本文選題：重癥肌無力 + 發(fā)病年齡　； 參考：《華中科技大學》2016年博士論文

【摘要】：目的：調(diào)查同濟醫(yī)院住院和門診的重癥肌無力(MG)成人患者的死亡率和相關危險因素。方法：對2013年前就診的MG患者做了詳細的登記,包含起病時間,發(fā)病時狀態(tài),分級,病程,用藥情況,激素,免疫抑制劑的使用,胸腺手術,合并癥如心功能不全,高血壓,糖尿病,慢性阻塞性肺部疾病,腦中風等。對死亡原因進行分析。采用COX生存分析和K-M曲線分析方法。結果：共收集2195位患者,129位MG患者死亡,病亡率為5.88%,死亡的原因有癌癥,MG危象,心肌梗塞,肺部疾病,中風,消化道出血和自殺。65.9%死亡發(fā)生在醫(yī)院,34.1%發(fā)生在社區(qū)醫(yī)院。與MG相關危險因素是病程,MG危象,MGFA Ⅲ型和Ⅳ型,乙酰膽堿受體(AchR)抗體水平,胸腺病理,免疫抑制劑的使用(p0.05)。另外,先前的中風,慢性阻塞性肺病(COPD),糖尿病,房顫,高脂血癥,心肌梗塞,惡性腫瘤和死亡有相關性(HR分別為3.251,4.173,3.738,3.886,1.945,2.177和14.7,p0.05),外周血管病(PVD),心功能不全,高血壓,慢性腎病和吸煙并沒有統(tǒng)計學意義(p0.05)。結論：入組時疾病的嚴重程度,AchR抗體的表達,胸腺病理,和病程是死亡的高危預測因素；合并癥,如中風,慢性阻塞性肺部疾病,糖尿病,房顫,高脂血癥,心肌梗塞,惡性腫瘤增加MG的死亡風險；免疫抑制劑的使用,胸腺切除手術能降低MG的死亡風險。目的：通過給SCID小鼠注入MG危象患者增殖的T細胞,來闡明T細胞在MG小鼠模型中的作用并檢測細胞因子。方法：共32只6-8周雄性SCID小鼠飼養(yǎng)于SPF級動物實驗室。環(huán)磷酰胺(CTX)按40mg/kg給小鼠腹腔注射,連續(xù)4天。從MG危象患者血中分離出的單個核細胞進行增殖(以T細胞為主,少量B細胞)。首次注射CTX第5天后,實驗組每周給SCID小鼠腹腔注射培養(yǎng)的2×106淋巴細胞,對照組給予PBS共8次。每位患者淋巴細胞移植到4只小鼠,共4位患者均為MGFA Ⅲ型。并完善小鼠臨床評分(Clinical scores),抓力試驗(Grip strength),翻籠試驗(Inverted screen test),小鼠行肌電圖檢測后,ELISA法檢測抗人乙酰膽堿受體抗體,IL-6和IL-4的水平。結果：實驗組共6只小鼠確定為MG模型,臨床評分,抓力試驗,翻籠試驗均差于對照組,6只小鼠的肌電圖顯示為陽性,乙酰膽堿受體抗體檢測實驗組高于對照組,而IL-6和IL-4沒有統(tǒng)計學意義。結論：MG危象患者T細胞增殖可以誘導出MG人源化SCID小鼠模型,為以后MG危象的個性化治療奠定基礎。目的：磁共振彌漫張量成像(DTI)和磁共振波譜分析(MRS)在肌萎縮側索硬化病人中的應用。方法：2013年10月到2014年7月19位肌萎縮側索硬化病人和13位年齡匹配的健康成人完善磁共振檢查,包含部分各向異數(shù)(FA),表觀擴散系數(shù)(ADC),N-乙酰天冬氨酸(NAA),膽堿(Cho),和肌酸(Cr)等定量結果。肌萎縮側索硬化功能評定量表修改版(ALSFRS-R)和疾病進展比例用來評估功能殘疾。分析患者和對照組的影像結果,影像和功能殘疾的相關性進行統(tǒng)計學分析。結果：雙側皮質(zhì)運動區(qū)的NAA/Cr和皮質(zhì)脊髓束(CST)的FA值比對照組明顯降低。兩組的Cho/Cr,纖維長度,纖維體積,ADC和NAA沒有統(tǒng)計學意義。ALS患者右側皮質(zhì)脊髓束FA(r=0.243, p=0.316);左側皮質(zhì)運動區(qū)NAA (r=0.095, p=0.699), NAA/Cr (r=0.172,p=0.481);右側的皮質(zhì)運動區(qū)NAA (r=0.320,p=0.182), NAA/Cr (r=0.193,p=0.492)和ALSFRS-R之間無明顯統(tǒng)計學意義。疾病進展比值和FA, NAA,或NAA/Cr沒有統(tǒng)計學意義。結論：NAA/Cr和FA能夠幫助診斷肌萎縮側索硬化。大腦局部NAA/Cr和FA值不能夠評估ALSFRS-R和疾病進展比值。
[Abstract]:Objective: To investigate the mortality and risk factors for adult patients with myasthenia gravis (MG) in Tongji Hospital. Methods: a detailed registration was made for patients with MG before 2013, including onset time, disease status, classification, course of disease, medication, hormone, use of immunosuppressive agents, thymic surgery, and cardiac function. Incomplete, hypertension, diabetes, chronic obstructive pulmonary disease, stroke and so on. Analysis of the causes of death. Using COX survival analysis and K-M curve analysis. Results: a total of 2195 patients were collected, 129 MG patients died and the death rate was 5.88%, the causes of death were cancer, MG crisis, myocardial infarction, lung disease, stroke, gastrointestinal bleeding and Suicide.65.9% death occurred in the hospital, 34.1% occurred in the community hospital. The risk factors associated with MG were the course of disease, the MG crisis, the MGFA III and IV type, the acetylcholine receptor (AchR) antibody level, the thymus pathology, the use of immunosuppressive agents (P0.05). In addition, the previous stroke, the chronic obstructive pulmonary disease (COPD), diabetes, atrial fibrillation, hyperlipidemia, myocardial infarction There was a correlation between malignant tumor and death (HR 3.251,4.173,3.738,3.886,1.945,2.177 and 14.7, P0.05), peripheral vascular disease (PVD), cardiac insufficiency, hypertension, chronic kidney disease and smoking (P0.05). Conclusion: the severity of the disease, the expression of the AchR antibody, the thymus pathology, and the course of the disease are Gao Weiyu's death. Test factors; complications such as stroke, chronic obstructive pulmonary disease, diabetes, atrial fibrillation, hyperlipidemia, myocardial infarction, and malignant tumor increase the risk of death of MG; immunosuppressive drugs, thymectomy can reduce the risk of MG death. Objective: to clarify the T cells in MG by injecting T cells into the T cells of the MG crisis patients. The function of the mouse model and the detection of cytokine. Methods: a total of 32 6-8 weeks male SCID mice were fed in the SPF animal laboratory. Cyclophosphamide (CTX) was injected into the abdominal cavity of the mice by 40mg/kg for 4 days. The mononuclear cells isolated from the blood of the MG crisis patients were proliferated (with T fine cells and a small amount of B cells). After the first injection of CTX, it was the first day of the injection of CTX. In the experimental group, 2 x 106 lymphocytes were injected into the abdominal cavity of SCID mice, and the control group was given a total of 8 times PBS. Each patient was transplanted into 4 mice. A total of 4 patients were all MGFA III. The clinical score of mice (Clinical scores), grasping test (Grip strength), cage test (Inverted screen test), and electromyography of mice were examined. After test, ELISA method was used to detect the anti human acetylcholine receptor antibody, IL-6 and IL-4 level. Results: 6 mice in the experimental group were determined to be MG model, the clinical score, the grasping test, the cage test were all poor in the control group, the electromyography of 6 mice was positive, the acetylcholine receptor antibody test group was higher than the control group, and the IL-6 and IL-4 did not count the statistics. Conclusion: the proliferation of T cells in MG crisis patients can induce the MG humanized SCID mouse model and lay the foundation for the individualized treatment of MG crisis. Objective: the application of magnetic resonance diffuse tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) in amyotrophic lateral sclerosis patients. Methods: 19 muscular atrophy from October 2013 to July 2014. Sclerosing patients and 13 age matched healthy adults perfected MRI, including partial anisotropy (FA), apparent diffusion coefficient (ADC), N- acetyl aspartic acid (NAA), choline (Cho), and creatine (Cr) quantitative results. The amyotrophic lateral sclerosis function assessment table modified version (ALSFRS-R) and disease progression ratio were used to assess functional disability. Analysis of the images of the patients and the control group, the correlation between the image and the functional disability was statistically analyzed. Results: the FA value of the NAA/Cr and the corticospinal tract (CST) in the bilateral cortical motor area was significantly lower than that of the control group. The two groups of Cho/Cr, fiber length, fiber volume, ADC and NAA were not statistically significant in the right lateral corticospinal tract FA of.ALS patients (r=0 .243, p=0.316); left cortical motor area NAA (r=0.095, p=0.699), NAA/Cr (r=0.172, p=0.481); there is no significant statistical significance between NAA (r=0.320, p=0.182) in the right cortical motor area. Atrophic lateral sclerosis. NAA/Cr and FA values in the brain do not assess the ratio of ALSFRS-R to disease progression.

【學位授予單位】：華中科技大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：R746.1

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