本文選題：關(guān)節(jié)置換術(shù) + 假體無菌性松動(dòng)　； 參考：《上海交通大學(xué)》2014年博士論文

【摘要】：【目的】對于與無菌性松動(dòng)相關(guān)的生物標(biāo)記物的高質(zhì)量研究進(jìn)行系統(tǒng)評價(jià),為無菌性松動(dòng)診斷研究中的生物標(biāo)志物的合理選擇提供科學(xué)依據(jù)。對接受了金屬對金屬的表面髖關(guān)節(jié)置換、金屬對聚乙烯和陶瓷對陶瓷的全髖置換術(shù)患者的臨床結(jié)果進(jìn)行回顧性隨訪比較,明確不同磨擦界面與骨溶解的關(guān)系,也為無菌性松動(dòng)的早期診斷研究的合理分組提供依據(jù)。明確多種骨溶解或骨重建的生物標(biāo)記物與人工髖關(guān)節(jié)假體早期無菌性松動(dòng)的關(guān)系,及其診斷價(jià)值。明確慢病毒介導(dǎo)的白介素1受體拮抗蛋白(Interleukin 1 receptor antagonist,IL-1Ra)基因是否能夠在小鼠骨髓間充質(zhì)干細(xì)胞體外穩(wěn)定的表達(dá)。【方法】經(jīng)過系統(tǒng)檢索納入了32篇縱向研究,采用牛津循證醫(yī)學(xué)中心證據(jù)水平和Newcastle-Ottawa質(zhì)量評價(jià)量表評價(jià)研究質(zhì)量,通過證據(jù)綜合分析評價(jià)每種標(biāo)記物對于無菌性松動(dòng)的診斷效能和推薦級別。選擇154例(171髖)施行全髖關(guān)節(jié)置換術(shù)的患者,包括27髖的金屬對金屬表面置換(第1)組,41例的陶瓷對陶瓷全髖置換(第2)組和103髖的金屬對聚乙烯全髖置換(第3)組。記錄年骨溶解率和術(shù)后并發(fā)癥等指標(biāo)。選擇105例研究對象,包括31例擬行關(guān)節(jié)翻修術(shù)的患者(晚期松動(dòng)組);15例具有臨床及影像學(xué)松動(dòng)表現(xiàn)但不需要翻修手術(shù)的患者(早期松動(dòng)組);19例無松動(dòng)表現(xiàn)的患者(穩(wěn)定假體組);40例健康成人。用酶免法檢測血漿骨保護(hù)素(Osteoprotegerin,OPG),細(xì)胞核因子κB受體活化因子配基(Receptor activator of the nuclear factorκB ligand,RANKL),Ⅰ型膠原N末端肽(Cross-linked N-telopeptide of type I collagen,NTX),I型前膠原羧基端肽(Carboxy terminal propeptide of type I procollagen,PICP),腫瘤壞死因子(Tumor necrosis factor,TNF)α和白介素(Interleukin-1,IL)1β的含量。各標(biāo)記物的血漿水平進(jìn)行組間單獨(dú)(SPSS軟件)和綜合(Reviewmanager軟件)的統(tǒng)計(jì)分析。介導(dǎo)IL-1Ra/cop GFP基因的慢病毒載體構(gòu)建后轉(zhuǎn)染小鼠骨髓間充質(zhì)干細(xì)胞,采用RT-q PCR和Western bolt檢測IL-1Ra的體外表達(dá)。用CCK-8試劑盒檢測細(xì)胞活力,并用臺(tái)盤藍(lán)染色和MTT分析檢測干細(xì)胞生長能力�！窘Y(jié)果】48種生物標(biāo)記物或細(xì)胞因子中,只有NTX有中等證據(jù),推薦級別為B;IL-1β,TNF-α,IL-8,抗酒石酸酸性磷酸酶,前列環(huán)素E2和骨鈣素有有限證據(jù),推薦級別為C。經(jīng)過平均5年的隨訪,校正后第1組的年骨溶解率顯著低于第2和3組(p值均0.0001)。第1組的術(shù)后并發(fā)癥最少,并且沒有金屬過敏反應(yīng)。晚期松動(dòng)組與對照組相比只有IL-1β和OPG的差異有顯著性(均為p0.05),血漿IL-1β診斷效能最強(qiáng)。6項(xiàng)標(biāo)記物血漿水平的聯(lián)合分析不但在晚期松動(dòng)組和穩(wěn)定組,而且在穩(wěn)定組和健康組之間差異也有顯著性(p值均為0.02),并且各組內(nèi)6項(xiàng)標(biāo)記物之間的異質(zhì)性極低(I2=0)。介導(dǎo)IL-1Ra/cop GFP基因的第三代慢病毒載體構(gòu)建良好,轉(zhuǎn)染小鼠骨髓間充質(zhì)干細(xì)胞后能穩(wěn)定表達(dá)IL-1Ra,細(xì)胞增殖周期短,但是早期生長能力好,而且相比未轉(zhuǎn)染的細(xì)胞活力更好。【結(jié)論】與人工關(guān)節(jié)假體無菌性松動(dòng)相關(guān)的生物標(biāo)記物中IL-1β,TNF-a,IL-8,抗酒石酸酸性磷酸酶,前列環(huán)素E2和骨鈣素,尤其是NTX有中等證據(jù),可以推薦作為可靠的檢測標(biāo)記物。三種全髖置換的界面材料中金屬對金屬表面置換的骨溶解進(jìn)展最少,而且沒有金屬顆粒副反應(yīng)。6項(xiàng)生物標(biāo)記物中IL-1β診斷效能最強(qiáng)。在傳統(tǒng)的體檢和影像學(xué)檢查認(rèn)為假體穩(wěn)定的全髖術(shù)后患者中多項(xiàng)標(biāo)記物的聯(lián)合分析有顯著升高。慢病毒轉(zhuǎn)染的小鼠骨髓間充質(zhì)干細(xì)胞能穩(wěn)定表達(dá)外源性IL-1Ra,細(xì)胞活力和增殖能力好。
[Abstract]:[Objective] to systematically evaluate the high quality study of biomarkers associated with aseptic loosening to provide a scientific basis for the rational selection of biomarkers in the diagnosis of aseptic loosening. The clinical results were followed up and compared to clarify the relationship between the different friction interfaces and osteolysis, and to provide the basis for the rational grouping of early diagnostic studies for aseptic loosening. Whether the interleukin 1 receptor antagonist (Interleukin 1 receptor antagonist, IL-1Ra) gene is able to express in vitro stable expression in mouse bone marrow mesenchymal stem cells in vitro. [Methods] 32 longitudinal studies were included through systematic retrieval, and the evaluation of evidence water level and Newcastle-Ottawa quality assessment scale in Oxford evidence-based medicine center was used. Quality, the diagnostic efficacy and recommended level of each marker for aseptic loosening were evaluated through a comprehensive analysis of evidence. 154 patients (171 hips) underwent total hip replacement, including 27 hip metal surface replacement (first), 41 ceramic to ceramic total hip replacement (second) and 103 hip metal to polyethylene total hip replacement. Third) group. Record annual osteolysis and postoperative complications. Select 105 subjects, including 31 patients with prosthetic revision (late loosening group); 15 patients with clinical and imaging looseness but no refurbishment (early loosening group); 19 patients with no loosening (stable prosthesis); 40 healthy adults. Osteoprotegerin (OPG), nuclear factor kappa B receptor activating factor ligand (Receptor activator of the nuclear factor kappa B ligand, RANKL), and collagen carboxyl terminated peptide of type I collagen, were detected by enzyme immunoassay. Ocollagen, PICP), the content of tumor necrosis factor (Tumor necrosis factor, TNF) alpha and interleukin (Interleukin-1, IL) 1 beta. Statistical analysis of the plasma levels of each marker (SPSS software) and synthesis (Reviewmanager software). The mouse bone marrow mesenchymal stem cells were transfected after the lentivirus vector of IL-1Ra/cop GFP gene was mediated. RT-q PCR and Western bolt were used to detect the expression of IL-1Ra in vitro. Cell viability was detected by CCK-8 kit, and the growth ability of stem cells was detected with table blue staining and MTT analysis. [results] only NTX has medium evidence, and the recommended grade is B; IL-1 beta, TNF- alpha, IL-8, tartaric acid acid phosphatase, before 48 kinds of biomarkers or cytokines. There was limited evidence of cyclin E2 and osteocalcin. The recommended grade was C. after an average of 5 years of follow-up. The annual osteolysis rate in the first groups was significantly lower than that of second and third groups (P 0.0001). The first group had the least postoperative complications and no metal anaphylaxis. The difference between the late loosening group and the control group was significantly higher than the control group (P0 and OPG). .05), the combined analysis of plasma levels of the strongest.6 markers in plasma IL-1 beta diagnosis was not only in the late loosening group and the stable group, but also between the stable group and the healthy group (the p value was 0.02), and the heterogeneity between the 6 markers in each group was very low (I2=0). The third generation of the lentivirus vector of the IL-1Ra/cop GFP gene was mediated. Well constructed, transfected mouse bone marrow mesenchymal stem cells can express IL-1Ra steadily, the cell proliferation cycle is short, but early growth ability is good, and compared with untransfected cells, the cell viability is better. [Conclusion] IL-1 beta, TNF-a, IL-8, tartaric acid acid phosphatase, prostacyclin in the biomarkers associated with aseptic loosening of artificial joint prosthesis E2 and osteocalcin, especially NTX, have medium evidence, which can be recommended as a reliable detection marker. Metal surface replacement osteolysis is the least in three total hip replacement interface materials, and no metal particle side reaction in.6 biomarkers has the strongest diagnostic efficacy of IL-1 beta. In traditional physical examination and imaging examination The combined analysis of multiple markers in patients with stable hip prosthesis has been significantly increased. The mouse bone marrow mesenchymal stem cells transfected by lentivirus can stabilize the expression of exogenous IL-1Ra, and the cell viability and proliferation ability are good.
【學(xué)位授予單位】：上海交通大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2014
【分類號】：R318.17;R687.4

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