Innate immune factors modulate ethanol interaction with GABAergic transmission in mouse central amygdala

Excessive ethanol drinking in rodent models may involve activation of the innate immune system, especially toll-like receptor 4 (TLR4) signaling pathways. We used intracellular recording of evoked GABAergic inhibitory postsynaptic potentials (eIPSPs) in central amygdala (CeA) neurons to examine the role of TLR4 activation by lipopolysaccharide (LPS) and deletion of its adapter protein CD14 in acute ethanol effects on the GABAergic system. Ethanol (44, 66 or 100 mM) and LPS (25 and 50 μg/ml) both augmented eIPSPs in CeA of wild type (WT) mice. Ethanol (44 mM) decreased paired-pulse facilitation (PPF), suggesting a presynaptic mechanism of action. Acute LPS (25 μg/ml) had no effect on PPF and significantly increased the mean miniature IPSC amplitude, indicating a postsynaptic mechanism of action. Acute LPS pre-treatment potentiated ethanol (44 mM) effects on eIPSPs in WT mice and restored ethanol’s augmenting effects on the eIPSP amplitude in CD14 knockout (CD14 KO) mice. Both the LPS and ethanol (44–66 mM) augmentation of eIPSPs was diminished significantly in most CeA neurons of CD14 KO mice; however, ethanol at the highest concentration tested (100 mM) still increased eIPSP amplitudes. By contrast, ethanol pre-treatment occluded LPS augmentation of eIPSPs in WT mice and had no significant effect in CD14 KO mice. Furthermore, (+)-naloxone, a TLR4-MD-2 complex inhibitor, blocked LPS effects on eIPSPs in WT mice and delayed the ethanol-induced potentiation of GABAergic transmission. In CeA neurons of CD14 KO mice, (+)-naloxone alone diminished eIPSPs, and subsequent co-application of 100 mM ethanol restored the eIPSPs to baseline levels. In summary, our results indicate that TLR4 and CD14 signaling play an important role in the acute ethanol effects on GABAergic transmission in the CeA and support the idea that CD14 and TLR4 may be therapeutic targets for treatment of alcohol abuse.     

产ESBLs肺炎克雷伯菌ESBLs基因与可移动遗传元件相关性分析

目的 了解产超广谱β-内酰胺酶(extended spectrum beta-lactamases, ESBLs)肺炎克雷伯菌(Klebsiella pneumoniae, Kpn)ESBLs基因与可移动遗传元件(mobile genetic elements, MGEs)标记基因的携带情况及其相关性。方法 收集从住院患者标本中分离出的产与非产ESBLs Kpn非重复菌株各100株，采用PCR检测细菌中4种ESBLs基因与8种MGEs标记基因，并作指标聚类分析。结果 产ESBLs Kpn中，ESBLs基因阳性率高达100%；MGEs标记基因以IS26、ISEcp1、traA、trbC和intI1基因为主，阳性率高于非产ESBLs Kpn(P<0.05)；ESBLs基因与MGEs标记基因的同时检出率明显高于非产ESBLs Kpn (P<0.05)；基因blaSHV-12、blaOXA-1与MGEs基因tnpU、tnp513、merA、intI1相关联，基因blaTEM-1、blaCTX-M-125与MGEs基因ISEcp1、IS26、traA相关联。产与非产ESBLs Kpn均没有只检出MGEs标记基因的菌株。结论 产ESBLs Kpn ESBLs基因和MGEs标记基因携带率高，两者存在相关性，可能是产ESBLs Kpn出现多重耐药的重要原因；MGEs标记基因在Kpn中可能不是单独存在的。     

延续护理对提高心脏瓣膜置换术后患者生存质量的研究

目的探讨延续护理对心脏瓣膜置换术患者出院后生活质量的影响。方法以2005年5月～2008年5月在我院心胸外科行人工机械瓣膜置换术的100名患者作为调查对象，随机分为实验组和对照组各50例。实验组行常规治疗和护理，患者出院后给予系统性延续护理2年。对照组按常规治疗和护理，患者出院后给予常规出院指导。两组患者分别于术后6个月、2年发放生存质量表进行问卷调查。比较两组患者的药物依从性、并发症发生率及生存质量。结果实验组术后6个月和2年的生存质量评分明显高于对照组，8项评价指标中差异有显著意义（P〈0．05）。结论延续护理可以促进心脏瓣膜置换术后病人早日康复，提高生存质量。     

Extended‐release antiepileptic drugs: A comparison of pharmacokinetic parameters relative to original immediate‐release formulations

Many antiepileptic drugs (AEDs) have short half‐lives with large fluctuations in peak‐to‐trough plasma concentrations. Consequences of these pharmacokinetic (PK) properties may include adverse events (AEs) and breakthrough seizures, potentially leading to poor adherence. To address these challenges, newer formulations of these AEDs have been developed using unique extended‐release (ER) technologies. These technologies extend the dosing interval such that dosing frequency can be minimized, which may improve patient adherence. Available ER formulations have the potential to minimize the spikes in maximum plasma concentrations (C_max) at steady‐state that often contribute to AEs during treatment with immediate‐release (IR) products. In so doing, tolerability advantages may lead to increased AED effectiveness by improving adherence and allowing higher doses if clinically indicated. Direct PK comparison studies of IR and ER formulations (e.g., carbamazepine, divalproate sodium, lamotrigine, oxcarbazepine, levetiracetam, and phenytoin) have found that dose‐normalized ER formulations may or may not be bioequivalent to their IR counterparts, but most ER formulations have a lower fluctuation index ([C_max–C_min]/C_avg) compared with the IR versions. This results in flatter concentration‐time plots. Not all ER preparations improve the various PK parameters to the same extent, and PK nuances may impact the effectiveness, tolerability, and adherence rates of various ER formulations.     

扩大联合脏器切除治疗T4b期胃癌的临床分析

目的探讨扩大联合脏器切除T4b期胃癌的疗效,总结手术经验。方法对2012年1月至2015年12月在哈尔滨医科大学附属第一医院手术治疗的128例T4b期胃癌临床资料进行回顾性分析。结果 85例行扩大联合脏器切除术(extended multi-organ resection,ER组),43例行姑息性手术(non-extended multi-organ resection,NER组)。随访ER组1年、2年、3年的生存率分别为65.38%、44.87%和38.46%,均高于NER组的35.13%、16.21%和5.41%,两者之间的差异均有统计学意义(P0.05)。ER组的并发症发生率为18.82%,高于NER组的4.65%,两组之间的差异有统计学意义(P0.05);ER组的围手术期病死率为2.35%,NER组为2.33%,两者之间的差异无统计学意义(P0.05)。结论扩大联合脏器切除是安全可行的,可以延长病人生存期,改善临床症状,提高生存质量。     

Ethanol-Induced Extracellular Signal Regulated Kinase: Role of Dopamine D1 Receptors

Background:  Addictive drugs activate extracellular signal regulated kinase (ERK) in brain regions critically involved in their affective and motivational properties. The aim of this study was to demonstrate the ethanol-induced activation of ERK in the nucleus accumbens (Acb) and in the extended amygdala [bed nucleus of the stria terminalis lateralis (BSTL) and central nucleus of the amygdala (CeA)] and to highlight the role of dopamine (DA) D₁ receptors in these effects.
Methods:  Ethanol (0.5, 1, and 2 g/kg) was administered by gavage and ERK phosphorylation was determined in the nucleus Acb (shell and core), BSTL, and CeA by immunohistochemistry. The DA D₁ receptor antagonist, SCH 39166 (SCH) (50 μg/kg), was administered 10 minutes before ethanol (1 g/kg).
Results:  Quantitative microscopic examination showed that ethanol, dose-dependently increased phospho-ERK immunoreactivity (optical and neuronal densities) in the shell and core of nucleus Acb, BSTL, and CeA. Pretreatment with SCH fully prevented the increases elicited by ethanol (1 g/kg) in all brain regions studied.
Conclusions:  The results of this study indicate that ethanol, similar to other addictive drugs, activates ERK in nucleus Acb and extended amygdala via a DA D₁ receptor-mediated mechanism. Overall, these results suggest that the D₁ receptors/ERK pathway may play a critical role in the motivational properties of ethanol.