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.     

Cefoperazone-sulbactam and risk of coagulation disorders or bleeding: a retrospective cohort study

ABSTRACT

Objectives: Limited evidence has suggested that cefoperazone-sulbactam causes coagulation disorders and bleeding.

Methods: The authors conducted a retrospective study to compare patients receiving cefoperazone-sulbactam versus those treated with cefoperazone-tazobactam or ceftazidime. Propensity-score matching was used to explore whether treatment with cefoperazone-sulbactam increased the risk of prothrombin time (PT) prolongation, coagulation disorders, and bleeding, or decreased platelets (PLT).

Results: The cohort included 23,242 patients. Among patients receiving cefoperazone-sulbactam, the risk of PT prolongation, coagulation disorders, decreased PLT, and bleeding was 5.3%, 9.2%, 15.7%, and 4.2%, respectively. Propensity-score matching analyses suggested that cefoperazone-sulbactam increased the risk of PT prolongation (aOR 2.26, 95% CI 1.61–3.18), coagulation disorders (aOR 1.81, 95% CI 1.43–2.30), and decreased PLT (aOR 1.46, 95% CI 1.25–1.72), but not increase bleeding (aOR 1.05, 95% CI 0.79–1.40) compared with ceftazidime. Patients receiving cefoperazone-sulbactam had higher risk of PT prolongation (aOR 1.53, 95% CI 1.11–2.10), coagulation disorders (aOR 1.53, 95% CI 1.21–1.95), but not decreased PLT (aOR 0.93, 95% CI 0.81–1.07) or bleeding (aOR 1.11, 95% CI 0.87–1.42), compared with those receiving cefoperazone-tazobactam.

Conclusion: Cefoperazone-sulbactam may be associated with a higher risk of PT prolongation and coagulation disorders compared with cefoperazone-tazobactam and ceftazidime.     

成人阴茎的三维数字化图像分析

目的对成人阴茎进行三维数字化图像分析,为阴茎整形修复获得手术前后形变参数及手术方案的选择,提供精确的形态学数据。方法采用Angel数字快速测量诊断系统,分别测量200例正常成人阴茎安静状态和勃起时的长度、周长、以及勃起时角度与阴茎长度、周径的关系。结果随着年龄和身高增长,阴茎也随之增长;身高与阴茎长度不成正比;阴茎勃起时随着角度的增加硬度增强,但勃起硬度变化时阴茎体积无明显变化。结论从不同径线不同角度对阴茎进行计算机三维测量分析,为阴茎整形修复术前设计、术后效果评价提供重要的量化指标。     

Effects of an exercise intervention for older heart failure patients on caregiver burden and emotional distress.

BACKGROUND: The impact of exercise programmes for heart failure on those close to the patient is largely unknown. We examined the effect of a hospital and home-based exercise intervention on burden, anxiety and depression of informal caregivers. DESIGN: The study was a randomized, controlled trial. Heart failure patients were randomized to a seated 12-week hospital-based exercise programme. Caregiver measures were gathered at baseline, 3 months later and 6 months following baseline. METHODS: Sixty caregivers (mean age 63.4 years, 65% female) of heart failure patients (n = 82, mean age 80.5 years, 44% female) participating in a trial of an exercise intervention were recruited. Caregiver burden, anxiety and depression were assessed. RESULTS: There were no differences in caregiver burden, depression or anxiety between the two groups of caregivers at baseline (caregiver burden, patient control 33.1 versus patient exercise 34.1; anxiety 4.1 versus 5.5; depression 2.8 versus 3.8). At 3 months there were no differences between caregivers in the two groups on outcomes. At 6-month follow-up caregivers of heart failure patients in the exercise group had burden scores that were significantly worse than the control group. There were no differences between the carers of exercise and control groups in anxiety and depression. Levels of anxiety and depression in the entire carer sample were marginally higher than reference values in a healthy non-clinical sample. CONCLUSION: The present exercise interventions for frail older patients did not benefit caregivers and was associated with an increase in caregiver burden. We suggest that future exercise interventions for heart failure patients should actively incorporate informal caregivers into research designs.     

肥胖与胆石病的多因素条件Logistic回归分析

目的探讨肥胖与结石病发病的关系。方法采用调查表的方式对1997年住院手术确诊为结石病的病人进行回顾性调查，内容包括：年龄、性别、体重、身高、是否吃早餐。对调查表进行多因素logstic统计分析。结果分析结果表明我们调查了我院102例结石病患者和101名正常人发现肥胖、女性、不经常吃早餐、饮用高硬度的水均是结石病的危险因紊，对那些长时间不吃早餐的人更容易患结石病，（相对危险度OR〉40．139）。结论我们建议今后应注意膳食营养的均衡，保持标准体重，饮用卫生水。     

Effects of recombinant humanen dothelial-derived interleukin-8 on hemorhagic shock in rats

目的：研究重组人内皮细胞衍生的白细胞介素－８（ＩＬ８）对失血性休克的作用．方法：大鼠股动脉放血至ＭＡＢＰ５３２ｋＰａ，维持９０ｍｉｎ，复制晚期失血性休克模型．输血后，静脉注射ＩＬ８２５０μｇ·ｋｇ－１．放免法测定血浆ＥＴ１和６ＫＰＧＦ１α含量．结果：给予ＩＬ８后，ＭＡＢＰ显著提高，休克状态改善，２ｈ存活率相应提高；休克晚期血浆ＥＴ１水平比正常明显升高（２１±４ｖｓ８２±１８ｎｇ·Ｌ－１，Ｐ＜００１），血浆６ＫＰＧＦ１α含量明显降低（１０７±１２ｖｓ１５７±１１ｎｇ·Ｌ－１，Ｐ＜００１）．ＩＬ８显著降低血浆ＥＴ１水平（１０±４ｎｇ·Ｌ－１，Ｐ＜００１），提高血浆６ＫＰＧＦ１α含量（３６８±１６ｎｇ·Ｌ－１，Ｐ＜００１）．结论：ＩＬ８具有较好的抗休克作用．     

高强度超声对犬前列腺组织损伤的实验研究

目的　探讨经尿道高强度超声 (transurethralhighintensityultrasound ,TUHIU)治疗良性前列腺增生症 (benignprostatichyperplasia ,BPH)的有效性和可行性。方法　对犬前列腺进行TUHIU辐照处理 ,辐照后不同时期处死动物以观察其急性、亚急性和慢性期大体及组织病理变化。同时观察辐照前后影像学变化。结果　TUHIU辐照前前列腺部尿道平均最大宽度为 0 66± 0 12 ( x±s)cm ,辐照 3周后前列腺部尿道平均最大宽度为 2 11± 1 0 7cm ,较辐照前显著增宽。辐照后可见靶区内尿道周围腺体发生凝固性坏死 ,3 0～ 60天后坏死组织脱落尿道呈囊腔状。光、电镜下均可见腺上皮及基质细胞发生均匀性凝固性坏死。辐照后经腹B超示前列腺内部出现液性暗区 ,前列腺呈囊性改变。辐照后即刻各犬均出现短暂性尿潴留、尿频、尿线变细 ,1月后恢复正常。结论　TUHIU可破坏前列腺组织 ,明显增加前列腺部尿道宽度。     

医疗侵权责任中的过失——论医师的注意义务

过失作为构成侵权行为的一个重要条件，在医疗侵权行为中主要表现为医师的过失，其本质是对“注意义务”的违反。因此正确认识医师的注意义务，对医疗侵权行为中的过失判断有着重要意义。     

血管紧张素对增生性瘢痕成纤维细胞纤维连接蛋白合成的影响

目的：探讨血管紧张素Ⅱ（AngⅡ）及其Ⅰ型、Ⅱ型受体阻断剂和钙调神经磷酸激酶（CaN）的阻滞利环胞素A（CsA）对增生性瘢痕来源的成纤维细胞纤维连接蛋白mRNA和蛋白表达的作用。方法：体外分离培养增生性瘢痕成纤维细胞，分别将一定浓度的AngⅡ（10^-9～10^-5mmol／L），和AngⅡ10^-6mmol／L加上不同阻滞剂losartan、PD123319、环胞素A（浓度均为10^-5mmol／L）加入细胞培养液中刺激48h，分别采用逆转录聚合酶链反应（RT—PCR）及Westernblot印迹方法检测增生性瘢痕成纤维细胞纤维连接蛋白（FN）的mRNA及蛋白表达。结果：体外成功地培养增生性瘢痕成纤维细胞。经AngⅡ刺激48h后，FN mRNA和蛋白表达量明显增高，增高程度与AngⅡ浓度呈正比；加入losaartan和环胞素A后，FN原mRNA和蛋白表达量较单用AngⅡ组下降，而加入PD123319后，FNmRNA和蛋白表达量较单用AngⅡ组无明显改变。结论：AngⅡ可促增生性瘢痕成纤维细胞的FN合成，可能在增生性瘢痕的发展过程中起重要作用，该作用主要通过AngⅡ的Ⅰ型受体介导完成，该作用可能与CaN信号通路有关。