慢性阻塞性肺部疾患缓解期患者血清氨基酸及微量元素分析

对２８例ＣＯＰＤ缓解期男性患者的血后分析发现，患者血清氨基酸含量与正常参考值比较无明显差别，支链氨基酸与芳香氨基酸比值也未见异常。血清微量元素含量，除锌、铬显著低于正常外（Ｐ＜０．０５），铁、铜、硒等元素的含量仍在正常范围内。     

单细胞RNA测序联合实验验证树突状细胞在慢性阻塞性肺疾病中的核心基因

目的 单细胞RNA测序(scRNA-Seq)联合实验验证树突状细胞在慢性阻塞性肺疾病(COPD)中的核心基因。方法从基因表达数据集(GEO)数据库下载单细胞数据GSE173896和芯片数据GSE38974。GSE173896进行质控、批次矫正、降维聚类、细胞类型注释及组间树突状细胞差异表达基因(DC-DEG)鉴定。GSE38974差异分析得到的差异基因(DEG)与DC-DEG取交集获取共有DC-DEG,评估共有DC-DEG对COPD的诊断效能和共有DC-DEG富集分析及其与GSE38974免疫细胞浸润中激活的树突状细胞(DC)、浆细胞样树突状细胞(pDC)和Th17细胞的相关性。肺气肿小鼠模型肺组织对共有DC-DEG的mRNA表达量进行实验验证。结果 GSE173896得到组间DC-DEG 18个,GSE38974得到646个DEG,两者取交集得到3个DC-DEG,包括白细胞介素1受体拮抗剂(IL1RN)、 S100钙结合蛋白A8(S100A8)和S100A9,曲线下面积(AUC)值分别为0.841、 0.804和0.966。基因本体论分析(GO)和京都基因与基因组百科全书(KEGG)...     

慢性阻塞性肺疾病大鼠尿Cys-C mRNA表达及肺肾之间的相关性探讨

观察慢性阻塞性肺病(COPD)大鼠尿半胱氨酸蛋白酶抑制剂-C(Cys-C)mRNA表达水平的变化、肺组织匀浆基质金属蛋白酶-9(MMP-9)含量及肺肾超微结构的变化,探讨COPD疾病状态下肺肾两脏之间的相关性。将大鼠随机分为空白组(N)、COPD组(B)、单纯肾损害组(D),COPD加肾损害组(E),每组8只,用改良烟熏加气管滴脂多糖(LPS)法建立COPD模型,腺嘌呤灌胃制作肾损害模型,RT-PCR法检测大鼠尿Cys-C mRNA表达,ELISA法检测肺组织匀浆基质金属蛋白酶-9(MMP-9)含量,光镜、透射电镜观察肺、肾组织及细胞的病理改变。与空白组相比,各实验组Cys-C mRNA的表达及MMP-9的含量均显著增加(P<0.01),与COPD组相比,COPD加肾损害组Cys-C mRNA的表达及MMP-9的含量均增加(P<0.05);与单纯肾损害组相比,COPD加肾损害组Cys-C mRNA的表达及MMP-9的含量均增加(P<0.05)。光镜、透射电镜观察,COPD加肾损害组肺、肾组织损害最严重,COPD组的肺、肾组织有损害,但是不及COPD加肾损害组的严重;与单纯肾损害组相比,COPD加肾损害组肺、肾损害更严重。COPD可引起一定的肾损害,而单纯的肾损害也会引起一定的肺损害,提示在COPD病程中肺肾之间的相关性。     

老年慢性阻塞性肺部疾病急性加重期患者住院死亡的危险因素及预后

目的 评估住院的慢性阻塞性肺疾病急性加重期(AECOPD)老年患者中外周血中性粒细胞计数和淋巴细胞计数比值(NLR)、C反应蛋白和血清白蛋白比值(CRP/ALB)的临床意义和应用价值。方法 收集2016年1月至2020年1月在合肥市第二人民医院老年医学科和呼吸内科住院的172例老年AECOPD患者。根据临床转归分为存活组(n=155)和死亡组(n=17),存活组按住院日分为≥10 d和<10 d分组。比较各组患者的临床和实验室检查指标的差异性,采用Logistic回归和受试者工作特征曲线(ROC)分析危险因素及其与住院死亡率的关系。结果 172例老年AECOPD住院患者中17例患者住院期间死亡,死亡率9.88%。死亡组和存活组在NLR、CRP、CRP/ALB、红细胞分布宽度(RDW)、吸烟、社区获得性肺炎(CAP)和多种合并症均存在差异,死亡组高于存活组(P<0.01)。同时存活出院的155例老年AECOPD按照住院日≥10 d和<10 d分成两组,发现NLR、CRP、CRP/ALB、RDW、吸烟和CAP也在两组间也存在差异,住院日≥10 d组高于住院日<10 ...     

慢性阻塞性肺气肿的治疗进展

慢性阻塞性肺气肿是一种以不完全可逆的气流受限为特征的疾病,在我国北方地区发病率、病死率均较高^[1]。严格地说,肺气肿不是一种独立的疾病,而是一个解剖,结构术语,是慢性支气管炎或其他慢性肺部疾患发展的结果,主要是肺组织终末支气管远端部分包括呼吸性细支气管、肺泡管、肺泡囊和肺泡的膨胀和过度充气,导致肺组织弹力减退,容积增大。     

膈神经传导检测在治疗慢性阻塞性肺疾病患者呼吸肌疲劳疗效评价中的作用

目的：评价膈神经传导检测在无创性正压通气（NPPV）治疗慢性阻塞性肺疾病（COPD）急性加重期患者呼吸肌疲劳的疗效中的作用。方法：采用前瞻性随机对照研究,将32例COPD患者随机分为两组：I组为常规治疗＋NPPV,Ⅱ组仅接受常规治疗,观察两个组治疗前后辅助呼吸肌动用评分、肺功能和膈神经运动传导的变化。结果：治疗前两个组患者均存在呼吸困难和辅助呼吸肌参与,膈神经运动传导的潜伏期与健康人比较差异无显著意义,但动作电位波幅明显低于健康人。治疗第8天,两个组患者的症状均改善,I组肺功能显著改善,而Ⅱ组仅第一秒用力呼气容积（FEV1）有增加。I组患者的膈神经动作电位波幅较Ⅱ组显著增高。结论：膈神经运动传导测定证实COPD急性加重期患者治疗前均存在不同程度的呼吸肌疲劳,应用NPPV能改善气体交换,缓解呼吸肌疲劳。膈神经运动传导测定可作为治疗COPD急性加重期患者呼吸疲劳的诊断及疗效的评价指标。     

慢性阻塞性肺疾病患者的护理体会

目的：研究综合护理干预对治疗COPD患者疗效的影响。方法本文选取了我院2013年2月~2014年2月收治的60例COPD的临床护理记录,将患者随机分为实验组和对照组各30例,对两组患者的生活满意度、遵医依从性进行比较分析。结果对照组采用常规护理,实验组在常规护理的基础上附加综合护理干预措施,比较2组患者的生活满意度、遵医依从性发现,实验组状况均有优于对照组,差异均具有统计学意义(<0.05)。结论综合护理干预可消除其负面情绪,积极主动的配合治疗,提高治愈率,提升患者的生活品质。     

吸烟者血清α1-抗胰蛋白酶、中性粒细胞弹性蛋白酶及组胺的变化

慢性阻塞性肺疾患 (COPD)是常见病、多发病。吸烟是COPD发病的重要因素 ,但其发病机理至今尚未完全阐明。九五期间我们的工作曾表明 ,吸烟伴有COPD者血清α1 抗胰蛋白酶 (α1 AT)明显低于不伴有COPD者[1 ] ,提示α1 AT可能是一重要的宿主高危因素。在此基础上本文继续观察吸烟伴和不伴COPD者血清α1 AT、中性粒细胞弹性蛋白酶 (NE) ,组胺含量及NE α1 AT比值变化 ,为COPD的发病学及早期诊断提供线索。1　材料与方法按病例 对照设计方法 ,从数据库中随机抽取吸烟 (吸烟指数≥ 30 0 )伴COPD者 (病例组 ,FE1 % <70 % )和…     

从肝肺组织病理改变及细胞超微结构变化探讨慢性阻塞性肺疾病中肺肝的相关性

通过观察慢性阻塞性肺疾病(COPD)大鼠肝肺组织γ-谷氨酰转肽酶(γ-GCS)mRAN表达水平变化、肺组织匀浆基质金属蛋白酶-9(MMP-9)含量、肺肝病理及超微结构的变化,探讨COPD疾病状态下肺肝两脏之间的相关性。清洁级健康雄性Wistar大鼠32只,随机分成4组:正常组(A组),COPD模型组(B组)、单纯肝损害组(C组)、COPD加肝损害组(D组),每组8只。采用改良烟熏加气管内注脂多糖的方法建立COPD模型,四氯化碳皮下注射法建立肝损害模型。RT-PCR法检测大鼠肺肝组织γ-GCS mRAN表达,ELISA法检测肺组织匀浆MMP-9含量,光镜、透射电镜下观察肺肝组织病理及超微结构变化。与A组比较,B组及D组肺组织MMP-9含量显著升高(P<0.01),C组也可见含量升高(P<0.05),D与B组比较有统计学意义(P<0.05)。与A组比较,B组、D组肺组织中γ-GCS基因表达明显增高(P<0.01),C中也见升高(P<0.05),D组与B组比较亦明显升高(P<0.01)。B组肝组织γ-GCS基因表达和正常组比较没有统计学意义,D组与C组肝组织织γ-GCS基因表达均明显增高(P<0.01),且二者比较,D组升高更明显(P<0.01)。光镜、透射电镜下观察,D组肺肝组织损害最重,D组与B组比较,肺损害更重,D组与C组比较,肝损害更重。在慢性阻塞性肺疾病状态下,肺脏损伤的同时肝脏也有不同程度的受损;而单纯肝脏受损的同时也会累及到肺脏,提示COPD病程中肺肝之间的相关性。     

microRNA-146a联合肺部超声评分对慢性阻塞性肺疾病急性发作期预后的价值研究

目的 探究微小核糖核酸-146a (microRNA-146a)联合肺部超声评分对慢性阻塞性肺疾病急性发作期（AECOPD）病情严重程度及预后的价值。方法 选择2018年8月至2021年7月在南京市胸科院区收治的86例AECOPD患者,其中男性56例,女性30例;年龄49～86岁,平均年龄71.82岁;体质量指数（BMI）19.03～28.46 kg/m2,平均BMI22.20 kg/m2;合并高血压30例,合并冠心病21例,合并其他肺部疾病15例;有吸烟史42例,有饮酒史35例;病情严重程度Ⅱ级13例,Ⅲ级38例,Ⅳ级17例;机械通气49例,呼吸衰竭53例。采用逆转录-聚合酶链式反应（RT-PCR）检测所有患者血清microRNA-146a水平。对比不同严重程度AECOPD患者血清microRNA-146a及肺部超声评分。入院后随访28 d,统计AECOPD患者生存情况,并依据其预后情况分为死亡组和存活组。对比死亡组和存活组患者的临床资料。Logistic回归分析影响AECOPD患者预后的相关因素。制作受试者工作特性（ROC）曲线,以曲线下面积（AUC）分析血清microRNA-14...     

Histamine synthesis is required for granule maturation in murine mast cells

Mast cells are the major sources of histamine, which is released in response to immunological stimulations. The synthesis of histamine is catalyzed by histidine decarboxylase (HDC). Previous studies have shown that Hdc^?/? mast cells exhibit aberrant granule morphology with severely decreased granule content. Here, we investigated whether the histamine synthesized in mast cells regulates the granule maturation of murine mast cells. Several genes, including those encoding granule proteases and enzymes involved in heparin biosynthesis, were downregulated in Hdc^?/? peritoneal mast cells. Impaired granule maturation was also found in Hdc^?/? BM‐derived cultured mast cells when they were cocultured with fibroblasts in the presence of c‐kit ligand. Exogenous application of histamine and several H₄ receptor agonists restored the granule maturation of Hdc^?/? cultured mast cells. However, the maturation of granules was largely normal in Hrh4^?/? peritoneal mast cells. Depletion of cellular histamine with tetrabenazine, an inhibitor of vesicular monoamine transporter‐2, did not affect granule maturation. In vivo experiments with mast cell deficient Kit^W/Kit^W‐v mice indicated that the expression of the Hdc gene in mast cells is required for granule maturation. These results suggest that histamine promotes granule maturation in mast cells and acts as an proinflammatory mediator.     

Histamine modulates mast cell degranulation through an indirect mechanism in a model IgE-mediated reaction

Histamine is released in inflammatory reactions and exerts an immunoregulatory function on cells present in the microenvironment. In this study, we compared the effect of histamine on degranulation of mast cells derived from animals bearing a parasitic infection with those from uninfected animals. Peritoneal mast cells (PMC) were obtained 24 days after infection of Wistar rats with Toxocara canis. The degree of degranulation was assessed either morphologically or by measuring the release of beta-hexosaminidase and TNF-alpha. Non-purified PMC or mast cells immunomagnetically purified with mAb AA4 were used. An increase in degranulation of non-purified mast cells from infected animals was observed after incubation with histamine in vitro or when histamine was injected into the peritoneal cavity. When a purified mast cell population was used, this effect was no longer observed. Supernatants from spleen cells stimulated with histamine induced degranulation of purified mast cells, and again, this was potentiated with PMC from infected animals. However, when supernatants from peritoneal macrophages similarly stimulated were used, a reduction in the degranulation of PMC from infected animals was observed. Our results suggest that histamine may act as a regulator of mast cell degranulation, thus modulating inflammatory responses due to infection with certain parasites.     

血管活性肠多肽及降钙素基因相关肽对大鼠腹腔肥大细胞组胺释放的作用

目的:研究血管活性肠多肽(Vasoactive intestinal peptide,VIP)及降钙素基因相关肽(Calcitonin gene relatedpeptide,CGRP)对大鼠腹腔肥大细胞脱颗粒的诱导作用;了解神经多肽与肥大细胞的相互关系。方法:分离、纯化SD大鼠腹腔肥大细胞;应用不同浓度的VIP和CGRP作用于大鼠腹腔肥大细胞后,同位素放射液态闪烁法检测肥大细胞的组胺释放、45Ca摄入的变化;同时观察大鼠腹腔肥大细胞经5×10-6mol/L VIP受体抑制剂L-8-K处理后,对VIP诱导脱颗粒作用的影响。结果:5×10-6mol/L的VIP作用后大鼠腹腔肥大细胞组胺释放及45Ca摄入明显增加,并且这种变化与VIP呈剂量效应关系;CGRP对大鼠腹腔肥大细胞组胺释放无诱导作用;L-8-K作用后,肥大细胞对VIP的诱导活化作用无改变。结论:VIP可引起肥大细胞钙内流增加,进一步诱导肥大细胞脱颗粒、释放组胺等生物活性物质,产生生物学效应;这种作用是受体非依赖性的,且与VIP的分子构型有关。     

Functional heterogeneity of mast cells from different species and tissues

Summary The systemic responses of different animals to a number of histamine liberators and the effects of these compounds on isolated tissue mast cells in vitro are examined. Mast cells from different species and even from individual tissues within a single animal are shown to vary markedly in their response to given inducers. On this basis, the usefulness of animal models in predicting whether a particular compound may act as a histamine liberator in man is discussed.     

Granule maturation in mast cells: Histamine in control

Mast cells are derived from committed progenitors that originate in the BM. They mature into histochemically distinguishable, metachromatic mast cells containing numerous cytoplasmic secretory granules. Accumulating evidence demonstrates that mast cell granule maturation is very tightly regulated by many factors including different granule components such as proteoglycans. In this issue of the European Journal of Immunology, Nakazawa et al. [Eur. J. Immunol. 2014. 44 : 204–214] highlight a role for mast cell derived histamine as another factor critical for mast cell maturation. Using histidine decarboxylase (HDC) deficient mice that are unable to make histamine, they show poorly formed secretory granules and decreased secretory granule protease expression in peritoneal mast cells. Co‐culturing BM‐derived mast cells with fibroblasts normally drives granule maturation, but HDC‐deficient BM‐derived mast cells fail to do so. Exogenously provided histamine partly restores granule differentiation as evidenced by increased tryptase and chymase activity, and this is histamine receptor type H₄‐dependent. However, H₄‐deficient mice have intact granule formation in peritoneal mast cells, suggesting that when HDC is functional, the intrinsic histamine production is sufficient for most granule maturation processes and H₄ is dispensable. This study highlights the role of histamine in the regulation of mast cell maturation, although the cytosolic target remains unknown.     

The Ultrastructural Spectrum of Lysosomal Storage Diseases

After the important advances that have been made in the diagnosis of inherited lysosomal disorders with the help of biochemical-enzymic methods, the importance of electron microscopy for the identification and study of these conditions has apparently declined. Nevertheless, numerous specimens continue to be submitted for ultrastructural examination when lysosomal storage diseases are suspected. The article summarizes the present role of electron microscopy in this area and depicts typical specific findings in comparison with suggestive and nonspecific lysosomal changes. It is concluded that ultrastructural examination remains a useful and occasionally compulsory diagnostic method. In addition, it contributes to the identification of new diseases, the study of animal models of storage diseases, and the assessment of novel therapeutic methods such as bone marrow transplantation.     

Histamine as an autocrine growth factor in experimental mammary carcinomas

The antisecretory effect of DS-4574, a mast cell stabilizer with peptidoleukotriene antagonism, on the hypersecretion of gastric acid stimulated by several secretagogues was examined in the pig. Goettingen miniature pigs with chronic gastric fistula were used. Intramuscular injection of carbachol (60 g/kg), tetragastrin (50 g/kg) or histamine (200 g/kg)-induced gastric acid hypersecretion. Intraduodenal administration of DS-4574 (10 and 20 mg/kg) significantly inhibited both the hypersecretion induced by carbachol and that by tetragastrin. On the other hand, DS-4574 (50 mg/kg, intraduodenal) did not suppress histamine-induced hypersecretion. In thein vitro study, no effect on hog gastric K⁺-dependent ATPase activity was found at concentrations of DS-4574 from 10^–7 to 10^–4 M. These results were highly similar to those in the rat. The suppression of histamine release from histamine-containing cells in the gastric mucosa of the rat was concluded to be an antisecretory effect of DS-4574.     

人肥大细胞的IgE依赖性组胺和类胰蛋白酶分泌

目的　利用人结肠组织的肥大细胞和肥大细胞激活的体外研究系统评价人肥大细胞释放类胰蛋白酶和组胺的能力及其机制。方法　经酶悬浮的人结肠肥大细胞与抗IgE抗体共同培养后记录浓度相关曲线和时间关系曲线。类胰蛋白酶用酶联免疫吸附试验的方法测量 ,而组胺则由一种以玻璃纤维为基础的荧光比色法测量。结果　抗IgE抗体可引起浓度相关性的组胺和类胰蛋白酶释放 ,最大组胺和类胰蛋白酶分泌量分别比基础分泌量超出 2 .7和 2 .5倍以上。抗IgE抗体的作用从加样后 10s开始 ,6min后达高峰并至少持续 15min。百日咳毒素和代谢抑制剂能够分别抑制抗IgE抗体引起的组胺和类胰蛋白酶释放。百日咳毒素还能够减少自发性类胰蛋白酶释放。结论　人结肠肥大细胞在受到抗IgE抗体刺激时具有平行释放类胰蛋白酶和组胺的能力 ,这个过程与肥大细胞膜G蛋白偶联受体的激活有关 ,并消耗能量。肥大细胞自发性释放组胺和类胰蛋白酶的功能可能是通过不同的机制实现的。     

天花粉蛋白对肥大细胞脱颗粒和组胺释放的影响及其与补体激活的关系

我们首先用Alcian蓝染色的肥大细胞脱颗粒试验和用荧光测定组胺的方法观察了天花粉蛋白对肥大细胞脱颗粒和组胺释放的影响。实验结果表明:(1)在体外试验中,不论有无血清的存在,天花粉蛋白都不引起肥大细胞的脱粒和组胺释放。(2)天花粉蛋白的体内用药,能引起Balb/c小鼠炎症局部的肥大细胞脱颗粒(Alcian着色的未脱颗粒肥大细胞由对照组的3.4±0.12×10~4/ml减少至1.7±0.28×10~4/l;P<0.01)和组胺水平的明显增高(皮下气囊内的组胺水平由36.39±0.94ng/ml升至41.07±0.78ng/ml;P<0.01)。(3)腹膜腔内注射天花粉蛋白后,Wistatr大鼠腹膜腔内蛋白明显渗出,同时全血组胺水平也明显增高(对照组:0.947±0.076ng/ml,实验组:1.574±0.105ng/ml;p<0.01)。(4)上述天花粉蛋白诱导的腹腔渗出液具有明显的肥大细胞脱颗粒作用(脱粒指数:对照组为1.6±3.8%,实验组为24.9±2.1%;P<0.01)。(5)用眼镜蛇毒素完全耗竭小鼠的补体对天花粉蛋白引起的肥大细胞脱粒因子的产生无明显影响。从这些结果可见:天花粉蛋白的体内应用能通过激活某些可溶性成分的产生而引起肥大细胞的脱颗粒和组胺释放。但是,这一过程与天花粉蛋白激活补体的作用似无明显关系。