维吾尔族支气管哮喘患儿白三烯C4合成酶基因多态性分析

目的:分析白三烯C4合成酶(LTC4S)基因A-444C位点基因型和等位基因在新疆维吾尔族支气管哮喘患儿中的分布频率,并比较其与不同种族支气管哮喘患儿间的分布差异,为制定维吾尔族支气管哮喘患儿哮喘个体化用药方案提供依据。方法:采用荧光染色原位杂交方法检测190例维吾尔族支气管哮喘患儿的LTC4S A-444C基因多态性,并与国内外不同种族支气管哮喘患儿的该位点基因多态性进行比较,分析基因型频率和等位基因频率间是否存在差异性。结果:190例新疆维吾尔族支气管哮喘患儿中,LTC4S A-444C三种基因型CC、AC和AA的分布频率分别为6.8%、49.0%和44.2%;A、C等位基因频率分别为68.7%、31.3%。维吾尔族支气管哮喘患儿LTC4S A-444C的基因型、等位基因频率与韩国、澳大利亚及中国东北地区汉族支气管哮喘患儿均差异均有统计学意义(P<0.05)。结论:新疆维吾尔族支气管哮喘患儿LTC4S A-444C的基因型与等位基因的分布频率与国内外不同种族支气管哮喘患儿存在较大差异性。通过此研究,可以指导维吾尔族支气管哮喘患儿临床个体化用药,使哮喘临床用药更具有针对性、高效性和安全性。     

Impact of flexible insulin therapy on blood glucose variability,oxidative stress and inflammation in type 1 diabetic patients: The VARIAFIT study

AimsHbA_1c only partially predicts vascular risk in patients with type 1 diabetes (T1D), and a role for blood glucose variability (BGV) is a matter of debate. For this reason, this study investigated the impact of an educational programme of flexible insulin therapy (FIT) on BGV and oxidative stress.MethodsTests were conducted on 30 adult T1D patients in a prospective, single-centre trial at baseline (M0), and at 3 and 6 months (M3 and M6, respectively) of the FIT programme to determine BGV, as reflected by mean amplitude of glycaemic excursions (MAGE), low blood glucose index (LBGI), lability index (LI), average daily risk range (ADRR), glycaemic lability (scored by two diabetologists), urinary leukotriene E₄ (LTE4), 11-dehydro-thromboxane B₂ (TXB2) and 8-iso-prostaglandin F2α (PGF2).ResultsHbA_1c (7.7 ± 0.9%), ADRR, MAGE, LBGI and LI did not change from M0 to M3 and M6, although ADRR and LBGI significantly improved at M3 and M6 in patients with the highest baseline indices (≥ 40 and ≥ 5, respectively). TXB2 declined at M6 (832 ± 625 vs. 633 ± 972 pg/mg; P = 0.048), whereas LTE4 and PGF2 remained stable. ADRR showed the strongest correlation with glycaemic lability scores at all visits (r ≥ 0.84, P < 0.0001).ConclusionA FIT educational programme improved BGV only in patients with the highest baseline variability, and led to no changes in HbA_1c, while ADRR closely correlated with glycaemic lability score. Our data do not support a relationship between BGV and oxidative stress in T1D patients, although the impact of variability on TXB2 deserves further investigation (ClinicalTrials.gov NCT00973492).     

Investigating the human immunodeficiency virus type 1-infected monocyte-derived macrophage secretome

Mononuclear phagocytes (bone marrow monocyte-derived macrophages, alveolar macrophages, perivascular macrophages, and microglia) are reservoirs and vehicles of dissemination for the human immunodeficiency virus type-1 (HIV-1). How virus alters mononuclear phagocyte immunoregulatory activities to complete its life cycle and influence disease is incompletely understood. In attempts to better understanding the influence of virus on macrophage functions, we used one-dimensional electrophoresis, and liquid chromatography tandem mass spectrometry to analyze the secretome of HIV-1-infected human monocyte-derived macrophages. We identified 110 proteins in culture supernatants of control (uninfected) and virus-infected cells. Differentially expressed cytoskeletal, enzymes, redox, and immunoregulatory protein classes were discovered and validated by Western blot tests. These included, but were not limited to, cystatin C, cystatin B, chitinase 3-like 1 protein, cofilin-1, l-plastin, superoxide dismutase, leukotriene A(4) hydrolase, and alpha-enolase. This study, using a unique proteomics platform, provides novel insights into virus-host cell interactions that likely affect the functional role of macrophages in HIV disease.     

白三烯C4合成酶基因多态性与儿童哮喘易感性及孟鲁司特疗效关联研究

目的 研究白三烯C4合成酶(LTC4S)基因 rs730012、rs3776944两个单核苷酸多态性位点(SNPs)与儿童哮喘易感性和孟鲁司特疗效的关系,以指导哮喘早期预防及精准治疗。方法 选取2016年5月-2017年8月沈阳军区总医院就诊的哮喘患儿215例为病例组,228例非哮喘儿童为对照组,应用聚合酶链反应(PCR)及测序法对所有研究对象LTC4S rs730012、rs3776944位点进行基因分型,并于孟鲁司特治疗前后进行肺功能、尿LTE4儿童哮喘控制测试问卷(C-ACT)评分。结果 1)病例组与对照组在rs730012及rs3776944 位点基因型频率差异均无统计学意义(χ²=0.079、0.617,P均＞0.05)。2)中重度哮喘组A/C+C/C基因型频率明显高于对照组和轻度哮喘组,差异有统计学意义(χ²=4.129、6.088,P均＜0.05)。3)A/C+C/C基因型哮喘患儿在经过孟鲁斯特钠治疗后FEF50、FEF75改善率明显高于A/A型患儿(P均＜0.05),而单纯应用布地奈德组患儿差异无显著性(P均＞0.05)。4)A/A基因型患儿应用孟鲁司特疗效更佳,较A/C+C/C基因型尿液LTE4改变率高,rs730012和rs3776944位点差异均有统计学意义(P均＜0.05)。结论 LTC4S rs730012 SNP与哮喘严重程度有关,rs730012及rs3776944 SNPs野生型应用孟鲁司特疗效更佳。     

An overview of monitoring and supplementation of omega 3 fatty acids in cystic fibrosis

Essential fatty acid deficiency has been increasingly reported in patients with cystic fibrosis. The purpose of this work is to critically summarize previous data on fatty acid status and ω3 supplementation in cystic fibrosis. Although the reported abnormalities differ from study to study, the two most consistent features appeared to be reduced circulating levels of linoleic acid and docosahexaenoic acid (DHA). On the assumption that the fatty acid composition of erythrocyte cell membranes may be similar to that of other organs, it seems appropriate to monitor the phospholipid profile from erythrocyte membranes together with circulating blood levels. Formulations containing widely variable DHA doses, ranging from 300 mg to 5 g per day, have been administered to patients with cystic fibrosis with discrepant outcomes. Randomized controlled trials are needed in order to draw firm conclusions on the therapeutic effect of ω3 fatty acid supplementation in cystic fibrosis.     

Consumption of cranberry beverage improved endogenous antioxidant status and protected against bacteria adhesion in healthy humans: a randomized controlled trial

Consumption of polyphenol-rich foods is associated with lower risk from many chronic diseases. We hypothesized that a single dose of cranberry beverage would improve indices of oxidative stress, inflammation, and urinary antibacterial adhesion activity in healthy humans. Six males and 6 females (18-35 years; body mass index, 19-25 kg/m²) consumed placebo, cranberry leaf extract beverage, or low-calorie cranberry juice cocktail (LCJC) once in a randomized, double-blind, placebo-controlled cross-over experimental design trial. The washout period between beverages was 1 week. Blood was collected 0, 2, 4, 8, and 24 hours after beverage consumption for measuring oxidative and inflammatory biomarkers. Urine was collected at 0, 0 to 3, 3 to 6, 6 to 9, 9 to 12, and 24 hours postintervention to assess antibacterial adhesion activity. Consumption of cranberry leaf extract beverage elevated (P < .05) blood glutathione peroxidase activity, whereas LCJC consumption increased (P < .05) glutathione concentrations and superoxide dismutase activity compared with placebo. Cranberry leaf extract beverage and LCJC consumption had no effect on the inflammatory biomarkers measured as compared with placebo. At 0 to 3 hours postconsumption, urine from participants who consumed cranberry beverages had higher (P < .05) ex vivo antiadhesion activity against P-fimbriated Escherichia coli compared with placebo. An acute dose of cranberry beverages improved biomarkers of antioxidant status and inhibition of bacterial adhesion in urine.     

Involvement of cysteinyl leukotriene receptor 1 in Aβ1–42-induced neurotoxicity in vitro and in vivo

Accumulation of amyloid-β (Aβ) is thought to be associated with the progressive neuronal death observed in Alzheimer's disease, but the mechanisms underlying neurotoxicity triggered by Aβ remain elusive. In the current study, we investigated the roles of cysteinyl leukotriene receptor 1 (CysLT₁R) in Aβ_1–42-induced neurotoxicity in vitro or in vivo. In vitro exposure of mouse primary neurons to Aβ_1–42 caused a gradual increases in CysLT₁R expression. In vivo bilateral intrahippocampal injection of Aβ_1–42 also elicited time-dependent increases of CysLT₁R expression in the hippocampus and cortex of mice. The CysLT₁R antagonist pranlukast not only reversed Aβ_1–42-induced upregulation of CysLT₁R, but also suppressed Aβ_1–42-triggered neurotoxicity evidenced by enhanced nuclear factor-kappa B p65, activated caspase-3, decreased B-cell lymphoma-2 and cell viability and impaired memory. Furthermore, chronic treatment with pranlukast produced similar beneficial effects on memory behavior and hippocampal long-term potentiation to memantine or donepezil in intrahippocampal Aβ_1–42-injected mice. Our data indicate that CysLT₁R is involved in Aβ_1–42-induced neurotoxicity, and that blockade of CysLT₁R, such as application of CysLT₁R antagonist, could be a novel and promising strategy for the treatment of Alzheimer's disease.     

基于Zelen's设计桂葛灵仙汤联合颈夹脊穴透灸法治疗神经根型颈椎病风寒湿痹证

目的:基于Zelen's设计,探讨桂葛灵仙汤联合夹脊穴透灸法治疗神经根型颈椎病(CSR)风寒湿痹证临床疗效及作用机制。方法:将120例CSR风寒湿痹证患者随机分为中药组和联合组,均60例,拟入中药组直接进入中药组,拟入联合组知情同意则进入联合组,不同意则进入中药组。中药组给予桂葛灵仙汤150 m L/次,2次/d口服,联合组患者在中药组治疗基础上给予颈部夹脊穴透灸治疗,30 min/次,1次/d,两组患者均治疗8周。记录入组患者CSR 20分量表评分,SF-36量表评分及典型症状体征缓解时间,治疗结束后统计总有效率和治愈率;酶联免疫夹心法检测治疗前后患者血清白三烯B_4(LTB_4),白三烯C_4(LTC_4),白三烯D_4(LTD_4),甲壳质酶蛋白-40(YKL-40),白细胞介素-1β(IL-1β)及肿瘤坏死因子-α(TNF-α)含量。结果:联合组总有效率为98.11%(52/53),治愈率为43.39%(23/52),优于中药组总有效率91.04%(61/69),治愈率20.89%(14/67)(P0.05);与中药组比较,联合组患者CSR 20分量表,SF-36量表评分升高(P0.05),典型症状体征缓解时间缩短(P0.05);血清中LTB_4,LTC_4,LTD_4,YKL-40,IL-1β及TNF-α含量降低(P0.05)。结论:Zelen's设计结果显示桂葛灵仙汤联合夹脊穴透灸法治疗CSR风寒湿痹证临床疗效确切,值得临床推广,其机制可能与抑制LT表达,减少IL-1β及TNF-α含量在血清中含量,从而促进颈椎软骨修复和提高疼痛阈值有关。     

The role of cysteinyl leukotrienes in the pathogenesis of asthma: Clinical study of leukotriene antagonist pranlukast for 1 year in moderate and severe asthma

Clinical studies have shown that pranlukast (Ono Pharmaceutical Co., Osaka, Japan) is effective for mild and moderate asthma. However, it is not well known that pranlukast is also effective on moderate and severe persistent asthma in the long term. We studied the effect of pranlukast on moderate and severe asthmatics by evaluating the change of peak expiratory flow (PEF) and therapeutic scores for 1 year before and during pranlukast therapy. We gave pranlukast 225 mg twice daily orally to 25 patients who were receiving more than 400 micrograms/day beclomethasone inhalation and beta 2 stimulant inhalation with or without oral corticosteroid. Pranlukast increased PEF more than 10 L/min in 14 patients in the first 4 weeks. In these 14 patients, 10 patients continued to monitor PEF and kept asthma diaries for 1 year. We compared the data for 1 year before and during the pranlukast therapy. During the pranlukast therapy, PEF significantly increased, puffs of beta 2 stimulant inhalation significantly decreased. The incidence of oral corticosteroid rescue therapy reduced, and the mean daily dose of oral corticosteroid decreased; however, they were not statistically significant. During treatment with pranlukast, no side effect was observed. From these results, we suggest that pranlukast is effective for more than half of the moderate and severe persistent asthmatics, and that the effectiveness continues for more than 1 year.