本文選題：早產(chǎn)兒視網(wǎng)膜病 + 視網(wǎng)膜激光光凝術(shù)　； 參考：《大連醫(yī)科大學(xué)》2017年碩士論文

【摘要】：第一部分雷珠單抗與視網(wǎng)膜激光光凝術(shù)治療ROP療效分析目的:探討298例早產(chǎn)兒視網(wǎng)膜病患兒首次采用雷珠單抗玻璃體腔注藥術(shù)或視網(wǎng)膜激光光凝術(shù)兩種治療方法的治療療效。方法:本研究采用回顧性病例對照研究,對2007年10月至2016年1月收治在陸軍總醫(yī)院附屬八一兒童醫(yī)院的298例需要首次接受雷珠單抗玻璃體腔注藥術(shù)或者視網(wǎng)膜激光光凝術(shù)治療的早產(chǎn)兒視網(wǎng)膜病患兒臨床資料進(jìn)行分析,比較兩不同治療組中患兒臨床特點是否存在差異,病變控制情況、治療次數(shù)、病變最終治愈率、遠(yuǎn)期預(yù)后等是否存在不同,從而對首次采用的兩種治療方法的治療療效進(jìn)行評價。結(jié)果:本研究中符合納入標(biāo)準(zhǔn)需要首次接受雷珠單抗玻璃體腔注藥術(shù)及視網(wǎng)膜激光光凝術(shù)治療的早產(chǎn)兒視網(wǎng)膜病患兒為298例,其中首次選擇的治療方法為雷珠單抗注藥術(shù)124例(41.61%)、激光術(shù)174例(58.39%)。根據(jù)病變分區(qū)不同,124例首次采用雷珠單抗注藥術(shù)治療人數(shù)中Ⅰ區(qū)病變?nèi)藬?shù)有72例,占58.06%,Ⅱ區(qū)病變?nèi)藬?shù)52例,占41.94%。174例首次采用視網(wǎng)膜激光術(shù)治療人數(shù)中Ⅰ區(qū)病變?nèi)藬?shù)有30例,占17.24%,Ⅱ區(qū)病變?nèi)藬?shù)135例,占77.59%,兩治療組在病變的分區(qū)比較中存在差異性(χ~2=49.310,P0.001)。首次采用的兩治療組中APROP與非APROP構(gòu)成比比較中無差異性(χ~2=0.154,P=0.695)。兩治療組患兒在出生體重、出生胎齡及其他多種臨床特點的比較中均為P0.05,無顯著性差異。在病變控制率的比較中兩治療組在首次治療后無差異(χ~2=0.059,P=0.808),且兩者分別在Ⅰ區(qū)和Ⅱ區(qū)不同病變區(qū)域中首次治療后的病變控制率比較中也未見顯著性差異(χ~2=1.436,P=0.231;χ~2=0.751,P=0.386)。不同病變類型比較中,兩治療組分別在急進(jìn)型ROP與非急進(jìn)型ROP首次治療后病變控制率比較無統(tǒng)計學(xué)差異性(急進(jìn)型ROPχ~2=0.475,P=0.491;非急進(jìn)型ROPχ~2=2.534,P=0.111)。首次采用兩種治療方法后兩組治療次數(shù)的比較上也無顯著差異(χ~2=0.818,P=0.664),且病變的最終治愈率上兩者基本一致。通過檢驗分析發(fā)現(xiàn)胎膜早破、壞死性小腸結(jié)腸炎、外院轉(zhuǎn)入ROP、病變分區(qū)、病變類型是否為APROP與病變控制情況相關(guān),經(jīng)Logistic回歸分析發(fā)現(xiàn)胎膜早破、壞死性小腸結(jié)腸炎、病變類型是否為APROP是影響病變控制的獨立危險因素(P0.05)。在激光術(shù)組隨訪人數(shù)較少的前提下,兩治療組遠(yuǎn)期預(yù)后比較無顯著性差異(P0.05)。結(jié)論:1.本研究中納入比較的兩治療組中患兒的臨床基本特點一致,因而兩治療組在治療療效上具有可比性。2.注藥術(shù)組中Ⅰ區(qū)病變所占比例高于激光術(shù)組中Ⅰ區(qū)病變所占比例,注藥術(shù)組Ⅰ區(qū)病變多,而激光術(shù)組以Ⅱ區(qū)病變?yōu)橹鳌?.兩治療組在首次治療后的病變控制率、病變治療次數(shù)及病變的最終治愈率的比較上并沒有顯著性差異,也說明兩者在短期治療效果上基本一致。4.通過隨訪發(fā)現(xiàn)兩治療組在首次治療后遠(yuǎn)期治療預(yù)后結(jié)果比較無統(tǒng)計學(xué)差異。5.在兩治療組臨床治療效果無差異的前提下,注藥術(shù)治療操作簡單、無需麻醉及有創(chuàng)通氣因而在臨床治療選擇中更優(yōu)于激光術(shù)組。第二部分ROP致病基因全外顯子測序分析目的:通過實驗篩選可能與早產(chǎn)兒視網(wǎng)膜病致病相關(guān)基因,分析其致病性,為下一步功能性驗證實驗做準(zhǔn)備。方法:對10例早產(chǎn)兒視網(wǎng)膜病患兒血液樣本進(jìn)行全基因外顯子測序,應(yīng)用Phenolyzer系統(tǒng)預(yù)測與早產(chǎn)兒視網(wǎng)膜病相關(guān)基因,將兩者進(jìn)行比對,通過基因表型驅(qū)動分析方法,找到表型與基因的相關(guān)性,篩選可能與早產(chǎn)兒視網(wǎng)膜病發(fā)生相關(guān)的候選致病基因,并根據(jù)研究結(jié)果分析其致病性。結(jié)果:本研究數(shù)據(jù)顯示測序質(zhì)量及測序深度均滿足研究要求,全基因外顯子測序獲得的基因總數(shù)為8211個,其中發(fā)生缺失突變的有687個,占8.37%,插入突變的有500個,占6.09%,單核苷酸突變(Single nucleotide variation,SNV)有7024個,占85.54%。缺失突變及插入突變主要以移碼突變及非移碼突變?yōu)橹?而SNV主要以錯義突變?yōu)橹?突變的類型不同導(dǎo)致最終編碼蛋白質(zhì)功能亦不同。而通過Phenolyzer系統(tǒng)預(yù)測出與ROP疾病相關(guān)基因有50種,將全基因測序結(jié)果與Phenolyzer系統(tǒng)預(yù)測的基因進(jìn)行表型驅(qū)動分析后發(fā)現(xiàn)LRP5基因可能為早產(chǎn)兒視網(wǎng)膜病致病基因。之后針對研究中基因突變類型、基因表達(dá)部位、人群中基因頻率、是否存在致病性等進(jìn)行分析,發(fā)現(xiàn)該基因突變?yōu)殄e義突變,可導(dǎo)致11號染色體1區(qū)3帶第2次亞帶中外顯子23的第2900位密碼子中間位置的堿基有G突變?yōu)門,最終導(dǎo)致第967位氨基酸由半胱氨酸變?yōu)楸奖彼?并且該基因突變?yōu)轱@性雜合突變,在三大人群中基因頻率均0.01,提示基因突變具有研究意義,且通過SIFT、Polyphen2、Mutation Taster軟件對該基因的致病性進(jìn)行預(yù)測,提示該基因是具有致病性的。因而預(yù)測LRP5基因突變可能導(dǎo)致ROP的發(fā)生。結(jié)論:10例研究樣本中1例樣本中攜帶有LRP5基因突變,其可能為導(dǎo)致ROP疾病發(fā)生的致病基因,但仍需進(jìn)一步的研究來驗證該基因的功能。
[Abstract]:The first part of the treatment of ROP with reelzumumab and retinal laser photocoagulation in the treatment of 298 cases of premature infants with retinopathy of retinopathy of the first use of rezumumab glass cavity injection or retinal laser photocoagulation two treatment methods. Methods: This study used a retrospective case control study, from October 2007 to 2016. In January, the clinical data of 298 children with retinopathy of preterm infants, which were first accepted by lizumumab, or retinal laser photocoagulation, were treated in the children's Hospital Affiliated to the General Hospital of the army general hospital. The clinical characteristics of the children in the two different treatment groups were compared. The final cure rate and the long-term prognosis are different, and the therapeutic effect of the first two methods of treatment is evaluated. Results: in this study, 298 cases of premature infants with retinopathy of preterm infants were first accepted by the inclusion criteria of rezumumab and retinal laser photocoagulation for the first time. The selected treatment was 124 cases (41.61%) and 174 cases (58.39%) with laser surgery. According to the diseased area, 124 cases of the first use of lezumab injection were 72 cases, 58.06%, and 52 cases in the second region, accounting for the first time in the 41.94%.174 cases by retina laser treatment. There were 30, 17.24%, 135, 77.59%, and two in the two treatment group (x, P0.001). There was no difference in the ratio of APROP to non APROP in the first two treatment group (x ~2=0.154, P=0.695). The children in the two treatment group were born in birth weight, birth gestational age and a variety of other clinical cases. The comparison of the characteristics was P0.05 without significant difference. In the comparison of the rate of disease control, there was no difference between the two treatment groups after the first treatment (x ~2=0.059, P=0.808), and there was no significant difference (x ~2=1.436, P=0.231; Chi ~2=0.751, P=0.386) in the first treatment of the first treatment in the region I and the region II. In the comparison of different types of lesions, there was no significant difference in the control rate between the two treatment groups after the first treatment of the emergency ROP and the non emergency ROP (ROP Chi ~2=0.475, P=0.491; the non urgent ROP x ~2=2.534, P=0.111). There was no significant difference in the comparison between the two groups after the first two treatments (x ~2=0.818, P=0). .664) and the final cure rate of the lesions were basically the same. Through the examination and analysis, it was found that premature rupture of the membranes, necrotizing enterocolitis, the external hospital was transferred to ROP, the lesion was divided, whether the type of APROP was related to the control of the disease, and the Logistic regression analysis found that the premature rupture of the membranes, necrotic enterocolitis, and the type of pathological changes were APROP. The independent risk factor (P0.05) for the control of rounded disease (P0.05). There was no significant difference in the long-term prognosis in the two treatment group (P0.05). Conclusion: the clinical basic characteristics of the children in the two treatment group were the same in the 1. study, so the two treatment group had the comparable.2. injection group in the therapeutic effect. The proportion of the lesion in the middle part I was higher than that in the laser group. The lesion in the group I was much more, and there was no significant difference in the rate of control, the number of treatment and the final cure rate of the lesion in the group of.3. two, which was the first treatment in the laser group. It also indicated that the two groups were treated in the short term. The curative effect was basically consistent with.4. through follow-up. It was found that there was no statistical difference between the two treatment groups after the first treatment and the prognosis of the long term treatment was no significant difference..5. was no difference in the effect of the clinical treatment in the two treatment group. The treatment operation was simple, no anesthesia and ventilation was needed, so second departments were better than the laser group in the clinical treatment. ROP pathogenic gene exon sequencing analysis objective: to screen the pathogenicity of retinopathy of premature infants by screening the genes related to retinopathy of prematurity, and to analyze its pathogenicity and prepare for the next functional verification experiment. Methods: the whole gene exon sequencing was carried out in 10 children with retinopathy of preterm infants, and the Phenolyzer system was used to predict and early. The genes related to retinopathy of birth were compared, and the correlation between phenotypes and genes was found by gene phenotypic driving analysis. The candidate genes associated with the occurrence of retinopathy in preterm infants were screened and the pathogenicity was analyzed according to the results. Results: the results of the study show that the quality of sequencing and the depth of sequencing are satisfied. The total number of gene exons sequenced is 8211, of which 687, 8.37%, 500, 6.09%, Single nucleotide variation, SNV, 8.37%, and 7024 of the single nucleotide mutations (variation, SNV), and the major 85.54%. deletion and the insertion mutation are mainly a code shift mutation and a non graft mutation, and SN V is mainly missense mutation, and the different types of mutation lead to the difference in the function of the final encoded protein, and 50 kinds of genes related to ROP disease are predicted by the Phenolyzer system. The LRP5 gene may be the pathogeny of the retinopathy of the premature infant after the analysis of the gene sequencing results and the gene predicted by the Phenolyzer system. Then the gene mutation type, the gene expression site, the gene frequency and the pathogenicity of the population were analyzed, and the mutation was found to be a missense mutation, which could lead to the G mutation of the G mutation of the base between the 2900th bits of the codon 23 of the second subbands of the 3 band and second subbands of the chromosome 1. Amino acids change from cysteine to phenylalanine, and the gene mutation is a dominant heterozygous mutation. The gene frequency of the gene is 0.01 in the three population, suggesting that the gene mutation is of research significance, and the pathogenicity of the gene is predicted by SIFT, Polyphen2, Mutation Taster software, suggesting that the gene is pathogenic. Therefore, the LRP5 base is predicted. Mutations may lead to the occurrence of ROP. Conclusion: in 1 samples of 10 cases, a mutation of LRP5 gene is carried in the sample, which may be a pathogenic gene that causes the occurrence of ROP disease, but further research is still needed to verify the function of the gene.

【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R774.1

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