發(fā)布時(shí)間：2018-09-12 09:29

【摘要】：第一部分原發(fā)痛經(jīng)對(duì)靜息態(tài)腦網(wǎng)絡(luò)功能及腦灰質(zhì)體積的影響目的首次應(yīng)用靜息態(tài)功能磁共振(functional magnetic resonance imaging, fMRI)技術(shù),在月經(jīng)期采集重度原發(fā)痛經(jīng)患者與健康對(duì)照女性的fMRI數(shù)據(jù),觀察長期重度痛經(jīng)患者是否存在大腦結(jié)構(gòu)和功能的改變,希望能從疼痛相關(guān)的中樞神經(jīng)系統(tǒng)機(jī)制入手探索痛經(jīng)的發(fā)病機(jī)制,為指導(dǎo)臨床治療,尋找新的治療靶點(diǎn)提供科學(xué)的理論依據(jù)。方法招募10名重度原發(fā)痛經(jīng)患者和10名健康育齡期女性。應(yīng)用Philips 3.OT磁共振掃描儀采集受試者月經(jīng)期靜息態(tài)fMRI及高分辨結(jié)構(gòu)像數(shù)據(jù)。采用基于Matlab2012平臺(tái)的REST工具包,在灰質(zhì)范圍內(nèi)分析2組受試者低頻振幅統(tǒng)計(jì)圖的差異。采用基于Matlab R2011b平臺(tái)的GIFT軟件進(jìn)行獨(dú)立成分分析,提取2個(gè)靜息態(tài)腦網(wǎng)絡(luò)：默認(rèn)網(wǎng)絡(luò)前部和后部。采用SPM8軟件內(nèi)的基于體素的形態(tài)學(xué)分析對(duì)高分辨結(jié)構(gòu)像進(jìn)行分割、空間標(biāo)準(zhǔn)化及平滑。應(yīng)用SPM8進(jìn)行統(tǒng)計(jì)分析,對(duì)比重度痛經(jīng)和正常對(duì)照組在2個(gè)靜息態(tài)腦網(wǎng)絡(luò)內(nèi)部的腦功能連接及全腦灰質(zhì)體積差異。結(jié)果20名受試者均得到合格的靜息態(tài)fMRI數(shù)據(jù)。(1)月經(jīng)期全腦及局部腦區(qū)灰質(zhì)體積在重度原發(fā)痛經(jīng)組與健康對(duì)照組之間未見明顯差異。(2)與健康對(duì)照組相比,重度痛經(jīng)組在經(jīng)期疼痛狀態(tài)下左側(cè)楔前葉活動(dòng)增強(qiáng),而雙側(cè)內(nèi)側(cè)前額葉活動(dòng)減弱。(3)重度痛經(jīng)組默認(rèn)網(wǎng)絡(luò)前部的左側(cè)前額葉功能連接明顯增加,而默認(rèn)網(wǎng)絡(luò)后部的右側(cè)第一軀體感覺皮質(zhì)功能連接明顯減低。結(jié)論重度原發(fā)痛經(jīng)患者在經(jīng)期疼痛狀態(tài)下部分與疼痛相關(guān)的腦區(qū)存在靜息態(tài)功能和腦網(wǎng)絡(luò)功能連接的改變。中樞敏化可能參與原發(fā)痛經(jīng)的發(fā)生和發(fā)展。長期痛經(jīng)患者腦區(qū)功能的改變可能出現(xiàn)在結(jié)構(gòu)變化之前。第二部分腦源性神經(jīng)營養(yǎng)因子與子宮內(nèi)膜異位癥疼痛關(guān)系的研究目的通過比較疼痛和無疼痛子宮內(nèi)膜異位癥患者異位病灶及在位內(nèi)膜中腦源性神經(jīng)營養(yǎng)因子(brain-derived neurotrophic factor, BDNF)和特異性神經(jīng)纖維標(biāo)記物蛋白基因產(chǎn)物9.5 (protein gene product 9.5, PGP9.5)的分布和表達(dá)情況,探討B(tài)DNF與內(nèi)異癥發(fā)病及疼痛的關(guān)系。材料與方法收集2014年10月至2015年9月期間于北京協(xié)和醫(yī)院婦產(chǎn)科住院手術(shù)并經(jīng)病理確診為卵巢型內(nèi)異癥和單純子宮肌瘤患者的異位和在位內(nèi)膜,各25例。應(yīng)用免疫組化方法檢測卵巢型內(nèi)異癥患者(疼痛組13例,無疼痛組12例)的異位和在位內(nèi)膜以及單純肌瘤且不伴疼痛患者的子宮內(nèi)膜中BDNF和PGP 9.5的分布和表達(dá)情況,分析其與內(nèi)異癥發(fā)生和疼痛癥狀的相關(guān)性。結(jié)果兩組患者在年齡,孕產(chǎn)次方面無統(tǒng)計(jì)學(xué)差異。首次發(fā)現(xiàn)BDNF染色陽性區(qū)域位于內(nèi)膜的上皮和間質(zhì),且上皮中的表達(dá)量明顯高于間質(zhì)。BDNF勺表達(dá)水平在非內(nèi)異癥患者在位內(nèi)膜的增殖期和分泌期之間未見明顯差異。BDNF在內(nèi)異癥卵巢病灶中的表達(dá)水平明顯高于其在位內(nèi)膜,同時(shí),在內(nèi)異癥在位內(nèi)膜中的表達(dá)水平也明顯高于非內(nèi)異癥在位內(nèi)膜。疼痛與無疼痛內(nèi)異癥患者異位和在位內(nèi)膜中的BDNF表達(dá)水平未見明顯差異。卵巢異位病灶內(nèi)未見PGP9.5染色陽性,而內(nèi)異癥在位內(nèi)膜中PGP9.5的陽性率高于非內(nèi)異癥在位內(nèi)膜(20%vs.8%,P0.05)。結(jié)論研究首次明確了BDNF在子宮內(nèi)膜異位癥異位和在位內(nèi)膜的上皮和間質(zhì)中表達(dá),且表達(dá)水平高于非內(nèi)異癥在位內(nèi)膜,提示BDNF可能參與內(nèi)異癥的發(fā)生和發(fā)展。第三部分子宮肌瘤剔除術(shù)后意外發(fā)現(xiàn)子宮肉瘤患者的臨床特點(diǎn)及治療經(jīng)驗(yàn)?zāi)康脑u(píng)估子宮肌瘤剔除術(shù)后意外發(fā)現(xiàn)子宮肉瘤的發(fā)生率以及電動(dòng)肌瘤粉碎器的使用對(duì)隱匿性子宮肉瘤患者臨床預(yù)后的影響。方法回顧性分析2009年1月至2013年12月期間于北京協(xié)和醫(yī)院婦產(chǎn)科行子宮肌瘤剔除術(shù)后意外發(fā)現(xiàn)為子宮肉瘤患者的臨床病歷資料,分析其臨床特點(diǎn)以及肌瘤粉碎器的使用對(duì)臨床預(yù)后的影響。結(jié)果5年間共有4248例患者行子宮肌瘤剔除術(shù),其中9例(0.21%)患者意外發(fā)現(xiàn)為子宮肉瘤,包括1例(0.02%)子宮平滑肌肉瘤和8例(0.19%)子宮內(nèi)膜間質(zhì)肉瘤。在3068例應(yīng)用肌瘤粉碎器完成腹腔鏡肌瘤剔除術(shù)的患者中意外發(fā)現(xiàn)5例(0.16%)子宮肉瘤,在1180例行開腹肌瘤剔除術(shù)的患者中意外發(fā)現(xiàn)4例(0.34%)子宮肉瘤,兩組意外發(fā)現(xiàn)子宮肉瘤的發(fā)生率無統(tǒng)計(jì)學(xué)差異(P0.05)。9例肉瘤患者均存活,腹腔鏡手術(shù)組和開腹手術(shù)組分別隨訪31.20個(gè)月和40.50個(gè)月。結(jié)論子宮肌瘤剔除術(shù)后意外發(fā)現(xiàn)為子宮肉瘤的總體發(fā)生率較低。目前對(duì)隱匿性子宮肉瘤應(yīng)用肌瘤粉碎器后,在短期內(nèi)似乎不會(huì)額外增加肉瘤播散的風(fēng)險(xiǎn)。
[Abstract]:Part I Effect of Primary Dysmenorrhea on Resting State Brain Network Function and Gray Matter Volume Objective To collect fMRI data of severe primary dysmenorrhea patients and healthy control women during menstrual period by resting state functional magnetic resonance imaging (fMRI) for the first time to observe whether there is brain in patients with long-term severe dysmenorrhea. The changes of structure and function were expected to explore the pathogenesis of dysmenorrhea from the pain-related central nervous system mechanism and provide scientific theoretical basis for guiding clinical treatment and finding new therapeutic targets.Methods 10 patients with severe primary dysmenorrhea and 10 healthy women of childbearing age were recruited. Using REST toolkit based on MATLAB 2012 platform, the differences of low-frequency amplitude statistics between two groups of subjects were analyzed in the gray matter range. GIFT software based on MATLAB R2011b platform was used for independent component analysis to extract two resting brain networks: the front and back of default network. Voxel-based morphological analysis in SPM8 software was used to segment, standardize and smooth high-resolution structural images. SPM8 was used for statistical analysis to compare the functional connectivity of brain and the volume difference of gray matter between severe dysmenorrhea and normal control group. (2) In severe dysmenorrhea group, the activity of left anterior cuneate lobe was increased, while the activity of bilateral medial prefrontal lobe was decreased in severe dysmenorrhea group. (3) In severe dysmenorrhea group, the volume of gray matter in whole brain and local brain regions was not significantly different between severe primary dysmenorrhea group and healthy control group. The functional connectivity of left prefrontal lobe was significantly increased, while the functional connectivity of right first somatosensory cortex was significantly decreased in the posterior part of default network. The changes of brain function in patients with chronic dysmenorrhea may occur before structural changes. Part II The relationship between brain-derived neurotrophic factors and pain in endometriosis Distribution and expression of BDNF and protein gene product 9.5 (PGP9.5) were investigated to investigate the relationship between BDNF and endometriosis and pain. The distribution and expression of BDNF and PGP 9.5 in ectopic and eutopic endometrium of patients with ovarian endometriosis (13 cases in pain group, 12 cases in pain-free group) and endometrium of patients with simple myoma without pain were detected by immunohistochemistry. Results There was no significant difference between the two groups in age, pregnancy and parity. For the first time, BDNF positive areas were found in the epithelium and stroma of endometrium, and the expression of BDNF spoon was significantly higher than that of stroma. The expression level of BDNF in eutopic and eutopic endometrium of endometriosis was significantly higher than that of non-endometriosis. The expression level of BDNF in ectopic and eutopic endometrium of patients with painful and non-painful endometriosis was not significantly different. No PGP 9.5 staining was found in eutopic endometrium of endometriosis, but the positive rate of PGP 9.5 in eutopic endometrium of endometriosis was higher than that in eutopic endometrium of non-endometriosis (20% vs. 8%, P 0.05). Objective To evaluate the incidence of unexpected uterine sarcoma after myomectomy and the effect of electromyomectomy on the clinical prognosis of patients with occult uterine sarcoma. Objective To analyze the clinical data of patients with uterine sarcoma accidentally discovered after myomectomy in Peking Union Medical College Hospital from January 2009 to December 2013. 21% of the patients were unexpectedly diagnosed as uterine sarcoma, including 1 (0.02%) leiomyosarcoma and 8 (0.19%) endometrial stromal sarcoma. There was no significant difference in the incidence of uterine sarcoma between the two groups (P 0.05). Nine patients with uterine sarcoma survived. The patients in the laparoscopic group and the open group were followed up for 31.20 months and 40.50 months, respectively. The smashing device does not seem to increase the risk of sarcoma dissemination in the short term.
【學(xué)位授予單位】：北京協(xié)和醫(yī)學(xué)院
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R711.51

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