瑜伽练习在慢性阻塞性肺疾病患者康复治疗中的作用
本文选题:慢性阻塞性肺疾病 + 瑜伽 ; 参考:《山东大学》2014年博士论文
【摘要】:研究背景 慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)严重影响人们的身体健康,是许多人致死或致残的最重要疾病之一,严重影响着公共健康,到2020,COPD将会是世界上第三位致死病因,社会负担将会增至第五位。COPD以不完全可逆性气流受限为特征,肺功能逐渐下降,有效肺组织逐渐减少,生活质量逐渐下降,致死率高。COPD全球倡议(Global Initiative for Chronic Obstructive Lung Disease, GOLD)的管理策略中,包括减轻症状,避免并发症出现,减少急性发作,提高活动耐力,改善健康状况,降低死亡率。近来,基于临床证据,一些COPD相关的指南或声明指出,在COPD管理策略中,肺康复做为最有效的非药物治疗手段,已被广泛接受。研究显示,一些肺康复锻炼方法,如上肢练习、太极、瑜伽等,可缓解呼吸困难,改善肺功能,提高COPD患者生活质量。瑜伽,其含意为“一致”、“结合”或“和谐”。是一个通过提升意识,帮助人类充分发挥潜能的体系。瑜伽姿势运用古老而易于掌握的技巧,改善人们生理、心理、情感和精神方面的能力,是一种达到身体、心灵与精神和谐统一的运动方式,包括调身的体位法、调息的呼吸法、调心的冥想法等,以达至身心的合一。瑜伽可以健身、健美形体、缓解精神压力、锻炼柔韧性,在西方世界中变得流行。研究显示,瑜伽练习可使一些疾病患者明显受益,如哮喘,心脏病,糖尿病,结核病,抑郁症,骨性关节炎,胸腔积液等。一些临床研究结果显示,瑜伽练习可以明显提高COPD患者肺功能。然而,这些研究资料并不系统。因此,我们通过对随机临床试验研究进行系统综述和Meta分析,来评价瑜伽练习对COPD患者肺功能及其他临床指标的影响,从而了解瑜伽练习对COPD患者肺康复中的价值。 目的 本研究通过对随机临床试验研究进行系统综述和Meta分析,来评价瑜伽练习对COPD患者肺功能及其他临床指标的影响,从而了解瑜伽练习对COPD患者肺康复中的价值。 方法 通过计算机及手工全面检索PubMed、EMBASE, the Cochrane Library, Google Scholar、 ClinicalTrials.gov databases、超星Medlink、中国全文期刊数据库、万方数据库。主要指标为第一秒用力呼气容积(forced expiratory volume in one second, FEV1)、FEV1占预计值百分比(FEV1%percentage predicted,FEV1%pred).次要指标为6分钟步行距离(6min walking distance,6MWD),动脉血氧分压(arterial oxygen tension,Pa02)及动脉血二氧化碳分压(arterial carbon diocide tension,PaC02).连续变量资料采用加权均数差(weighted mean differences, WMDs),其以95%可信区间(confidence intervals,CIs)表示。异质性大小程度用12异质性的定量分析。 结果 5篇文献被纳入,包括233例患者。瑜伽练习可显著提高FEV1(WMD123.57ml,95%CI4.12-243,P=0.04),FEV1%pred(WMD3.90%,95%CI2.27-5.54,P0.00001)和6MWD (WMD38.84m,95%CI15.52-62.16,P=0.001);瑜伽练习对PaO2(WMD1.29mmHg,95%CI-1.21-3.78,P=0-31)和PaC02(WMD-0.76mmHg,95%CI-2.06-0.53,P=0.25)没有影响。 结论 瑜伽练习可改善肺功能和活动耐力,可做为COPD患者肺康复治疗的一种有效方法,瑜伽练习对COPD患者肺康复的长期疗效需进一步研究。 研究背景 近年来,肺癌的发病率和病死率都在迅速上升。肺癌主要有小细胞肺癌(small cell lung cancer, SCLC)和非小细胞肺癌(non small cell lung carcinoma, NSCLC),小细胞肺癌一般在晚期发现,生存率远远低于非小细胞肺癌的生存率,因此,谈及小细胞肺癌,人们总是将之与死亡直接挂钩。伊立替康和顺铂方案目前已被美国国立综合癌症网络(National Comprehensive Cancer Network, NCCN)临床治疗指南定为广泛期SCLC的一线标准治疗方案。伊立替康在体内经强酸酯酶转化为7-乙基-10-羟基喜树碱,后者是一种拓扑异构酶I的抑制剂,能够抑制DNA单链断裂后的修复作用,从而干扰DNA复制和转录,产生毒性效应,而在体内,伊立替康代谢的关键酶是尿苷二磷酸葡萄糖苷酸转移酶(UGT1A1),该酶基因启动子区存在大量的TA碱基重复序列,野生型的UGT1A1为6个TA重复序列,即TA6/TA6,当其启动子区有7个TA重复学列,即UGT1A1*28,可分为两种突变型:TA7/TA7和TA6/TA7。 UGT1A1启动子区插入性突变可以降低其转录水平,因此,理论上讲,重复序列越多,基因转录表达就越少。UGT1A1家族常见的SNP共有3种,UGT1A1*1, UGT1A1*28, UGT1A1*6,而临床肿瘤报道最多的是UGT1A1*28多态性。小分子RNA (miRNA)是一类大小约为22个核苷酸的非编码单链分子,它在肿瘤发生发展过程中发挥重要作用。据报道,miRNA在肺癌中通过调控细胞周期,抑癌基因/癌基因和细胞凋亡等,调控了肺癌的发生发展。但是,在小细胞肺癌中,调控UGT1A1的1miRNAs的报道很少,因此,本研究致力于在大量小细胞肺癌患者中发现调控UGT1A1的miRNA,同时对临床样本UGT1A1*6多态性进行分析。 目的 1.对临床样本UGT1A1*6多态性进行分析。 2.寻找小细胞肺癌患者中调控UGT1A1的miRNA。 3.探索小细胞肺癌患者个体化治疗的分子靶标。 方法 通过定量聚合酶链反应(Polymerase Chain Reaction, PCR)检测了临床分离的138例小细胞肺癌和100例正常人群中UGT1A1和miR-143的相对表达,通过Sanger测序检测了小细胞肺癌人群和正常人群中UGT1A1多态性UGT1A1*6的分布;通过双荧光素酶报告系统确定了miR-143与UGT1A1的3'-UTR的结合,并将miR-143拟似物转染小细胞肺癌细胞株通过免疫印迹法确认了miR-143对UGT1A1的表达抑制作用。 结果 UGT1A1在小细胞肺癌患者体内显著低表达,miR-143显著抑制了荧光素酶的表达且miR-143在小细胞肺癌患者体内的表达与UGT1A1显著负性相关,同时UGT1A1多态性UGT1A1*6在小细胞肺癌和正常人群中的分布无统计学差异,但是其在使用了伊立替康治疗的小细胞肺癌患者体内高频率出现。 结论 通过检测UGT1A1*6多态性有助于指导小细胞肺癌患者伊立替康的个性化治疗,并且通过检测小细胞肺癌外周静脉血中UGT1A1基因的表达量能有效评估伊立替康对小细胞肺癌的疗效,从而指导临床用药。
[Abstract]:Research background
Chronic obstructive pulmonary disease (COPD) seriously affects people's health, is one of the most important diseases that cause death or disability, and seriously affects public health. By 2020, COPD will be the third fatal cause in the world, and the social burden will increase to fifth.COPD with incomplete and reversible gas. Flow limitation is characterized by a gradual decline in lung function, a gradual decrease in the effective lung tissue, a gradual decline in the quality of life, and a management strategy for the.COPD Global Initiative (Global Initiative for Chronic Obstructive Lung Disease, GOLD), including alleviating symptoms, avoiding complications, reducing acute attacks, improving activity endurance, and improving health Recently, based on clinical evidence, some COPD related guidelines or statements suggest that lung rehabilitation is the most effective non drug therapy in the COPD management strategy, and it has been widely accepted. Some methods of lung rehabilitation, such as upper limb exercises, Tai Chi, yoga, etc., can relieve dyspnea, improve lung function, and improve COP D patients' quality of life. Yoga, which implies "unity", "combination" or "harmony", is a system of promoting the full potential of human beings by promoting consciousness. Yoga poses the ability to improve people's physical, psychological, emotional and spiritual harmony by using ancient and easy to master skills to achieve physical, mental and spiritual harmony. A unified way of exercise, including the body position method, the breath method of interest adjustment, the meditation method of the heart, and so on to reach the combination of body and mind. Yoga can exercise, body building, relieve stress, exercise flexibility and become popular in the western world. Research shows that yoga exercises can benefit some disease patients, such as asthma, heart disease, diabetes. Diseases, tuberculosis, depression, osteoarthritis, pleural effusion, and so on. Some clinical studies have shown that yoga exercises can significantly improve the lung function of COPD patients. However, these data are not systematic. Therefore, we evaluate the lung function of patients with COPD by systematic review and Meta analysis of the randomized clinical trials. The influence of other clinical indicators on the value of yoga practice in pulmonary rehabilitation of COPD patients.
objective
In this study, a systematic review of randomized clinical trials and a Meta analysis were conducted to evaluate the effects of yoga exercises on the lung function and other clinical indicators of COPD patients so as to understand the value of yoga exercises for the pulmonary rehabilitation of patients with COPD.
Method
PubMed, EMBASE, the Cochrane Library, Google Scholar, ClinicalTrials.gov databases, superstar Medlink, Chinese full text journal database, and square database. The main target is the first second forced expiratory volume (forced expiratory). Ercentage predicted, FEV1%pred). The secondary index is 6 minutes walk distance (6min walking distance, 6MWD), arterial oxygen partial pressure (arterial oxygen tension, Pa02) and arterial blood carbon dioxide partial pressure. The confidence interval (confidence intervals, CIs) indicates that the heterogeneity is quantitatively analyzed by 12 heterogeneity.
Result
5 papers were included, including 233 patients. Yoga exercises can significantly improve FEV1 (WMD123.57ml, 95%CI4.12-243, P=0.04), FEV1%pred (WMD3.90%, 95%CI2.27-5.54, P0.00001) and 6MWD (WMD38.84m, 95%CI15.52-62.16, P=0.001). It doesn't affect.
conclusion
Yoga exercises can improve lung function and activity endurance, and can be used as an effective method for lung rehabilitation in COPD patients. The long-term effect of yoga practice on lung rehabilitation of patients with COPD needs further study.
Research background
In recent years, the incidence and fatality rate of lung cancer are rising rapidly. Lung cancer mainly includes small cell lung cancer (small cell lung cancer, SCLC) and non small cell lung cancer (non small cell lung carcinoma, NSCLC). Small cell lung cancer is generally found in late stage, and the survival rate is far below the survival rate of non small cell lung cancer. Therefore, small cell lung cancer is discussed. People have always linked them directly to death. Erintecan and cisplatin has now been defined as a first-line standard treatment for broad phase SCLC by the National Comprehensive Cancer Network (NCCN) clinical treatment guide. Erinthecan is converted into 7- ethyl -10- hydroxycamptothecin through strong acid esterase in the body, and the latter is the latter. It is an inhibitor of topoisomerase I, which inhibits the repair effect of DNA single strand breaks and interferes with DNA replication and transcription and produces toxic effects. In vivo, the key enzyme for the metabolism of irinotecan is the uridine two phosphorylate glucosidase (UGT1A1), which has a large number of TA base repeat sequences in the promoter region, and the wild type UGT1A1 is 6 TA repeat sequences, that is, TA6/TA6, when the promoter region has 7 TA repeating columns, that is, UGT1A1*28, can be divided into two mutant types: TA7/TA7 and TA6/TA7. UGT1A1 promoter region insertion mutation can reduce its transcriptional level. Therefore, in theory, the more repeat sequences, the less common SNP common SNP in the.UGT1A1 family. The 3 species, UGT1A1*1, UGT1A1*28, UGT1A1*6, and the most commonly reported clinical tumor are UGT1A1*28 polymorphism. Small molecule RNA (miRNA) is a class of non coded single chain molecules of about 22 nucleotides. It plays an important role in the development of tumor. It is reported that miRNA is regulated by the cell cycle, the oncogene / oncogene and the gene in the lung cancer. Apoptosis, such as cell apoptosis, regulates the development of lung cancer. However, there are few reports on the regulation of UGT1A1's 1miRNAs in small cell lung cancer. Therefore, this study is devoted to the discovery of UGT1A1 miRNA in a large number of small cell lung cancer patients and the analysis of UGT1A1*6 polymorphism in clinical samples.
objective
1. the UGT1A1*6 polymorphism of clinical samples was analyzed.
2. searching for miRNA. for UGT1A1 in patients with small cell lung cancer
3. explore molecular targets for individualized treatment in patients with small cell lung cancer.
Method
The relative expression of UGT1A1 and miR-143 in 138 cases of small cell lung cancer and 100 normal people was detected by quantitative polymerase chain reaction (Polymerase Chain Reaction, PCR). The distribution of UGT1A1 polymorphic UGT1A1*6 in small cell lung cancer population and normal population was detected by Sanger sequencing, and the double luciferase reporter system was used to detect the distribution of UGT1A1 polymorphism in small cell lung cancer population and normal population. The combination of miR-143 and UGT1A1 3'-UTR was determined, and miR-143 mimetic transfected to small cell lung cancer cell lines confirmed the inhibitory effect of miR-143 on the expression of UGT1A1 by immunoblotting.
Result
The expression of UGT1A1 was significantly lower in the patients with small cell lung cancer, and the expression of luciferase was significantly inhibited by miR-143 and the expression of miR-143 in small cell lung cancer patients was negatively correlated with UGT1A1, and the distribution of UGT1A1 polymorphism UGT1A1*6 in small cell lung cancer and normal population was not statistically different, but it was used in erinotecan. Treatment of small cell lung cancer patients appeared in high frequency.
conclusion
The detection of UGT1A1*6 polymorphism can help guide the individualized treatment of erinotecan in small cell lung cancer patients and can effectively evaluate the efficacy of erinotecan to small cell lung cancer by measuring the expression of UGT1A1 gene in peripheral venous blood of small cell lung cancer, thus guiding clinical medication.
【学位授予单位】:山东大学
【学位级别】:博士
【学位授予年份】:2014
【分类号】:R563.9
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