老年髖部骨折患者環(huán)狀RNA差異表達(dá)的研究
發(fā)布時間：2018-08-03 10:44
【摘要】：髖部骨折是老年人最易發(fā)生的骨折之一,國內(nèi)外很多研究都顯示與同年齡正常人群相比老年髖部骨折患者的死亡率以及死亡風(fēng)險都明顯更高。老年髖部骨折后出現(xiàn)的過度全身炎性反應(yīng)導(dǎo)引發(fā)多種器官功能損害,是導(dǎo)致死亡事件的獨立危險因素。目前臨床已經(jīng)運(yùn)用一些評分系統(tǒng)和多種生物標(biāo)記物,以期更精準(zhǔn)的評估病情以及高危風(fēng)險程度,減輕器官損害程度,改善患者的預(yù)后。但目前全身炎癥反應(yīng)導(dǎo)致的多臟器功能衰竭的精準(zhǔn)診治及相應(yīng)的機(jī)制研究仍存在一定的不足,需要進(jìn)一步完善,特別是需要尋找更加可靠、特異性強(qiáng)、靈敏度高的生物標(biāo)志物用于該領(lǐng)域疾病的進(jìn)程監(jiān)測以及治療評價。隨著對環(huán)狀RNA系統(tǒng)深入的研究,發(fā)現(xiàn)其在該領(lǐng)域具有很強(qiáng)的創(chuàng)新與現(xiàn)實性意義,為臨床診療提供了新的思路和方向。第一部分:環(huán)狀RNA在老年髖部骨折患者中差異表達(dá)的研究目的:應(yīng)用環(huán)狀RNA芯片技術(shù)分析老年髖部骨折患者外周血血漿中環(huán)狀RNA的差異表達(dá),為老年髖部骨折后初期病情進(jìn)展及后期轉(zhuǎn)歸預(yù)測提供的有效的生物標(biāo)志物及其調(diào)控機(jī)制研究奠定基礎(chǔ)。方法:選擇符合條件的研究對象3例普通老年髖部骨折患者(實驗組)、3例體檢健康老年人(對照組)。分別收集研究對象外周靜脈血4-5ml,分離出血漿,提取總RNA,利用circRNA芯片技術(shù),篩查老年髖部骨折患者血漿中差異性表達(dá)的環(huán)狀RNA,利用生物信息學(xué)方法預(yù)測各項差異表達(dá)的環(huán)狀RNA的相關(guān)miRNA。結(jié)果:實驗組和對照組根據(jù)circRNA表達(dá)水平的不同,兩組之間折疊倍率(Fold Change, FC)2.0或-2.0, P0.05的有統(tǒng)計學(xué)差異的顯著差異表達(dá)的circRNA數(shù)據(jù)。circRNA表達(dá)水平在實驗組和對照組中的差異性表達(dá)相比,共得到2169種circRNA顯著差異性表達(dá),其中包括1173種表達(dá)上調(diào),差異倍數(shù)大于5倍有213種,996種表達(dá)下調(diào),差異倍數(shù)大于5倍有151種。生物信息學(xué)統(tǒng)計結(jié)果顯示環(huán)狀RNA可以通過與miRNA相互作用參與調(diào)控老年髖部骨折后初期病程的發(fā)展過程。結(jié)論:老年髖部骨折患者外周血血漿內(nèi)環(huán)狀RNA的表達(dá)較普通健康老年人具有異性,經(jīng)生物信息學(xué)統(tǒng)計差異性表達(dá)的環(huán)狀RNA有助于老年髖部骨折患者初期病情進(jìn)展及后期轉(zhuǎn)歸預(yù)測的研究,為相應(yīng)的機(jī)制研究提供有益的參考和補(bǔ)充。第二部分:環(huán)狀RNA在老年髖部骨折后死亡患者中差異表達(dá)的研究目的:應(yīng)用環(huán)狀RNA芯片技術(shù)分析老年髖部骨折后死亡患者外周血血漿中環(huán)狀RNA的差異表達(dá),為進(jìn)一步研究差異性表達(dá)的環(huán)狀RNA作為老年髖部骨折后死亡風(fēng)險評估、以及病情進(jìn)展轉(zhuǎn)歸的生物標(biāo)志物及其調(diào)控機(jī)制研究奠定基礎(chǔ)。方法:研究對象為老年髖部骨折患者30例,其中男性12例,女性18例,經(jīng)過骨折后一年的隨訪,3例因肺部感染死亡。3例髖部骨折后一年內(nèi)死亡的患者(死亡組)、3例普通老年髖部骨折患者(對照組),分別收集研究對象外周靜脈血4-5ml,分離出血漿,提取總RNA,利用circRNA芯片技術(shù),篩查老年髖部骨折后死亡患者血漿中差異性表達(dá)的環(huán)狀RNA,利用生物信息學(xué)方法預(yù)測各項差異表達(dá)的環(huán)狀RNA的相關(guān)miRNA,最后對部分感興趣的環(huán)狀RNA采用實時定量PCR進(jìn)行驗證。結(jié)果:死亡組和對照組根據(jù)circRNA表達(dá)水平的不同,兩組之間折疊倍率(Fold Change, FC)2.0或-2.0, P0.05的有統(tǒng)計學(xué)差異的顯著差異表達(dá)的circRNA數(shù)據(jù)。circRNA表達(dá)水平在死亡組和對照組中的差異性表達(dá)相比,共得到1263種circRNA顯著差異性表達(dá),其中包括670種表達(dá)上調(diào),差異倍數(shù)大于5倍有131種,593種表達(dá)下調(diào),差異倍數(shù)大于5倍有119種。其中對hsa-circRNA-103637、hsa-circRNA-092417兩種環(huán)狀RNA經(jīng)實時定量PCR驗證呈上調(diào)趨勢;另外3種環(huán)狀 RNA: hsa-circRNA-100035、hsa-circRNA-045308、hsa-circRNA-001057 經(jīng)實時定量PCR驗證表達(dá)呈下調(diào)趨勢,和芯片結(jié)果一致。生物信息學(xué)統(tǒng)計結(jié)果顯示環(huán)狀RNA可以通過與miRNA相互作用參與調(diào)控老年髖部骨折后導(dǎo)致死亡主要并發(fā)癥的發(fā)生和發(fā)展過程。結(jié)論:老年髖部骨折后死亡患者外周血血漿內(nèi)環(huán)狀RNA的表達(dá)較普通骨折患者具有差異性,顯著差異的和特異性表達(dá)的環(huán)狀RNA有望成為老年髖部骨折后死亡事件發(fā)生潛在的診斷標(biāo)志物。此外,經(jīng)生物信息學(xué)統(tǒng)計差異性表達(dá)的環(huán)狀RNA有助于老年髖部骨折患者死亡事件機(jī)制的研究,為機(jī)制研究提供有益的參考和補(bǔ)充。
[Abstract]:Hip fractures are one of the most likely fractures in the elderly. Many studies at home and abroad have shown that the mortality and death risk of hip fractures in the elderly are significantly higher than those of the normal age group. The excessive systemic inflammatory response to the elderly hip fracture leads to multiple organ dysfunction, which is the only one that causes death. At present, some scoring systems and several biomarkers have been used to evaluate the severity of the disease and the risk of risk, reduce the degree of organ damage and improve the prognosis of the patients. However, there are still some studies on the accurate diagnosis and treatment of multiple organ failure caused by systemic inflammatory response and the corresponding mechanism research. It needs further improvement, especially the need to find more reliable, specific and sensitive biomarkers for the process monitoring and treatment evaluation of the disease in this field. With the in-depth study of the circular RNA system, it is found that it has a strong innovative and practical significance in this field, and provides a new way of thinking for clinical diagnosis and treatment. Part 1: Study of differential expression of annular RNA in elderly hip fracture patients: analysis of the differential expression of ring RNA in peripheral blood plasma in elderly hip fracture patients by circular RNA chip technology, and to provide effective biomarkers and regulation for the early progression and prognosis of the elderly hip fracture. Methods: 3 cases of common elderly hip fracture (experimental group) and 3 healthy aged people (control group) were selected. The 4-5ml of peripheral venous blood was collected, the bleeding plasma was separated and the total RNA was extracted. The differential table of plasma in the elderly patients with hip fracture was screened by circRNA chip technology. The cyclic RNA of Da was used to predict the related miRNA. results of different expressions of cyclic RNA using bioinformatics methods: the experimental group and the control group based on the difference of the circRNA expression level, the two groups of folding rates (Fold Change, FC) 2 or -2.0, and the significant difference in the statistical difference expressed in P0.05, the.CircRNA expression level of the circRNA data was true Compared with the difference expression in the test group and the control group, 2169 different expressions of circRNA were obtained, including 1173 kinds of expression up regulation, the difference multiplier is more than 5 times 213, the 996 kinds of expressions are down, the difference multiple is more than 5 times 151. The bioinformatics statistics show that the ring RNA can participate in the regulation of the aged by interacting with miRNA. The development process of the initial course after hip fracture. Conclusion: the expression of annular RNA in peripheral blood plasma in elderly hip fracture patients is more heterosexual than that of normal healthy old people. The circular RNA expressed differently by bioinformatics is helpful to the study of the early progression and prognosis of the elderly hip fracture patients, which is the corresponding mechanism. The study provides useful references and supplements. The second part: the study of differential expression of annular RNA in elderly patients with hip fracture. Objective: to analyze the differential expression of cyclic RNA in peripheral blood plasma in elderly patients with hip fracture after the aged hip fracture, and to further study the differential expression of circular RNA as the elderly hip. The risk assessment of post fracture death, and the study of biomarkers and regulatory mechanisms of the progression of the disease were established. Methods: 30 elderly patients with hip fractures were studied, including 12 males and 18 females. After one year of follow-up after fracture, 3 patients died within one year of.3 cases of hip fracture due to pulmonary infection and death (death group). 3 cases of common aged hip fracture (control group) were collected, the peripheral venous blood 4-5ml was collected, the hemorrhagic pulp was separated and the total RNA was extracted. The differential expression of circular RNA in the plasma of the dead patients after the hip fracture was screened by circRNA chip technology, and the related miR related to the differential expression of annular RNA was predicted by the method of bioinformatics. NA, at last, some interesting circular RNA were verified by real time quantitative PCR. Results: the death and control groups based on the difference of the circRNA expression level, the two groups of folding rates (Fold Change, FC) 2 or -2.0, and the statistically significant difference expressed in P0.05, the.CircRNA expression of circRNA data was in the death and control groups There were 1263 different expressions of circRNA, including 670 up-regulated expressions, 131 different multiplier than 5 times, 593 down-regulation and 119 different multiplier than 5 times, of which hsa-circRNA-103637, hsa-circRNA-092417 two ring RNA showed up trend by real-time quantitative PCR verification; the other 3 rings were up. The expression of RNA: hsa-circRNA-100035, hsa-circRNA-045308, and hsa-circRNA-001057 was down regulated by real-time quantitative PCR. The results of bioinformatics statistics show that ring RNA can participate in the occurrence and development of the major complications of death and death through the interaction with miRNA in the regulation of hip fracture in the elderly. The expression of annular RNA in the peripheral blood plasma of the elderly patients with hip fracture is different from that of the common fracture patients. The significant difference and specific expression of cyclic RNA may be a potential diagnostic marker for the death events of the elderly hip fracture. Furthermore, the cyclic RNA expressed by bioinformatics statistics is helpful to the elderly. The study on the mechanism of death in patients with hip fracture in the year provides useful reference and supplement for mechanism research.
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R683
本文編號：2161498
[Abstract]:Hip fractures are one of the most likely fractures in the elderly. Many studies at home and abroad have shown that the mortality and death risk of hip fractures in the elderly are significantly higher than those of the normal age group. The excessive systemic inflammatory response to the elderly hip fracture leads to multiple organ dysfunction, which is the only one that causes death. At present, some scoring systems and several biomarkers have been used to evaluate the severity of the disease and the risk of risk, reduce the degree of organ damage and improve the prognosis of the patients. However, there are still some studies on the accurate diagnosis and treatment of multiple organ failure caused by systemic inflammatory response and the corresponding mechanism research. It needs further improvement, especially the need to find more reliable, specific and sensitive biomarkers for the process monitoring and treatment evaluation of the disease in this field. With the in-depth study of the circular RNA system, it is found that it has a strong innovative and practical significance in this field, and provides a new way of thinking for clinical diagnosis and treatment. Part 1: Study of differential expression of annular RNA in elderly hip fracture patients: analysis of the differential expression of ring RNA in peripheral blood plasma in elderly hip fracture patients by circular RNA chip technology, and to provide effective biomarkers and regulation for the early progression and prognosis of the elderly hip fracture. Methods: 3 cases of common elderly hip fracture (experimental group) and 3 healthy aged people (control group) were selected. The 4-5ml of peripheral venous blood was collected, the bleeding plasma was separated and the total RNA was extracted. The differential table of plasma in the elderly patients with hip fracture was screened by circRNA chip technology. The cyclic RNA of Da was used to predict the related miRNA. results of different expressions of cyclic RNA using bioinformatics methods: the experimental group and the control group based on the difference of the circRNA expression level, the two groups of folding rates (Fold Change, FC) 2 or -2.0, and the significant difference in the statistical difference expressed in P0.05, the.CircRNA expression level of the circRNA data was true Compared with the difference expression in the test group and the control group, 2169 different expressions of circRNA were obtained, including 1173 kinds of expression up regulation, the difference multiplier is more than 5 times 213, the 996 kinds of expressions are down, the difference multiple is more than 5 times 151. The bioinformatics statistics show that the ring RNA can participate in the regulation of the aged by interacting with miRNA. The development process of the initial course after hip fracture. Conclusion: the expression of annular RNA in peripheral blood plasma in elderly hip fracture patients is more heterosexual than that of normal healthy old people. The circular RNA expressed differently by bioinformatics is helpful to the study of the early progression and prognosis of the elderly hip fracture patients, which is the corresponding mechanism. The study provides useful references and supplements. The second part: the study of differential expression of annular RNA in elderly patients with hip fracture. Objective: to analyze the differential expression of cyclic RNA in peripheral blood plasma in elderly patients with hip fracture after the aged hip fracture, and to further study the differential expression of circular RNA as the elderly hip. The risk assessment of post fracture death, and the study of biomarkers and regulatory mechanisms of the progression of the disease were established. Methods: 30 elderly patients with hip fractures were studied, including 12 males and 18 females. After one year of follow-up after fracture, 3 patients died within one year of.3 cases of hip fracture due to pulmonary infection and death (death group). 3 cases of common aged hip fracture (control group) were collected, the peripheral venous blood 4-5ml was collected, the hemorrhagic pulp was separated and the total RNA was extracted. The differential expression of circular RNA in the plasma of the dead patients after the hip fracture was screened by circRNA chip technology, and the related miR related to the differential expression of annular RNA was predicted by the method of bioinformatics. NA, at last, some interesting circular RNA were verified by real time quantitative PCR. Results: the death and control groups based on the difference of the circRNA expression level, the two groups of folding rates (Fold Change, FC) 2 or -2.0, and the statistically significant difference expressed in P0.05, the.CircRNA expression of circRNA data was in the death and control groups There were 1263 different expressions of circRNA, including 670 up-regulated expressions, 131 different multiplier than 5 times, 593 down-regulation and 119 different multiplier than 5 times, of which hsa-circRNA-103637, hsa-circRNA-092417 two ring RNA showed up trend by real-time quantitative PCR verification; the other 3 rings were up. The expression of RNA: hsa-circRNA-100035, hsa-circRNA-045308, and hsa-circRNA-001057 was down regulated by real-time quantitative PCR. The results of bioinformatics statistics show that ring RNA can participate in the occurrence and development of the major complications of death and death through the interaction with miRNA in the regulation of hip fracture in the elderly. The expression of annular RNA in the peripheral blood plasma of the elderly patients with hip fracture is different from that of the common fracture patients. The significant difference and specific expression of cyclic RNA may be a potential diagnostic marker for the death events of the elderly hip fracture. Furthermore, the cyclic RNA expressed by bioinformatics statistics is helpful to the elderly. The study on the mechanism of death in patients with hip fracture in the year provides useful reference and supplement for mechanism research.
【學(xué)位授予單位】：中國人民解放軍醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2017
【分類號】：R683
【參考文獻(xiàn)】
相關(guān)期刊論文 前2條
1 李紹光;劉智;孫天勝;任繼鑫;;老年髖部骨折術(shù)后1年死亡率及危險因素分析[J];北京醫(yī)學(xué);2015年11期
2 夏世金;高文;胡明冬;劉露梅;邰先桃;;環(huán)狀RNA的研究現(xiàn)狀及展望[J];中華肺部疾病雜志(電子版);2014年06期
，本文編號：2161498
本文鏈接：http://sikaile.net/yixuelunwen/waikelunwen/2161498.html
最近更新
教材專著
