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.     

上海市黄浦区社会办医疗美容机构《医疗美容管理办法》知晓情况调查

目的了解上海市黄浦区社会办医疗美容机构的管理人员和医师对《医疗美容管理办法》相关内容的掌握情况,发现存在的问题并提出改善建议.方法采用现场调查与现场问卷调查相结合的方式,对在上海市黄浦区开展医疗美容科目的所有社会办医疗机构(共计38家)进行全覆盖现场调查,并对其中的管理人员41人、相关医师31人进行问卷调查.结果38家社会办医疗美容机构中,美容外科和美容皮肤科的开展率较高,分别为96.8%和97.2%,而美容牙科开展率为52.4%,美容中医科开展率最低(25.0%).管理人员关于非主诊医师可在主诊医师指导下工作的知晓率仅68.3%.关于美容外科、皮肤科、中医科、牙科主诊医师应具备的工作年限,管理人员答对率为90.2%,医师答对率为72.0%,二者有显著性差异(P<0.05).结论社会办医疗美容机构中的二级科目设置需进一步优化,以减少资源空置.应加强对医疗机构管理人员和医师的法律培训,改变经营模式,制定明确的准入与退出机制,从而减少违法违规行为的发生.     

Steep Decrease of Gender Difference in DSM-IV Alcohol Use Disorder: A Comparison of Two Nation-wide Surveys Conducted 10 Years Apart in Korea

While decreasing trend in gender differences in alcohol use disorders was reported in Western countries, the change in Asian countries is unknown. This study aims to explore the shifts in gender difference in alcohol abuse (AA) and dependence (AD) in Korea. We compared the data from two nation-wide community surveys to evaluate gender differences in lifetime AA and AD by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Face-to-face interviews using the Composite International Diagnostic Interview (CIDI) were applied to all subjects in 2001 (n=6,220) and 2011 (n=6,022). Male-to-female ratio of odds was decreased from 6.41 (95% CI, 4.81-8.54) to 4.37 (95% CI, 3.35-5.71) for AA and from 3.75 (95% CI, 2.96-4.75) to 2.40 (95% CI, 1.80-3.19) for AD. Among those aged 18-29, gender gap even became statistically insignificant for AA (OR, 1.59; 95% CI, 0.97-2.63) and AD (OR, 1.18; 95% CI, 0.80-2.41) in 2011. Men generally showed decreased odds for AD (0.55; 95% CI, 0.45-0.67) and women aged 30-39 showed increased odds for AA (2.13; 95% CI 1.18-3.84) in 2011 compared to 2001. Decreased AD in men and increased AA in women seem to contribute to the decrease of gender gap. Increased risk for AA in young women suggests needs for interventions.     

What to expect when you're expecting a hepatopancreatobiliary surgeon: self-reported experiences of HPB surgeons from different training pathways

BackgroundHepatopancreatobiliary (HPB) surgery fellowship training has multiple paths. Prospective trainees and employers must understand the differences between training pathways. This study examines self-reported fellowship experiences and current scope of practice across three pathways.MethodsAn online survey was disseminated to 654 surgeons. These included active Americas Hepato-Pancreato-Biliary Association (AHPBA) members and recent graduates of HPB, transplant–HPB and HPB–heavy surgical oncology fellowships.ResultsA total of 416 (64%) surgeons responded. Most respondents were male (89%) and most were practising in an academic setting (83%). 290 (70%) respondents underwent formal fellowship training. Although fellowship experiences varied, current practice was largely similar. Minimally invasive surgery (MIS) and ultrasound were the most commonly identified areas of training deficiencies and were, respectively, cited as such by 47% and 34% of HPB-, 49% and 50% of transplant-, and 52% and 25% of surgical oncology-trained respondents. Non-HPB cases performed in current practice included gastrointestinal (GI) and general surgery cases (56% and 49%, respectively) for HPB-trained respondents, transplant and general surgery cases (87% and 21%, respectively) for transplant-trained respondents, and GI surgery and non-HPB surgical oncology cases (70% and 28%, respectively) for surgical oncology-trained respondents.ConclusionsFellowship training in HPB surgery varies by training pathway. Training in MIS and ultrasound is deficient in each pathway. The ultimate scope of non-transplant HPB practice appears similar across training pathways. Thus, training pathway choice is best guided by the training experience desired and non-HPB components of anticipated practice.     

Quantitative chemical exchange saturation transfer (qCEST) MRI – omega plot analysis of RF‐spillover‐corrected inverse CEST ratio asymmetry for simultaneous determination of labile proton ratio and exchange rate

Chemical exchange saturation transfer (CEST) MRI is sensitive to labile proton concentration and exchange rate, thus allowing measurement of dilute CEST agent and microenvironmental properties. However, CEST measurement depends not only on the CEST agent properties but also on the experimental conditions. Quantitative CEST (qCEST) analysis has been proposed to address the limitation of the commonly used simplistic CEST‐weighted calculation. Recent research has shown that the concomitant direct RF saturation (spillover) effect can be corrected using an inverse CEST ratio calculation. We postulated that a simplified qCEST analysis is feasible with omega plot analysis of the inverse CEST asymmetry calculation. Specifically, simulations showed that the numerically derived labile proton ratio and exchange rate were in good agreement with input values. In addition, the qCEST analysis was confirmed experimentally in a phantom with concurrent variation in CEST agent concentration and pH. Also, we demonstrated that the derived labile proton ratio increased linearly with creatine concentration (P < 0.01) while the pH‐dependent exchange rate followed a dominantly base‐catalyzed exchange relationship (P < 0.01). In summary, our study verified that a simplified qCEST analysis can simultaneously determine labile proton ratio and exchange rate in a relatively complex in vitro CEST system. Copyright © 2015 John Wiley & Sons, Ltd.     

Increased Morbidity and Mortality of Emergency Laparotomy in Elderly Patients

Background

There is an increasing incidence of elderly patients requiring emergency laparotomy. Our study compares the outcomes of elderly patients undergoing emergency laparotomy against the outcomes of non-elderly patients.

Methodology

Patients who underwent emergency laparotomy between 2015 and 2017 from the National University Hospital, Singapore, were included. Apart from demographic data, indication of surgery and surgical procedure performed were collected. Prospectively collected nutritional scores were evaluated. Outcome measures included duration of surgery, length of ICU and total hospital stay, post-operative complications, and mortality indices. We performed multivariate Cox regression analysis to determine the contribution of various risk factors towards overall survival following emergency laparotomy.

Results

A total of 170 emergency laparotomies were performed. Compared to non-elderly patients, elderly patients had a significantly longer mean stay in hospital (31.5 vs. 18.6 days, p = 0.006) and mean stay in ICU (13.1 vs. 5.3 days, p = 0.003). More elderly patients suffered from post-laparotomy complications compared with non-elderly patients (65.8% vs. 37.4%, p < 0.001). 30-day mortality (31.5% vs. 8.8%, p = 0.019) and 1-year mortality (27.9% vs. 14.3%, p = 0.023) were higher in elderly patients compared with non-elderly patients. Interestingly, there was no statistically significant difference between elderly and non-elderly groups in both the global 3-MinNS as well as the global SGA nutritional scores. ASA status (HR 2.61, 95% CI 1.05–6.45, p = 0.038) was an independent risk factor for decreased survival following emergency laparotomy. Notably, while age ≥ 65 demonstrated a significant correlation with survival on univariate analysis (HR 1.03 (1.01–1.05), p = 0.003), this effect was lost following multivariate regression (HR 1.01 (0.453–2.23), p = 0.989).

Conclusion

Elderly patients suffer worse morbidity and mortality following emergency laparotomy. This is likely contributed by comorbidities resulting in higher ASA status.

     

Effects of box handle position and carrying range on bi-manual carrying capacity for females

This study utilizes a psychophysical approach to examine the effects on carrying capacity for bi-manual carrying tasks involving different handle positions and carrying ranges. A total of 16 female subjects participated in the experiment in groups of two people, and each group of subjects performed the tasks in a random order with 12 different combinations of carrying task. The independent variables are handle position (upper, middle, lower) and carrying range (F–F: floor height carried to floor height, F–W: floor height carried to waist height, W–W: waist height carried to waist height, W–F: waist height carried to floor height), the dependent variable is the maximum acceptable carried weight (MAWC), heart rate (HR), and the rating of perceived exertion (RPE). The results show that the handle position has a significant effect on MAWC and overall RPE but no significant effect on HR. Carrying range has a significant effect on the MAWC and HR, but no significant effect on overall HR. The handle position and carrying range have a significant interaction on the MAWC and HR. The RPE for different body parts shows significant differences, and the hands feel the most tired. Overall, this study confirms that the lower handle position with the W–W carrying range is the best combination for a two-person carrying task.     

Exploration of D022-Type Al3TM(TM = Sc,Ti, V,Zr, Nb,Hf, Ta): Elastic Anisotropy,Electronic Structures,Work Function and Experimental Design

The structural properties, elastic anisotropy, electronic structures and work function of D0₂₂-type Al₃TM (TM = Sc, Ti, V, Y, Zr, Nb, La, Hf, Ta) are studied using the first-principles calculations. The results indicate that the obtained formation enthalpy and cohesive energy of these compounds are in accordance with the other calculated values. It is found that the Al₃Zr is the most thermodynamic stable compound. The mechanical property indexes, such as elastic constants, bulk modulus, shear modulus, Young’s modulus, Poisson’s ratio, and Vickers hardness are systematically explored. Moreover, the calculated universal anisotropic index, percent anisotropy and shear anisotropic factors of D0₂₂-type Al₃TM are analyzed carefully. It demonstrates that the shear modulus anisotropy of Al₃La is the strongest, while that of Al₃Ta is the weakest. In particular, the density of states at Fermi level is not zero, suggesting that these phases have metal properties and electrical conductivity. More importantly, the mechanisms of correlation between hardness and Young’s modulus are further explained by the work function. Finally, the experimental design proves that D0₂₂-Al₃Ta has an excellent strengthening effect.