Leptin in the Anterior Piriform Cortex Affects Food Intake in Rats

Leptin administered intracerebroventricularly (ICV) or intrahypothalamically inhibits food intake (FI), however, to our knowledge the effects of leptin administration have only been examined in one extrahypothalamic site (dorsal raphe nucleus). Our objectives were t. (1) determine the FI effects of leptin administration into the anterior piriform cortex (APC), an area linked to the control of FI in amino acid (AA) deficiency, (2) examine leptin action during short term anorexia that develops in response to AA deficiency. Bilateral injections of leptin (0.25 μ) into the APC suppressed FI of a balanced diet between 6 and 12 h by 36% (p < 0.01) and over the first 12 and 24 h by 15% (p < 0.05). Bilateral administration of leptin (0.1 μg) inhibited FI between 12 and 24 h by approximately 48% (p < 0.05) on a threonine-imbalanced diet without significantly affecting FI on a threonine-corrected diet. The increase of plasma leptin concentrations in response to feeding a threonine-basal diet was greater than that following an AA imbalanced diet, suggesting that suppression of FI by an AA imbalanced diet is not mediated by an increase of leptin. Our results suggest that (1) administration of leptin into a brain area outside the hypothalamus suppresses FI, and (2) leptin is unlikely to play a selective role in the short term anorectic response to AA deficiency. These data are consistent with the hypothesis that endogenous leptin can act within the APC to modulate FI.     

临床科室医疗设备使用管理探讨

医疗设备的临床使用是当前医疗设备管理链条上的薄弱环节;为保障医疗安全和医疗质量,本文从制度建设、记录方法、管理员设置和质量考核等方面,阐述强化医疗设备临床使用管理的措施。     

Unraveling toxicological mechanisms and predicting toxicity classes with gene dysregulation networks

The use of genes for distinguishing classes of toxicity has become well established. In this paper we combine the reconstruction of a gene dysregulation network (GDN) with a classifier to assign unseen compounds to their appropriate class. Gene pairs in the GDN are dysregulated in the sense that they are linked by a common expression pattern in one class and differ in this pattern in another class. The classifier gives a quantitative measure on this difference by its prediction accuracy. As an in‐depth example, gene pairs were selected that were dysregulated between skin cells treated with either sensitizers or irritants. Pairs with known and novel markers were found such as HMOX1 and ZFAND2A, ATF3 and PPP1R15A, OXSR1 and HSPA1B, ZFP36 and MAFF. The resulting GDN proved biologically valid as it was well‐connected and enriched in known interactions, processes and common regulatory motifs for pairs. Classification accuracy was improved when compared with conventional classifiers. As the dysregulated patterns for heat shock responding genes proved to be distinct from those of other stress genes, we were able to formulate the hypothesis that heat shock genes play a specific role in sensitization, apart from other stress genes. In conclusion, our combined approach creates added value for classification‐based toxicogenomics by obtaining novel, well‐distinguishing and biologically interesting measures, suitable for the formulation of hypotheses on functional relationships between genes and their relevance for toxicity class differences. Copyright © 2012 John Wiley & Sons, Ltd.     

毒蛇咬伤治疗前后肾功能变化规律的探讨

目的：探讨各种毒蛇咬伤患者治疗前后肾功能的变化情况。方法选择近两年住院治疗、属于何种蛇伤诊断明确的毒蛇咬伤患者作为研究对象,这些患者在治疗前后各时段均进行5项肾功能指标检测,按蛇种、时段及病情对检测结果作出统计分析。结果与治疗前比较,各种毒蛇咬伤在治疗后1d除个别指标外其检测均值都有不同程度地升高趋势、特别是治疗后2d升高更明显,有些指标的升高具有显著性差异（ P＜0．05或P＜0．01）。与治疗后2 d比较,治疗后4 d各项指标均有不同程度下降。治疗前后各时段除尿酸外,其它指标均值基本上是蝰蛇咬伤显著高于银环蛇咬伤、竹叶青蛇咬伤、眼镜蛇咬伤和眼镜王蛇咬伤（P＜0．05或P＜0．01）。结论5种毒蛇咬伤均可能导致肾功能损害,其损害程度以眼镜王蛇咬伤最轻,蝰蛇咬伤最重。     

白细胞介素-10诱导的大鼠树突状细胞体外免疫功能的研究

目的　研究白细胞介素 10 (IL 10 )诱导的大鼠未成熟树突状细胞 (imDCs)体外诱导免疫耐受的可行性。方法　在经典诱导方案的基础上 ,应用IL 10 ( 10 μg/L)抑制大鼠骨髓来源DCs的成熟 (IL 10组 ,10例 ) ,并设对照组 (IL 4组 ,10例 )。培养期间观察DCs形态 ,检测DCs表型、摄取抗原能力、体外免疫功能及培养上清细胞因子水平。结果　与IL 4组比较 ,IL 10组DCs细胞表面CD80 、CD86及OX6低度表达 ( 2 5 .3 %、42 .4%、3 2 .3 % ) ,吞噬能力较强 ( 81.9) ,刺激同种异体淋巴细胞增殖能力下降 ,该淋巴细胞具有抗原特异性低反应性 ;培养上清中IL 12水平 ( 4 0 6.5pg/L)及初次MLR培养上清IL 2水平 ( 2 45 .4ng/L)均较低 ,差异有非常显著性 (P <0 .0 1)。 结论　IL 10作用的大鼠imDCs具有诱导免疫耐受的应用价值。     

龟板提取物诱导神经干细胞向神经元分化过程中相关microRNA表达变化

【目的】观察龟板提取物诱导神经干细胞（neural stem cells, NSCs）向神经元细胞定向分化过程中相关microRNA表达的变化。【方法】分离培养孕14 d SD胎鼠原代神经干细胞,经免疫荧光染色鉴定神经干细胞的特异抗原及其多向分化能力。神经干细胞随机设空白对照组、龟板提取物低浓度组（3μg/mL）、龟板提取物高浓度组（30μg/mL）。诱导分化7 d,提取各组细胞总RNA,采用实时荧光定量PCR法检测不同组别miR-124和miR-9的变化。【结果】与空白对照组比较,龟板提取物低浓度组miR-124和miR-9表达均无显著变化,龟板提取物高浓度组均显著升高（P<0．05）。【结论】龟板提取物可能通过调控miR-124、 miR-9表达在NSCs向神经元细胞定向分化过程中起重要作用。     

Pragmatic clinical trials in the context of regulation of medicines

Abstract

The pragmatic clinical trial addresses scientific questions in a setting close to routine clinical practice and sometimes using routinely collected data. From a regulatory perspective, when evaluating a new medicine before approving marketing authorization, there will never be enough patients studied in all subgroups that may potentially be at higher risk for adverse outcomes, or sufficient patients to detect rare adverse events, or sufficient follow-up time to detect late adverse events that require long exposure times to develop. It may therefore be relevant that post-marketing trials sometimes have more pragmatic characteristics, if there is a need for further efficacy and safety information. A pragmatic study design may reflect a situation close to clinical practice, but may also have greater potential methodological concerns, e.g. regarding the validity and completeness of data when using routinely collected information from registries and health records, the handling of intercurrent events, and misclassification of outcomes. In a regulatory evaluation it is important to be able to isolate the effect of a specific product or substance, and to have a defined population that the results can be referred to. A study feature such as having a wide and permissive inclusion of patients might therefore actually hamper the utility of the results for regulatory purposes. Randomization in a registry-based setting addresses confounding that could otherwise complicate a corresponding non-interventional design, but not any other methodological issues. Attention to methodological basics can help generate reliable study results, and is more important than labelling studies as ‘pragmatic’.     

骨碎补总黄酮对Masquelet技术诱导膜内血管形成的影响

【目的】探讨骨碎补总黄酮对Masquelet技术诱导膜内血管形成的影响。【方法】将72只SD大鼠随机分成4组,分别为模型组,药物高、中、低剂量组,每组18只。复制SD大鼠股骨中段临界骨缺损模型,并在骨缺损区行聚甲基丙烯酸甲酯(PMMA)骨水泥旷置诱导生物膜形成。从术后第1天开始,各药物组大鼠分别给予骨碎补总黄酮高、中、低剂量(0.44、0.22、0.11 g·kg~(-1)·d~(-1))灌胃治疗,模型组予等量生理盐水灌胃。给药6周后取材,采用苏木素—伊红(HE)染色法观察诱导膜组织病理变化,分别采用酶联免疫吸附(ELISA)法和实时荧光定量逆转录—聚合酶链反应(RT-qPCR)法检测诱导膜中转化生长因子-β1(TGF-β1)、血管内皮生长因子(VEGF)的蛋白及其mRNA表达。【结果】骨碎补总黄酮高剂量组诱导膜组织形成的新生血管多于其余各组。药物高、中、低剂量组诱导膜组织中TGF-β1、VEGF的蛋白及其mRNA表达水平均明显高于模型组(P0.05),除VEGF mRNA指标外,其余指标的表达均具有剂量依赖性。【结论】骨碎补总黄酮在诱导膜形成期可促进TGF-β1及VEGF的表达,加速血管化进程,促进后期骨缺损重建。