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Dave Singh 《British journal of clinical pharmacology》2015,79(5):695-708
Fixed dose combination (FDC) dual bronchodilators that co-administer a long acting β2-adrenoceptor agonist (LABA) and a long acting muscarinic antagonist (LAMA) are a new class of inhaled treatment for chronic obstructive pulmonary disease (COPD). This review focuses on the clinical evidence for the benefit of LABA/LAMA FDCs compared with monocomponent treatments, and also compared with active comparators that are widely used for the treatment of COPD, namely tiotropium and salmeterol-fluticasone. Novel FDC dual bronchodilators include QVA149 and umeclidinium/vilanterol (UMEC/VI). Long term clinical trials show that QVA149 and UMEC/VI are superior to monocomponent therapy in terms of trough forced expiratory volume in 1 s (FEV1), although the FEV1 improvement was limited to approximately 80–90% of the added monocomponent values. This suggests that the effect of combining a LABA and a LAMA is not fully additive. LABA/LAMA FDC were associated with the largest mean changes in symptoms and health status that were above the minimal clinically important difference, in contrast to the monocomponents. Furthermore, these LABA/LAMA FDCs demonstrated superiority over the active comparators tiotropium and salmeterol-fluticasone in terms of trough FEV1 and patient-reported outcomes. LABA/LAMA FDCs offer a simplified means of maximizing bronchodilation for COPD patients, with the improvements in lung function being mirrored by benefits in terms of symptoms and exacerbations. The use of LABA/LAMA FDCs in clinical practice is set to grow and further studies are needed to define their optimal place in treatment guidelines. 相似文献
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Pingping Yan Miaojuan Xia Fei Gao Guanxiu Tang Hui Zeng Shuo Yang Hongmei Zhou Dan Ding Lina Gong 《International journal of clinical and experimental pathology》2015,8(11):15177-15183
We conducted a case-control study to evaluate the association of miR-146a rs2910164 (C>G), miR-149 rs2292832 (T>C), miR-196a2 rs11614913 (T>C) and miR-499 rs3746444 (T>C) polymorphisms with the risk of hepatocellular carcinoma. A total of 274 patients with HCC were collected between January 2013 and December 2014. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was taken to determine the polymorphism of miR-146a C>G, miR-149 T>C, miR-196a2 T>C and miR-499 T>C. By comparing with control groups, patients with HCC were more likely to be males (OR=2.01, 95% CI=1.38-2.95), have older age (OR=1.52, 95% CI=1.09-2.13), have a history of alcohol drinking (OR=2.09, 95% CI=1.49-2.93), and be infected with HBV (OR=32.98, 95% CI=19.70-55.46) and HCV (OR=56.26, 95% CI=23.28-152.98) infection. By conditional regression analysis, individuals carrying the TC and CC genotypes of miR-196a2 T>C were found to be associated with an elevated risk of HCC compared to the TT genotype, and the adjusted odds ratio were 1.50 (1.03-2.17) and 2.86 (1.60-5.16), respectively. Moreover, the TC+CC genotype was correlated with an increased risk of HCC (OR=1.69, 95% CI=1.19-2.41) compared to the wide-type genotype. In conclusion, our results suggested that miR-196a2 T>C polymorphism is associated with HCC risk in Chinese population. 相似文献
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【摘要】 目的 探讨妊娠期糖尿病(GDM)患者血清miR-149水平与胰岛素抵抗的关系。 方法 选取2017年1月~2018年8月陕西省人民医院收治的63例妊娠期糖尿病患者设为观察组,选择本院同期产检健康妊娠产妇63例设为对照组,用自动糖化血红蛋白检测仪测定糖化血红蛋白(HbA1c),用生化分析仪检测受试者餐前空腹血糖(FPG),用免疫测定分析仪检测血清空腹胰岛素(FINS),计算胰岛素抵抗指数(HOMA IR)=FPG×FINS/22.5。采用实时荧光定量PCR(qRT-PCR)法检测所有研究对象血清miR-149表达水平。用Pearson分析miR-149与血糖、胰岛素等指标的相关性。对影响胰岛素抵抗的相关因素进行Logistic回归分析。 结果 与对照组相比,观察组孕妇HOMA-IR、FPG、FINS、HbA1C水平、miR-149水平较高(P<0.05);Pearson法分析显示观察组孕妇血清miR-149水平与FPG、FINS、HOMA-IR呈正相关(P<0.05),与HbA1C无相关性(P>0.05);多因素Logistic回归分析显示血清miR-149水平升高是影响胰岛素抵抗的危险因素。 结论 妊娠期糖尿病患者血清miR-149水平上调,可能与妊娠期糖尿病孕妇胰岛素抵抗有关。 相似文献
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目的 观察miR-149-5P对胃癌细胞BGC-823和MKN28迁移的影响。方法 采用qRT-PCR方法检测miR-149-5P在胃粘膜上皮细胞(GES-1)与BGC-823和MKN28细胞中的表达。分别转染miR-149-5P mimics、NC、inhibitor和inhibitor-NC,采用qRT-PCR方法验证转染效率,采用细胞划痕实验和Transwell实验检测过表达或抑制miR-149-5P后胃癌细胞BGC-823和MKN28迁移能力。采用Western Blot检测转染miR-149-5P mimics或inhibitor后BGC-823和MKN28细胞中β-catenin、MMP2、E-cadherin蛋白表达水平。结果 qRT-PCR实验结果显示:与GES-1相比,miR-149-5P在BGC-823和MKN28细胞中表达显著降低;转染mimics后,BGC-823和MKN28细胞中miR-149-5P表达水平显著升高,而转染inhibitor后,BGC-823和MKN28细胞中miR-149-5P表达水平下降。细胞划痕实验和Transwell实验结果显示:转染mimics后可以抑制BGC-823和MKN28细胞迁移,而转染inhibitor后,可以促进BGC-823细胞迁移,MKN28细胞并无明显变化。Western Blot实验结果显示:在BGC-823和MKN28细胞中过表达miR-149-5P可上调E-cadherin的蛋白表达,抑制β-catenin和MMP2蛋白表达,而抑制miR-149-5P的表达可下调E-cadherin的蛋白表达,促进BGC-823细胞中β-catenin和MMP2蛋白表达,但转染inhibitor后MKN28细胞中E-cadherin、β-catenin和MMP2蛋白表达水平并无明显变化。结论 miR-149-5P可以抑制胃癌细胞BGC-823和MKN28迁移。 相似文献
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Craniofacial bone atrophy in Parry Romberg syndrome demonstrated using a Bayesian hierarchical model
Quentin Hennocq Arianna Facchini Bothild Kverneland Christine Bodemer Arnaud Picard Roman H. Khonsari 《Journal of cranio-maxillo-facial surgery》2019,47(6):909-914
PurposeParry Romberg syndrome (PRS) is a condition characterized by progressive hemifacial atrophy, predominantly affecting the soft tissues. Associated bone retraction is a common clinical feature of PRS but has never been assessed. Here we used 3D imaging and Bayesian statistics in order to demonstrate and quantify bone atrophy in PRS.Materials and methodsTen non-operated patients with PRS (4/10 males) and 12 age-matched controls (7/12 males) were included into the study. The average age at CT-scan was 9.67 ± 4.13 years for PRS patients and 12.5 ± 4.37 years for controls. Soft and hard tissue atrophy levels were quantified using computed tomography scans, based on the distances between surfaces of the affected side and the non-affected contralateral side, both for the skin and the bone. We used a hierarchical Bayesian model with clinical priors in order to assess the relationship between hard and soft tissue atrophies.ResultsPRS patients had significant hard tissue atrophy, and atrophy extents were similar for soft and hard tissues. There was a trend for a correlation between the extent of hard tissue retraction and the extent of soft tissue retraction, and we could not demonstrate that the relationship between hard and soft tissue retractions was different in PRS and controls.ConclusionOur results indicated that bone atrophy was most probably a primary process rather than a phenomenon secondary to soft tissue retraction. We have provided the first assessment of bone atrophy in PRS patients using Bayesian statistics. 相似文献
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目的探讨陕西省汉族人群miR-149基因多态性的分布情况及其与缺血性脑卒中(ischemicstroke,IS)的关系。方法缺血性脑卒中组357例,对照组373例,应用聚合酶链反应一限制性内切酶片段长度多态性方法进行基因分型。比较各基因型和等位基因频率分布及其与缺血性脑卒中的关系。结果受试者携带CC基因型比携带TT基因型[(0R(95%CI):1.739(1.088-2.781),P=0.020]患IS的风险要高。或至少携带一个C等位基因的受试者比携带T等位基因的受试者更易患IS[OR(95%CI):1.243(1.003-1.539),P=0.046]。CC基因型患者血浆叶酸水平低于TT基因型患者。结论在汉族人群中,microRNA-149C〉T单核苷酸多态性与缺血性脑卒中有关。 相似文献
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Plasma levels, half-life values, and correlation with physiologic assays for growth and immunity 总被引:3,自引:0,他引:3
O C Green R J Winter F S Kawahara L S Phillips P R Lewy R L Hart L M Pachman 《The Journal of pediatrics》1978,93(2):299-303
To assess the gonadal effects of chlorambucil given to prepubertal and pubertal boys, testicular function of 21 adolescents or young men, treated with chlorambucil for nephrotic syndrome before or during puberty, have been evaluated. Evaluations have been based on penis and testicular size, serum FSH, LH and testosterone values, and sperm count. Nine patients have testicular hypotrophy, 13 have significantly elevated FSH, 17 have azoospermia, two have severe oligospermia, and repetitive sperm counts show no improvement. A quiescent state of the epithelium of the seminiferous tubules does not protect against chlorambucil toxicity, which seems to be related to the cumulative dose. Chlorambucil should be used with caution, even in children. 相似文献