Endogenous level of TIGAR in brain is associated with vulnerability of neurons to ischemic injury

In previous studies,we showed that TP53-induced glycolysis and apoptosis regulator(TIGAR) protects neurons against ischemic brain injury.In the present study,we investigated the developmental changes of TIGAR level in mouse brain and the correlation of TIGAR expression with the vulnerability of neurons to ischemic injury.We found that the TIGAR level was high in the embryonic stage,dropped at birth,partially recovered in the early postnatal period,and then continued to decline to a lower level in early adult and aged mice.The TIGAR expression was higher after ischemia/reperfusion in mouse brain 8and 12 weeks after birth.Four-week-old mice had smaller infarct volumes,lower neurological scores,and lower mortality rates after ischemia than 8- and12-week-old mice.TIGAR expression also increased in response to oxygen glucose deprivation(OGD)/reoxygenation insult or H_2O_2 treatment in cultured primary neurons from different embryonic stages(E16 and E20).The neurons cultured from the early embryonic period had a greater resistance to OGD and oxidative insult.Higher TIGAR levels correlated with higher pentose phosphate pathway activity and less oxidative stress.Older mice and more mature neurons had more severe DNA and mitochondrial damage than younger mice and less mature neurons in response to ischemia/reperfusion or OGD/reoxygenation insult.Supplementation of cultured neurons with nicotinamide adenine dinuclectide phosphate(NADPH) significantly reduced ischemic injury.These results suggest that TIGAR expression changes during development and its expression level may be correlated with the vulnerability of neurons to ischemic injury.     

内镜黏膜下剥离术中穿孔患者应用二氧化碳注气的护理

目的探讨二氧化碳代替空气注气在内镜黏膜下剥离术中并发消化道穿孔时的应用和护理配合。方法对34例内镜黏膜下剥离术术中穿孔患者,及时使用二氧化碳代替空气作为注气媒介,观察腹部体征和皮下气肿,注意监测呼气末二氧化碳;术后注意引流物、胸腹体征的观察和饮食护理。结果 32例手术成功,2例转外科治疗。其中27例有腹胀,5例发生气腹,3例有皮下气肿,均对症处理后好转,无严重并发症发生。结论内镜黏膜下剥离术术中并发穿孔时使用二氧化碳注气能及时避免严重并发症发生,术前正确评估、周密准备,术中密切观察、及时发现穿孔并正确使用二氧化碳送气,术后加强监测为其护理重点。     

肝移植受者照顾者真实照护体验的质性研究

目的了解肝移植受者照顾者在照料患者期间的感受,为针对性干预提供依据。方法采用质性研究中的现象学研究方法,对肝移植受者照顾者16人进行半结构式深度访谈后对资料进行归纳分析。结果提炼出照护任务繁重、心理负担过重、缺乏专业支持、适应角色转变、实现自我价值5个主题。结论肝移植受者照顾者存在较重的心身压力,医护人员在对肝移植患者进行随访的同时,需对其照顾者提借知识指导及心理支持,以减轻照顾者心身负担。     

临床护理教学全程双向评价的实践

目的探讨全程双向评价对临床护理教学质量的影响。方法选取2011年8月至2012年4月实习的护生65人为对照组,采用传统的评价与考核方法;选取2012年8月至2013年4月实习的护生67人为研究组,采用全程双向评价方法,即在教学背景、教学过程、教学终末3个阶段均采用带教老师与护生相互评价,并增加护生自评。结果研究组终末考核成绩、护生对带教老师教学质量评价及对科室带教的满意度显著高于对照组(均P<0.01)。结论全程双向评价可提高临床护理教学质量和护生对带教的满意度。     

Brain magnetic resonance and cognitive function changes in maintenance hemodialysis patients

Objective To investigate cerebrovascular lesions on maintenance hemodialysis (MHD) patients, including types of cerebrovascular disease, and cognitive function changes. Methods A cross-sectional study was applied. A total of 270 MHD patients at hemodialysis center of Peking Union Medical College Hospital were screened, and finally 117 cases were enrolled. Demographic information, aboratory data, MRI and MRA data were collected and assessed. Cognitive function was evaluated with C - MMSE (Chinese mini mental test examination) and C - MoCA (Chinese montreal cognitive assessment). The related factors were selected by Spearman correlation analysis, multiple linear regression and logistic regression analysis. Results The patients’average age was (56.0± 12.5) years, average hemodialysis age was (73.5±60.8) months. Only 5.1% patients had clinical history of cerebral infarction or hemorrhage. Pre - hemodialysis blood pressure was (142.7/80.3±18.2/12.9) mmHg, Post-hemodialysis blood pressure was (130.2/79.1±23.4/14.9) mmHg. A total of 18.8% patients had intra-hemodialysis hypotension, spKt/V was (1.45±0.25). MR results showed that 12.0% patients had cerebral artery stenosis, 5.1% patients had cortical infarcts, 39.3% patients had lacunar infarcts, 47.0% patients had microbleeds, 7.7% patients had chronic hematoma, 52.1% patients had abnormal brain whiter matter lesions (WMLs). In cognitive function evaluation, 20.9% patients had abnormal C-MMSE scores, but 65.2% patients had abnormal C-MoCA results. Multiple linear regression showed age (b=0.059, P＜0.01), dialysis age (b=0.005, P＜0.05) were associated with WMLs in MHD patients. Intra-hemodialysis hypotension was an independent risk factor of lacunar infarcts (b=2.123, P＜0.01) and microbleeds (b=3.531, P＜0.01). Low serum albumin level was an independent risk factor of cognitive decline (b=0.314, P＜0.05). Logistic regression analysis showed pre - hemodialysis systolic blood pressure was an independent risk factor of cortical infarcts [OR=1.088, 95%CI (1.018-1.152), P＜ 0.05]. Gender, dialysis age and pre - dialysis serum TCO2 level were related with chronic hematoma. Conclusions WMLs is related with dialysis voltage. Lacunar infarcts and mirobleeds are related with intra - hemodialysis hypotension. Lacunar infarcts, WMLs and nutritional status are contributed to decline of cognition in MHD patients.     

Time-average albumin predicts the long-term prognosis of IgA nephropathy patients achieved remission

Objective To clarify the long-term renal prognosis and related risk factors of progression for IgA nephropathy (IgAN) patients who achieved remission under current therapy. To identify the target value of the serum albumin level for Chinese patients with IgAN. Methods The patients with biopsy-proven primary IgAN in Nephrology Department of Renji Hospital in Shanghai were studied．The survival of renal and the relationships between clinical parameters and renal outcome were assessed. Results A total of 369 patients between Jan 2005 and Dec 2010 were included with a median follow-up time of 49.0 (38.0-65.8) months. All the subjects had achieved a complete remission (CR) or partial remission (PR) following six months’ therapy after diagnosis. Progressive renal disease had occurred in 61 cases at the end of follow-up. Three variables had a significant independent effect on renal outcome in patients achieving remission under current therapy regimen for IgAN, including time-average serum creatinine (TA-Scr) [HR(95%CI): 1.03(1.01-1.04)], time-average serum albumin (TA-Alb) [HR(95%CI): 0.83 (0.69-0.99)], and eGFR ratio within one year [HR(95%CI): 0.00(0.00-0.01)]. By multivariate Cox analyses, each 1 g/L drop of TA-Alb was related with 17.2% increase in the risk of renal progression. The ROC curve indicated that combination of serum albumin at baseline and during a long-term had a more significant value in prediction of renal outcome than independent predictor alone. By Kaplan-Meier analyses, patients with TA-Alb﹤38 g/L had a 10.4 fold sincreased risk of progressive disease compared with that of TA-Alb﹥38 g/L. Conclusions IgAN patients with lower eGFR ratio, higher TA-Scr and lower TA-Alb would progress to ESRD more quickly, and serum albumin during follow-up is important for predicting IgAN progression.     

Effect of high volume hemofiltration on CHOP protein from a canine model of multiple organ dysfunction syndrome

Objective To observe the effect of high volume hemofiltration (HVHF) on the expression of CCAAT enhancer binding protein(CHOP) during the treatment of multiple organ dysfunction syndrome (MODS). To investigate the role of CHOP protein act in apoptosis pathway mediated by the endoplasmic reticulum stress. Methods Twelve Beagle dogs were subjected to hemorrhagic shock plus resuscltation and endotixemia to establish MODS model, then they were randomly divided into two groups: HVHF group (n=6) and MODS group (n=6). After endotoxin injection completed, the HVHF group received HVHF treatment for 24 hours; MODS group did not receive. Vivo experiments: Blood samples were obtained at different time points(before operation, 0 h, 6 h, 12 h, 24 h after the injection of endotoxin). The dogs were killed and the tissue samples from lung, liver and kidney were took, then the expression of CHOP mRNA was determined. Vitro experiments: human umbilical vein endothelial cells (HUVECs) were induced by two groups’ blood samples to establish the apoptosis model. Gene expression, protein quantification and cell apoptosis rate were determined before and after the interference. Results Vivo experiments: The levels of CHOP mRNA from lung, liver and kidney had no significant difference between the two groups (P＞0.05). Vitro experiments: (1)The expression of CHOP mRNA: Compared with MODS group, the expression levels of CHOP mRNA were significantly decreased in HVHF group at 6 h, 24 h after the injection of endotoxin (P＜0.05). Compared with before, the expression levels of CHOP mRNA in the two groups were both significantly decreased after CHOP siRNA interference (P＜0.05). (2)The expression of CHOP protein: Compared with MODS group, the expression levels of CHOP protein were significantly decreased in HVHF group at each time points (P＜0.05). Compared with before, the expression levels of CHOP protein in the two groups were both significantly decreased after CHOP siRNA interference(P＜0.05). (3)Endothelial cell apoptosis rate: Compared with the preoperative rate, the two group’s endothelial cell apoptosis rate was decreased significantly at each time points(P＜0.05). Compared with MODS group, the endothelial cell apoptosis rate was significantly decreased in HVHF group at each time points(P＜0.05). Compared with before, the endothelial cell apoptosis rate in the two groups was both significantly decreased after CHOP siRNA interference(P＜0.05). Conclusion In the treatment of MODS process, HVHF can reduce endothelial cell apoptosis which may be related to the inhibition of CHOP mRNA expression and protein synthesis.     

Association of serum sclerostin level with mineral disorder and bone density in patients on maintenance hemodialysis

Objective To explore the relationship between serum sclerostin level, and mineral metabolism, bone density, abdominal aortic calcification in maintenance hemodialysis (MHD) patients. Methods Serum sclerostin levels from 175 cases of MHD patients were measured by ELISA. Calcaneus bone mineral density (BMD) was measured by quantitative ultrasound (QUS). The abdominal aortic calcification was detected by abdomen lateral plain radiographs. Interrelations among above parameters were examined statistically. Results The median sclerostin concentration of 175 patients was 160.50(100.67, 256.39) pmol/L. Serum sclerostin levels were correlated positively with age, BMI, serum calcium and serum 25(OH)-vitamin D, while negatively with spKt/v and serum iPTH. In multiple regression analysis, serum sclerostin levels were associated significantly and independently with age, sex, BMI and serum iPTH. Compared to patients with normal BMD (T score≥-1s), the patients with low BMD (T score<-1s) had lower serum sclerostin level [142.97(99.52, 226.02) vs 201.13(107.40, 327.84) pmol/L, P=0.035]. Serum sclerostin levels were correlated significantly and positively with calcaneus BMD. Multivariate logistic regression analysis showed that serum sclerostin level was an independent protective factor for low BMD in MHD patients[OR=0.241, 95%CI (0.078, 0.749), P=0.014]. Conclusions Serum sclerostin levels are associated with mineral disorder and bone density. Sclerostin may become a promising marker of bone turnover in MHD patients.     

微小RNA-126在食管鳞癌中的表达及作用机制

目的 观察微小RNA-126(miR-126)在食管鳞癌组织中的表达及其可能调控的靶基因.方法 采用实时定量反转录聚合酶链反应(RT-qPCR)法,检测75例患者食管鳞癌组织和其匹配的癌旁组织中miR-126的表达水平,应用软件预测miR-126的靶基因,免疫组织化学法分析靶蛋白在癌组织中的表达,在食管鳞癌细胞中提高或降低miR-126表达水平,验证其对靶基因的调控作用.结果 对75组配对标本分析,癌组织中miR-126的相对表达量为0.28±0.32,癌旁组织为0.45±0.47,差异有统计学意义(P＜0.01);miR-126低表达与食管鳞癌分化程度、淋巴结转移、肿瘤浸润深度和临床分期相关(P＜0.05);胰岛素受体底物-1(IRS-1)在食管鳞癌组织中过表达,与肿瘤分化程度有关(P＜0.01);上调食管鳞癌细胞Eca9706、Eca109、TE-1中miR-126的表达会导致IRS-1蛋白的表达量(0.785±0.337、1.873±0.684、1.938±1.081)较空白组(1.188±0.336、2.756±1.097、3.028±0.789)下降(P＜0.01),下调食管鳞癌细胞中miR-126的表达会导致IRS-1蛋白的表达量(2.543±0.610、5.182±1.897、5.940±0.997)相对升高(P＜0.01).结论 食管鳞癌组织中miR-126表达水平下降,IRS-1蛋白的表达受miR-126的负调控,IRS-1可能是miR-126在食管鳞癌中发挥抑癌基因功能的靶基因之一.     

小干扰RNA特异性沉默c-myc基因对人胰腺癌SW1990细胞生物学影响

目的 观察小干扰RNA(siRNA)沉默c-myc基因的表达对人胰腺癌细胞株SW1990细胞生物学影响.方法 用siRNA沉默胰腺癌SW1990细胞中c-myc基因,用实时定量反转录聚合酶链反应(RT-qPCR)及Western blot技术检测c-myc mRNA及蛋白的表达量;噻唑蓝(MTT)法检测siRNA沉默c-myc基因对SW1990细胞增殖的影响;膜联蛋白V/碘化丙锭(Annexin V/PI)双染流式细胞术检测沉默c-myc基因细胞凋亡水平;Transwell细胞迁移实验检测siRNA沉默c-myc基因对SW1990细胞迁移能力的影响.结果 靶向c-myc的特异性siRNA可以高效抑制人胰腺癌SW1990细胞c-myc基因表达,在mRNA水平(0.263±0.048)较转染对照质粒组(0.970±0.012)明显降低,c-myc蛋白质表达量及细胞增值率均较转染对照质粒组明显降低;转染后48 h c-myc siRNA组细胞凋亡率为(19.90±2.09)％,明显高于siRNA阴性对照组(4.93±0.25)％和空白对照组(4.40±0.34)％;Transwell实验结果示细胞穿膜数c-myc siRNA组[(34.3±1.2)个]较siRNA-NC组[(68.3±5.8)个]和空白组[(72.3±1.2)个]均明显降低.结论 c-myc siRNA能够显著抑制c-myc基因在人胰腺癌SW1990细胞中的表达,降低细胞的增殖和迁移能力,促进细胞的凋亡.