消咳平喘汤联合特布他林和孟鲁司特钠治疗儿童咳嗽变异性哮喘的临床研究

目的研究消咳平喘汤联合硫酸特布他林片和孟鲁司特钠咀嚼片治疗儿童咳嗽变异性哮喘的临床疗效。方法选取2016年1月—2018年1月于成都市新都区中医医院接受治疗的咳嗽变异性哮喘儿童98例为研究对象,按照随机数表法分为对照组和治疗组,每组各49例。对照组口服硫酸特布他林片,0.065 mg/kg,3次/d,用量不超过1.25 mg/次。同时口服孟鲁司特钠咀嚼片,1片/次,1次/d,5岁及以下患者4mg/次,6岁及以上患者5mg/次。治疗组在对照组基础上加用消咳平喘汤,每日水煎1剂,共100 mL,分早、中、晚3次服用。14 d为1个疗程,两组患者共治疗2个疗程。观察两组患者的临床疗效,比较治疗前后两组患者的咳嗽症状缓解情况、血清免疫球蛋白E(IgE)和嗜酸性粒细胞(EOS)水平、肺功能指标。结果治疗后,对照组总有效率为83.7%,治疗组总有效率为93.9%,两组总有效率比较差异具有统计学意义(P0.05)。治疗后,治疗组咳嗽缓解时间、咳嗽消失时间明显短于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清IgE和EOS水平较治疗前均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组血清IgE和EOS水平明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者FEV1、FEF25%、FEF50%、FEF75%均显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组肺功能指标水平明显高于对照组,两组比较差异具有统计学意义(P0.05)。结论消咳平喘汤联合硫酸特布他林片和孟鲁司特钠咀嚼片治疗儿童咳嗽变异性哮喘具有较好的临床疗效,能够改善患者临床症状和肺功能,降低血清IgE和EOS水平,具有一定的临床推广应用价值。     

射干煎剂对支气管哮喘患者肺功能、EOS与ECP的影响

目的:研究射干煎剂对支气管哮喘患者肺功能、外周血嗜酸性粒细胞(EOS)计数与嗜酸性粒细胞阳离子蛋白(ECP)水平的影响。方法:48例支气管哮喘患者随机分为治疗组24例,对照组24例。对照组采用常规治疗方法,治疗组在常规治疗基础上加用射干煎剂每次30mL,每天3次。疗程均为4周。观察2组治疗后的临床疗效、肺功能指标、治疗前后外周血EOS计数、ECP水平。结果:治疗组总有效率(95.8%)高于对照组(83.3%);治疗组第1秒用力呼气流速(FEV1)下降率和呼气峰流速(PEF)下降率均显著高于对照组(P<0.05)。2组治疗后外周血EOS计数、ECP水平较治疗前均显著降低(P<0.05),且治疗组外周血ECP水平显著低于对照组(P<0.05)。结论:射干煎剂能明显改善支气管哮喘患者肺功能,降低外周血EOS计数与ECP水平。     

玉屏风滴丸联合丙酸氟替卡松治疗支气管哮喘的临床研究

目的研究玉屏风滴丸联合丙酸氟替卡松吸入气雾剂治疗支气管哮喘的临床疗效。方法选取2016年4月—2018年4月中国人民解放军联勤保障部队第九八八医院收治的240例支气管哮喘患者为研究对象,将所有患者随机分为对照组和治疗组,每组各120例。对照组患者吸入丙酸氟替卡松吸入气雾剂,2揿/次,2次/d;治疗组患者在对照组治疗的基础上口服玉屏风滴丸,1袋/次,3次/d。两组患者持续治疗14 d。观察两组的临床疗效,比较两组的临床症状缓解时间、肺功能指标、血清细胞因子水平。结果治疗后,对照组和治疗组的总有效率分别为78.33%、95.00%,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组咳嗽消失时间、肺部啰音消失时间、发热消退时间均短于对照组患者,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者一秒用力呼气容积(FEV1)、呼气高峰流量(PEFR)和FEV1/用力肺活量(FVC)均显著升高,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组FEV1、PEFR和FEV1/FVC显著高于对照组,两组比较差异有统计学意义(P0.05)。治疗后,两组患者肿瘤坏死因子-α(TNF-α)、超敏C反应蛋白(hs-CRP)和白细胞介素-6(IL-6)平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);并且治疗组TNF-α、hs-CRP和IL-6水平显著低于对照组(P0.05)。结论玉屏风滴丸联合丙酸氟替卡松吸入气雾剂治疗支气管哮喘具有较好的临床疗效,能够缓解患者临床症状,改善肺功能指标,降低血清炎性因子水平,安全性较高,具有一定的临床推广应用价值。     

丙酸氟替卡松联合布地奈德治疗小儿支气管哮喘的临床研究

目的探讨丙酸氟替卡松吸入气雾剂联合吸入用布地奈德混悬液治疗小儿支气管哮喘的临床疗效。方法选取2015年1月—2016年1月在第四军医大学第一附属医院治疗的支气管哮喘患儿96例作为研究对象,利用随机数字表法将患儿分为对照组和治疗组,每组各48例。对照组雾化吸入吸入用布地奈德混悬液,0.5 mg/次,2次/d。治疗组在对照组基础上吸入丙酸氟替卡松吸入气雾剂,2揿/次,2次/d。两组患儿均连续治疗12周。观察两组的临床疗效,比较两组肺功能、血气指标和炎性因子情况。结果治疗后,对照组和治疗组总有效率分别为83.3%、95.8%,两组比较差异有统计学意义(P0.05)。治疗后,两组呼气峰流速值(PEF)、1 s用力呼气容积(FEV1)、呼气高峰流量(PEFR)和FEV_1/用力肺活量(FVC)均明显上升,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标明显高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血氧分压(Pa O_2)和酸碱度(p H)值均显著上升,二氧化碳分压(Pa CO2)均显著下降,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标的改善程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组肿瘤坏死因子α(TNF-α)、超敏C反应蛋白(hs-CRP)、白细胞介素4(IL-4)、白细胞介素8(IL-8)和白细胞介素13(IL-13)水平均明显下降,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论丙酸氟替卡松吸入气雾剂联合吸入用布地奈德混悬液治疗小儿支气管哮喘具有较好的疗效,可改善肺功能,缓解炎症反应,具有一定临床推广应用价值。     

咳露口服液联合酮替芬治疗咳嗽变异性哮喘的疗效观察

目的探讨咳露口服液联合酮替芬治疗咳嗽变异性哮喘的临床疗效和安全性。方法选取2016年11月—2017年11月于洛阳市中心医院就诊的咳嗽变异性哮喘患者120例,随机分成对照组和治疗组,每组各60例。对照组口服富马酸酮替芬片,1片/次,2次/d;治疗组患者在对照组的基础上口服咳露口服液,15 mL/次,3次/d。两组患者均连续治疗2个月。观察两组患者临床疗效,同时比较治疗前后两组患者哮喘控制测试(ACT)评分、日常生活活动(ADL)评分、咳嗽症状积分、嗜酸性粒细胞(EOS)绝对值、肺功能和不良反应。结果治疗后,对照组和治疗组临床有效率分别为81.67%和95.00%,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者ACT和ADL评分显著升高(P0.05),咳嗽症状积分显著降低(P0.05),且治疗组患者ACT、ADL及咳嗽症状积分水平明显好于对照组(P0.05)。治疗后,两组EOS绝对值显著降低(P0.05),肺功能指标用力肺活量(FVC)和第1秒钟用力呼吸容积(FEV1)显著升高(P0.05),且治疗组患者EOS绝对值及肺功能较对照组患者改善更明显(P0.05)。治疗期间,治疗组患者不良反应发生率为3.33%,显著低于对照组的15.00%,两组比较差异具有统计学意义(P0.05)。结论咳露口服液联合酮替芬治疗咳嗽变异性哮喘疗效显著,安全性好,具有一定的临床推广应用价值。     

布地奈德联合异丙托溴铵治疗慢性阻塞性肺疾病的临床研究

目的探讨布地奈德气雾剂联合异丙托溴铵吸入溶液治疗慢性阻塞性肺疾病的临床疗效。方法选取2018年1月—2019年1月襄阳市中心医院收治的80例慢性阻塞性肺疾病患者为研究对象,根据随机数表法分为对照组和治疗组,每组各40例。对照组患者雾化吸入异丙托溴铵吸入溶液,40μg/次,3次/d;治疗组患者在对照组治疗10 min后雾化经口吸入布地奈德气雾剂,2 mg/次,2次/d。两组连续治疗14 d。观察两组的临床疗效,比较两组的临床症状缓解时间、血清炎症因子水平、肺功能指标、氧化应激指标。结果治疗后,对照组和治疗组的总有效率分别为75.00%、92.50%,两组比较差异有统计学意义(P0.05)。治疗后,治疗组咳嗽缓解时间、喘息缓解时间、退热时间、咳脓痰缓解时间、肺啰音消失时间均短于对照组,差异有统计学意义(P0.05)。治疗后,两组患者血清白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)水平均显著降低,同组治疗前后比较差异有统计学意义(P0.05);且治疗组患者血清炎症因子水平明显高于对照组,差异有统计学意义(P0.05)。治疗后,两组患者第一秒用力呼气容积(FEV1)、用力肺活量(FVC)、FEV1/FVC均显著升高,同组治疗前后比较差异有统计学意义(P0.05)且治疗组患者肺功能指标明显高于对照组,差异有统计学意义(P0.05)。治疗后,两组患者血清丙二醛(MDA)、活性氧(ROS)水平均显著降低,超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPX)水平均显著升高,同组治疗前后比较差异有统计学意义(P0.05);且治疗组氧化应激指标水平明显高于对照组,差异有统计学意义(P0.05)。结论布地奈德气雾剂联合异丙托溴铵吸入溶液治疗慢性阻塞性肺疾病具有较好的临床疗效,能改善肺功能,降低炎性因子水平,抑制氧化应激反应,安全性较好,具有一定的临床推广使用价值。     

槐杞黄颗粒联合布地奈德治疗儿童咳嗽变异性哮喘的临床研究

目的探讨槐杞黄颗粒联合布地奈德气雾剂治疗儿童咳嗽变异性哮喘的临床疗效。方法选取2016年1月—2017年1月吉林大学第一医院儿科收治的咳嗽变异性哮喘患儿106例进行回顾性分析,根据治疗方法的不同将患儿分为对照组和治疗组,每组各53例。对照组吸入布地奈德气雾剂,2岁:100μg/次,≥2岁:200μg/次,2次/d。治疗组在对照组基础上口服槐杞黄颗粒,2~3岁:5 g/次,3~12岁:10 g/次,2次/d。两组患儿均连续治疗3个月。观察两组的临床疗效,比较两组的肺功能指标、免疫功能指标、血清免疫球蛋白E(Ig E)和细胞因子水平。结果治疗后,对照组和治疗组的总有效率分别为83.0%、90.6%,两组比较差异具有统计学意义(P0.05)。治疗后,两组肺活量(FVC)、第一秒呼出气体容积(FEV1)、FEV1/FVC均显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组这些肺功能指标明显高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组CD~(4+)、CD~(4+)/CD~(8+)水平均显著下降,CD~(8+)水平显著升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组这些观察指标的改善程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组γ-干扰素(IFN-γ)水平显著升高,Ig E、白细胞介素-4(IL-4)水平均显著下降,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组这些观察指标的改善程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。结论槐杞黄颗粒联合布地奈德气雾剂治疗儿童咳嗽变异性哮喘具有较好的临床疗效,可改善患儿肺功能,调节免疫功能,降低复发率,具有一定的临床推广应用价值。     

利肺片联合异丙托溴铵治疗支气管哮喘慢性持续期的临床研究

目的探讨利肺片联合异丙托溴铵气雾剂治疗支气管哮喘慢性持续期的临床疗效。方法选择2015年1月—2017年12月武汉市红十字会医院收治的支气管哮喘患者105例为研究对象,按随机数字表法随机分为对照组(52例)和治疗组(53例)。对照组雾化吸入异丙托溴铵气雾剂,2掀/次,2次/d。治疗组在对照组治疗的基础上饭后30 min口服利肺片,2片/次,3次/d。两组均连续治疗14 d。观察两组的临床疗效,比较两组的肺功能指标和血清因子水平。结果治疗后,对照组和治疗组的总有效率分别为84.62%、96.23%,两组比较差异有统计学意义(P0.05)。治疗后,两组用力肺活量(FVC)、1秒用力呼气容积(FEV1)和最大呼气流速(PEF)均显著升高,同组治疗前后比较差异有统计学意义(P0.05);且治疗组肺功能指标明显高于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清白细胞介素17(IL-17)、白三烯B4(LTB4)、中性粒细胞(PMN)均显著下降,同组治疗前后比较差异有统计学意义(P0.05);且治疗组血清因子水平明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论利肺片联合异丙托溴铵气雾剂治疗支气管哮喘慢性持续期具有较好的临床疗效,能改善肺功能,调节IL-17、LTB4水平,降低PMN计数,安全性较好,具有一定的临床推广应用价值。     

多索茶碱片联合布地奈德治疗支气管哮喘的临床研究

目的探讨多索茶碱片联合吸入用布地奈德混悬液治疗支气管哮喘的临床疗效。方法选取2014年1月—2015年7月延安市人民医院收治的支气管哮喘患者96例,按随机数字表法分为对照组和治疗组,每组各48例。对照组给予吸入用布地奈德混悬液200μg,1次/d。治疗组在对照组的基础上口服多索茶碱片0.2 g,2次/d。两组均连续治疗3个月。观察两组临床疗效,比较两组患者临床症状消失时间、嗜酸粒细胞比例、呼出气一氧化氮(FeNO)、细胞因子水平、肺功能和ACT评分。结果治疗后,对照组、治疗组的总有效率分别为77.1%、91.7%。两组总有效率比较差异具有统计学意义(P0.05)。治疗后,治疗组哮鸣音消失时间、气喘消失时间、咳嗽消失时间均明显短于对照组,两组间比较差异具有统计学意义(P0.05)。治疗1、3个月后,两组患者嗜酸粒细胞比例、FeNO均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组这些观察指标的降低幅度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗1、3个月后,两组患者IL-4水平显著降低,IFN-γ水平明显升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组这些观察指标的改善幅度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗1、3个月后,两组FVC、FEV1、FEV1%、PEF明显升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组这些观察指标的升高幅度均明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗1、3个月后,两组ACT评分明显升高,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组这些观察指标的升高幅度均明显优于对照组,两组比较差异具有统计学意义(P0.05)。结论多索茶碱片联合吸入用布地奈德混悬液可有效治疗支气管哮喘,降低患者嗜酸性粒细胞比例、FeNO、细胞因子,改善哮喘症状和肺功能,升高ACT评分,值得临床推广和应用。     

孟鲁司特对咳嗽变异性哮喘患儿支气管肺泡灌洗液中的嗜酸性粒细胞计数的调节作用

目的 探讨孟鲁司特对咳嗽变异性哮喘患儿支气管肺泡灌洗液(BALF)中的嗜酸性粒细胞(EOS)计数的调节作用。方法 选择我院门诊及住院的咳嗽变异性哮喘患儿81例,分成随机分为对照组(n=37)和治疗组(n=44)。对照组给予常规治疗,治疗组在对照组基础上加口服孟鲁司特钠咀嚼片5mg,每日1次,治疗12周。比较2组治疗前后肺功能与BALF-EOS比例变化,观察两组有无统计学差异。 结果 治疗前对照组和治疗组 EOS比例分别为：(4.65±0.76)%和(4.51±0.67)%,两组比较差异无显著性( P>0.05);治疗后对照组和治疗组 EOS比例分别为：(3.04±0.58)%和(1.93±0.51)%,两组比较差异有显著性( P<0.01)。 结论 孟鲁司特钠可以明显降低儿童咳嗽变异性哮喘中BALF-EOS水平。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.