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991.
Jie Chen Lanlan Wang Yang Fu Yi Li Yangjuan Bai Limei Luo Yun Liao 《Hepatology International》2014,8(1):55-63
Objective
Chronic hepatitis B (CHB) affects 400 million people and is the most common cause of liver cirrhosis (LC) and hepatocellular carcinoma (HCC) worldwide. Cellular immune regulation plays an important role in determining the infection outcome. Co-signal molecules and Th17/Treg were studied to explore their association with the progression of HBV infection.Methods
Ninety-four HBV-infected patients were categorized into three groups: 31 patients with LC caused by CHB, 30 with HCC caused by CHB and 33 with HCC caused by CHB. Co-signal molecules, Th17/Treg, and Stat3 and Stat5 were analyzed by flow cytometry.Results
CHB patients who progressed to LC or HCC showed a significantly higher level of co-inhibitory molecules such as BTLA and PD-1, while there was no significant difference in co-stimulatory molecules among LC, HCC and CHB. Stat3 and Stat5 were significantly increased in LC and HCC compared to CHB patients.Conclusion
Co-inhibitory molecules play more important roles than co-stimulatory molecules. Increased PD-1 and BTLA/HVEM inhibited immune cells and the immune process. At the same time activated Stat3 and Stat5 stimulate the key factors in differentiation of Th17 and Treg, thus leading to imbalanced expansion of Th17 and Treg; immune tolerance was induced and HBV persistent. This resulted in hepatic inflammation that progressed to cirrhosis and carcinoma. 相似文献992.
Tao Zhang Min Fang Zi-Mu Fu He-Chun Du Hua Yuan Gui-Yu Xia Jie Feng Gui-Yun Yin 《Asian Pacific journal of tropical medicine》2014,7(4):309-312
Objective:To analyze the expression of phosphatidylinositol 3 kinase(PI3-K),protein kinase B(PKB)and glycogen synthase kinase 3 beta(GSK-3β)in skeletal muscle tissue of gestational diabetes mellitus(GDM).Methods:A total of 90 cases of pregnant women were divided into observation group and control group according to the occurrence of GDM with 45 cases in either,and the expression of PI3-K,PKB,GSK-3βmRNA expression in skeletal muscle tissue was compared between two groups.Results:The total PI3-K p85 protein was significantly higher in the observation group compared with the control group,the activity of PI3-K was lower than that of the latter;The total PKB,GSK-3βprotein in skeletal tissue had no significant difference between two groups,while the serine phosphorylation levels of PKB and GSK-3βwere significantly lower in observation group compared with the control group.Conclusions:The downregulation of PI3-K,PKB and GSK-3βin skeletal tissue of GDM caused by phosphorylation dysfunction of signaling molecules is the reason for insulin resistance and transporter function decline which lead to GDM. 相似文献
993.
994.
目的探讨吡柔比星(THP)对多发性骨髓瘤细胞增殖、凋亡的影响及其作用机制。方法 2014年4月-2019年3月在郴州市第一人民医院实验室进行实验。应用终浓度为0.1mg/L、1mg/L、2.5mg/L、5 mg/L吡柔比星处理多发性骨髓瘤细胞KM3,记为THP 0.1mg/L组、THP 1 mg/L组、THP 2.5mg/L组、THP 5mg/L组;未经任何处理的KM3细胞作空白对照(Con)组;转染pcDNA3.1为pcDNA3.1组,转染pcDNA3.1-PCDH10为pcDNA3.1-PCDH10组,转染si-NC后用1 mg/L的THP处理为THP 1 mg/L+si-NC组,转染si-PCDH10后用1 mg/L的THP处理为THP1 mg/L+si-PCDH10组。MTT法检测细胞活性,流式细胞术检测细胞凋亡,Western-blot法检测蛋白表达。结果不同浓度THP处理后,KM3细胞活性显著降低,细胞凋亡率显著升高,Cyclin D1、Bcl-2蛋白的表达水平显著降低,p21、Bax、PCDH10蛋白的表达水平显著升高(P <0.05);过表达PCDH10后,KM3细胞活性显著降低,细胞凋亡率显著升高,Cyclin D1、Bcl-2蛋白的表达水平显著降低,p21、Bax蛋白表达水平显著升高(P<0.05);抑制PCDH10表达后,THP处理的KM3细胞活性显著升高,细胞凋亡率显著降低,Cyclin D1、Bcl-2蛋白表达水平显著升高,p21、Bax蛋白的表达水平显著降低(P<0.05)。结论吡柔比星可抑制多发性骨髓瘤细胞的增殖,促进其凋亡,其机制可能与调控PCDH10表达相关。 相似文献
995.
996.
探讨甘氨酸对脑出血大鼠神经损伤的保护作用及其机制。将48只大鼠随机分为假手术组、模型组、甘氨酸组(分别给予0.5 mg/kg或2 mg/kg甘氨酸)。采用侧脑室注射自体血建立大鼠脑出血模型;干湿重法检测脑组织含水量,甲酰胺法检测血脑屏障通透性,原位末端标记法(TUNEL)法检测脑组织细胞凋亡的情况,实时聚合酶链反应(Real-time PCR)检测蛋白激酶B(Akt)、磷酸酶与张力蛋白同源物基因(PTEN)mRNA的表达,免疫印迹(Western blot)法检测脑组织中Akt、PTEN蛋白的表达水平。结果显示,与模型组比较,2 mg/kg甘氨酸组大鼠脑组织含水量、EB含量、血肿块体积、凋亡细胞数量显著降低,Akt mRNA和蛋白的表达显著升高,PTEN mRNA和蛋白的表达水平显著降低(P<0.05)。结果表明甘氨酸对大鼠脑出血造成的大鼠脑神经的损伤有一定的保护作用,这可能与甘氨酸干预的PTEN/Akt通路有关。 相似文献
997.
目的从培训角度改进急诊气道管理,探讨基于临床流程为导向的急诊气道管理培训模式。方法根据以病人安全为中心的临床处理原则,结合临床实际流程,设计气道管理培训课程。课程以气道管理的CHANNEL流程为主线,重点讲述人工通气和氧疗技术,快速诱导插管技术。授课过程以临床处理流程为主线,采用实物展示、视频演示和事物联系的方法进行讲解。以自由报名或定向招生开课。课后采用网络问卷的形式,收集急诊气道管理课程学员对课程的反馈意见,并进行分析。结果在全国13个城市举办了15场培训,参加学员566名。收到反馈问卷185份,单项课程内容,学员认为较难理解的部分前三位是氧疗(48人,25.9%)、CHANNEL流程讲解与演练(48人,25.9%)、快速诱导插管流程(47人,25.4%)。课后41人(22.2%)改变了急诊气道管理的工作流程,140人(75.7%)部分改变了急诊气道管理的工作流程,4人(2.2%)依然采用原来的工作流程。结论基于临床流程为导向的急诊气道管理课程符合目前临床需求,可以更好地实现临床岗位胜任力的培训。 相似文献
998.
目的 调查医学院校学生学业拖延行为现状及其影响因素,并提出降低医学院校学生学业拖延的建议。方法 抽取黑龙江省三所医学院校的统招本科学生1 327名进行生活满意度、焦虑、学业拖延问卷调查。应用SPSS 23.0对数据进行统计分析。结果 ①医学院校学生学业拖延总分为(35.00±8.92)分;②成绩水平、性别、选择本专业原因、是否独生子女四个方面的不同人口学特征的医学院校学生在学业拖延方面差异有统计学意义(P<0.05),不同年龄、不同年级医学院校学生学业拖延差异无统计学意义(P>0.05);③医学院校学生拖延程度与其焦虑水平成正相关(r=0.102,P<0.01),与生活满意度成负相关(r=-0.117,P<0.01);④回归分析显示,成绩水平、性别、生活满意度、焦虑、选择本专业的原因以及是否独生子女六个预测变量共可以有效解释医学院校学生学业拖延14.2%的变异量。结论 医学院校学生学业拖延总体程度高于非医学院校学生拖延;医学院校学生的成绩水平、性别、生活满意度、焦虑、选择本专业的原因以及是否独生子女是学业拖延的影响因素。 相似文献
999.
Yuan Lin Haipeng Zhang Jiankai Liang Kai Li Wenbo Zhu Liwu Fu Fang Wang Xiaoke Zheng Huijuan Shi Sihan Wu Xiao Xiao Lijun Chen Lipeng Tang Min Yan Xiaoxiao Yang Yaqian Tan Pengxin Qiu Yijun Huang Wei Yin Xinwen Su Haiyan Hu Jun Hu Guangmei Yan 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(42):E4504-E4512
Oncolytic virotherapy is a growing treatment modality that uses replicating viruses as selective antineoplastic agents. Safety and efficacy considerations dictate that an ideal oncolytic agent would discriminate between normal and cancer cells on the basis of common genetic abnormalities in human cancers. Here, we identify a naturally occurring alphavirus (M1) as a novel selective killer targeting zinc-finger antiviral protein (ZAP)-deficient cancer cells. In vitro, in vivo, and ex vivo studies showed potent oncolytic efficacy and high tumor tropism of M1. We showed that the selectivity depends on ZAP deficiency by systematic identification. A large-scale multicenter pathology study using tissue microarrays reveals that ZAP is commonly deficient in human cancers, suggesting extensive application prospects for M1. Additionally, M1 killed cancer cells by inducing endoplasmic reticulum stress-mediated apoptosis. Our report provides novel insights into potentially personalized cancer therapy using oncolytic viruses.Despite advances in cancer therapy over the past few decades, cancer is still a major health problem all over the world (1). One innovative class of targeted anticancer strategies is the use of replicating oncolytic viruses with selective tropism for cancerous cells and tissues (2, 3). The tumor selectivity of oncolytic virus is primarily based on the genetic abnormalities of malignant cells, including innate immune defects, aberrant oncogenic signaling, and tumor-specific receptors (4–6). The thriving viruses in tumor cells may lead to direct cell lysis, anticancer immune response, or modulation of tumor vasculature (3, 7). Moreover, some of the cancer-targeted multimechanistic oncolytic viruses have been proven to be well-tolerated in clinical trials, with patients exhibiting only mild flu-like symptoms, offering great potential for increasing efficacy while eliminating the side effects (8). To date, several oncolytic viruses have been tested in preclinical and clinical trials, of which the milestone is a pivotal phase III trial using talimogene laherparepvec for unresected melanoma (2, 3, 9). Although a few therapeutic viruses are performing well in clinical trials, not all patients showed good response. Novel oncolytic viruses that grow better in some cancer cells in a predictable manner remain to be discovered for potentially personalized cancer therapy.M1 is a strain of Getah-like alphavirus that was isolated from culicine mosquitoes collected on Hainan Island of China (10, 11). Getah virus is transmitted mainly among horses and pigs, and it has not been linked to human illness (12–14). Also, M1 does not cause apparent disease symptoms in mice or rats, even on administration of doses up to 3 × 107 pfu per mouse or 3 × 108 pfu per rat. Earlier, we reported that M1 induces apoptosis in glioma cells (10). Thus, we hypothesized that an apathogenic cancer cell-killing virus could be a candidate for systemic oncolytic therapy.In this study, we sought to investigate the anticancer effectiveness and tumor tropism of M1 and uncover the mechanisms, aiming to identify a candidate for personalized oncolytic virotherapy. 相似文献