本文選題：顱內(nèi)動脈瘤 + 病理學(xué)��； 參考：《山東大學(xué)》2016年博士論文

【摘要】：第一部分 NOS在顱內(nèi)動脈瘤發(fā)病機(jī)制中的作用研究研究背景：顱內(nèi)動脈瘤(Intracranial Aneurysm, IA)是動脈管壁病理性局限性擴(kuò)張產(chǎn)生的腦血管瘤樣突起,其破裂是引起人類自發(fā)性蛛網(wǎng)膜下腔出血(Subarachnoid Hemorrhage, SAH)最常見的原因。IA的發(fā)病率在我國腦血管意外中排第三位,僅次于缺血性腦卒中和高血壓腦出血。該病診治的難點(diǎn)在于臨床癥狀隱匿,大多數(shù)在破裂后才被發(fā)現(xiàn),致死率和致殘率極高。目前對于IA無理想的早期預(yù)防和篩查手段,是由于該病的病理學(xué)改變及發(fā)病機(jī)制尚未完全明確。最近的研究表明,受損動脈壁在血流動力學(xué)改變與炎性反應(yīng)的共同作用下暴露出一些抗原分子,引發(fā)分子水平上的一系列的級聯(lián)反應(yīng),最終導(dǎo)致動脈壁降解,引起IA的形成及破裂。其中一氧化氮合酶(Nitric Oxide Synthase, NOS)在這一分子級聯(lián)反應(yīng)中發(fā)揮重要作用。目前已有動物實(shí)驗(yàn)表明IA模型中存在特征性的病理學(xué)及NOS表達(dá)水平的改變,由于人體IA標(biāo)本難于獲取,尚缺乏活體動脈瘤標(biāo)本的病理學(xué)及NOS表達(dá)水平研究。如果能發(fā)現(xiàn)人體動脈瘤標(biāo)本中NOS明顯改變,則可以證實(shí)NOS可能在IA形成過程中發(fā)揮重要作用,將對IA的早期預(yù)防和篩查具有重要意義。眾多的研究表明,在IA形成和破裂過程中,除了NOS外尚有大量的細(xì)胞因子及炎性介質(zhì)等蛋白分子的表達(dá)及活性均會發(fā)生改變。因此,在這些紛繁復(fù)雜的細(xì)胞因子和蛋白分子相互作用網(wǎng)絡(luò)中,篩選出一些相對重要的樞紐環(huán)節(jié)或關(guān)鍵因子,明確它們在IA病理生理中的調(diào)控作用,就可能成為IA發(fā)病機(jī)制研究的突破口。以同位素標(biāo)記相對和絕對定量(Isobaric Tags for Relative and Absolute Quantitation, iTRAQ)技術(shù)為基礎(chǔ)的定量蛋白質(zhì)組學(xué)方法是近年來發(fā)展起來的一種高通量蛋白分子篩選方法,是目前差異表達(dá)蛋白分子篩選最強(qiáng)有力的工具。本研究擬對手術(shù)獲取的腦動脈瘤標(biāo)本進(jìn)行常規(guī)病理檢查,觀察動脈瘤壁的病理學(xué)變化及超微結(jié)構(gòu)改變；通過免疫組化方法檢測NOS在動脈瘤標(biāo)本內(nèi)表達(dá)情況；同時(shí)通過iTRAQ技術(shù)篩選動脈瘤標(biāo)本中差異表達(dá)蛋白分子,探討它們在動脈瘤形成和破裂中可能的作用,為進(jìn)一步闡明動脈瘤發(fā)病分子機(jī)制提供依據(jù),同時(shí)也為動脈瘤生物學(xué)治療的發(fā)展奠定基礎(chǔ)。目的：觀察動脈瘤的病理學(xué)及超微結(jié)構(gòu)改變,檢測NOS在顱內(nèi)動脈瘤中的表達(dá),通過iTRAQ技術(shù)篩選動脈瘤差異表達(dá)的蛋白分子,探討它們在動脈瘤形成和破裂中可能發(fā)揮的作用,為進(jìn)一步闡明動脈瘤發(fā)病分子機(jī)制提供依據(jù)。方法：選取山東大學(xué)齊魯醫(yī)院及濰坊市人民醫(yī)院神經(jīng)外科2012年5月～2014年11月神經(jīng)外科手術(shù)夾閉的腦動脈瘤標(biāo)本,同時(shí)以顱腦外傷手術(shù)患者頭皮斷裂的顳淺動脈(Superficial Temporal Artery, STA)及皮層動脈作為對照,1.用常規(guī)光鏡、電鏡觀察IA及正常血管的病理形態(tài)學(xué)變化及超微結(jié)構(gòu)改變。2.免疫組化SABC法測定動脈瘤中誘導(dǎo)型一氧化氮合酶(Inducible Nitric Oxide Synthase, iNOS)表達(dá)水平,同時(shí)測定動脈瘤標(biāo)本中NOS蛋白含量。3.iTRAQ技術(shù)篩選顱內(nèi)動脈瘤標(biāo)本中差異蛋白分子。結(jié)果：1.動脈瘤的病理變化：HE結(jié)果顯示動脈瘤典型的三層結(jié)構(gòu)消失,內(nèi)膜連續(xù)性中斷,內(nèi)彈力板較薄,消失或中斷,內(nèi)皮細(xì)胞變性或壞死。中膜平滑肌細(xì)胞少見,細(xì)胞外基質(zhì)破壞嚴(yán)重,并見大量炎性細(xì)胞浸潤,其中以巨噬和中性粒細(xì)胞為主。電鏡超微結(jié)構(gòu)觀察顯示動脈瘤內(nèi)皮細(xì)胞損傷、壞死,可見細(xì)胞固縮或空泡變性；中膜正常內(nèi)部結(jié)構(gòu)消失,細(xì)胞外基質(zhì)模糊不清,平滑肌細(xì)胞壞死,部分見凋亡小體；瘤壁可見炎性細(xì)胞浸潤,主要為巨噬細(xì)胞。而對照組動脈的結(jié)構(gòu)是正常的,內(nèi)皮細(xì)胞完整、均勻,中膜內(nèi)平滑肌纖維排列有序、密集,基質(zhì)纖維清晰可見,并沒有發(fā)現(xiàn)炎癥反應(yīng)。2.NOS表達(dá)：iNOS在25例對照組標(biāo)本中23例無表達(dá)(23/25),2例弱表達(dá)(2/25),36例動脈瘤組中6例中表達(dá)(6/36),30例強(qiáng)表達(dá)(30/36),動脈瘤組iNOS表達(dá)水平與對照組相比顯著增加,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。動脈瘤組iNOS含量為13.3129±2.4581 U/mg蛋白,對照組為7.5623±2.0321 U/mg蛋白,iNOS在動脈瘤組明顯增高,有統(tǒng)計(jì)學(xué)意義(P=0.0320.05)。動脈瘤組總一氧化氮合酶(Total NOS)為24.5631±6.5684U/mg蛋白,對照組為22.1325±6.1358 U/mg蛋白,差異無統(tǒng)計(jì)學(xué)意義(P=0.5620.05)。動脈瘤組中iNOS/TNOS之比明顯升高,差異有統(tǒng)計(jì)學(xué)意義(P=0.0390.05)。3.iTRAQ結(jié)果：通過iTRAQ技術(shù)共鑒定出有定量信息的蛋白分子816個(gè),與對照組相比,差異2倍以上的有162個(gè),包括80個(gè)上調(diào)蛋白和82個(gè)下調(diào)蛋白,其中與細(xì)胞外基質(zhì)降解有關(guān)的基質(zhì)金屬蛋白酶-9(Matrix MetalloProteinase, MMP-9)上調(diào)3.7倍。上調(diào)蛋白主要是炎性反應(yīng)相關(guān)蛋白,其次是細(xì)胞遷移、侵襲和細(xì)胞免疫補(bǔ)體復(fù)合物蛋白；除細(xì)胞骨架連接蛋白外,下調(diào)蛋白較多的是在內(nèi)皮細(xì)胞遷移、增殖以及信號傳導(dǎo)中發(fā)揮重要作用一類蛋白。結(jié)論：1.動脈瘤的病理及超微結(jié)構(gòu)改變主要是內(nèi)皮細(xì)胞壞死及炎癥細(xì)胞浸潤,特別是單核巨噬細(xì)胞,平滑肌細(xì)胞凋亡,細(xì)胞外基質(zhì)破壞,提示內(nèi)皮細(xì)胞壞死及炎癥細(xì)胞特別是巨噬細(xì)胞浸潤在動脈瘤壁病理改變中發(fā)揮重要作用。2.動脈瘤標(biāo)本中以iNOS為主的NOS的表達(dá)增高說明,iNOS可能在動脈瘤發(fā)生發(fā)展過程中發(fā)揮重要作用。3.破裂動脈瘤有多種蛋白分子表達(dá)異常,它們可能參與了動脈瘤形成和破裂的分子機(jī)制。4.顱內(nèi)動脈瘤的形成是由NOS介導(dǎo)的多種蛋白分子參與的復(fù)雜過程。第二部分顱內(nèi)多發(fā)動脈瘤個(gè)體化治療研究研究背景：顱內(nèi)多發(fā)動脈瘤(Multiple Intracranial Aneurysms, MIAs)是指顱內(nèi)同時(shí)存在2個(gè)或2個(gè)以上的動脈瘤。與單發(fā)性顱內(nèi)動脈瘤(Single Intracranial Aneurysm, SIA)相比,破裂機(jī)會更多,診治更加復(fù)雜,預(yù)后更差。MIAs發(fā)病率約占顱內(nèi)動脈瘤的5%-30%,其檢出率隨著影像學(xué)尤其是3D-CTA、 3D-DSA的發(fā)展不斷提高,處理MIAs將成為顱內(nèi)動脈瘤治療的重點(diǎn)。目前對于MIAs臨床治療措施,尚未達(dá)成一致意見,爭議主要存在以下四個(gè)方面：一是MIAs中未破裂動脈瘤(Unruptured Intracranial Aneurysms, UIA)手術(shù)還是保守治療；二是血管內(nèi)治療還是顯微外科手術(shù)治療；三是一期還是分期手術(shù)治療；四是已發(fā)生腦血管痙攣的情況下手術(shù)時(shí)機(jī)的選擇。顱內(nèi)鏡像動脈瘤(Mirror Aneurysms, MAs)是MIAs的一種特殊類型,指位于兩側(cè)對稱位置的動脈瘤,由于其空間分布的特殊性,臨床治療較棘手。本文回顧性分析了我科收治經(jīng)外科治療的106例MIAs(包括37例MAs)患者的臨床資料,多因素回歸分析影響MIAs預(yù)后的臨床因素,總結(jié)我科治療經(jīng)驗(yàn),為MIAs個(gè)體化治療策略的制定提供參考。目的：探討MIAs及MAs的個(gè)體化治療方案及MIAs患者的預(yù)后影響因素。方法：回顧分析2007年1月-2015年12月濰坊市人民醫(yī)院神經(jīng)外科收治的經(jīng)外科手術(shù)治療的106例MIAs(共232枚動脈瘤,其中包括37例MAs)患者的完整資料。根據(jù)患者具體情況,按照治療措施分為三組,顯微手術(shù)、介入栓塞、介入栓塞和顯微手術(shù)聯(lián)合治療；按照治療的時(shí)機(jī)分為僅處理責(zé)任動脈瘤,一期及分期處理動脈瘤三組。106例MIAs中開顱夾閉58例,介入栓塞44例,手術(shù)聯(lián)合介入4例；其中39例僅處理責(zé)任動脈瘤,一期治療53例,分期處理14例。37例MAs開顱夾閉21例,介入栓塞15例,手術(shù)聯(lián)合介入1例；其中18例僅處理責(zé)任動脈瘤,一期治療13例,分期處理6例。探討的術(shù)前臨床因素包括：患者性別、年齡、動脈瘤部位、側(cè)別、數(shù)量、術(shù)前Fisher分級、Hunt-Hess分級、治療措施、處理時(shí)機(jī)。出院時(shí)G08評分評估術(shù)后療效。分別應(yīng)用單因素分析及多因素Logistic回歸分析術(shù)前各因素、治療方案對治療效果的影響。結(jié)果：出院時(shí)MIAs患者GOS評分5分75例,4分10例,3分9例,2分4例,1分8例。預(yù)后良好(4-5分)85例,差(1-3分)21例。MAs患者出院時(shí)GOS評分5分31例,4分2例,3分3例,2分0例,1分1例。預(yù)后良好(4-5分)33例,差(卜3分)4例。各治療組GOS評分：介入44例中,良好37例,差7例；手術(shù)58例中,良好45例,差13例；介入+手術(shù)4例中,良好3例,差1例。MIAs患者年齡、部位、術(shù)前Fisher及Hunt-Hess分級經(jīng)單因素分析顯示與預(yù)后相關(guān)(P0.05),患者年齡越大,預(yù)后越差,動脈瘤位于后循環(huán)預(yù)后差,術(shù)前Fisher及Hunt-Hess分級級別越高,預(yù)后越差。多因素Logistic回歸分析結(jié)果顯示MIAs患者各因素中年齡、部位及Fisher分級與預(yù)后相關(guān)(P0.05)。結(jié)論：MIAsI臨床多見,而MAs少見,二者均多見于后交通動脈,主要依靠DSA診斷,應(yīng)在診斷全面的基礎(chǔ)上,正確判斷責(zé)任動脈瘤并早期積極治療,對于非責(zé)任病灶需要綜合評估出血風(fēng)險(xiǎn),采取個(gè)體化治療措施,盡量一期治療所有動脈瘤,減少再出血風(fēng)險(xiǎn)�；颊吣挲g、部位、術(shù)前Fisher和Hunt-Hess分級是影響MIAs患者術(shù)后療效的關(guān)鍵因素。根據(jù)患者的實(shí)際情況選擇開顱手術(shù)、介入栓塞或開顱手術(shù)+介入栓塞等個(gè)體化治療方案是改善MIAs患者預(yù)后的關(guān)鍵。
[Abstract]:Part I research background of the role of NOS in the pathogenesis of intracranial aneurysm: Intracranial Aneurysm (IA) is the cerebral angiomatoid protuberance produced by the pathological localized dilatation of the arterial wall, and its rupture is the most common cause of human spontaneous subarachnoid hemorrhage (Subarachnoid Hemorrhage, SAH),.IA. The incidence of the disease is third in China's cerebrovascular accident, second only to ischemic stroke and hypertensive intracerebral hemorrhage. The difficulty in the diagnosis and treatment of the disease lies in the concealment of clinical symptoms, most of which are found after the rupture, and the mortality and disability rate are very high. At present, there is no ideal early prevention and screening for IA because of the pathological changes and hair of the disease. The mechanism of the disease is not completely clear. Recent studies have shown that the damaged arterial wall exposes some of the antigen molecules under the combination of hemodynamic and inflammatory reactions, triggering a series of cascade reactions on the molecular level, resulting in the degradation of the arterial wall and causing the formation and rupture of IA. Among them, the nitric oxide synthase (Nitric Oxide Synthas) E, NOS) plays an important role in the cascade reaction of this molecule. Now animal experiments have shown that there is a characteristic pathology and the change of NOS expression in the IA model. Because of the difficult to obtain in human IA specimens, the pathology of the specimens of living aneurysm and the level of NOS expression are still lacking. If NOS is found in the specimens of human aneurysm. The significant changes can be shown that NOS may play an important role in the formation of IA and will be of great significance for the early prevention and screening of IA. Many studies have shown that in the process of formation and rupture of IA, there are a large number of cytokines and inflammatory mediators, such as the expression and activity of protein molecules, except NOS. In the complex interaction network of cytokine and protein molecules, some important key links or key factors are screened, and their regulation role in the pathophysiology of IA may be a breakthrough point in the study of the pathogenesis of IA. Relative and absolute isotope labeling (Isobaric Tags for Relative and Absolute Q) Uantitation, iTRAQ) based quantitative proteomics is a high throughput protein molecular screening method developed in recent years. It is the most powerful tool for screening differentially expressed protein molecules at present. This study is to examine the pathological changes of the aneurysm specimens obtained by surgery to observe the pathological changes of the aneurysm wall. The expression of NOS in the aneurysm specimens was detected by immunohistochemical method, and the differentially expressed protein molecules in the aneurysm specimens were screened by iTRAQ technique, and the possible role of the proteins in the formation and rupture of aneurysms was explored to provide the basis for further elucidate the molecular mechanism of the aneurysm and also to act as a move. Objective: to establish the basis for the development of the biological treatment of the aneurysm. Objective: To observe the pathological and ultrastructural changes of the aneurysm, to detect the expression of NOS in intracranial aneurysms, to screen the protein molecules expressed differently by iTRAQ technique and to explore their possible role in the formation and rupture of aneurysms to further elucidate the incidence of aneurysms. The molecular mechanism provides the basis. Methods: the cerebral aneurysm of the Qilu Hospital in Shandong University and Department of Neurosurgery of the Shandong University from May 2012 to November 2014 was selected, and the superficial temporal artery (Superficial Temporal Artery, STA) and the cortical artery were used as the control, 1. Routine light microscopy and electron microscope observation of the pathological changes of IA and normal blood vessels and ultrastructural changes,.2. immunohistochemical SABC method was used to determine the expression of inducible nitric oxide synthase (Inducible Nitric Oxide Synthase, iNOS) in the aneurysm, and the determination of NOS protein content in the aneurysm specimens by.3.iTRAQ technique in the selection of intracranial aneurysm specimens Results: pathological changes of 1. aneurysms: HE results showed that the typical three layer structure of the aneurysm disappeared, the endometrium was interrupted, the internal elastic plate was thinner, disappearing or interrupted, the endothelial cells were denatured or necrotic. The middle membrane smooth muscle cells were rare, the extracellular matrix was destroyed seriously, and a large number of inflammatory cells were infiltrated. The ultrastructural observation showed that the endothelial cells of the aneurysm were damaged, necrosis, cell fixation or vacuolar degeneration; the normal internal structure of the middle membrane disappeared, the extracellular matrix was blurred, the smooth muscle cells were necrotic, and some of the apoptotic bodies were seen; the tumor wall showed inflammatory cell infiltration, mainly macrophages. And the control artery The structure was normal, the endothelial cells were complete and uniform. The smooth muscle fibers in the middle membrane were arranged in order, dense, and the matrix fibers were clearly visible. There was no expression of.2.NOS in the inflammatory reaction. 23 cases were not expressed (23/25), 2 cases of weak expression (2/25), 6 cases (6/36), 30 cases of strong expression (30/36), aneurysm and aneurysm in the 25 cases of control group. The expression level of group iNOS was significantly increased compared with the control group (P0.05). The iNOS content of the aneurysm group was 13.3129 + 2.4581 U/mg protein, the control group was 7.5623 + 2.0321 U/mg protein, iNOS was significantly increased in the aneurysm group, and was statistically significant (P=0.0320.05). The total nitric oxide synthase (Total NOS) was 24.5631 + 6.5684U (Total NOS) in the arteria group. /mg protein, the control group was 22.1325 + 6.1358 U/mg protein, the difference was not statistically significant (P=0.5620.05). The ratio of iNOS/TNOS in the aneurysm group was significantly higher, the difference was statistically significant (P=0.0390.05).3.iTRAQ results: 816 of the protein fractions with quantitative information were identified by iTRAQ technology, and 162 more than the control group, the difference was 2 times more than that of the control group. It includes 80 up-regulated proteins and 82 down regulated proteins, of which the matrix metalloproteinase -9 (Matrix MetalloProteinase, MMP-9), which is related to the degradation of extracellular matrix, is up to 3.7 times. The up-regulated protein is mainly inflammatory response related protein, followed by cell migration, invasion and cell immune complement complex protein, except for cytoskeleton connexin. More protein is a kind of protein which plays an important role in the migration, proliferation and signal transduction of endothelial cells. Conclusion: the pathological and ultrastructural changes of 1. aneurysms are mainly endothelial cell necrosis and inflammatory cell infiltration, especially mononuclear macrophages, smooth muscle cells apoptosis, extracellular matrix destruction, indicating endothelial cells necrosis and Inflammatory cells, especially macrophage infiltration, play an important role in the pathological changes of the aneurysm wall. The increased expression of iNOS based NOS in the.2. aneurysm specimens indicates that iNOS may play an important role in the development of aneurysm. There are various protein molecular tables in the aneurysm of.3. ruptured aneurysm, which may be involved in the formation of aneurysm. The formation of.4. intracranial aneurysms, the molecular mechanism of rupture, is a complex process involving multiple protein molecules mediated by NOS. The study background of the individualized treatment of second part intracranial multiple aneurysms: intracranial multiple aneurysms (Multiple Intracranial Aneurysms, MIAs) is the simultaneous existence of 2 or more than 2 aneurysms in the cranium. Compared with Single Intracranial Aneurysm (SIA), the chance of rupture is more, the diagnosis and treatment are more complicated and the prognosis is worse, the incidence of.MIAs is about 5%-30% of intracranial aneurysm. The detection rate is increasing with the imaging, especially the 3D-CTA, 3D-DSA, and the treatment MIAs will be the focal point of the treatment of intracranial aneurysm. Currently, the treatment of MIAs is the key to the treatment of the intracranial aneurysm. Bed treatment measures have not been agreed, the main four aspects of the dispute are the following four aspects: one is the unruptured aneurysm (Unruptured Intracranial Aneurysms, UIA) operation or conservative treatment; two is intravascular or microsurgical treatment; three is one stage or staging operation; four is cerebrovascular spasm. Mirror Aneurysms (MAs) is a special type of MIAs, which refers to the aneurysm located on both sides of the symmetrical position. The clinical treatment is difficult because of its spatial distribution, and the clinical treatment of 106 cases of MIAs (including 37 cases of MAs) in our department is reviewed. Bed data, multiple factor regression analysis of the clinical factors affecting the prognosis of MIAs, summarize the experience of our treatment and provide reference for the formulation of MIAs individualized treatment strategies. Objective: To explore the individualized treatment scheme of MIAs and MAs and the prognostic factors of MIAs patients. Methods: retrospective analysis of the nerve outside of Weifang People's Hospital in December January 2007. 106 cases of MIAs (a total of 232 aneurysms, including 37 cases of MAs) were treated with complete data. According to the specific conditions of the patients, the patients were divided into three groups according to the treatment measures, microsurgery, interventional embolization, interventional embolization and microsurgery combined treatment. Three.106 cases of aneurysm were treated with craniotomy in 58 cases, interventional embolization in 44 cases, and operation combined intervention in 4 cases, of which 39 cases treated only responsible aneurysm, one stage treatment 53 cases, 14 cases of.37 cases with 21 cases of MAs craniotomy, 15 cases involving interventional embolization, 1 cases with interventional embolization, and 18 cases only dealing with responsible aneurysm, one-stage treatment 13. 6 cases were treated. The preoperative clinical factors included: sex, age, aneurysm site, side, quantity, preoperative Fisher classification, Hunt-Hess classification, treatment measures, treatment timing. G08 score was used to evaluate the postoperative effect. The single factor analysis and multiple factor Logistic regression were used to analyze the preoperative factors respectively. Results: the GOS score of MIAs patients at discharge was 5 points, 4 points 10 cases, 3 points 9 cases, 2 points 4 cases, 1 8 cases, 8 cases with good prognosis (4-5 points), bad (1-3 scores) GOS scores in the patients at discharge. 37 cases were good, 7 cases were poor, 45 cases were good, 13 cases were bad, 3 cases were good in 4 cases of interventional + operation, and the age, location, Fisher and Hunt-Hess classification of.MIAs patients were correlated with prognosis (P0.05), the older the age was, the worse the prognosis, the poor prognosis of the aneurysm in the posterior circulation, Fisher and Hunt-Hess grading level before operation. The higher the prognosis, the worse the prognosis. The results of multiple factor Logistic regression analysis showed that the age, location and Fisher classification of the MIAs patients were associated with the prognosis (P0.05). Conclusion: MIAsI is more common, but MAs is rare, and all of the two are mostly found in the posterior communicating artery and mainly rely on the diagnosis of DSA. On the basis of a comprehensive diagnosis, the aneurysm should be correctly judged and early in the diagnosis of the responsible aneurysm. Active treatment requires a comprehensive assessment of the risk of bleeding for non responsible lesions, adopt individualized treatment measures, try to treat all aneurysms and reduce the risk of rebleeding. Age, location, preoperative Fisher and Hunt-Hess classification are the key factors affecting the postoperative effect of MIAs patients. Individualized treatment including embolization or craniotomy plus interventional embolization is the key to improve the prognosis of MIAs patients.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R743

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 王剛;馮文峰;張國忠;李明洲;何小艷;彭四維;漆松濤;;顱內(nèi)多發(fā)動脈瘤的診斷與治療策略[J];南方醫(yī)科大學(xué)學(xué)報(bào);2015年01期

2 孫正輝;武琛;王芙昱;薛哲;許百男;周定標(biāo);;顱內(nèi)鏡像動脈瘤的外科治療[J];中華外科雜志;2013年10期

3 孫正輝;許百男;王芙昱;武琛;姜燕;;單側(cè)入路夾閉雙側(cè)復(fù)雜大腦中動脈瘤[J];中華外科雜志;2013年04期

4 吳中學(xué);李佑祥;楊新健;姜除寒;呂明;呂憲利;;顱內(nèi)多發(fā)動脈瘤的血管內(nèi)治療[J];中華神經(jīng)外科雜志;2012年11期

5 楊全喜;李美華;;顱內(nèi)動脈瘤形成的血流動力學(xué)機(jī)制[J];國際腦血管病雜志;2012年09期

6 于金錄;許侃;丁小博;王宏磊;羅祺;;多發(fā)顱內(nèi)前循環(huán)動脈瘤的顯微外科治療[J];中華神經(jīng)外科雜志;2012年05期

7 謝秀枝;王欣;劉麗華;董世雷;皮雄娥;劉偉;;iTRAQ技術(shù)及其在蛋白質(zhì)組學(xué)中的應(yīng)用[J];中國生物化學(xué)與分子生物學(xué)報(bào);2011年07期

8 繆洪平;陳志;唐衛(wèi)華;蔣周陽;朱剛;林江凱;馮華;;顱內(nèi)多發(fā)動脈瘤的治療[J];中國臨床神經(jīng)外科雜志;2011年01期

9 張施遠(yuǎn);游潮;;36例顱內(nèi)多發(fā)性動脈瘤顯微手術(shù)分析[J];中華神經(jīng)外科疾病研究雜志;2008年05期

10 李國新,尹連虎,孫建新,曲元明,宋玉tD;顱內(nèi)多發(fā)動脈瘤的顯微手術(shù)治療[J];中華外科雜志;2001年09期

，

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