ICU治疗策略的新进展

在过去的5年中,重症医学领域的许多新试验已经改变了传统的治疗策略。在这个领域的许多方面,出现了令人惊喜的成就,如脓毒性休克和急性呼吸窘迫综合征(ARDS)的治疗,以及重症患者的支持治疗(镇静、胰岛素)。值得注意的是,在这些试验中,一些传统的治疗措施被证明是失败的,如肺动脉导管在ARDS患者中的应用并不能改善ARDS患者的预后。该文总结8项主要的试验,以帮助研究者寻找更好的治疗方法。     

对1例痛风患者长期应用糖皮质激素的分析与监护

目的:探讨长期应用糖皮质激素的剂量与疗效、不良反应之间的关系,为临床合理用药提供参考依据。方法:对1例长期应用糖皮质激素的痛风患者进行跟踪观察,比较不同剂量引起的疗效与不良反应之间的关系。结果:药物疗效不与剂量成正相关,但不良反应与剂量成正相关性。结论:临床医师应合理应用糖皮质激素,以减少对患者的药源性损害。     

Acute stressors increase plasma corticosterone and decrease locomotor activity in a terrestrial salamander (Desmognathus ochrophaeus)

Vertebrates respond to the onset of an acute stressor with an acute increase in plasma glucocorticoids. The increase in plasma glucocorticoids is believed to be adaptive, helping an animal cope until the stressful episode subsides. Although much is known about the effects of chronic elevation of glucocorticoids, far less is known about the role of acute increases in glucocorticoids in mediating stress responses. To better understand the regulation and function of acute increases in plasma glucocorticoids, we measured stress-induced increases in plasma corticosterone (CORT) and the effects of stressors and exogenous CORT on activity in male Allegheny dusky salamanders (Desmognathus ochrophaeus). Capture and handling of field-caught salamanders resulted in an acute elevation of plasma CORT during the nonmating season but not during the mating season. In laboratory-housed salamanders, a handling stressor that simulated capture resulted in decreased locomotor activity. Noninvasive elevation of plasma CORT via dermal patches did not replicate the handling-induced decrease in activity. Together, this work indicated that 1) the CORT response to the acute stressor of capture and handling was seasonally variable, 2) handling induced a decrease in locomotor activity in the laboratory, and 3) acute increases in plasma CORT did not contribute to stress-induced changes in locomotor activity. Future studies using noninvasive methods to elevate plasma CORT should illuminate the role of acute increases in plasma glucocorticoids in coordinating organismal responses to acute stressors.     

Molecular mechanisms of repeated social defeat-induced glucocorticoid resistance: Role of microRNA

Glucocorticoid (GC) resistance is a severe problem associated with various inflammatory diseases. Previous studies have shown that repeated social stress induces GC resistance in innate immune cells, but the underlying molecular mechanisms have not been fully elucidated. Therefore, the purpose of this study was to examine potential underlying molecular mechanism(s) of repeated social defeat (RSD) stress on GC resistance in splenic macrophages. It was hypothesized that mRNA expression of receptors for GC and nuclear translocating-associated regulators in splenic macrophages would be affected by RSD, and that these changes would be associated with epigenetic modification. The data showed that the mRNA expression of GC and mineralocorticoid receptors were significantly decreased in splenic macrophages by RSD. RSD also induced a significantly decreased mRNA expression in FK506-binding protein 52 (FKBP52), consequently resulting in a significantly increased ratio of FKBP51 to FKBP52. Moreover, DNA methyltransferases 3a and 3b showed a significant decrease in their mRNA expression in the RSD group as did mRNA expression of histone deacetyltransferase 2. The RSD group also showed a significantly reduced quantity of methylated DNA in splenic macrophages. Based on microRNA (miRNA) profiling data, it was determined that RSD induced significantly increased expression of 9 different miRNAs that were predicted to interact with mRNAs of the GC receptor (6 miRNAs), mineralocorticoid receptor (3 miRNAs) and FKBP52 (2 miRNAs). Spearman correlation analysis revealed significantly strong correlations between the expression of 2 miRNAs and their target mRNA expression for GC receptors. Among these miRNAs, we verified direct effects of miRNA-29b and -340 overexpression on mRNA expression of GC receptors in L929 cells. The overexpression of miRNA-29b or -340 in L929 cells significantly reduced LPS-induced overexpression of GC receptors. In conclusion, this study provides evidence that epigenetic regulation, such as DNA methylation and miRNA expression, may play a role in the RSD-induced GC resistance that we have observed in splenic macrophages.     

Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice

Chronic psychological stress is one of the most important triggers and environmental risk factors for neuropsychiatric disorders. Chronic stress can influence all organs via the secretion of stress hormones, including glucocorticoids by the adrenal glands, which coordinate the stress response across the body. In the brain, glucocorticoid receptors (GR) are expressed by various cell types including microglia, which are its resident immune cells regulating stress-induced inflammatory processes. To study the roles of microglial GR under normal homeostatic conditions and following chronic stress, we generated a mouse model in which the GR gene is depleted in microglia specifically at adulthood to prevent developmental confounds. We first confirmed that microglia were depleted in GR in our model in males and females among the cingulate cortex and the hippocampus, both stress-sensitive brain regions. Then, cohorts of microglial-GR depleted and wild-type (WT) adult female mice were housed for 3 weeks in a standard or stressful condition, using a chronic unpredictable mild stress (CUMS) paradigm. CUMS induced stress-related behavior in both microglial-GR depleted and WT animals as demonstrated by a decrease of both saccharine preference and progressive ratio breakpoint. Nevertheless, the hippocampal microglial and neural mechanisms underlying the adaptation to stress occurred differently between the two genotypes. Upon CUMS exposure, microglial morphology was altered in the WT controls, without any apparent effect in microglial-GR depleted mice. Furthermore, in the standard environment condition, GR depleted-microglia showed increased expression of pro-inflammatory genes, and genes involved in microglial homeostatic functions (such as Trem2, Cx3cr1 and Mertk). On the contrary, in CUMS condition, GR depleted-microglia showed reduced expression levels of pro-inflammatory genes and increased neuroprotective as well as anti-inflammatory genes compared to WT-microglia. Moreover, in microglial-GR depleted mice, but not in WT mice, CUMS led to a significant reduction of CA1 long-term potentiation and paired-pulse ratio. Lastly, differences in adult hippocampal neurogenesis were observed between the genotypes during normal homeostatic conditions, with microglial-GR deficiency increasing the formation of newborn neurons in the dentate gyrus subgranular zone independently from stress exposure. Together, these findings indicate that, although the deletion of microglial GR did not prevent the animal’s ability to respond to stress, it contributed to modulating hippocampal functions in both standard and stressful conditions, notably by shaping the microglial response to chronic stress.     

小剂量糖皮质激素对类风湿关节炎患者血脂水平的影响

目的探讨联合短期小剂量糖皮质激素疗法对类风湿关节炎患者血脂水平的影响。方法74例活动期类风湿关节炎患者随机分为糖皮质激素（GC）组和非Gc组，所有患者在基线和治疗6个月时计算DAS28评分及测定血沉、C反应蛋白、血脂水平，比较两组的差异。结果系统治疗6个月后，两组患者DAS28评分均有下降；HDL-C水平较基线时升高。但Gc组和非GC组之间治疗后的血脂水平无统计学差异。结论联合应用短期、小剂量GC治疗RA，对患者的血脂水平亦并无不利影响。小剂量GC有利于患者系统炎症的控制，从减轻系统慢性炎症的角度降低患者动脉粥样硬化的风险，从而有利于减少患者的心血管并发症。     

糖皮质激素治疗腺病毒感染的不良反应及早期防治措施

目的 探讨糖皮质激素甲强龙治疗腺病毒感染的不良反应,分析导致股骨头坏死的机制及早期综合防治的疗效。方法 收集51例确诊为腺病毒感染患者,根据甲强龙单日最大剂量分组,分为≥320 mg组18例,〈320 mg组33例,对病程中出现的不良反应进行统计学分析。测定2组三酰甘油、总胆固醇、低密度脂蛋白、血钙、血磷、D-二聚体,并进行统计学分析。≥320 mg组根据出现的异常指标,分别给予口服阿托伐他汀钙、皮下注射低分子肝素钠、口服华法林、前列地尔静滴、口服钙剂、骨化三醇和阿仑膦酸钠片等综合防治,治疗前后测定以上指标,进行统计学分析。结果 ≥320 mg组患者出现血脂异常、心动过速、电解质紊乱、继发真菌感染、血糖异常、撤药综合征等不良反应,与〈320 mg组相比,总胆固醇、三酰甘油、低密度脂蛋白、血磷、D-二聚体升高,血钙下降。≥320 mg组治疗后与治疗前相比,总胆固醇、D-二聚体降低,血钙升高,血磷降低,甘油三酯、低密度脂蛋白降低。结论 糖皮质激素治疗腺病毒感染是一把双刃剑,可能导致严重后果,临床诊治过程中要注意早期防治,减少后期出现股骨头坏死机率。     

糖皮质激素在大前庭水管综合征患儿不同频率听力损失中的临床效果观察

目的探讨糖皮质激素（glucocorticoid,GC）改善大前庭水管综合征（large vestibular aquduct syndrome,LVAS）不同频率听力的效果。方法 2008-01/2013-12月作者医院收治的22例（44耳）LVAS患儿,给予口服强的松、金纳多、维生素B1、B6、甲钴胺治疗;对比治疗前后听力损伤程度及各频率听阈。结果患儿治疗前中重度聋、重度聋、极重度聋分别占9.09%、25.00%、65.91%,治疗2周后中度聋、中重度聋、重度聋、极重度聋为2.27%、15.91%、36.36%、45.45%。治疗前后听力损失程度无明显差异（P〉0.05）。患儿治疗前0.25、0.5、1、2、4 kHz纯音听阈分别为（61.53±6.24）、（65.32±8.34）、（69.23±8.48）、（84.83±7.89）、（86.58±7.84）dB HL,治疗2周后0.25、0.5、1、2、4 kHz纯音听阈分别为（43.32±7.35）、（52.36±7.53）、（66.64±7.39）、（79.34±8.94）、（85.83±7.96）dB HL。患儿经治疗后对0.25、0.5 kHz纯音的听阈明显提高（P〈0.05）;而对1、2、4 kHz纯音的听阈则无明显改善（P〉0.05）。结论口服GC配合神经营养剂能够提高LVAS患儿的低频听力,但对其高频听力无改善效果。     

Transdermal delivery of corticosterone in terrestrial amphibians

Stressors elicit allostatic responses that allow animals to cope with changing and challenging environments and also cause release of glucocorticoid hormones (GCs). Compared to other vertebrate classes, relatively little is known about amphibian behavioral and physiological responses to GCs. To understand the effects of elevated plasma GCs in amphibians, exogenous application of GCs is necessary, but traditional methods to elevate GCs require handling and/or anesthesia which themselves are stressors. A less invasive alternative successfully used in birds and reptiles utilizes transdermal delivery by applying GCs via a dermal patch. We asked whether dermal patches containing corticosterone (CORT, the main GC in amphibians) would elevate plasma CORT in terrestrial salamanders and frogs. We explored the use of the dermal patch to deliver CORT in an acute, sustained, and repeated manner. Patches adhered well to the amphibians’ moist skin and were easily removed to regulate the time course of CORT delivery. Application of CORT treated patches elevated plasma CORT concentrations compared to vehicle patches in all species. Patches delivered physiological levels of plasma CORT in ecologically relevant time frames. Repeated application and removal of CORT patches were used to simulate exposure to repeated stressors. Application of patches did not represent a stressor because plasma CORT concentrations were similar between animals that received vehicle patches and untreated animals. Thus, transdermal delivery of GCs represents a potentially useful tool to better understand amphibian allostatic responses to stressors, and perhaps amphibian population declines.     

31例确诊EV71感染所致重型手足口病诊治体会

目的:探讨肠道病毒71型(EV71)感染所致重型手足口病的临床特点和治疗方法。方法:采用描述性流行病学方法对31例确诊EV71感染所致重型手足口病患儿的临床资料进行回顾性分析。结果:男19例,女12例,年龄1岁～6岁8个月,患儿主要表现为持续高热、精神差、易惊、肢体抖动、呕吐;外周血WBC升高为主(67.8%);采用以糖皮质激素加静脉丙种球蛋白为主的综合治疗,31例患儿均治愈。结论:早期识别重型手足口病,采用以激素加丙球为主的综合治疗,能够取得满意的疗效。