本文選題：慢性阻塞性肺疾病 + 瑜伽�。� 參考：《山東大學(xué)》2014年博士論文

【摘要】：研究背景 慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)嚴(yán)重影響人們的身體健康,是許多人致死或致殘的最重要疾病之一,嚴(yán)重影響著公共健康,到2020,COPD將會(huì)是世界上第三位致死病因,社會(huì)負(fù)擔(dān)將會(huì)增至第五位。COPD以不完全可逆性氣流受限為特征,肺功能逐漸下降,有效肺組織逐漸減少,生活質(zhì)量逐漸下降,致死率高。COPD全球倡議(Global Initiative for Chronic Obstructive Lung Disease, GOLD)的管理策略中,包括減輕癥狀,避免并發(fā)癥出現(xiàn),減少急性發(fā)作,提高活動(dòng)耐力,改善健康狀況,降低死亡率。近來(lái),基于臨床證據(jù),一些COPD相關(guān)的指南或聲明指出,在COPD管理策略中,肺康復(fù)做為最有效的非藥物治療手段,已被廣泛接受。研究顯示,一些肺康復(fù)鍛煉方法,如上肢練習(xí)、太極、瑜伽等,可緩解呼吸困難,改善肺功能,提高COPD患者生活質(zhì)量。瑜伽,其含意為“一致”、“結(jié)合”或“和諧”。是一個(gè)通過(guò)提升意識(shí),幫助人類充分發(fā)揮潛能的體系。瑜伽姿勢(shì)運(yùn)用古老而易于掌握的技巧,改善人們生理、心理、情感和精神方面的能力,是一種達(dá)到身體、心靈與精神和諧統(tǒng)一的運(yùn)動(dòng)方式,包括調(diào)身的體位法、調(diào)息的呼吸法、調(diào)心的冥想法等,以達(dá)至身心的合一。瑜伽可以健身、健美形體、緩解精神壓力、鍛煉柔韌性,在西方世界中變得流行。研究顯示,瑜伽練習(xí)可使一些疾病患者明顯受益,如哮喘,心臟病,糖尿病,結(jié)核病,抑郁癥,骨性關(guān)節(jié)炎,胸腔積液等。一些臨床研究結(jié)果顯示,瑜伽練習(xí)可以明顯提高COPD患者肺功能。然而,這些研究資料并不系統(tǒng)。因此,我們通過(guò)對(duì)隨機(jī)臨床試驗(yàn)研究進(jìn)行系統(tǒng)綜述和Meta分析,來(lái)評(píng)價(jià)瑜伽練習(xí)對(duì)COPD患者肺功能及其他臨床指標(biāo)的影響,從而了解瑜伽練習(xí)對(duì)COPD患者肺康復(fù)中的價(jià)值。 目的 本研究通過(guò)對(duì)隨機(jī)臨床試驗(yàn)研究進(jìn)行系統(tǒng)綜述和Meta分析,來(lái)評(píng)價(jià)瑜伽練習(xí)對(duì)COPD患者肺功能及其他臨床指標(biāo)的影響,從而了解瑜伽練習(xí)對(duì)COPD患者肺康復(fù)中的價(jià)值。 方法 通過(guò)計(jì)算機(jī)及手工全面檢索PubMed、EMBASE, the Cochrane Library, Google Scholar、 ClinicalTrials.gov databases、超星Medlink、中國(guó)全文期刊數(shù)據(jù)庫(kù)、萬(wàn)方數(shù)據(jù)庫(kù)。主要指標(biāo)為第一秒用力呼氣容積(forced expiratory volume in one second, FEV1)、FEV1占預(yù)計(jì)值百分比(FEV1％percentage predicted,FEV1％pred).次要指標(biāo)為6分鐘步行距離(6min walking distance,6MWD),動(dòng)脈血氧分壓(arterial oxygen tension,Pa02)及動(dòng)脈血二氧化碳分壓(arterial carbon diocide tension,PaC02).連續(xù)變量資料采用加權(quán)均數(shù)差(weighted mean differences, WMDs),其以95%可信區(qū)間(confidence intervals,CIs)表示。異質(zhì)性大小程度用12異質(zhì)性的定量分析。 結(jié)果 5篇文獻(xiàn)被納入,包括233例患者。瑜伽練習(xí)可顯著提高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)；瑜伽練習(xí)對(duì)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)沒(méi)有影響。 結(jié)論 瑜伽練習(xí)可改善肺功能和活動(dòng)耐力,可做為COPD患者肺康復(fù)治療的一種有效方法,瑜伽練習(xí)對(duì)COPD患者肺康復(fù)的長(zhǎng)期療效需進(jìn)一步研究。 研究背景 近年來(lái),肺癌的發(fā)病率和病死率都在迅速上升。肺癌主要有小細(xì)胞肺癌(small cell lung cancer, SCLC)和非小細(xì)胞肺癌(non small cell lung carcinoma, NSCLC),小細(xì)胞肺癌一般在晚期發(fā)現(xiàn),生存率遠(yuǎn)遠(yuǎn)低于非小細(xì)胞肺癌的生存率,因此,談及小細(xì)胞肺癌,人們總是將之與死亡直接掛鉤。伊立替康和順鉑方案目前已被美國(guó)國(guó)立綜合癌癥網(wǎng)絡(luò)(National Comprehensive Cancer Network, NCCN)臨床治療指南定為廣泛期SCLC的一線標(biāo)準(zhǔn)治療方案。伊立替康在體內(nèi)經(jīng)強(qiáng)酸酯酶轉(zhuǎn)化為7-乙基-10-羥基喜樹(shù)堿,后者是一種拓?fù)洚悩?gòu)酶I的抑制劑,能夠抑制DNA單鏈斷裂后的修復(fù)作用,從而干擾DNA復(fù)制和轉(zhuǎn)錄,產(chǎn)生毒性效應(yīng),而在體內(nèi),伊立替康代謝的關(guān)鍵酶是尿苷二磷酸葡萄糖苷酸轉(zhuǎn)移酶(UGT1A1),該酶基因啟動(dòng)子區(qū)存在大量的TA堿基重復(fù)序列,野生型的UGT1A1為6個(gè)TA重復(fù)序列,即TA6/TA6,當(dāng)其啟動(dòng)子區(qū)有7個(gè)TA重復(fù)學(xué)列,即UGT1A1*28,可分為兩種突變型：TA7/TA7和TA6/TA7。 UGT1A1啟動(dòng)子區(qū)插入性突變可以降低其轉(zhuǎn)錄水平,因此,理論上講,重復(fù)序列越多,基因轉(zhuǎn)錄表達(dá)就越少。UGT1A1家族常見(jiàn)的SNP共有3種,UGT1A1*1, UGT1A1*28, UGT1A1*6,而臨床腫瘤報(bào)道最多的是UGT1A1*28多態(tài)性。小分子RNA (miRNA)是一類大小約為22個(gè)核苷酸的非編碼單鏈分子,它在腫瘤發(fā)生發(fā)展過(guò)程中發(fā)揮重要作用。據(jù)報(bào)道,miRNA在肺癌中通過(guò)調(diào)控細(xì)胞周期,抑癌基因／癌基因和細(xì)胞凋亡等,調(diào)控了肺癌的發(fā)生發(fā)展。但是,在小細(xì)胞肺癌中,調(diào)控UGT1A1的1miRNAs的報(bào)道很少,因此,本研究致力于在大量小細(xì)胞肺癌患者中發(fā)現(xiàn)調(diào)控UGT1A1的miRNA,同時(shí)對(duì)臨床樣本UGT1A1*6多態(tài)性進(jìn)行分析。 目的 1.對(duì)臨床樣本UGT1A1*6多態(tài)性進(jìn)行分析。 2.尋找小細(xì)胞肺癌患者中調(diào)控UGT1A1的miRNA。 3.探索小細(xì)胞肺癌患者個(gè)體化治療的分子靶標(biāo)。 方法 通過(guò)定量聚合酶鏈反應(yīng)(Polymerase Chain Reaction, PCR)檢測(cè)了臨床分離的138例小細(xì)胞肺癌和100例正常人群中UGT1A1和miR-143的相對(duì)表達(dá),通過(guò)Sanger測(cè)序檢測(cè)了小細(xì)胞肺癌人群和正常人群中UGT1A1多態(tài)性UGT1A1*6的分布；通過(guò)雙熒光素酶報(bào)告系統(tǒng)確定了miR-143與UGT1A1的3'-UTR的結(jié)合,并將miR-143擬似物轉(zhuǎn)染小細(xì)胞肺癌細(xì)胞株通過(guò)免疫印跡法確認(rèn)了miR-143對(duì)UGT1A1的表達(dá)抑制作用。 結(jié)果 UGT1A1在小細(xì)胞肺癌患者體內(nèi)顯著低表達(dá),miR-143顯著抑制了熒光素酶的表達(dá)且miR-143在小細(xì)胞肺癌患者體內(nèi)的表達(dá)與UGT1A1顯著負(fù)性相關(guān),同時(shí)UGT1A1多態(tài)性UGT1A1*6在小細(xì)胞肺癌和正常人群中的分布無(wú)統(tǒng)計(jì)學(xué)差異,但是其在使用了伊立替康治療的小細(xì)胞肺癌患者體內(nèi)高頻率出現(xiàn)。 結(jié)論 通過(guò)檢測(cè)UGT1A1*6多態(tài)性有助于指導(dǎo)小細(xì)胞肺癌患者伊立替康的個(gè)性化治療,并且通過(guò)檢測(cè)小細(xì)胞肺癌外周靜脈血中UGT1A1基因的表達(dá)量能有效評(píng)估伊立替康對(duì)小細(xì)胞肺癌的療效,從而指導(dǎo)臨床用藥。
[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.

【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2014
【分類號(hào)】：R563.9

【共引文獻(xiàn)】

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1 熊明霞;microRNA在腎間質(zhì)纖維化中作用的研究[D];南京醫(yī)科大學(xué);2010年

2 李仲杰;1：microRNAs參與7，，8-二氫二醇-9，10-環(huán)氧苯并（a）芘誘發(fā)的FL細(xì)胞應(yīng)答反應(yīng)研究 2：地塞米松誘導(dǎo)的DNA聚合酶β過(guò)表達(dá)和反義阻斷穩(wěn)定細(xì)胞系的建立[D];浙江大學(xué);2011年

3 王海強(qiáng);MicroRNA-155調(diào)控在人椎間盤退變中的作用研究[D];第四軍醫(yī)大學(xué);2011年

4 阮靈偉;深海熱液區(qū)管狀蠕蟲的分子特征及對(duì)蝦microRNA的初探[D];廈門大學(xué);2009年

5 王曉映;阿爾茨海默病中microRNA-34a作用機(jī)制的研究[D];中國(guó)協(xié)和醫(yī)科大學(xué);2009年

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8 李輝;一個(gè)新的調(diào)節(jié)成骨細(xì)胞分化的microRNA的克隆及其功能研究[D];中南大學(xué);2010年

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5 賈音;血漿中的MicroRNA在肝損傷性疾病檢測(cè)中的應(yīng)用[D];第二軍醫(yī)大學(xué);2010年

6 張平;小鼠著床前胚胎miR-125a,miR-295和miR-181b表達(dá)的實(shí)驗(yàn)研究[D];第四軍醫(yī)大學(xué);2009年

7 倪航航;血漿microRNA-122與肝癌手術(shù)肝損傷的相關(guān)性研究[D];廣西醫(yī)科大學(xué);2012年

8 王宇歌;HIV-1感染者血漿microRNA分布變化研究[D];北京協(xié)和醫(yī)學(xué)院;2012年

9 開(kāi)天瀚;聯(lián)用技術(shù)在生物分子檢測(cè)中的應(yīng)用[D];中南大學(xué);2012年

10 金吉春;OSW-1在microRNA-122對(duì)肝癌細(xì)胞基因及Wnt信號(hào)通路作用中的研究[D];延邊大學(xué);2012年

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