【摘要翻译】 胸腺基质淋巴生成素( TSLP) 触发树突状细胞介导的Th2 型炎症反应。一个位于TSLP 基因启动子区域的rs3806933 位点的单核苷酸多态性能产生转录因子激活蛋白( AP) -1 的结合位点。这种变异增强了AP-1 结合到调控元件的能力, 并增强聚肌苷酸胞苷酸刺激人类正常支气管上皮细胞时TSLP 启动子-报告子反应活性。我们研究了这种包括rs3806933 位点的多态性是否影响支气管哮喘的易感性和临床表型。我们选择了三个具有代表性的单核苷酸多态位点进行TSLP 基因相关性研究, 对象为两个独立的人群( 其中一个为693 例儿童特应性哮喘患者和838 例对照者, 另一个为641 例成年哮喘患者和376 名对照者) 。我们进一步检测了糖皮质激素和长效β2 受体激动剂( 沙美特罗) 对聚肌苷酸胞苷酸刺激的人类正常支气管上皮细胞TSLP 基因表达的影响。我们发现启动子多态性位点rs3806933、rs2289276 与儿童特应性哮喘和成人哮喘的易感性均显著相关。功能单核苷酸多态性位点rs3806933 与哮喘相关( Meta 分析, P = 0. 000056; 比值比, 1. 29; 95% 可信区间, 1. 14 ～1. 47) 。Rs2289278 的基因型和肺功能相关。并且, 糖皮质激素和沙美特罗可协同性地抑制聚肌苷酸胞苷酸刺激导致人类正常支气管上皮细胞TSLP mRNA 及蛋白的上调表达。TSLP 多态性变异与支气管哮喘和肺功能显著相关。因此, TSLP可能作为联合治疗的分子靶点。【述评】 越来越多的研究表明哮喘是一种环境和遗传因素相互作用的疾病。本研究不但发现TSLP 启动子多态rs3806933、rs2289276 与儿童特应性哮喘和成人哮喘的易感性均显著相关, 并研究了其导致哮喘炎症反应可能与该多态性位点产生激活蛋白( AP) -1 的转录因子的结合位点。这种变异增强了AP-1 结合到调控元件从而导致基因表达异常。同时, 作者还发现临床常用的哮喘治疗药物ICS 与LABA 的联合制剂可调节TSLP 表达。这些数据表明TSLP在哮喘发病中起重要作用, 并进一步阐明ICS 与LABA 联合治疗的分子机制。该研究不但从分子遗传和分子生物学的角度阐明TSLP多态性在哮喘发病中的分子机制, 并从分子药理层面进一步证实目前常用哮喘治疗方案的合理性, 研究较为深入。
ObjectiveTo investigate the fatigue of asthma patients, and to analyze its influencing factors, and provide a reference for clinical intervention.MethodsThe convenience sampling method was adopted to select asthma patients who were in clinic of the First Affiliated Hospital of Guangxi Medical University from November 2018 to March 2019. The patients’ lung function were measured. And questionnaires were conducted, including general data questionnaire, Chinese version of Checklist Individual Strength-Fatigue, Asthma Control Test, Chinese version of Self-rating Depression Scale. Relevant data were collected for multiple stepwise linear regression analysis.ResultsFinally, 120 patients were enrolled. The results of multiple stepwise linear regression analysis showed that age, education level, place of residence, time period of frequent asthma symptoms, degree of small airway obstruction, Asthma Control Test score and degree of depression were the influencing factors of fatigue in asthma patients (P≤0.05). Multivariate linear stepwise regression analysis showed that degree of small airway obstruction, degree of depression and time period of frequent asthma symptoms were the main influencing factors of fatigue in asthma patients, which could explain 51.8% of the variance of fatigue (ΔR2=0.518).ConclusionsThe incidence of fatigue in asthma patients is at a relatively high level. Medical staff should pay attention to the symptoms of fatigue in asthma patients. For asthma patients, it is recommended to strengthen standardized diagnosis and treatment, reduce the onset of symptoms at night and eliminate small airway obstruction. Psychological intervention methods are needed to improve patients’ depression, reduce fatigue symptoms, and improve quality of life.
ObjectiveTo investigate the efficacy of Orem's self-care model in school-age children with asthma. MethodsSeventy-four children with asthma treated between March 2012 and June 2014 were divided into observation group (n=37) and control group (n=37) randomly. Orem's self-care model was applied in the observation group, while routine nursing was carried out in the control group. We observed the pulmonary function, therapeutic compliance and quality of life in children of both the two groups before and one year after treatment. ResultsOne year after treatment, forced expiratory volume in one second and peak expiratory flow increased significantly (P<0.05), and increase in the observation group was significantly more than that in the control group (P<0.05). Compared with the control group, the observation group showed significant increased treatment compliance rate (P<0.05). Pediatric asthma quality of life questionare scale results showed that one year after treatment, the two groups got significantly increased scores in the dimensions of emotion, symptom and activity (P<0.05), and the scores were significantly higher in the observation group (P<0.05). ConclusionOrem's self-care model has a significant curative effect for the improvement of lung function in school-age children with asthma, which can promot the treatment compliance and quality of life of the patients.
目的:探讨妊娠合并哮喘的临床表现及治疗方法。方法:对32 例妊娠合并支气管哮喘患者的临床资料进行回顾性分析。结果:经过适当的治疗,32例支气管哮喘合并妊娠患者症状缓解,随访至产后1 个月,婴儿和母亲均正常。结论:支气管哮喘合并妊娠时,妊娠早期可选用对胎儿无影响的药物如头孢菌素类抗生素、β2 受体激动剂、糖皮质激素(吸入布地奈德,强的松口服,短期甲强龙静滴),妊娠中晚期还可选用茶碱类药物及全身使用糖皮质激素等药物。
ObjectiveTo systematically review the association between ADAM33 (a disintegrin and metalloproteinase domain33) T2 (rs2280090), S2 (rs528557), and V4 (rs2787094) polymorphisms and asthma in Chinese Han population. MethodsWe electronically searched databases including PubMed, Web of Science, CNKI, WanFang Data and VIP from inception to December 2014, to collect case-control studies about the association between ADAM33 polymorphisms and asthma in Chinese Han population. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using Stata 12.1 software. ResultsA total of 8 case-control studies including 1651 asthma patients and 1639 controls were included. The results of meta-analysis showed that: ADAM33 T2 polymorphism was associated with decreased risk of asthma (AA+AG vs. GG: OR=0.316, 95%CI 0.151 to 0.659, P=0.002), and the S2 polymorphism was associated with increased risk of asthma (GG+GC vs. CC: OR=1.271, 95%CI 1.023 to 1.578, P=0.030). However, no significant association was found between asthma risk and V4 polymorphism (GG+GC vs. CC: OR=1.561, 95%CI 0.638 to 3.823, P=0.330). Subgroup analysis by age indicated that the T2 polymorphism was associated with decreased risk of asthma in both adults and children, the S2 polymorphism was only associated with increased risk of asthma in adults, however, no significant association was found between asthma and the ADAM33 V4 polymorphism in both adults and children subgroups. ConclusionCurrent evidence shows that the ADAM33 T2 and S2 polymorphisms are associated with risk of asthma in Chinese Han population. Due to the limited quantity and quality of the studies, the above conclusion still need to be verified by further more high-quality studies.
ObjectiveTo evaluate the prevalence of obstructive sleep apnea hypopnea syndrome (OSAHS) in patients with asthma, and explore the association of OSAHS with asthma. MethodsPatients who were diagnosed as asthma between March 2014 and February 2015 were recruited in the study. They were categorized into an OSAHS group and a non-OSAHS group according to the Berlin questionnaire. The data of clinical characteristics and pulmonary function test were collected. Logistic regression analysis was performed to evaluate the factors associated with the incidence of OSAHS in asthma. ResultsA total of 64 patients with asthma were enrolled and 36 patients were complicated with OSAHS. The body mass index (BMI), allergic rhinitis history, inspiratory capacity, maximal mid-expiratory flow and provoking dose which make FEV1 reduce 20% were significantly different between two groups (all P < 0.05). Multivariate logistic regression analysis revealed that the increased BMI was an independent risk factor of OSAHS in patients with asthma. ConclusionThe occurrence of OSAHS with asthma is very high, and BMI may be an important associated risk factor.
Objective To investigate the effects of a mixed bacterial lysate (OM-85 BV) on lung function and serum IgE in asthmatic mice under acute attack, and to explore the therapeutic effect of OM-85 BV on acute attack and the application value of OM-85 BV in non-acute attack. Methods A total of 30 SPF Kunming mice aged 4 to 6 weeks were randomly divided into 3 groups, namely a blank control group (Group A), an asthma model group (Group B), and an OM-85 BV intervention group (Group C). The mice in groups B and C were sensitized by intraperitoneal injection of ovalbumin on day 1, 8 and 15, respectively. From day 22, the asthma model was stimulated by inhalation of 5% ovalbumin every day for 30 min for 5 consecutive days. The mice in group C were treated with OM-85 BV dissolved in normal saline from day 1, and each mouse was gavaged continuously for 10 days. The intraperitoneal injection, intragastric administration and aerosol inhalation reagent of mice in group A were all replaced by normal saline, while the intragastric administration of mice in group B was replaced by normal saline. One hour after the last stimulation, the mice were anesthetized, their lung function was measured, blood was collected from the eyeballs and then they were sacrificed, and the blood was centrifuged and the serum was separated and stored. Hematoxylin and eosin staining was used for pathological examination. Serum IgE was determined by enzyme-linked immunosorbent assay. Results Compared with group A, forced vital capacity in 0.15 second (FEV0.15), FEV0.15/forced vital capacity (FVC) and peak expiratory flow (PEF) of mice in group B were significantly decreased. The lung function of group C was improved compared with group B. In group B, the pathological manifestations were dysplasia and collapse of bronchial epithelium, infiltration of inflammatory cells, mainly lymphocytes and eosinophils, a small amount of mucus and shed epithelial cells in the tracheal lumen, and significant thickening of airway wall. The asthma mouse model was well established. The pathological manifestations of airway in group C were less severe than those in group B, the thickness of airway wall was reduced, and the inflammatory cells were also significantly reduced. The serum IgE concentration in groups B and C increased, and the IgE level in group C decreased significantly compared with group B. The differences were statistically significant (all P<0.05). Conclusions Exogenous administration of OM-85 BV in asthmatic mice can effectively reduce the concentration of serum IgE, alleviate airway inflammation, reduce eosinophil infiltration, and improve the pulmonary function performance of asthmatic mice during acute attack, showing that FEV0.15/FVC, FEV0.15 and PEF indicators are significantly improved. OM-85 BV can alleviate the symptoms of bronchial asthma in the acute attack of mice, improve the physiological function of the lung during the acute attack, inhibit airway inflammation, and have certain application value in the stable asthma control.
Objective To observe the effect of NLRP3 inflammasome inhibitor MCC950 intervention on airway Muc5ac level in asthmatic mice, and to explore the role and mechanism of NLRP3 inflammasome in asthmatic airway mucus hypersecretion. Methods A total of 50 SPF grade BALB/c female mice aged 6 - 8 weeks were randomly divided into normal control group (NS group), asthma model group (AS group), dexamethasone group (Dex group), MCC950 high-dose intervention group (MH group) and MCC950 low-dose intervention group (ML group), with 10 mice in each group. Furthermore, the bronchoalveolar lavage fluid (BALF) of mice in each group was counted by total cell count, associated with white blood cell different count. In addition, the concentrations of interleukin (IL)-18 and IL-1β in BALF were tested by enzyme-linked immunosorbent assay; The lung tissues were prepared into paraffin-embedded sections, which were then subject to hematoxylin-eosin (HE) staining, Alcian blue-periodic acid Schiff base staining and Masson staining to observe the pathological changes of lung tissues. Immunohistochemistry was used to detect the protein expression levels of Muc5ac, NLRP3 and caspase-1 in lung tissues. Real-time quantitative polymerase chain reaction was performed to detect the relative mRNA expressions of Muc5ac, NLRP3 and Caspase-1 in lung tissues. Results Compared with NS group, AS group showed significant increase in total cell count of BALF, the percentage of eosinophils, the infiltration score of inflammatory cells around the airway, the positive relative staining area of airway mucus and the deposition area of airway collagen fibers in mice (P<0.05), upregulated protein expression levels of Muc5ac, NLRP3 and Caspase-1 in lung tissues (P<0.05), elevated relative mRNA expressions of Muc5ac, NLRP3 and Caspase-1 in lung tissues (P<0.05), and raised concentrations of IL-18 and IL-1β in BALF (P<0.05). While compared with AS group, the above indicators were reduced in MH group and ML group (P<0.05). Moreover, in relative to Dex group, these indicators were increased in MH group ML group (P<0.05). In addition, no statistically significant difference was observed in the aforementioned indications between MH group and ML group.Conclusions MCC950 intervention can inhibit airway inflammation and airway mucus secretion in asthmatic mice. Its mechanism is speculated to be related to the suppression of NLRP3, Caspase-1, IL-18 and IL-1β expressions, downregulation of Muc5ac expression, and inhibition in airway mucus hypersecretion.
ObjectiveTo investigate the effect of ADAM33 gene silencing in VSMCs on the proliferation and lumen formation of airway vascular endothelial cells (VECs) in a co-culture system and the possible regulatory mechanism. MethodsThe Human aortic smooth muscle cells (HASMCs) and human pulmonary microvascular endothelial cells (HPMECs) were used to construct a cell co-culture system. ADAM33 gene expression was silenced by lentivirus transfection technique, and the subjects were divided into endothelial cell blank group, co-culture group, co-culture +shRNA negative control group, and co-culture + ADAM33-SHRNA group. The expressions of sADAM33, VEGFA,VEGER2, ang-1 and ang-2 in co-culture system were detected by ELISA. The proliferation and lumen formation of HPMECs were observed by CCK-8 and Transwell experiments. The protein expression of Tie2, PI3K, Akt, and mTOR key molecules in Tie2/PI3K/Akt/mTOR signaling pathway and the phosphorylation levels of AKT and mTOR were detected by Western-blotting method. Results① Compared with the co-culture group (0.851±0.036) and the co-culture + shRNA negative control group (0.828±0.047), the OD value of the co-culture + ADAM33shRNA group (0.699±0.038) was significantly decreased (P<0.05). ② Compared with the co-culture group (159.169±15.740) and the co-culture +shRNA negative control group (157.357±21.612), the tube length of the co-culture +ADAM33shRNA group (120.812±2.791) was also significantly decreased (P<0.05). ③ After ADAM33 gene expression of HASMCs was silted in co-culture system, the expression levels of VEGFA, VEGFR2, ang-1 and ang-2 were significantly decreased (P<0.05), while the expression levels of Tie2, PI3K, P-Akt and P-mtor were decreased (P<0.05). ConclusionsSilencing the expression of the ADAM33 gene could reduce the release of sADAM33 from the membrane of the airway VSMCs, regulate the proliferation and lumen formation of airway VECs by reducing the expression of VEGF/VEGFR and inhibiting the activities of the Tie2/PI3K/Akt/mTOR signaling pathways,and then participate in airway vascular remodeling in asthma.