【摘要翻译】 一 氧化氮合酶( NOS) -2( NOS-2) 的诱导和一氧化氮产物增加是过敏性气道疾病的共同特征。严重哮喘与气道S-亚硝基硫醇减少相关。S-亚硝基硫醇是NO的生化产物, 可通过促炎症转录因子NF-κB 的S-亚硝基化抑制炎症反应。因此, 重建气道S-亚硝基硫醇对治疗可能有益。我们对此假设在以卵清蛋白诱导的过敏性炎症大鼠模型中进行验证。未使用或使用卵清蛋白致敏的动物均在卵清蛋白激发前于气管内灌注S-亚硝基谷胱甘肽( GSNO;50 μl, 10 mM) , 并在48 h 以后进行分析。GSNO 给药增加了肺组织S-亚硝基硫醇水平。与对照组比, GSNO 降低了卵清蛋白致敏动物NF-κB 的活性, 但对支气管肺泡灌洗细胞总数、分类计数及杯状细胞化生标记物均无显著影响。GSNO给药也改变了HIF-1 的活性, 导致未致敏大鼠HIF-1 活化,但抑制卵清蛋白致敏大鼠的HIF-1 活性。我们使用NOS-2基因敲除小鼠来评价内源性一氧化氮合成酶-2 在调节NF-κB和( 或) HIF-1 活性及气道过敏性炎症的作用。尽管在NOS-2 基因敲除小鼠中卵清蛋白诱导的NF-κB 活力轻度增高, 这与支气管肺泡灌洗中性粒细胞轻度增加有关, 其他的过敏性炎症指标和HIF-1 活性在NOS-2 基因敲除及野生型小鼠之间却无明显相差。总体来说, 我们的研究表明GSNO灌注能抑制气道过敏性炎症中NF-κB 活性, 但是并不能显著地影响大部分炎症及杯状细胞化生指标, 这样可能因为对其他信号通道( 比如HIF-1) 的影响而限制了它的治疗价值。【述评】 GSNO 是近年哮喘治疗研究的热点。既往的研究发现GSNO 在哮喘治疗中有一定前景。本研究却发现GSNO 气管内滴注虽能抑制过敏性气道炎症中NF-κB 活性,但并不能显著抑制气道炎症反应及杯状细胞化生这两个哮喘关键病理改变, 可能与GSNO 同时影响了HIF-1 等其他信号通路有关。该研究表明GSNO 对哮喘气道炎症治疗效果有限, 同时表明哮喘气道炎症调控机制较为复杂, 治疗药物的设计需考虑多种信号通路对哮喘气道炎症的影响。
ObjectivesTo detect expressions of trefoil factor 1 (TFF1) and TFF3 in the mice with acute allergic airway disease (AAD) after different interventions, and explore primitively the effect of recombinant TFF3 on airway inflammation and mucous secretion.MethodsForty BALB/c mice were randomly divided into 5 groups, each group with 8 mice, ie. a normal saline control group (group A), an AAD group (group B), a budesonide intervention group (group C), a recombinant TFF3 intervention group (group D), and a budesonide+recombinant TFF3 intervention group (group D). The BALB/c mice were sensitized and challenged with ovalbumin to induce AAD. Lung tissue sections were stained with hematoxylin-eosin staining for assessment of airway inflammation, and immunohistochemistry was used for detecting TFF1/TFF3 expression in the airway. Alcian blue stain was applied to determine mucous secretion.ResultsAirway inflammation score and airway mucous secretion: Group B was significantly more than group A (P<0.01); Group C was less than group B (P<0.05), and there was no significant difference between group D and group B (P>0.05); There was no significant difference between group C and group E (P>0.05). Expression of TFFs: TFF1 and TFF3 were expressed in epithelial cells, goblet cells and submucosal gland cells of bronchi and bronchioles in all groups; The expressions of TFF1 and TFF3 in group B were significantly higher than those in group A (P<0.01), while the expressions of TFF1 and TFF3 in group C were lower than those in group B (P<0.05). TFF1 expression in airway epithelium was positively correlated with inflammatory score (r=0.876, P=0.000) and mucin expression (r=0.807, P=0.000). TFF3 level was positively correlated with inflammatory score (r=0.654, P=0.006) and mucin expression (r=0.666, P=0.005).ConclusionsOvalbumin-induced acute allergic airway inflammation significantly increases TFF1/TFF3 expression. Intranasal TFF3 treatment may not influence airway inflammation and mucus secretion. Inhaled corticosteroids to some extent inhibit expressions of TFF1 and TFF3, simultaneously suppress airway inflammation and mucus secretion in the mouse model of acute AAD .
ObjectiveTo improve clinicians' knowledge of hypersensitivity pneumonitis (HP). MethodsWe retrospectively analyzed the clinical data of 24 HP patients who were diagnosed in the Affiliated Drum Tower Hospital of Nanjing University Medical School during February 2005 to February 2013. The clinical,radiological and pathological features of those patients were summarized. ResultsAmong those 24 patients,15 were male and 9 were female,with mean age of (48±13) years. All patients had a history of environmental exposure. Two patients showed acute clinical manifestations,and there were 17 subacute and 5 chronic cases. The main clinical manifestations were dyspnea,cough,sputum,fever and weight loss with hypoxemia via blood gas analysis. Restrictive ventilatory impairment was the most frequent functional pattern,and the carbon monoxide diffusing capacity was decreased. Pulmonary function test showed restrictive ventilatory defect and gas interchange disturbance. The features of chest HRCT included diffuse ground-glass attenuation and/or patchy consolidation,centrilobular micronodules,mosaic sign,reticular and/or honeycombing lesions. Bronchoalveolar lavage fluid (BALF) demonstrated an increase of total cell counts with predominant lymphocytosis. The transbronchoscopic lung biopsy (TBLB) pathological examination revealed lymphocytic alveolitis,noncaseating granuloma,and interstial pneumonia. All patients were treated by corticosteroid and avoided antigen exposure and showed significant clinical and radiological improvement. ConclusionThe diagnosis of HP is difficult. In most cases (acute and subacute HP),a diagnosis can be made by combination history of exposure,chest HRCT manifestations,cell classification of BALF and pathological examination of TBLB. For atypical cases (chronic HP),a surgery lung biopsy is needed for multi-disciplinary diagnosis including pathologist,radiologist and pulmonologists.
Sleep deprivation can cause hyperalgesia, and the mechanisms involve glutamic acid, dopamine, serotonin, metabotropic glutamate receptor subtype 5, adenosine A2A receptor, nicotinic acetylcholine receptor, opioid receptor, brain-derived neurotrophic factor, melatonin, etc. The mechanisms of hyperalgesia caused by sleep deprivation are complex. The current treatment methods are mainly to improve sleep and relieve pain. This paper reviews the mechanism and treatment progress of hyperalgesia induced by sleep deprivation, and aims to provide scientific evidence for the treatment of hyperalgesia caused by sleep deprivation.
目的:分析输血反应类型,分布及概率。方法:回顾性分析我院2008年11月至2009年4月各类输血事件,收集输血不良反应回报单,进行统计分析。结果:在共计8996人次输血中,发生输血不良反应47人次,其中输注血浆引起的输血不良反应率为0.68％,输注红细胞悬液的不良反应率为0.30％,总的输血不良反应率0.98％,不同血液制品输血不良反应发生率具显著性差异(Plt;0.05)。其中主要表现为过敏反应,占63％,其次为发热反应.结论:如何提高临床科室科学合理用血水平的方法需进一步探讨。