心房颤动患者心房组织囊性纤维化跨膜转运调节体氯通道基因表达

目的探讨心房颤动(简称房颤)患者心房组织囊性纤维化跨膜转运调节体(CFTR)氯通道基因的表达。方法应用半定量逆转录多聚酶链反应(RT-PCR)比较窦性心律(SR)组(n=31)、阵发性房颤(PAF)组(n=7)和慢性房颤(CAF)组(n=33)患者心房组织CFTR氯通道基因的表达。结果与SR组相比,PAF组CFTR的mRNA表达有增加但未达到统计学意义(P>0.05),CAF组的表达明显增加,CAF组较PAF组亦明显增加(1.20±0.12 vs1.08±0.18,P<0.05)。CFTR的mRNA表达与左房内径呈正相关(r=0.312,P=0.008)。结论慢性房颤患者心房组织CFTR氯通道基因表达上调,可能在房颤心房电重构中起作用。     

Loss of inositol 1,4,5-trisphosphate receptors from bile duct epithelia is a common event in cholestasis

BACKGROUND AND AIMS: Cholestasis is one of the principal manifestations of liver disease and often results from disorders involving bile duct epithelia rather than hepatocytes. A range of disorders affects biliary epithelia, and no unifying pathophysiologic event in these cells has been identified as the cause of cholestasis. Here we examined the role of the inositol 1,4,5-trisphosphate receptor (InsP3R)/Ca(2+) release channel in Ca(2+) signaling and ductular secretion in animal models of cholestasis and in patients with cholestatic disorders. METHODS: The expression and distribution of the InsP3R and related proteins were examined in rat cholangiocytes before and after bile duct ligation or treatment with endotoxin. Ca(2+) signaling was examined in isolated bile ducts from these animals, whereas ductular bicarbonate secretion was examined in isolated perfused livers. Confocal immunofluorescence was used to examine cholangiocyte InsP3R expression in human liver biopsy specimens. RESULTS: Expression of the InsP3R was selectively lost from biliary epithelia after bile duct ligation or endotoxin treatment. As a result, Ca(2+) signaling and Ca(2+)-mediated bicarbonate secretion were lost as well, although other components of the Ca(2+) signaling pathway and adenosine 3',5'-cyclic monophosphate (cAMP)-mediated bicarbonate secretion both were preserved. Examination of human liver biopsy specimens showed that InsP3Rs also were lost from bile duct epithelia in a range of human cholestatic disorders, although InsP3R expression was intact in noncholestatic liver disease. CONCLUSIONS: InsP3-mediated Ca(2+) signaling in bile duct epithelia appears to be important for normal bile secretion in the liver, and loss of InsP3Rs may be a final common pathway for cholestasis.     

运动诱导骨骼肌线粒体生成中沉默信息调节因子1的作用

背景：沉默信息调节因子 1 是新近受到体育科学领域关注的能量代谢调节因子,在运动骨骼肌线粒体生成中与其他信号分子一起发挥作用。目的：综述沉默信息调节因子 1 在运动诱导骨骼肌线粒体生物合成中的作用及机制。方法：应用计算机检索 PubMed 和 Highwire 数据库 2000 年 1 月至 2013 年 1 月有关运动、沉默信息调节因子 1、骨骼肌线粒体生物合成的文献,检索词为 SIRT1,AMPK,PGC-1α,mitochondrial biogenesis,skeletalmuscle, exercise,限定文章语言为 English。对资料进行初审,选取沉默信息调节因子 1 与运动诱导骨骼肌线粒体生物合成有关的文献,排除重复研究。结果与结论：共收集相关文献 165 篇,排除重复研究,纳入 62 篇。沉默信息调节因子 1 作为一种 NAD＋依赖的去乙酰化酶,在运动中被激活,通过上调过氧化物酶体增殖物激活受体辅激活因子表达而诱导骨骼肌线粒体生物合成,其分子机制涉及一磷酸腺苷激活的蛋白激酶、低氧诱导因子 2α等信号分子。但近年来的一些研究对沉默信息调节因子 1 在骨骼肌线粒体生物合成中的作用提出了质疑,认为其并非为运动诱导的骨骼肌线粒体生物合成所必需。沉默信息调节因子 1 在运动诱导的骨骼肌线粒体生物合成中发挥重要调控作用,但采用蛋白和活性等不同检测方法,在实验结果上可能会造成较大差异。     

Gene sequences regulating the production of apoE and cerebral palsy of variable severity

BackgroundThe apoE protein is the most important lipid transporter in the brain and has also been shown to have several regulatory functions in the central nervous system. The production of apoE is regulated by a number of genes and increases under certain conditions such as cerebral injury in adults.AimsOur aim was to study whether variations in genes regulating the expression of the APOE gene were associated with severity of cerebral palsy (CP).MethodsChildren enrolled in the Cerebral Palsy Register of Norway (CPRN) were invited to participate in this cross-sectional study; 281 of the invited 703 children (40%) returned swabs with buccal cells collected by parents. Six genetic variations thought to affect the production of apoE were genotyped and correlated with clinical data recorded in the CPRN.ResultsCompared with children carrying the GG allele, children with genotype GT or TT in a specific genetic variation (rs59007384 located in the nearby TOMM40 gene) had excess risk for worse fine motor function (Odds ratio (OR): 1.82; 95% Confidence interval (CI): 1.10–2.99; p = 0.019) and epilepsy (OR: 2.32; CI: 1.17–4.61; p = 0.016). There was no association between severity of CP and any of the other five genetic variations analyzed.ConclusionOur findings suggest that genetic variations in one of the sequences regulating the expression of APOE, may be associated with worse clinical outcome in children with cerebral palsy.     

一次性可调节输液器的准确输入速度及相关滴速测定

目的在液体性质、液面高度、头皮针型号固定的状态下,观察一次性可调节输液器的输液速度与实际输入量的差距及调整规律。方法取上述一项因素为变量,固定其他因素,依次测试某一输液速度的实际输入量及调整速度量,以此速度量调整一定范围内的输液速度,测定调整速度后的输入量与输液速度实际要求量的差距,并观察对应的莫菲滴管内滴速。结果液体性质对滴速的影响有统计学意义,P<0.05;液面高度对滴速的影响有统计学意义,P<0.05;不同液量对滴速的影响无统计学意义,P>0.05;头皮针型号对滴速的影响有统计学意义,P<0.05。结论在输液刻度15-60ml的范围内,各调整7ml后,其输出量与输液速度要求量相近。     

微生态调节剂在严重烧伤中的应用及护理

从微生态调节剂的类型、烧伤后肠道的菌群变化、肠道机械屏障的改变、肠道局部免疫功能改变、抗生素与微生态调节剂联合应用注意事项、益生菌服用方法等方面介绍了微生态调节剂在严重烧伤中的应用及护理。     

Protein regulator of cytokinesis 1 overexpression predicts biochemical recurrence in men with prostate cancer

BackgroundProtein regulator of cytokinesis 1 (PRC1) has been reported to be implicated into the completion of cytokinesis and is dys-regulated in a cancer-specific manner. However, it roles in human prostate cancer (PCa) remain unclear. In the current study, we aimed to investigate the expression pattern of PRC1 and its clinical significance in this malignancy.Materials and methodsPRC1 protein expression in human PCa and non-cancerous prostate tissues was detected by immunohistochemistry, which was validated by microarray-based Taylor data at mRNA level. Then, the associations of PRC1 expression with clinicopathological features and clinical outcome of PCa patients were statistically analyzed.ResultsPRC1 expression in PCa tissues, at both mRNA and protein levels, were significantly higher than those in non-cancerous prostate tissues. In addition, the PCa patients with PRC1 overexpression more frequently had high Gleason score, advanced pathological stage, positive metastasis, short overall survival time and positive PSA failure than those with low Gleason score, early pathological stage, negative metastasis, long overall survival time and negative PSA failure (all P < 0.05). Moreover, PRC1 expression was identified as an unfavorable prognostic factor of biochemical recurrence-free survival in PCa patients (P < 0.001).ConclusionThese findings suggest that the aberrant expression of PRC1 may predict biochemical recurrence in men with PCa highlighting its potential as a prognostic marker of this malignancy.     

Lectin conjugates as potent, nonabsorbable CFTR inhibitors for reducing intestinal fluid secretion in cholera

BACKGROUND & AIMS: Inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel are predicted to prevent intestinal fluid secretion in cholera. We previously discovered low- affinity glycine hydrazide (GlyH) CFTR inhibitors that block CFTR at its external pore. The goal of this study was to develop potent CFTR inhibitors that are minimally absorbed and washed out of the intestinal lumen for application as antisecretory agents in cholera. METHODS: GlyH analogs (malonic hydrazides, MalH) were chemically conjugated to various lectins ("MalH-lectin") and purified. CFTR inhibition potency was measured by short-circuit current analysis, mechanism of action by patch-clamp, and antidiarrheal efficacy in closed-loop and suckling mouse models. RESULTS: By lectin conjugation, we improved CFTR inhibitory potency by approximately 100-fold (to 50 nmol/L) and retarded washout. High-affinity CFTR inhibition was abolished by MalH-lectin heat denaturation, protease digestion, or competition by mannose or unconjugated lectin. Patch-clamp analysis indicated CFTR inhibition by an external pore occlusion mechanism. Fluorescently labeled MalH-lectin remained membrane bound for >6 hours after washout, whereas washout occurred in a few minutes without the lectin. MalH-ConA and MalH-wheat (IC50 50-100 pmol) blocked cholera toxin-induced intestinal fluid secretion in closed intestinal loops in mice and greatly reduced mortality in a suckling mouse model of cholera. CONCLUSIONS: The high potency of MalH-lectin conjugates results from "anchoring" the CFTR-blocking MalH to cell surface carbohydrates by the lectin. The high-affinity, slow washout, and external site of action of the MalH-lectin conjugates support their further development as antisecretory drugs for enterotoxin-mediated secretory diarrheas.     

抑制羰基应激改善老龄小鼠心肌缺血预处理的保护作用

目的 本研究旨在探讨激活乙醛脱氢酶2（ALDH2）对老龄小鼠缺血预处理（IPC）心肌保护作用的影响。通过观察成年和老龄小鼠心肌沉默信息调节因子相关酶1（SIRT1）活性在IPC过程中的差异,分析老龄鼠心肌IPC保护作用减退的可能机制。方法 成年（2月龄）和老龄（20月龄）雄性C57小鼠（每组各6只）在体给予3个5min缺血/5min再灌注循环的IPC处理后,以冠状动脉左前降支结扎缺血30min再灌注4h建立在体小鼠急性心肌I/R模型。离体心脏行Langendorff灌流给予3个循环的5min停流/5min再灌注以模拟全心IPC,同时记录心功能变化。在体或离体再灌注结束后取心肌组织检测ALDH2和SIRT1活性,及蛋白质羰基化程度。结果 与成年组相比,IPC处理并不能有效地改善衰老心肌的I/R损伤和SIRT1活性。检测心肌ALDH2活性显示,老龄鼠心肌ALDH2的活性较成年组显著降低并导致衰老心肌在I/R后出现羰基应激增强（均P＜0.05）。IPC并不能有效改善老龄鼠心肌ALDH2活性和羰基应激程度。预先激活老龄鼠心肌的ALDH2可显著抑制衰老心肌的羰基应激,改善IPC对老龄鼠I/R心肌SIRT1有激活作用（P＜0.05）,进而促进老龄鼠心肌I/R后收缩舒张功能的恢复。结论 激活心肌ALDH2可显著改善老龄鼠心肌IPC的保护作用,其机制可能与抑制羰基应激引起的SIRT1失活有关。