005), HOMA-IR (p = 0.005), and lower HDL-C (p = 0.031). Significant discrepancy of age (OR 1.052, p = 0.001), ALT (OR 0.964, p = 0.047), HOMA-IR (OR 0.801, p = 0.005), and T-PINP (OR 1.022, p = 0.008) was found using multivariate logistic regression model. Significant discrepancy of T-PINP was found in T2DM patients with and without NAFLD. Further studies are needed to explore whether T-PINP could be used as a predictor of fatty liver disease, osteoporosis, and other related complications in patients with T2DM.     

非高密度脂蛋白胆固醇水平与冠心病患者冠状动脉病变Gensini评分的相关性研究

目的 探讨非高密度脂蛋白胆固醇水平(non-HDL-C)与冠心病(CHD)患者冠状动脉病变Gensini评分的关系及临床意义。方法 对225例疑诊或既往临床诊断CHD患者予以冠状动脉造影(CAG),将造影阴性的39例作为对照组(HC组),造影阳性的186例患者诊断为CHD,结合临床特点分为心绞痛组(AP组)122例和心肌梗死组(AMI组)64例。采用Gensini评分对冠状动脉病变程度评分,测定患者全套血脂水平,探讨non-HDL-C及相关脂质成分与冠状动脉病变程度Gensini评分的相关性;同时对他汀类药物强化降脂达标,低密度脂蛋白胆固醇(LDL-C)<1.80 mmol/L的AP组患者进行non-HDL-C与冠状动脉病变程度Gensini评分的亚组分析。结果 AMI组non-HDL-C水平高于AP组及HC组,AP组non-HDL-C水平高于HC组,差异均有统计学意义(P<0.05);CHD患者non-HDL-C水平与Gensini评分呈正相关(r=0.562,P<0.05);LDL-C控制达标的AP组患者,高non-HDL-C组(≥2.60 mmol/L)比低non-HDL-C组(<2.60 mmol/L)Gensini评分明显升高,差异均有统计学意义(P<0.05)。结论 non-HDL-C与冠状动脉病变程度密切相关,non-HDL-C在评估LDL-C控制达标患者的冠状动脉病变程度及再发心血管事件风险上有一定价值,可作为LDL-C达标后心血管残余风险新的观察指标。     

郑州市三甲医院急诊科护士道德困境与职业倦怠的现状及相关性研究

目的 调查郑州市三甲医院急诊科护士的道德困境与职业倦怠的现状,并分析两者之间的相关性。方法 采用便利抽样法选取郑州市5所三甲医院的228名急诊科护士作为研究对象,采用一般资料调查表、中文版护士道德困境量表、护士职业倦怠量表对其进行问卷调查。结果 郑州市三甲医院急诊科护士道德困境总分为(49.41±13.35)分,职业倦怠总分为(63.51±17.25)分。单因素分析显示,不同学历、工作年限的急诊护士的道德困境得分比较,差异均有统计学意义(F=4.830,P=0.015; F=6.302,P=0.001);不同年龄急诊护士的职业倦怠得分比较,差异有统计学意义 (F=8.328,P=0.005),急诊科护士道德困境与职业倦怠呈正关性(r=0.412,P<0.05)。结论 郑州市三甲医院急诊科护士的道德困境与职业倦怠普遍存在,护士的道德困境与职业倦怠呈正相关。     

Changes in Bone Marrow Adipose Tissue in Transgender and Gender Non-Conforming Youth Undergoing Pubertal Suppression: A Pilot Study

Pubertal suppression with gonadotropin-releasing hormone (GnRH) agonists in transgender and gender non-conforming (TGNC) youth may affect acquisition of peak bone mass. Bone marrow adipose tissue (BMAT) has an inverse relationship with bone mineral density (BMD). To evaluate the effect of pubertal suppression on BMAT, in this pilot study we prospectively studied TGNC youth undergoing pubertal suppression and cisgender control participants with similar pubertal status over a 12-month period. BMD was measured by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Magnetic Resonance T1 relaxometry (T1-R) and spectroscopy (MRS) were performed to quantify BMAT at the distal femur. We compared the change in BMD, T1-R values, and MRS lipid indices between the two groups. Six TGNC (two assigned female and four assigned male at birth) and three female control participants (mean age 10.9 and 11.7 years, respectively) were enrolled. The mean lumbar spine BMD Z-score declined by 0.29 in the TGNC group, but increased by 0.48 in controls (between-group difference 0.77, 95% CI: 0.05, 1.45). Similar findings were observed with the change in trabecular volumetric BMD at the 3% tibia site (-4.1% in TGNC, +3.2% in controls, between-group difference 7.3%, 95% CI: 0.5%-14%). Distal femur T1 values declined (indicative of increased BMAT) by 7.9% in the TGNC group, but increased by 2.1% in controls (between-group difference 10%, 95% CI: -12.7%, 32.6%). Marrow lipid fraction by MRS increased by 8.4% in the TGNC group, but declined by 0.1% in controls (between-group difference 8.5%, 95% CI: -50.2%, 33.0%). In conclusion, we observed lower bone mass acquisition and greater increases in BMAT indices by MRI and MRS in TGNC youth after 12 months of GnRH agonists compared with control participants. Early changes in BMAT may underlie an alteration in bone mass acquisition with pubertal suppression, including alterations in mesenchymal stem cells within marrow.     

Everyday footwear: An overview of what we know and what we should know on ill-fitting footwear and associated pain and pathology

Footwear has been used to protect feet for millennia with socially exclusive population adopting stylish and fashionable shoes with expensive materials. In terms of historic timeline, only more recently footwear has been worn by all classes in the western world as an integral part of their apparel. Traditionally, footwear has been constructed from natural materials, mainly leather, but has recently benefitted from the flexibility that technology has provided with a plethora materials and new design innovations. Although it has expanded the availability for a variety of consumers, the choice and fit continue to be problematic with many individuals wearing shoes that are ill-fitting. Provision of specific footwear advice for problem feet is poorly evidenced and is heavily practitioner dependant limiting its efficacy. There is limited understanding as to the changes that can occur from regularly wearing footwear that is unsuitable in shape, style and construction which is referred to as ill-fitting. Current research on the effect that everyday footwear has on foot function and pain focuses mainly on women’s shoes, particularly high heels. Defining what is a good fitting shoe, that does not damage the foot or mechanics of walking, may need to be individualised, but best fit is based on loose historical parameters rather than research evidence. The aim of this overview is to highlight aspects of current research, establishing what is known about the effect’s shoes have on the feet as well as exploring the mythology around footwear fit and advice that is often historical in nature.     

Discovering novel lung cancer associated antigens and the utilization of their autoantibodies in detection of lung cancer

ObjectiveThe identification of tumor-associated antigens (TAAs) and their corresponding autoantibodies in lung cancer (LC) may expand our vision of cancer immunity. This study aims to screen novel TAAs to distinguish LC from the healthy population.MethodsIn our previous study, 35 genes encoding LC-associated TAAs were identified from the serological analysis of recombinant cDNA expression libraries (SEREX), and Oncomine database was further used to identify potential genes in cancer progression. Autoantibody to TAAs were tested by enzyme-linked immunosorbent assay (ELISA) in sera from 1379 participants in validation set and verification set.FindingsBased on analysis of three independent microarrays in Oncomine, ten genes were consistently dysregulated in LC. The sera level and positive frequency of the anti-TOP2A, anti-ACTR3, anti-RPS6KA5 and anti-PSIP1 from LC patients were higher than normal control in validation set. The area under curve (AUC) of anti-TOP2A, anti-ACTR3, anti-RPS6KA5 and anti-PSIP1 was respectively 0.758, 0.787, 0.707, 0.668. The sensitivity of these four autoantibodies for LC detection ranged from 26.63 % to 32.07 % with the specificity over 90 %. Data from the verification set confirmed the results. Except that, the frequency of serum autoantibody against TOP2A (43.3 %) and ACTR3 (50.0 %) was significantly higher in early stage LC than late stage (23.6 % and 22.3 %, respectively).ConclusionTOP2A, ACTR3, RPS6KA5 and PSIP1 can elicit humoral immune response in LC and their autoantibodies have relationship with the tumorigenesis of LC. Anti-TOP2A and anti-ACTR3 have the potential to serve as a serological biomarkers in early stage LC.