本文選題：急性主動脈夾層 + 基因芯片�。� 參考：《北京協(xié)和醫(yī)學(xué)院》2015年博士論文

【摘要】：第一部分A型急性主動脈夾層主動脈組織差異表達(dá)基因的篩選和驗證摘要目的：急性主動脈夾層(Acute aortic dissection, AAD)是臨床常見的危急重癥,具有較高的致死性,但其分子機制尚未闡明。本研究通過全基因組轉(zhuǎn)錄譜芯片分析篩選AAD患者病變主動脈組織和正常對照主動脈組織差異表達(dá)的基因,通過生物信息學(xué)分析挑選核心差異表達(dá)基因在蛋白水平進(jìn)行驗證,為后續(xù)尋找新的有關(guān)主動脈夾層發(fā)生的重要信號傳導(dǎo)途徑和重要基因及探討這些基因在AAD發(fā)生、發(fā)展中的作用和機制奠定基礎(chǔ)。方法：采用標(biāo)準(zhǔn)的組織收集方法分別收集8例AAD患者和8例正常器官捐獻(xiàn)者的升主動脈標(biāo)本。AAD患者和正常對照各選取4例升主動脈組織標(biāo)本進(jìn)行全基因組表達(dá)譜芯片分析,篩選AAD患者和正常對照主動脈組織差異表達(dá)的基因,利用生物信息學(xué)分析差異表達(dá)的基因可能的生物學(xué)功能,根據(jù)生物信息學(xué)分析結(jié)果挑選可能在AAD發(fā)生、發(fā)展中具有重要作用的信號傳導(dǎo)通路和核心基因；然后提取8例AAD患者和8例正常對照的主動脈組織蛋白,通過Western blotting驗證mRNA表達(dá)明顯差異的核心基因在AAD患者和正常對照主動脈組織中的蛋白表達(dá)差異；由于轉(zhuǎn)化生長因子-β(Transform growth factor-β, TGF-β)信號通路是已知的與AAD發(fā)生相關(guān)的分子通路,同時在8例AAD患者和8例正常對照主動脈組織中通過Western blotting分析了TGF-β通路中關(guān)鍵分子SMAD2和SMAD3的蛋白表達(dá)是否有差異。結(jié)果：(1)基因表達(dá)譜芯片分析顯示,AAD患者病變主動脈組織與正常對照主動脈組織比較,mRNA表達(dá)差異大于2倍的基因有129個,其中83個基因表達(dá)上調(diào),46個基因表達(dá)下調(diào)。生物信息學(xué)分析提示,差異表達(dá)的基因主要涉及粘附斑(FN1、ITGA9、PAK7、C0L6A3、FLNC)和肌動蛋白骨架調(diào)節(jié)(FN1、ITGA9、PAK7、PIP5K1B, RRAS2)兩條信號通路,其中ITGA9基因是編碼整合素α9亞基的基因,在兩條信號傳導(dǎo)通路中具有關(guān)鍵作用,表達(dá)下調(diào)達(dá)50%。因此本研究挑選了ITGA9作為可能與AAD發(fā)病相關(guān)的核心關(guān)鍵基因；(2)Western blotting分析證實,AAD患者主動脈組織中ITGA9的表達(dá)顯著低于正常對照(P=0.003)；(3)Western blotting分析顯示,AAD患者病變主動脈組織中磷酸化SMAD2 (p-SMAD2)表達(dá)下調(diào)(P0.05),而總SMAD2、總SMAD3、磷酸化SMAD3(p-SMAD3)和正常對照無顯著差異(P值均0.05)。結(jié)論：通過組織表達(dá)譜芯片分析發(fā)現(xiàn)AAD患者病變主動脈組織和正常對照主動脈組織的基因表達(dá)譜有較大差異。生物信息分析顯示,主動脈夾層病變組織中表達(dá)明顯差異的兩條通路是粘附斑和肌動蛋白骨架調(diào)節(jié)相關(guān)通路,其中ITGA9基因是同時參與兩條通路的核心基因；在蛋白水平證實AAD患者病變主動脈組織的ITGA9表達(dá)降低,而傳統(tǒng)TGF-β信號通路中的p-SMAD2蛋白表達(dá)水平在AAD患者中顯著降低,但其他關(guān)鍵成分無明顯變化,提示ITGA9基因可能是參與AAD發(fā)生的重要基因,需要進(jìn)一步的功能研究驗證其在AAD發(fā)生發(fā)展中的作用；p-SMAD2是否與ITGA9相互作用參與AAD發(fā)病機制尚需要進(jìn)一步實驗研究。第二部分ITGA9對大鼠主動脈血管平滑肌細(xì)胞表型的影響摘要目的：主動脈中層退行性變是目前被廣為認(rèn)同的主動脈夾層的主要發(fā)病機制,但其確切的分子機制尚不明確。血管平滑肌細(xì)胞(Vascular smooth muscle cell, VSMC)是維持主動脈正常結(jié)構(gòu)和功能的主要成分。VSMC有收縮型和合成型兩種表型,VSMC的表型轉(zhuǎn)換是主動脈退行性變的分子機制之一。前期實驗中我們通過基因芯片和蛋白水平驗證發(fā)現(xiàn)整合素α9亞基的編碼基因ITGA9在AAD患者病變主動脈組織中表達(dá)顯著低于正常對照。由于ITGA9在主動脈VSMC胞膜表達(dá),且同時參與細(xì)胞粘附和骨架蛋白調(diào)節(jié)通路,因此推測ITGA9在AAD的發(fā)病中可能具有重要作用。本實驗部分?jǐn)M通過細(xì)胞學(xué)實驗研究ITGA9表達(dá)改變對VSMC表型的影響,探討ITGA9表達(dá)下調(diào)在AAD發(fā)病中的可能機制。方法：首先通過組織塊貼壁法原代培養(yǎng)大鼠主動脈VSMC并證實大鼠主動脈VSMC表達(dá)ITGA9;然后將熒光標(biāo)記的小分子RNA探針轉(zhuǎn)染VSMC,觀察小分子RNA在大鼠VSMC中的轉(zhuǎn)染效率；明確小分子RNA可轉(zhuǎn)染大鼠VSMC后,針對大鼠ITGA9基因設(shè)計特異性的短鏈干擾RNA (Short interfering RNA, siRNA),轉(zhuǎn)染大鼠VSMC敲低VSMC ITGA9的表達(dá),Western blotting檢測ITGA9敲低后VSMC收縮型標(biāo)志物(SM22α和α-SMA)和合成型標(biāo)志物(OPN和SMemb)表達(dá)變化以及細(xì)胞劃痕試驗觀察ITGA9敲低后VSMC增殖、遷移能力的變化；最后構(gòu)建腺病毒——ITGA9重組載體,包裝腺病毒,感染經(jīng)血小板源性生長因子(PDGF)誘導(dǎo)呈合成型的VSMC過表達(dá)ITGA9,Western blotting檢測過表達(dá)ITGA9后VSMC收縮型標(biāo)志物(SM22a和α-SMA)和合成型標(biāo)志物(SMemb)表達(dá)變化。結(jié)果：(1)組織塊貼壁法成功培養(yǎng)出原代大鼠主動脈VSMC并經(jīng)免疫熒光所鑒定；(2) Western blotting證實,大鼠主動脈VSMC表達(dá)ITGA9,為下一步干預(yù)ITGA9的表達(dá)奠定了基礎(chǔ)；(3)熒光標(biāo)記的小分子RNA能順利轉(zhuǎn)染大鼠主動脈VSMC;(4)針對ITGA9設(shè)計的三條siRNA,其中一條能高效敲低VSMC中ITGA9的表達(dá)；(5)ITGA9敲低后,經(jīng)Western blotting證實,VSMC收縮型標(biāo)志物(SM22 α和α-SMA)表達(dá)降低,合成型標(biāo)志物(OPN和SMemb)表達(dá)升高；細(xì)胞劃痕試驗顯示,ITGA9敲低后VSMC增殖、遷移能力增強,提示VSMC表型從收縮型向合成型轉(zhuǎn)換；(6)成功構(gòu)建腺病毒-ITGA9重組載體,腺病毒包裝后病毒滴度達(dá)病毒滴度達(dá)1×109PFU/mL;(7)重組腺病毒感染大鼠主動脈VSMC過表達(dá)ITGA9后,VSMC收縮型標(biāo)志物SM22 α顯著升高(P=0.017),α-SMA表達(dá)也升高(P=0.119), SMemb表達(dá)降低(P=0.104),但未到達(dá)統(tǒng)計學(xué)意義。結(jié)論：ITGA9表達(dá)改變會引起VSMC表型的轉(zhuǎn)化,ITGA9的低表達(dá)可能通過誘導(dǎo)VSMC從收縮型向合成型轉(zhuǎn)換參與AAD的發(fā)生。本實驗結(jié)果提示ITGA9基因表達(dá)異�？赡軈⑴c主動脈夾層發(fā)生的分子機制。敲低后,經(jīng)Western blotting證實,VSMC收縮型標(biāo)志物(SM22 α和α-SMA)表達(dá)降低,合成型標(biāo)志物(OPN和SMemb)表達(dá)升高；細(xì)胞劃痕試驗顯示,ITGA9敲低后VSMC增殖、遷移能力增強,提示VSMC表型從收縮型向合成型轉(zhuǎn)換；(6)成功構(gòu)建腺病毒-ITGA9重組載體,腺病毒包裝后病毒滴度達(dá)病毒滴度達(dá)1×109PFU/mL;(7)重組腺病毒感染大鼠主動脈VSMC過表達(dá)ITGA9后,VSMC收縮型標(biāo)志物SM22 α顯著升高(P=0.017),α-SMA表達(dá)也升高(P=0.119), SMemb表達(dá)降低(P=0.104),但未到達(dá)統(tǒng)計學(xué)意義。結(jié)論：ITGA9表達(dá)改變會引起VSMC表型的轉(zhuǎn)化,ITGA9的低表達(dá)可能通過誘導(dǎo)VSMC從收縮型向合成型轉(zhuǎn)換參與AAD的發(fā)生。本實驗結(jié)果提示ITGA9基因表達(dá)異常可能參與主動脈夾層發(fā)生的分子機制。第三部分入院時D-二聚體水平對A型急性主動脈夾層患者短期和長期死亡的影響摘要目的：D-二聚體是交聯(lián)的纖維蛋白降解產(chǎn)物,其升高提示凝血和纖溶系統(tǒng)的激活。先前研究提示D-二聚體可作為輔助診斷或排除急性主動脈夾層(Acute aortic dissection, AAD)的分子標(biāo)志物,但其作為預(yù)后評估因素的研究較少。本研究通過相對大樣本的研究評估入院時D-二聚體水平對A型AAD患者住院期間和長期隨訪死亡的影響,旨在探討入院時D-二聚體水平對AAD短期和長期預(yù)后的預(yù)測價值。方法：本研究設(shè)計為單中心、前瞻性、觀察性研究,研究對象為連續(xù)入選從2010年3月至2011年6月就診于阜外心血管病醫(yī)院急診中心并經(jīng)CT證實的A型AAD患者。排除標(biāo)準(zhǔn)為主動脈壁內(nèi)血腫、主動脈透壁潰瘍、外傷性主動脈破裂、醫(yī)源性夾層、妊娠、馬凡綜合征、家族性胸主動脈夾層等。采集患者入院時的基線資料,檢測患者入院時D-二聚體水平,并記錄患者住院期間的其他臨床資料。主要終點事件為住院期間全因死亡率和長期隨訪全因死亡率。首先比較存活患者和死亡患者入院時D-二聚體水平的差異；然后按入院時D-二聚體水平四分位分組比較各組患者住院死亡率和長期死亡率；通過單因素和多因素Cox回歸分析入院時D-二聚體水平和住院死亡和長期死亡的相關(guān)性。由手術(shù)治療對患者預(yù)后有顯著影響,將患者分為手術(shù)治療組和保守治療組,比較兩組中不同D-二聚體水平(6.10μg/mL和≤6.10 μ g/mL)的患者住院死亡率和長期死亡率的差異。結(jié)果：入選2010年3月至2011年6月間就診于阜外心血管病醫(yī)院并經(jīng)主動脈CT檢查確診的AAD患者共375例,其中A型AAD 225例,B型AAD 150例。排除13例患者臨床資料不全、失訪或符合排除標(biāo)準(zhǔn),共212例A型AAD進(jìn)入統(tǒng)計分析�；颊咧形蛔≡禾鞌�(shù)14天(25%~75%,9~20天),出院后中位隨訪時間18.8月(25%-75%,6.7-24.4月)�；颊咂骄挲g48.5±11.5歲,男性比例較高(75.9%)。住院期間全因死亡率和長期隨訪全因死亡率分別為12.7%(27/212)和12.4%(23/185)。與存活者相比,死亡患者入院時D-二聚體水平顯著增高(中位數(shù)6.8 vs.2.5 μg/mL, P0.001)、白細(xì)胞計數(shù)、肌酐水平也顯著高于存活組患者(P值均0.001),但接受手術(shù)治療的比例顯著低于存活組患者(14.0% vs.74.7%,P0.001)。將患者按入院時D-二聚體四分位分組(Ql:≤1.06 μg/mL; Q2:1.07~2.82 μg/mL; Q3:2.83-6.10 μg/mL; Q4:6.10μg/mL),第四分位(Q4)組患者住院期間死亡率(30.2%)和長期隨訪死亡率(24.3%)均顯著高于其他組患者(P0.001和P=0.046)。多因素Cox回歸分析顯示,在校正了其他影響住院期間死亡和長期隨訪死亡的因素后,入院時D-二聚體6.10 μg/mL是影響A型AAD患者住院期間死亡的獨立危險因素(HR=6.124,95%CI 1.345-27.892, P=0.019),但入院時D-二聚體水平和AAD患者長期死亡無顯著相關(guān)性。是否接受手術(shù)治療是影響AAD患者住院期間死亡和長期隨訪死亡最主要因素。將患者按是否接受手術(shù)治療分組后,接受手術(shù)治療的患者中,入院時D-二聚體6.10μg/mL和≤6.10μg/mL的患者比較住院期間死亡率和長期隨訪死亡率無顯著差異,而保守治療的患者中,入院時D-二聚體6.10μg/mL的患者住院期間死亡率和長期隨訪死亡率均顯著高于入院時D-二聚體≤6.10μg/mL的患者。結(jié)論:(1)手術(shù)治療是降低A型AAD患者住院期間死亡和長期死亡的主要措施；(2)入院時D-二聚體水平增高(6.10μg/mL)增加住院期間死亡風(fēng)險,但和長期死亡無相關(guān)性；(3)入院時D-二聚體水平對保守治療的A型AAD患者預(yù)后可能有更好的預(yù)測價值。
[Abstract]:Selection and validation of differentially expressed genes in aortic dissection of type A acute aortic dissection (Acute aortic dissection, AAD) is a common clinical critical disease, with high lethality, but its molecular mechanism has not been elucidated. This study screened AAD by whole genome transcriptional chip analysis. The gene differentially expressed in the aortic tissue and the normal control of the aorta, selected the core differentially expressed genes through bioinformatics analysis to verify the protein level, in order to find out the important signal transduction pathways and important bases related to the occurrence of aortic dissection and to explore the development of these genes in AAD. Methods: a standard tissue collection method was used to collect 8 cases of AAD patients and 8 normal organ donors in the ascending aorta of.AAD patients and normal controls, and 4 ascending aorta tissue specimens were selected for total genomic chip analysis. The difference between the selected AAD patients and the normal control aorta was poor. Differentially expressed genes, using bioinformatics to analyze the possible biological functions of differentially expressed genes, select the signal transduction pathways and core genes that may play an important role in the development of AAD according to the bioinformatics analysis results, and then extract 8 cases of AAD and 8 normal controls of the aortic tissue protein, through Western Blotting verifies the difference in the protein expression in the AAD patients and the normal control aorta, while the mRNA signaling pathway is known to be a known molecular pathway associated with AAD, and in 8 cases of AAD and 8 normal controls. Western blotting was used to analyze the difference in the protein expression of SMAD2 and SMAD3 key molecules in TGF- beta pathway. Results: (1) gene expression chip analysis showed that there were 129 genes in the AAD patients' aorta and the normal control aorta, and the expression of mRNA was more than 2 times, of which 83 genes were up-regulated and 46. The bioinformatics analysis suggests that the differentially expressed genes are mainly involved in two signaling pathways: FN1, ITGA9, PAK7, C0L6A3, FLNC, and actin cytoskeleton regulation (FN1, ITGA9, PAK7, PIP5K1B, RRAS2), of which ITGA9 gene is the gene encoding integrin 9 subunit, which plays a key role in the two signal transduction pathways. In this study, ITGA9 was selected as a key key gene for the pathogenesis of AAD, and (2) Western blotting analysis confirmed that the expression of ITGA9 in the aorta of AAD patients was significantly lower than that of the normal control (P=0.003); (3) Western blotting analysis showed that the phosphorylation SMAD2 in the pathological aorta tissues of AAD patients. There was no significant difference in expression (P0.05), while total SMAD2, total SMAD3, phosphorylated SMAD3 (p-SMAD3) and normal controls were not significantly different (P value was 0.05). Conclusion: the gene expression profiles of the aorta and normal control aorta of the patients with AAD were significantly different by tissue expression chip analysis. Bioinformatics analysis showed that the aortic dissection was dissecting. The two pathways that express distinct differences in the tissues are the regulatory pathway of the adhesion and actin framework, in which the ITGA9 gene is the core gene involved in the simultaneous participation of two pathways, and the protein level indicates that the ITGA9 expression in the pathological aorta of the patients with AAD is reduced, while the level of p-SMAD2 protein expression in the traditional TGF- beta signaling pathway is in AAD patients. The ITGA9 gene may be an important gene involved in the occurrence of AAD. It needs further functional study to verify its role in the development of AAD, and the interaction of p-SMAD2 with ITGA9 to participate in the pathogenesis of AAD still needs further experimental study. The second part of ITGA9 is active to rats. Objective: the effect of the phenotype of vascular smooth muscle cells (Vascular smooth muscle cell, VSMC) is the major component of the normal structure and function of the aorta,.VSM, the main pathogenesis of aortic dissection, which is widely recognized. C has two types of phenotype of contractile and synthetic type. The phenotypic conversion of VSMC is one of the molecular mechanisms of the degeneration of the aorta. In previous experiments, we found that the encoding gene ITGA9 of the integrin alpha 9 subunit was significantly lower than the normal control in the diseased aorta of AAD patients. As ITGA9 is in the aorta VS MC membrane expression, and also involved in cell adhesion and cytoskeleton regulation pathway, thus speculates that ITGA9 may play an important role in the pathogenesis of AAD. This experiment is to study the effect of ITGA9 expression on the VSMC phenotype by cytological experiments and to explore the possible mechanism of ITGA9 expression down regulation in AAD hair disease. The rat aorta VSMC was cultured and VSMC expressed ITGA9 in rat aorta, and then ITGA9 was expressed in rat aorta. Then VSMC was transfected by small molecule RNA probe labeled with fluorescence. The transfection efficiency of small molecule RNA in rat VSMC was observed. After the small molecule RNA could be transfected to rat VSMC, the specific short chain interference RNA (Short) aimed at the rat ITGA9 gene was designed. Ng RNA, siRNA), transfection of VSMC knockout low VSMC ITGA9 expression in rats, Western blotting detected VSMC contractile markers (SM22 alpha and alpha -SMA) and synthetic markers, and cell scratch test. VSMC overexpressed ITGA9 was induced by platelet derived growth factor (PDGF), and Western blotting was used to detect VSMC contractile markers (SM22a and -SMA) and synthetic markers (SMemb) after ITGA9 expression. Results: (1) tissue block adherence method successfully cultured primary rat aorta and was immune Identified by pestilence fluorescence; (2) Western blotting confirmed that VSMC expressed ITGA9 in rat aorta, which laid the foundation for further intervention in ITGA9 expression; (3) the fluorescent labeled small molecule RNA could successfully transfect VSMC in rat aorta; (4) three siRNA designed against ITGA9, one of which could knock low VSMC ITGA9 expression; (5) ITGA9 was low, The expression of VSMC contractile markers (SM22 and alpha -SMA) was reduced by Western blotting, and the expression of synthetic markers (OPN and SMemb) increased. The cell scratch test showed that the VSMC proliferation and migration ability increased after the knockout of ITGA9, suggesting that the VSMC phenotype changed from contractile to synthetic; (6) the adenovirus -ITGA9 recombinant vector was successfully constructed, adenovirus package was successfully constructed. After loading, the titer of virus titer reached 1 x 109PFU/mL; (7) after VSMC overexpressed ITGA9 in rat aorta of recombinant adenovirus, SM22 alpha of VSMC contraction marker increased significantly (P=0.017), the expression of alpha -SMA increased (P=0.119), SMemb expression decreased (P=0.104), but it was not statistically significant. Conclusion: ITGA9 expression change will cause the VSMC phenotypes to turn. The low expression of ITGA9 may be involved in the occurrence of AAD by inducing the convergent transformation of VSMC from contractile type. The results of this experiment suggest that abnormal ITGA9 gene expression may be involved in the molecular mechanism of aortic dissection. After the knock down, the expression of VSMC contraction markers (SM22 A and alpha -SMA) is reduced by Western blotting, and the synthetic marker (OPN and VSMC) The expression of SMemb increased, and the cell scratch test showed that the VSMC proliferation and migration ability increased after the ITGA9 knockout, suggesting that the VSMC phenotype was converted from contractile to co forming; (6) the recombinant adenovirus -ITGA9 recombinant vector was successfully constructed. The virus titer of the adenovirus was 1 * 109PFU/ mL after the adenovirus package, and (7) the recombinant adenovirus infected rat aorta VSMC overexpressed ITGA. After 9, the SM22 alpha of VSMC contraction marker increased significantly (P=0.017), the expression of alpha -SMA increased (P=0.119) and SMemb expression decreased (P=0.104), but it did not reach statistical significance. Conclusion: the change of ITGA9 expression may cause the transformation of the VSMC phenotype, and the low expression of ITGA9 may be involved in the occurrence of AAD, by inducing VSMC contractile type transformation. Results suggest that abnormal ITGA9 gene expression may participate in the molecular mechanism of aortic dissection. Third the effect of D- two polymer level on short-term and long-term death of patients with type A acute aortic dissection at admission: D- two polymer is a cross-linked fibrin degradation product, and its elevation suggests activation of coagulation and fibrinolytic system. The study suggests that D- two polymer can be used as a molecular marker for the diagnosis or exclusion of acute aortic dissection (Acute aortic dissection, AAD), but it is less studied as a prognostic factor. This study evaluated the effects of D- two polymer levels at admission to patients with A AAD during hospitalization and long-term follow-up by relatively large sample studies. The purpose of this study was to explore the predictive value of D- two polymer level on the short-term and long-term prognosis of AAD. Methods: This study was designed as a single center, prospective, observational study. The object of this study was to be selected from March 2010 to June 2011 in the emergency center of Fuwai Hospital of Cardiovascular Disease and the A type AAD patients confirmed by CT. The exclusion criteria were the aorta. Intramural hematoma, transmural ulcer of aorta, traumatic rupture of aorta, iatrogenic interlayer, pregnancy, Marfan syndrome, familial thoracic aortic dissection, etc.. Baseline data of hospitalized patients were collected, D- two polymer levels were detected at admission, and the patient's clinical data were recorded during hospitalization. The main terminal event was the death of all patients during hospitalization. Death rate and long-term follow-up all cause mortality. First, compare the difference in the D- two polymer level between the survivors and the death patients at admission, and then compare the hospitalized mortality and long-term mortality of the patients at the admission of the D- two polymer level Four Division at admission, and the D- two polymer level and hospital death at admission by single factor and multiple factor Cox regression analysis. The correlation between death and long-term death. The surgical treatment had a significant impact on the prognosis of the patients. The patients were divided into surgical and conservative treatment groups. The differences in hospitalization and long-term mortality were compared between the two groups of the two groups (6.10 mu g/mL and < 6.10 g/mL). There were 375 patients with AAD diagnosed by CT in Fuwai Hospital of Cardiovascular Disease, including 225 cases of A AAD and 150 cases of B AAD, excluding 13 patients with incomplete clinical data, missing or conforming to the exclusion criteria, 212 cases of A type AAD entered the statistical analysis. The median hospital days were 14 days (25%~ 75%, 9~20 days), and the median follow-up time after discharge was 18.8 months (25%-75%). The average age of the patients was 48.5 + 11.5 years, and the male ratio was higher (75.9%). The total cause and long-term follow-up mortality of the patients were 12.7% (27/212) and 12.4% (23/185). Compared with the survivors, the level of D- two polymer was significantly higher at admission (median 6.8 vs.2.5, g/mL, P0.001), white blood cell count, creatinine water. The level was significantly higher than that in the survival group (P value was 0.001), but the proportion of surgical treatment was significantly lower than that in the survival group (14% vs.74.7%, P0.001). The patients were divided into four sub groups (Ql: < 1.06 mu g/mL; Q2:1.07~2.82 u g/mL; Q3:2.83-6.10 mu g/mL; Q4:6.10 Mu g/mL), and the mortality rate of the fourth division patients during hospitalization. (30.2%) and long-term follow-up mortality (24.3%) were significantly higher than those in other groups (P0.001 and P=0.046). Multiple factor Cox regression analysis showed that D- two polymer 6.10 mu g/mL was an independent risk factor affecting the death of A type AAD patients during hospitalization after admission to other factors affecting death and long-term follow-up death. CI 1.345-27.892, P=0.019), but there was no significant correlation between the level of D- two polymer at admission and the long-term death of AAD patients. Whether surgical treatment was the most important factor affecting death and long-term follow-up of AAD patients was the most important factor. The patients who were treated with surgical treatment were admitted to the hospital after the operation, and the D- two polymer was 6.10 mu g at admission. Patients with /mL and less than 6.10 g/mL had no significant difference in hospital mortality and long-term follow-up mortality, while patients with conservative treatment had no significant difference.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號】：R543.1
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本文編號：2058747