糖皮质激素类联合肾上腺素能β激动剂对慢性阻塞性肺疾病急性加重期患者的疗效分析

目的 探讨糖皮质激素类联合肾上腺素能β激动剂对慢性阻塞性肺疾病急性加重期(AECOPD)患者的疗效.方法 选取AECOPD患者100例,依据随机数字表法分为联合用药组和对照组,每组50例.对照组给予常规对症和布地奈德雾化吸入治疗,联合用药组在此基础上加用沙丁胺醇雾化吸入治疗.调查所有患者治疗前后肺功能、血清肿瘤坏死因子-α、白细胞介素-8、C-反应蛋白、不良反应、病情严重程度和生活质量情况.结果 联合用药组治疗后1秒用力呼气量、肺总量、1秒用力呼气量用力肺活量百分比显著高于对照组(P<0.05);联合用药组治疗后血清肿瘤坏死因子-α、白细胞介素-8、C-反应蛋白水平低于对照组(P<0.05),治疗后1个月、3个月慢性阻塞性肺疾病评估测试评分和St George呼吸疾病问卷得分低于对照组,差异有统计学意义(P<0.05);两组治疗期间不良反应发生率、治疗后6个月慢性阻塞性肺疾病评估测试评分和St George呼吸疾病问卷得分差异无统计学意义(P>0.05).结论 糖皮质激素类联合肾上腺素能β激动剂治疗可有改善AECOPD患者的肺功能、炎症状态、病情、生活质量和提高疗效,且具有良好的安全性.     

支气管扩张剂联合吸入性糖皮质激素治疗慢性阻塞性肺病的疗效观察及对生活质量的影响

目的对慢性阻塞性肺病患者给予支气管扩张剂联合吸入性糖皮质激素治疗,并对临床疗效和患者生活质量的影响情况进行观察。方法选取2016年3月—2017年3月医院收治的慢性阻塞性肺病(COPD)患者80例,根据随机数字表法将其分为研究组和对照组。给予对照组支气管扩张剂进行治疗,给予研究组支气管扩张剂联合吸入性糖皮质激素进行治疗。对两组治疗前后肺通气功能、血气分析情况、生活质量评分、临床疗效和不良反应等进行比较分析。结果在各项肺通气功能指标(FEV1、FVC、FEV1/FVC)方面,两组治疗后均较治疗前明显提高,且研究组提高程度显著优于对照组(P<0.05);在血气分析方面,两组治疗后血氧分压(PaO_2)明显提高,动脉二氧化碳分压(PaCO_2)明显降低,且研究组各指标改善程度均显著优于对照组(P<0.05);在生活质量(SF-36)评分方面,研究组得分均较对照组明显提高,差异具有统计学意义(P<0.05);治疗后,研究组治疗总有效率(95.0%)较对照组(75.0%)明显提高,差异具有统计学意义(P<0.05);在不良反应方面,两组发生率间比较差异无统计学意义(P>0.05)。结论对慢性阻塞性肺病患者给予支气管扩张剂联合吸入性糖皮质激素治疗能够取得显著的临床疗效,可使患者肺通气功能、血气状况和生活质量明显改善,且疗效安全可靠,对稳定患者病情具有非常重要的价值,值得临床上进一步推广应用。     

糖皮质激素辅助治疗难治性肺炎支原体肺炎的Meta分析

目的:系统评价糖皮质素辅助治疗难治性肺炎支原体肺炎的疗效。方法:检索PubMed、Medline、Embase、Cochrane 图书馆、中国生物医学文献数据库、中国知网、万方数据库及维普数据库,检索时间从建库至2017年5月31日,收集糖皮质激素治疗儿童难治性肺炎支原体肺炎的RCT文献。应用RevMan 5.3软件进行Meta分析。结果:共纳入9篇RCT文献(n =920)。激素治疗后,试验组总有效率、住院时间、退热时间、肺部阴影消失时间与对照组比较差异有统计学意义(P<0郾01)。各研究文献住院时间、退热时间存在异质性。结论:糖皮质激素辅助治疗难治性肺炎支原体肺炎能提高疗效,缩短住院时间、退热时间、肺部阴影消失时间。     

Adrenal gland-dependent augmentation of plasminogen activator inhibitor-1 expression in streptozotocin-induced diabetic mice

BACKGROUND: Diabetes is associated with an excess risk of cardiac events, and one risk factor for infarction is an elevated level of plasminogen activator inhibitor-1 (PAI-1). OBJECTIVES AND METHODS: To evaluate whether the glucocorticoid hormones are involved in the diabetes-induced PAI-1 production, we examined expression profiles of PAI-1 mRNA in adrenalectomized (ADX) mice with streptozotocin (STZ)-induced diabetes. RESULTS: The diabetes-induced augmentation of plasma PAI-1 levels and PAI-1 mRNA expression in the heart and lungs was completely normalized in diabetic ADX mice. The glucocorticoid receptor antagonist RU486 significantly, but only partly suppressed PAI-1 induction in STZ-induced diabetic mice, suggesting that factors other than glucocorticoids are also involved in PAI-1 induction provoked by diabetes. CONCLUSION: Our results suggested that the adrenal gland plays a critical role in the progression of thrombosis in diabetic patients by inducing expression of the PAI-1 gene.     

系统应用糖皮质激素患者的FRAX骨折风险评估分析

目的 通过使用糖皮质激素（glucocorticoid,GC）校正的骨折危险性评估工具（fracture risk assessment tool,FRAX）,评估系统应用GC对风湿病患者群体骨折风险的影响。方法 纳入2019年1月至2020年1月于解放军总医院第四医学中心就诊且行髋部和腰椎骨密度检测的风湿病患者180例和同期健康体检者180名,风湿病患者均系统性使用GC治疗超过3个月,按照日均GC剂量（等同于醋酸泼尼松）分为GC≤7.5 mg组,7.5 mg＜GC＜30 mg组和≥30 mg组,并对剂量超过7.5 mg的两组进行骨折风险校正,使用FRAX评估系统评估未来10年主要骨质疏松性骨折（PMOF）和髋部骨折（PHF）发生概率,并比较组间的差异。结果 ①激素使用组PMOF和PHF高于健康对照组,且差异有统计学意义（P＜0.05）;②按GC使用时间分为＞2年组和≤2年组,GC使用＞2年组PMOF和PHF均高于≤2年组,且差异有统计学意义;③FRAX校正前GC≤7.5 mg组的PMOF与PHF高于另外两组,差异有统计学意义;④FRAX校正后GC≤7.5 mg组PMOF与PHF仍高于另外两组,与GC≥30 mg组相比差异有统计学意义;⑤按骨质疏松治疗阈值PMOF 20 %、PHF 3 %计算,激素使用组达到PMOF和PHF治疗阈值者分别为0例和9例（5 %）;按2017年GIOP推荐的骨质疏松治疗阈值PMOF 10 %、PHF 1 %计算,达治疗阈值者分别为8例（4.44 %）和41例（22.78 %）。结论 经GC校正后可提高基于FRAX计算出的风湿病患者的骨折风险,且校正后增加了达到骨质疏松治疗阈值的人数,能更有效的预测使用GC的风湿病群体骨折概率,尽早实施预防骨质疏松,从而降低骨折概率。     

淫羊藿苷抑制亮氨酸拉链蛋白表达调节糖皮质激素诱导的MC3T3-E1成骨基因的表达失衡

目的考察成骨细胞MC3T3-E中亮氨酸拉链蛋白（GILZ）的表达与淫羊藿苷（icraiin,ICR）和糖皮质激素地塞米松（dexamethasone,DEX）之间的关系以及对部分成骨相关基因的表达影响。方法将诱导成熟分化的MC3T3-E1细胞分为3组,分别为DEX组、ICR组以及ICR＋DEx组,通过Real—TimeRT—PCR来检测不同组中GILZ、骨保护素（OPG）、破骨细胞分化因子（RANKL）、骨钙素（Oc）和碱性磷酸酶（ALP）mRNA表达。结果DEX能够提升GILZ、RANKL和ALP的表达,降低OPG、OC的表达,提高RANKL／OPG表达比率。ICR能够抑制G[LZ、RANKL和ALP的表达,提升OPG、OC的表达,降低RANKL／OPG表达比率。并且ICR能够抑制DEX诱导的GILZ、RANKL和ALP表达升高,逆转DEX诱导的OPG、OC的表达抑制。同时显著降低了RANKL／OPG表达比率。结论ICR通过抑制GILZ的mRNA表达,降低RANKL／OPG的表达比率,抑制破骨细胞成熟激活。ICR通过抑制ALP表达和提高OC表达提高成骨细胞的增殖能力。     

Intracellular Zn2+ signaling in cognition

Brain zinc homeostasis is strictly controlled under healthy conditions, indicating the importance of zinc for physiological function in the brain. A part of zinc in the brain exists in the synaptic vesicles, is released from a subclass of glutamatergic neurons (i.e., zincergic neurons), and serves as a signal factor (Zn²⁺ signal) in the intracellular (cytosol) compartment as well as in the extracellular compartment. Zn²⁺ signaling is dynamically linked to glutamate signaling and may be involved in synaptic plasticity, such as long‐term potentiaion and cognitive activity. In zincergic synapses, intracellular Zn²⁺ signaling in the postsynaptic neurons, which is linked to Zn²⁺ release from zincergic neuron terminals, plays a role in cognitive activity. When nonzincergic synapses participate in cognition, on the other hand, it is possible that intracellular Zn²⁺ signaling, which is due mainly to Zn²⁺ release from the internal stores and/or metallothioneins, also is involved in cognitive activity, because zinc‐dependent system such as zinc‐binding proteins is usually required for cognitive process. Intracellular Zn²⁺ dynamics may be modified via an endocrine system activity, glucocorticoid secretion in both zincergic and nonzincergic neurons, which is linked to a long‐lasting change in synaptic efficacy. On the basis of the evidence of cognitive decline caused by the lack and/or the blockade of synaptic Zn²⁺ signaling, this article summarizes the involvement of intracellular Zn²⁺ signaling in zincergic synapses in cognition and a hypothetical involvement of that in nonzincergic synapses. © 2014 Wiley Periodicals, Inc.     

Cannabinoid Receptor Activation Prevents the Effects of Chronic Mild Stress on Emotional Learning and LTP in a Rat Model of Depression

Most psychiatric disorders are characterized by emotional memory or learning disturbances. Chronic mild stress (CMS) is a common animal model for stress-induced depression. Here we examined whether 3 days of treatment using the CB1/2 receptor agonist WIN55,212-2 could ameliorate the effects of CMS on emotional learning (ie, conditioned avoidance and extinction), long-term potentiation (LTP) in the hippocampal-accumbens pathway, and depression-like symptoms (ie, coping with stress behavior, anhedonia, and weight changes). We also examined whether the ameliorating effects of WIN55,212-2 on behavior and physiology after CMS are mediated by CB1 and glucocorticoid receptors (GRs). Rats were exposed to CMS or handled on days 1–21. The agonist WIN55,212-2 or vehicle were administered on days 19–21 (IP; 0.5 mg/kg) and behavioral and electrophysiological measures were taken on days 23 and 28. The CB1 receptor antagonist AM251 (IP; 0.3 mg/kg) or the GR antagonist RU-38486 (IP; 10 mg/kg) were co-administered with WIN55,212-2. Our results show that CMS significantly modified physiological and behavioral reactions, as observed by the impairment in avoidance extinction and LTP in the hippocampal-accumbens pathway, and the alterations in depression-like symptoms, such as coping with stress behavior, weight gain, and sucrose consumption. The most significant effect observed in this study was that 3 days of WIN55,212-2 administration prevented the CMS-induced alterations in emotional memory (ie, extinction) and plasticity. This effect was mediated by CB1 receptors as the CB1 receptor antagonist AM251 prevented the ameliorating effects of WIN55,212-2 on extinction and LTP. The GR antagonist RU-38486 also prevented the CMS-induced alterations in extinction and plasticity, and when co-administered with WIN55,212-2, the preventive effects after CMS were maintained. The findings suggest that enhancing cannabinoid signaling could represent a novel approach to the treatment of cognitive deficits that accompany stress-related depression.