本文選題：鼻咽癌 + RS��； 參考：《福建醫(yī)科大學(xué)》2016年博士論文

【摘要】：拉曼光譜技術(shù)(Raman Spectroscopy,RS)及表面增強(qiáng)拉曼光譜技術(shù)(Surface Enhanced Raman Spectroscopy,SERS)是當(dāng)今國(guó)際生物醫(yī)學(xué)領(lǐng)域的研究熱點(diǎn),本研究結(jié)合臨床上鼻咽癌診斷的需要,利用RS和SERS技術(shù)的高靈敏性,檢測(cè)鼻咽癌患者組織,血液,唾液等樣本,并結(jié)合PCA(Principle Components Analysis,主成分分析)及LDA(linear discriminant analysis,線性判別分析)多元統(tǒng)計(jì)模型,試圖研發(fā)一種快速、無損、客觀、準(zhǔn)確的基于RS及SERS技術(shù)的鼻咽癌早期診斷方法。主要研究工作包括五部分:1.常規(guī)拉曼光譜技術(shù)(RS)在早晚期鼻咽癌組織中診斷價(jià)值研究目的:本研究旨在比較鼻咽癌患者早晚期病理組織的拉曼光譜差異,評(píng)估拉曼光譜技術(shù)在鼻咽癌早晚期診斷中的價(jià)值。材料與方法:使用常規(guī)拉曼光譜技術(shù)(RS)分別檢測(cè)30例鼻咽癌早期(T1-2)患者與46例鼻咽癌晚期(T3-4)患者組織標(biāo)本的拉曼光譜,利用主成分分析法(PCA)并結(jié)合線性判別分析法(LDA)建立常規(guī)拉曼光譜技術(shù)診斷方法的多元統(tǒng)計(jì)算法模型。結(jié)果:鼻咽癌早期與晚期患者組織RS信號(hào)差異明顯,PCA-LDA判別區(qū)分的靈敏性、特異性和準(zhǔn)確性分別為70%、78.3%及75%。結(jié)論:RS技術(shù)結(jié)合PCA-LDA統(tǒng)計(jì)分析能夠較好地區(qū)分鼻咽癌患者早晚期組織標(biāo)本,表明在早晚期鼻咽癌判別上RS方法可行。2.鼻咽癌患者唾液的表面增強(qiáng)拉曼光譜技術(shù)(SERS)直接法檢測(cè)研究目的:本文目的在于預(yù)測(cè)基于受試者唾液的表面增強(qiáng)拉曼光譜技術(shù)(SERS)對(duì)鼻咽癌的無損診斷意義。材料與方法:共收集52例鼻咽癌患者及60例健康志愿者的唾液樣本,分別檢測(cè)其SERS光譜,并對(duì)獲得的SERS光譜進(jìn)行譜峰歸屬分析。結(jié)果:鼻咽癌患者與健康志愿者的唾液SERS光譜差異明顯,主要位于447,496,635,729,1134,1270,和1448 cm-1處,譜峰歸屬分析提示,健康受試者與鼻咽癌患者之間唾液中糖類、蛋白、核酸及脂肪酸存在差別。統(tǒng)計(jì)結(jié)果分析顯示,基于鼻咽癌唾液SERS檢測(cè)技術(shù)診斷鼻咽癌的特異度為91.7%,靈敏度為82.7%,準(zhǔn)確率為87.5%。結(jié)論:本研究表明,直接法檢測(cè)唾液表面增強(qiáng)拉曼光譜技術(shù)(SERS)結(jié)合PCA-LDA分析可以較好地區(qū)分鼻咽癌患者與健康志愿者,該技術(shù)對(duì)于鼻咽癌無損診斷具有潛在的臨床應(yīng)用價(jià)值。3.不同T分期鼻咽癌血漿表面增強(qiáng)拉曼光譜(SERS)檢測(cè)研究目的:本研究評(píng)估基于血漿無標(biāo)記的表面增強(qiáng)拉曼光譜(SERS)技術(shù)區(qū)分不同T分期鼻咽癌血漿的可行性。Au(金)納米顆粒作為SERS活性的納米結(jié)構(gòu)直接與人類血液混合成等離子體獲得增強(qiáng)的拉曼散射信號(hào)。材料與方法:我們共檢測(cè)60例健康志愿者血漿樣本,25例T1期鼻咽癌和75例T2-T4鼻咽癌患者血漿樣本。結(jié)果:表明T1期與健康受試者,T2-T4期與健康受試者的血漿,其差異診斷敏感性分別為84%和92%,特異性為83.3%和95%,準(zhǔn)確性為83.5%和93.3%。然而,T1期與T2-T4鼻咽癌血漿之間差異的敏感性、特異性和準(zhǔn)確性僅有64%,62.7%和63%,區(qū)分度不夠理想;這個(gè)探索性研究表明基于SERS納米生物技術(shù)結(jié)合PCA-LDA統(tǒng)計(jì)方法可以實(shí)現(xiàn)早期T1和健康志愿者;T2-T4和健康志愿者的血漿之間的區(qū)別,但早晚期之間差異區(qū)分較難。結(jié)論:該方法可以作為臨床上診斷鼻咽癌重要的輔助手段,但要區(qū)分早晚期鼻咽癌還有較大的挑戰(zhàn)。4.鼻咽癌組織DNA的表面增強(qiáng)拉曼光譜技術(shù)(SERS)檢測(cè)研究目的:研究表面增強(qiáng)拉曼光譜技術(shù)在鼻咽癌早晚期及健康受試者鼻咽組織DNA的差異,探討表面增強(qiáng)拉曼光譜技術(shù)在鼻咽癌組織DNA分子診斷中的應(yīng)用價(jià)值。材料與方法:本研究采用SERS技術(shù)檢測(cè)鼻咽癌病理組織與正常鼻咽組織中DNA的差別,分別提取26例早期鼻咽癌、35例晚期鼻咽癌患者病理組織與30例健康受試者鼻咽組織的DNA進(jìn)行SERS檢測(cè),對(duì)比分析三組拉曼散射光譜的差異。結(jié)果:研究發(fā)現(xiàn)鼻咽癌早、晚期組織與健康受試者鼻咽組織的DNA在譜峰上存在著明顯差異,經(jīng)過PCA-DFA分析發(fā)現(xiàn),早期鼻咽癌組織診斷的靈敏度為80.8%,特異度為84.6%,準(zhǔn)確率為86.8%,晚期鼻咽癌組織診斷的靈敏度為85.7%,特異度為82.1%,準(zhǔn)確率為92.3%,具有較高的診斷準(zhǔn)確率。結(jié)論:本研究提示基于SERS納米生物技術(shù)結(jié)合PCA-DFA統(tǒng)計(jì)分析作為臨床早晚期鼻咽癌的補(bǔ)充檢測(cè)具有較好的前景。5.鼻咽內(nèi)窺鏡下活體鼻咽癌熒光成像和拉曼光譜檢測(cè)目的:鼻咽癌最常用的篩選方法是鼻咽鏡下對(duì)可疑病變部位進(jìn)行組織病理活檢,但可能造成漏診和誤診。為避免漏診及誤診,我們探討鼻咽纖維鏡下鼻咽癌體內(nèi)拉曼光譜檢測(cè)的可行性。材料與方法:本文采用鼻咽內(nèi)窺鏡下在體鼻咽癌熒光成像及拉曼光譜技術(shù),檢測(cè)了鼻咽癌活體熒光圖像和拉曼光譜。結(jié)果:首次獲得了鼻咽癌實(shí)時(shí)活體拉曼光譜。結(jié)論:表明將鼻咽鏡下活體熒光成像和拉曼光譜技術(shù)相結(jié)合,提高鼻咽癌診斷的有效性和客觀性方面具有一定的潛力。
[Abstract]:Raman Spectroscopy (RS) and surface enhanced Raman spectroscopy (Surface Enhanced Raman Spectroscopy, SERS) are the hot spots in the field of international biomedical research. This study combines the high sensitivity of RS and SERS techniques to detect the tissues, blood, saliva and other samples of nasopharyngeal carcinoma patients with the needs of the diagnosis of the clinical nasopharyngeal carcinoma. This paper, combined with PCA (Principle Components Analysis, principal component analysis) and LDA (linear discriminant analysis, linear discriminant analysis) multivariate statistical model, attempts to develop a fast, nondestructive, objective and accurate method for early diagnosis of nasopharyngeal carcinoma based on RS and SERS technology. The main research work includes five parts: 1. conventional Raman spectroscopy (R) S) a study on the diagnostic value of nasopharyngeal carcinoma in the early and late stage of nasopharyngeal carcinoma. The purpose of this study was to compare the differences in the Raman spectrum of the early and late pathological tissues of nasopharyngeal carcinoma and to evaluate the value of Raman spectroscopy in the early diagnosis of nasopharyngeal carcinoma. Materials and methods: 30 patients with nasopharyngeal carcinoma (T1-2) and 46 were detected by conventional Raman spectroscopy (RS). The Raman spectrum of the tissue specimens of patients with advanced nasopharyngeal carcinoma (T3-4), using the principal component analysis (PCA) and linear discriminant analysis (LDA) to establish the multivariate statistical algorithm model of the conventional Raman spectroscopy diagnostic method. Results: the difference of RS signal in the early and late stage of nasopharyngeal carcinoma is obvious, and the sensitivity and specificity of PCA-LDA discriminant distinction And the accuracy is 70%, 78.3% and 75%. conclusion: RS technique combined with PCA-LDA statistical analysis can better distinguish the early and late tissue specimens of nasopharyngeal carcinoma patients, indicating that the RS method is feasible for the direct detection of saliva of.2. nasopharyngeal carcinoma patients in the early and late stage of nasopharyngeal carcinoma identification. The purpose of this article is to preview the purpose of this study. A total of 52 cases of nasopharyngeal carcinoma and 60 healthy volunteers were collected from the saliva samples of 52 cases of nasopharyngeal carcinoma and 60 healthy volunteers. The spectra of the saliva of 52 cases of nasopharyngeal carcinoma and 60 healthy volunteers were collected, and the spectrum peaks of the obtained SERS spectra were analyzed. The difference of SERS spectra in saliva was obvious, mainly located at 44749663572911341270, and 1448 cm-1. The analysis of spectrum peak attribution indicated that there were differences in saliva sugar, protein, nucleic acid and fatty acids between healthy subjects and nasopharyngeal carcinoma patients. The analysis showed that the specificity of the diagnosis of nasopharyngeal carcinoma based on the SERS detection technique of nasopharyngeal carcinoma was 91.. 7%, the sensitivity is 82.7% and the accuracy is 87.5%. conclusion: This study shows that direct detection of saliva surface enhanced Raman spectroscopy (SERS) combined with PCA-LDA analysis can be a better region for nasopharyngeal carcinoma and healthy volunteers. This technique has potential clinical application value for nasopharyngeal carcinoma nondestructive diagnosis,.3. different T staging nasopharyngeal carcinoma plasma surface The purpose of enhanced Raman spectroscopy (SERS) detection: This study evaluated the feasibility of using plasma unlabeled surface enhanced Raman spectroscopy (SERS) to distinguish the feasibility of different T staging nasopharyngeal carcinoma plasma,.Au nanoparticles were used as SERS active nanostructures to obtain enhanced Raman scattering signals directly from human blood mixed plasma. And methods: We measured plasma samples of 60 healthy volunteers, 25 cases of T1 nasopharyngeal carcinoma and 75 patients with T2-T4 nasopharyngeal carcinoma. Results: the diagnostic sensitivity of phase T1 and healthy subjects, T2-T4 and healthy subjects was 84% and 92%, the specificity was 83.3% and 95%, the accuracy was 83.5% and 93.3%., however, T1 phase and 93.3%. The sensitivity, specificity and accuracy of plasma differences between T2-T4 nasopharyngeal carcinoma (nasopharyngeal carcinoma), specificity and accuracy were only 64%, 62.7% and 63%, and the difference was not ideal; this exploratory study showed that SERS based nanobiotechnology combined with PCA-LDA statistics could achieve early T1 and healthy volunteers, and the difference between T2-T4 and healthy volunteers, but the difference between early and late stages Conclusion: this method can be used as an important auxiliary method in clinical diagnosis of nasopharyngeal carcinoma, but it is necessary to distinguish the early and late stage nasopharyngeal carcinoma and the large challenge of the.4. nasopharyngeal carcinoma tissue DNA surface enhanced Raman spectroscopy (SERS) detection research purpose: the study of surface enhanced Raman spectroscopy in nasopharyngeal carcinoma early and healthy subjects nose The difference between the DNA of the pharynx tissue and the application value of surface enhanced Raman spectroscopy in the diagnosis of DNA in nasopharyngeal carcinoma. Materials and methods: This study used SERS to detect the difference between the pathological tissue of nasopharyngeal carcinoma and the normal nasopharyngeal tissue, and to extract 26 cases of early nasopharyngeal carcinoma, 35 cases of advanced nasopharyngeal carcinoma and 30 cases of health. The DNA of the nasopharynx tissues of the subjects was detected by SERS. The differences between the three groups were compared and analyzed. Results: the study found that the nasopharyngeal carcinoma was early, and the DNA of the nasopharynx tissues in the late tissues and the healthy subjects were significantly different. The sensitivity of the early nasopharyngeal carcinoma was 80.8% and the specificity was 84.6% after PCA-DFA analysis. The accuracy rate is 86.8%, the sensitivity of the advanced nasopharyngeal carcinoma tissue is 85.7%, the specificity is 82.1%, the accuracy is 92.3%, and the diagnostic accuracy is high. Conclusion: This study suggests that the SERS nano biotechnology combined with the statistical analysis of PCA-DFA is a good prospect for nasopharyngeal carcinoma in the early and late stage of the nasopharyngeal carcinoma with.5. nasopharynx endoscopy. Fluorescence imaging and Raman detection of somatic nasopharyngeal carcinoma: the most commonly used method of screening nasopharyngeal carcinoma is the histopathological biopsy of the suspected site under the nasopharynx, but it may cause missed diagnosis and misdiagnosis. In order to avoid missed diagnosis and misdiagnosis, we discuss the feasibility of Raman spectrum detection in nasopharyngeal carcinoma in nasopharyngeal carcinoma. Materials and methods: The fluorescence and Raman spectra of nasopharyngeal carcinoma were detected by fluorescence imaging and Raman spectroscopy under nasopharyngeal endoscopy. Results: the real time living body Raman spectra of nasopharyngeal carcinoma were obtained for the first time. Conclusion: it is shown that the combination of the living fluorescent imaging and Raman spectroscopy under nasopharynx can improve the effectiveness of the diagnosis of nasopharyngeal carcinoma. There is a certain potential in objectivity.

【學(xué)位授予單位】：福建醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R739.63

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6 馬，

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