本文選題：早產(chǎn)兒視網(wǎng)膜病變 + 圖文診斷系統(tǒng)��； 參考：《南方醫(yī)科大學(xué)》2011年博士論文

【摘要】：研究背景： ROP是目前國(guó)內(nèi)外兒科和眼科研究的熱點(diǎn)之一。1984年國(guó)際ROP會(huì)議制定了ROP的分期標(biāo)準(zhǔn),2003年早產(chǎn)兒視網(wǎng)膜病早期協(xié)作治療組進(jìn)一步完善ROP的分期標(biāo)準(zhǔn)。近幾年來(lái),國(guó)外研究學(xué)者已就ROP的高危因素、病因與治療等方面開(kāi)展了相關(guān)的基礎(chǔ)試驗(yàn)與臨床實(shí)踐的研究,并取得可喜的研究成果。然而,ROP檢查手段的研究仍然不十分成熟。目前不僅缺乏統(tǒng)一、高效、安全、可普及的檢查工具,從臨床角度,對(duì)ROP的發(fā)病規(guī)律、眼底視網(wǎng)膜的形態(tài)學(xué)變化等研究也無(wú)法深入開(kāi)展。 臨床研究發(fā)現(xiàn),大約85%未經(jīng)治療的ROP自行消退并發(fā)育成完全血管化的視網(wǎng)膜,標(biāo)準(zhǔn)的治療可以預(yù)防剩下5%的兒童視力喪失,大約6%到10%的ROP患者最終出現(xiàn)嚴(yán)重的視力喪失。到底在什么樣情況下ROP會(huì)自行消退,什么樣的情況它會(huì)發(fā)展乃至出現(xiàn)視網(wǎng)膜脫離最終導(dǎo)致失明?對(duì)這些ROP發(fā)病規(guī)律的研究,將使我們對(duì)ROP的發(fā)展趨勢(shì)進(jìn)一步了解,從而準(zhǔn)確地對(duì)ROP病人選擇性進(jìn)行早期干預(yù)性的治療,更加有效地把握治療的最佳時(shí)機(jī),既可以防治過(guò)度治療,又可以避免因把握不當(dāng)而導(dǎo)致病程惡化乃至無(wú)法控制的局面出現(xiàn)。因此,如何確定早期ROP的病變特點(diǎn),從而客觀、準(zhǔn)確地對(duì)早期ROP做出診斷,并進(jìn)行早期追蹤和有效的干預(yù)性治療已成為了國(guó)內(nèi)外學(xué)者研究的方向。目前,國(guó)內(nèi)外眼科醫(yī)生主要使用雙目間接檢眼鏡進(jìn)行ROP的篩查,它具有立體感、照明強(qiáng)度強(qiáng)、視野寬、成像清晰等特點(diǎn),被公認(rèn)為是ROP篩查的“金標(biāo)準(zhǔn)”和首選檢查工具。但是,由于雙目間接檢眼鏡下眼底圖像的采集與輸出困難,眼底檢查結(jié)果無(wú)法記錄,一直以來(lái)采用畫(huà)圖描述的方法保存資料,缺乏客觀性結(jié)果。為了解決這個(gè)問(wèn)題,雖然國(guó)外學(xué)者進(jìn)行了多方面的嘗試,但是始終沒(méi)有獲得最佳辦法。在廣州市、廣東省科研機(jī)構(gòu)的支持下,我們采用雙目間接檢眼鏡成像與眼底圖像輸出技術(shù)為檢查手段,建立了計(jì)算機(jī)輔助的雙目間接檢驗(yàn)鏡ROP檢查體系。 成熟的視網(wǎng)膜出現(xiàn)新生血管常導(dǎo)致視力下降,甚至視力喪失。視網(wǎng)膜新生血管(retinal neovascularization, RNV)多見(jiàn)于糖尿病性視網(wǎng)膜病變、早產(chǎn)兒視網(wǎng)膜病變、缺血性視網(wǎng)膜靜脈栓塞,病因復(fù)雜,發(fā)病機(jī)制尚未明確。隨著新生兒重癥監(jiān)護(hù)的建立及醫(yī)療護(hù)理技術(shù)的進(jìn)步,早產(chǎn)低出生體重兒的成活率大大提高,早產(chǎn)兒視網(wǎng)膜病(ROP)的發(fā)生率也呈上升趨勢(shì),在出生體重小于1000g的超低出生體重兒中發(fā)病率高達(dá)80%以上,占兒童視力損害的比例逐年增加,已引起人們的重視。但是,該病的發(fā)病機(jī)制仍未明確,目前研究表明新生血管的形成可能起主導(dǎo)作用。抑制新生血管形成,可達(dá)到防治ROP的目的。因而越來(lái)越多的學(xué)者從該病的發(fā)病機(jī)制著手,希望通過(guò)抑制新生血管的生長(zhǎng)阻斷該病的進(jìn)展,這在動(dòng)物實(shí)驗(yàn)中被證實(shí)是可行的。但是,新生血管抑制劑同時(shí)也可抑制正常的血管發(fā)育,阻礙眼球正常的解剖和功能發(fā)育,這也是尚未解決的問(wèn)題。 目前大多數(shù)對(duì)ROP的基礎(chǔ)研究多停留在單基因以及基因水平。但是,機(jī)體生理機(jī)能的真正執(zhí)行者是蛋白質(zhì),有研究表明細(xì)胞內(nèi)mRNA水平和蛋白質(zhì)的表達(dá)峰度并不完全一致,因此從蛋白質(zhì)水平對(duì)疾病進(jìn)行研究顯得特別重要。然而,傳統(tǒng)的對(duì)單個(gè)蛋白質(zhì)或某幾種蛋白質(zhì)進(jìn)行研究的方式難以系統(tǒng)透徹地整體闡釋ROP形成及病情發(fā)展的基本機(jī)制。要對(duì)其復(fù)雜活動(dòng)有全面深入的認(rèn)識(shí),必然要在整體、動(dòng)態(tài)、網(wǎng)絡(luò)的水平上對(duì)蛋白質(zhì)進(jìn)行研究。蛋白質(zhì)組是一個(gè)基因組所能編碼的所有蛋白的組合。蛋白質(zhì)組學(xué)是對(duì)一個(gè)基因組、一種生物、一種細(xì)胞、組織所表達(dá)的全部蛋白質(zhì)及其相互作用的研究,提供的資料更真實(shí)地反映基因、組織、器官的實(shí)際功能狀態(tài)。細(xì)胞因子抗體芯片技術(shù)是在蛋白質(zhì)組概念上發(fā)展起來(lái)的高通量實(shí)驗(yàn)檢測(cè)方法。在疾病的診斷、病程觀察、療效判斷及細(xì)胞因子治療監(jiān)測(cè)方面有重要意義。研究細(xì)胞因子有助于闡明分子水平的功能調(diào)節(jié)機(jī)制,特別是利用細(xì)胞因子治療腫瘤、感染、造血功能障礙以及自身免疫病等已收到初步療效,具有非常廣闊的應(yīng)用前景。 研究目的 1.本研究擬在前期工作基礎(chǔ)上,建立ROP圖文報(bào)告系統(tǒng),并通過(guò)視網(wǎng)膜圖像的分析,了解早產(chǎn)兒視網(wǎng)膜解剖結(jié)構(gòu)的形態(tài)學(xué)特點(diǎn),探索早產(chǎn)兒視網(wǎng)膜發(fā)育的特點(diǎn),掌握ROP視網(wǎng)膜的病變特點(diǎn),進(jìn)一步闡明ROP的早期發(fā)病特點(diǎn)及規(guī)律,尋求ROP的臨床治療干預(yù)時(shí)機(jī)。同時(shí)通過(guò)對(duì)該圖文報(bào)告系統(tǒng)的統(tǒng)計(jì)與研究分析,可以了解廣州地區(qū)早產(chǎn)兒視網(wǎng)膜病變的發(fā)生情況,對(duì)發(fā)現(xiàn)的早產(chǎn)兒視網(wǎng)膜病變進(jìn)行早期治療,摸索出對(duì)該病預(yù)防、臨床治療的經(jīng)驗(yàn)。 2.本研究擬將利用新生血管相關(guān)細(xì)胞因子抗體芯片技術(shù)檢測(cè)正常早產(chǎn)兒、ROP患兒術(shù)前及術(shù)后血清中55種相關(guān)細(xì)胞因子的表達(dá),有助于從全局及整體角度考慮新生血管相關(guān)細(xì)胞因子對(duì)ROP形成及發(fā)展過(guò)程的影響。 研究方法 1.利用計(jì)算機(jī)輔助雙目間接檢眼鏡錄制早產(chǎn)兒視網(wǎng)膜病變篩查視頻； 2.構(gòu)建圖文診斷系統(tǒng),在錄制視頻后能及時(shí)截圖,打印報(bào)告 3.從獲得的大量圖文報(bào)告中分析早產(chǎn)兒視網(wǎng)膜解剖學(xué)及形態(tài)學(xué)特點(diǎn)； 4.隨機(jī)抽取正常早產(chǎn)兒、ROP術(shù)前及術(shù)后一周患兒血清,取血后血液在冰上靜置1h,0℃離心5000r/min 10 min。分離血清,并凍存于-80℃以備后用。 5. RayBioTM人血管新生細(xì)胞因子抗體芯片檢測(cè)血清中55種可能相關(guān)的細(xì)胞因子表達(dá)； 結(jié)果： 1、計(jì)算機(jī)輔助ROP圖文報(bào)告系統(tǒng)的臨床應(yīng)用 1)、檢查前的準(zhǔn)備工作：早產(chǎn)兒需要使用五次復(fù)方托吡卡胺滴眼液,才可以達(dá)到理想狀態(tài)。進(jìn)行ROP篩查工作需要醫(yī)院眼科、新生兒科及婦幼保健新生兒科合作進(jìn)行。 2)、計(jì)算機(jī)輔助ROP圖文報(bào)告系統(tǒng)結(jié)果分析 我們的研究結(jié)果表明：“計(jì)算機(jī)輔助雙目間接檢眼鏡成像技術(shù)”能夠有把握地讓我們回答早產(chǎn)兒視網(wǎng)膜病變的重要指標(biāo)存在與否：周邊部視網(wǎng)膜是否存在無(wú)血管區(qū)；血管區(qū)與無(wú)血管區(qū)之間是否存在明顯的分界線；分界線是否有隆起；隆起處血管是否有增生和血管纖維增殖。因此,我們能夠有把握地診斷該早產(chǎn)兒是否ROP患者。 3)、同時(shí),與其他疾病鑒別(牽�；ňC合征、視網(wǎng)膜母細(xì)胞瘤、早產(chǎn)兒眼底出血、正常周邊灰白色視網(wǎng)膜)中,該系統(tǒng)可以提供永久的確鑿的證據(jù)支持診斷。 4)、通過(guò)研究雙目間接檢眼鏡成像技術(shù)下獲得的眼底檢查錄像、典型眼底病變圖像回顧,可以在ROP工作開(kāi)展中對(duì)醫(yī)務(wù)人員進(jìn)行教學(xué)培訓(xùn)。 2、正常早產(chǎn)兒與ROP患兒血清中血管相關(guān)細(xì)胞因子檢測(cè)發(fā)現(xiàn)有14組蛋白表達(dá)差異顯著,而正常早產(chǎn)兒與ROP術(shù)后一周時(shí)間的血清學(xué)檢查發(fā)現(xiàn)了14種蛋白表達(dá)差異。其中： 1)：相對(duì)于正常早產(chǎn)兒及術(shù)前,激光光凝術(shù)后1周ROP患兒FGF basic、IGFBP-3表達(dá)水平從異常增高到正常表達(dá),證明了這兩個(gè)細(xì)胞因子在ROP病理生理過(guò)程中具有重要作用：視網(wǎng)膜細(xì)胞的凋亡與血清內(nèi)大量表達(dá)的IGFBP-3可能相關(guān),bFGF的存在可能對(duì)于視網(wǎng)膜神經(jīng)節(jié)細(xì)胞進(jìn)一步損傷有預(yù)防作用?這提示我們?cè)赗OP中要考慮到神經(jīng)發(fā)育與血管新生的相互影響,考慮神經(jīng)系統(tǒng)與ROP形成的相關(guān)性。 2)：一部分炎性反應(yīng)相關(guān)因子Amphiregulin、GMCSF, MMP-8表達(dá)水平由異常降低到正常,及IL-1β由正常表達(dá)到輕度升高,說(shuō)明ROP患兒術(shù)后產(chǎn)生了炎性反應(yīng),但是嚴(yán)重程度不足以對(duì)患兒產(chǎn)生不利影響。 3):PIGF可以減輕病理性血管新生而并不影響正常生理性血管新生、Vaschibin唯一的以負(fù)反饋為作用機(jī)制調(diào)節(jié)血管新生的蛋白。PIGF及Vaschibin由術(shù)前的低表達(dá)變?yōu)樾g(shù)后正常表達(dá)。提示PIGF、Vasohibin有可能成為治療ROP的有效手段。 結(jié)論： 1.整理出一套行之有效的ROP的圖文診斷體系； 2.睫狀后長(zhǎng)神經(jīng)是ROP篩查中要觀察的重要解剖部位； 3.應(yīng)用新生血管形成相關(guān)細(xì)胞因子芯片技術(shù)獲得正常早產(chǎn)兒、ROP患兒術(shù)前及術(shù)后一周血清標(biāo)志蛋白表達(dá)的實(shí)驗(yàn)方法穩(wěn)定可行； 4.提出在ROP中要考慮到神經(jīng)發(fā)育與血管新生的相互影響,考慮神經(jīng)系統(tǒng)與ROP形成的相關(guān)性； 5.從炎性細(xì)胞因子表達(dá)角度證明視網(wǎng)膜激光光凝術(shù)的有效性及安全性； 6. PIGF、Vasohibin有可能成為治療ROP的有效手段。 7.ROP的病理生理過(guò)程是一個(gè)復(fù)雜的血管新生細(xì)胞因子間相互調(diào)節(jié)過(guò)程。 創(chuàng)新 1.構(gòu)建了行之有效的ROP圖文診斷報(bào)告系統(tǒng)； 2.首次提出神經(jīng)系統(tǒng)可能通過(guò)分泌神經(jīng)肽刺激血管新生細(xì)胞因子的激活參與機(jī)體的新生血管形成,影響ROP發(fā)生發(fā)展。提出神經(jīng)系統(tǒng)參與了ROP生理病理過(guò)程的觀點(diǎn)。 3.提出PIGF、Vasohibin有可能成為治療ROP的新靶標(biāo)。
[Abstract]:Research background:
ROP is one of the hotspots in the research of Pediatrics and ophthalmology at home and abroad at present.1984 international ROP meeting set up the staging standard of ROP. In 2003, the early cooperative treatment group of retinopathy of preterm infants further perfected the staging standard of ROP. In recent years, foreign researchers have carried out the basic test of the high risk factors, etiology and treatment of ROP. The research of clinical practice and clinical practice has been studied. However, the research of ROP examination is still not very mature. At present, there is not only a lack of unified, efficient, safe and universal inspection tools. From the clinical point of view, the research on the regularity of ROP and the morphological changes of the retina of the fundus can not be carried out in depth.
Clinical studies have found that about 85% of the untreated ROP subsided and developed into a fully vascularized retina. Standard treatment can prevent the loss of vision in 5% of the children, and about 6% to 10% of ROP patients eventually have severe loss of vision. In what case, ROP will fade away, and what kind of situation it will develop or even be. The occurrence of retinal detachment eventually leads to blindness? The study of these ROP pathogenesis will enable us to further understand the trend of the development of ROP, and thus accurately treat ROP patients with early intervention, and more effectively grasp the best time for treatment, not only to prevent over treatment, but also to avoid the improper control of the treatment. Therefore, how to determine the characteristics of early ROP disease, so as to make an objective and accurate diagnosis of early ROP, and to carry out early tracking and effective intervention therapy have become the research direction of domestic and foreign scholars. At present, ophthalmologists at home and abroad mainly use binocular indirect ophthalmoscope for R OP screening, which has the characteristics of stereoscopic sense, strong lighting intensity, wide field of vision, clear imaging and so on, is recognized as the "gold standard" and the preferred inspection tool for ROP screening. However, because of the difficulty in collecting and exporting of the ocular fundus image under binocular indirect ophthalmoscope, the results of fundus inspection cannot be recorded, and the method of drawing description has been used to save the data. In order to solve this problem, in order to solve this problem, although foreign scholars have tried many aspects, the best method has never been obtained. Under the support of scientific research institutions in Guangzhou, Guangdong Province, we used binocular indirect ophthalmoscope imaging and fundus image output technology as inspection means to establish a computer aided binocular indirect method. The inspection mirror ROP inspection system.
The emergence of neovascularization in mature retina often leads to visual loss and even loss of vision. Retinal neovascularization (retinal neovascularization, RNV) is often seen in diabetic retinopathy, retinopathy of prematurity, ischemic retinal vein embolism, complicated pathogeny, and the pathogenesis is not clear. With the establishment of neonatal intensive care system As well as the progress of medical and nursing technology, the survival rate of premature birth weight infants is greatly increased. The incidence of retinopathy of preterm infants (ROP) is also rising. The incidence of the infant birth weight is up to 80% in the ultra low birth weight infants less than 1000g, which is increasing year by year in children's visual impairment. However, the disease has been paid more attention. The pathogenesis is still not clear. The current research shows that the formation of new blood vessels may play a leading role. Inhibition of the formation of new blood vessels can be used to prevent and control ROP. Therefore, more and more scholars start from the pathogenesis of the disease and hope to block the progress of the disease by inhibiting the growth of the neovascularization, which is proved to be feasible in animal experiments. However, neovascularization inhibitors can also inhibit normal vascular development and prevent normal anatomical and functional development of the eyeball, which is also an unsolved problem.
Most of the basic studies on ROP remain at the single gene and gene level. However, the real executors of the body's physiological functions are proteins. Studies have shown that the intracellular mRNA level and protein expression kurtosis are not completely consistent. Therefore, it is particularly important to study the disease from protein level. It is difficult to systematically and thoroughly interpret the basic mechanism of ROP formation and disease development in a systematic and comprehensive way. It is necessary to understand the complex activities of a protein in an overall, dynamic, and network level. The protein group is all the proteins that a genome can encode. Proteomics is a study of all proteins and their interactions expressed in a genome, a species, a cell, a tissue, and the information provided more truly to reflect the actual functional state of genes, tissues and organs. Cytokine antibody chip technology is a high throughput test developed in the concept of proteome. It is of great significance in the diagnosis of disease, the observation of the course of the disease, the evaluation of the curative effect and the monitoring of the cytokine treatment. It is helpful to elucidate the functional regulation mechanism of the molecular level, especially the treatment of tumor, infection, hematopoiesis and self - free disease by the use of cytokine. The prospect of application.
research objective
1. on the basis of the earlier work, this study is to establish the ROP graphic and text reporting system, and through the analysis of retinal images to understand the morphological features of the retina anatomy of preterm infants, explore the characteristics of retina development in preterm infants, grasp the characteristics of ROP retinopathy, further elucidate the characteristics and laws of the early onset of ROP, and seek the clinical practice of ROP. At the same time, we can understand the occurrence of retinopathy in preterm infants in Guangzhou, and make early treatment for the retinopathy of preterm infants, and find out the experience of prevention and treatment of the disease.
2. the purpose of this study is to detect normal preterm infants by using new blood vessel related cytokine antibody chip technology. The expression of 55 related cytokines in serum of ROP children before and after operation is helpful to consider the influence of neovascular related cytokines on the formation and development of ROP from the global and overall perspective.
research method
1. using computer-assisted binocular indirect ophthalmoscope to record video screening for retinopathy of prematurity.
2. build a graphic diagnostic system. After recording the video, it can capture and print the report in time.
3. to analyze the anatomical and morphological characteristics of retina in premature infants from a large number of graphic reports.
4. the normal preterm infants were randomly selected. Before ROP and one week after the operation, the blood serum was collected on the ice and 1H was placed on the ice. The serum was centrifuged and 5000r/min 10 min. was centrifuged at 0 centigrade. The serum was frozen at -80.
5. RayBioTM human angiogenesis factor antibody chip was used to detect 55 possible cytokines expression in serum.
Result:
1, the clinical application of computer-aided ROP graphic reporting system.
1) pre examination: preterm infants need to use five Compound Tropicamide Eye Drops to achieve their ideal status. ROP screening needs to be conducted in the Department of Ophthalmology, newborn pediatrics and maternity and child care.
2) computer aided ROP graphic report system results analysis
Our results show that "computer assisted binocular ophthalmoscope" can give us a good grasp of the existence of an important indicator of retinopathy in preterm infants: whether there is a vascular area in the peripheral retina; whether there is a clear dividing line between the vascular area and the vascular area; whether there is a boundary line or not. There is a proliferation of blood vessels and proliferation of blood vessels in the uplift. Therefore, we can be able to diagnose whether the premature infant is ROP.
3), at the same time, the system can provide permanent and conclusive evidence to support the diagnosis of other diseases (morning glory syndrome, retinoblastoma, preterm fundus hemorrhage, and normal peripheral white retina).
4), through the study of the fundus examination video obtained under the binocular indirect ophthalmoscope imaging technique, the typical fundus lesion image review can be used in the training of medical staff in the work of ROP.
2, the serum levels of vascular related cytokines in normal preterm infants and ROP children showed that there were significant differences in the expression of 14 groups of proteins, and 14 kinds of protein expression differences were found in normal preterm infants and one week after ROP.
1): compared with normal preterm infants and preoperative, FGF basic in children with ROP, 1 weeks after laser photocoagulation, the expression level of IGFBP-3 from abnormal to normal expression, proves that these two cytokines play an important role in the pathophysiological process of ROP: the apoptosis of retina cells may be related to the large amount of IGFBP-3 in the serum, and the existence of bFGF may be possible. There is a preventive effect on further damage to retinal ganglion cells, which suggests that we should consider the interaction between neurodevelopment and angiogenesis in ROP, and consider the correlation between the nervous system and the formation of ROP.
2): a part of the inflammatory response related factors Amphiregulin, GMCSF, MMP-8 expression level from abnormal to normal, and IL-1 beta from normal to mild elevation, indicating that ROP children have an inflammatory response after operation, but the severity is not enough to have adverse effects on the children.
3): PIGF can reduce the pathological angiogenesis without affecting the normal physiological angiogenesis. The only negative feedback as the mechanism to regulate the angiogenesis of the protein.PIGF and Vaschibin from the preoperative low expression to normal expression after the operation, suggesting that PIGF, Vasohibin may be an effective means for the treatment of ROP.
Conclusion:
1. sort out a set of effective ROP diagnostic system.
2. the long posterior ciliary nerve is an important anatomical site to be observed in ROP screening.
3. the normal preterm infants were obtained by the technique of neovascularization related cytokine microarray. The experimental methods for the expression of serum markers before and after the operation of ROP were stable and feasible.
4. it is proposed that the interaction between neural development and angiogenesis should be considered in ROP, and the correlation between nervous system and ROP formation should be considered.
5. to demonstrate the effectiveness and safety of retinal laser photocoagulation from the perspective of inflammatory cytokines expression.
6. PIGF, Vasohibin may become an effective way to treat ROP.
The pathophysiology of 7.ROP is a complex process of regulation of angiogenesis factors.
innovate
1. an effective ROP graphic diagnostic report system has been constructed.
2. it is the first time that the nervous system may be stimulated by the activation of neuropeptides to stimulate neovascularization of the body and affect the development of ROP. It is suggested that the nervous system is involved in the physiological and pathological process of ROP.
3. it is suggested that PIGF and Vasohibin may become new targets for the treatment of ROP.
【學(xué)位授予單位】：南方醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2011
【分類(lèi)號(hào)】：R774.1;R722.6

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 ;早產(chǎn)兒治療用氧和視網(wǎng)膜病變防治指南[J];中國(guó)生育健康雜志;2004年03期

2 王惕;韓麗榮;鮑蘭;;血管內(nèi)皮細(xì)胞生長(zhǎng)因子受體嵌合蛋白抑制視網(wǎng)膜新生血管化的實(shí)驗(yàn)研究[J];眼科新進(jìn)展;2006年06期

3 趙勁松,宋躍,張曉光;胚胎視網(wǎng)膜血管發(fā)生方式及其促進(jìn)因子[J];眼科研究;2000年01期

4 王曉英;單清;馬萍;陳鵬;郭啟煜;錢(qián)煥文;;神經(jīng)生長(zhǎng)因子對(duì)激光致視網(wǎng)膜損傷后bFGF蛋白表達(dá)的影響[J];眼科研究;2007年04期

5 楊霜英;徐旭東;;超聲圖文信息管理系統(tǒng)的研究及應(yīng)用[J];醫(yī)療衛(wèi)生裝備;2007年07期

6 孫鯤;張宏;徐小軍;徐林;;超聲網(wǎng)絡(luò)信息系統(tǒng)的應(yīng)用[J];醫(yī)療衛(wèi)生裝備;2007年07期

7 王文吉;;早產(chǎn)兒視網(wǎng)膜病變[J];中華眼底病雜志;1996年01期

8 單海冬,趙培泉;RetCam數(shù)字視網(wǎng)膜照相機(jī)在早產(chǎn)兒視網(wǎng)膜病變篩查中的應(yīng)用[J];中華眼底病雜志;2005年05期

9 宋躍,趙勁松,張曉光,王宜,李浩川,梁文妹,何素云;血管內(nèi)皮生長(zhǎng)因子對(duì)人胚胎視網(wǎng)膜血管發(fā)生的調(diào)節(jié)作用[J];中華眼底病雜志;1999年01期

10 曹宏力;早產(chǎn)兒視網(wǎng)膜病變的研究進(jìn)展[J];中國(guó)優(yōu)生與遺傳雜志;2005年08期

相關(guān)博士學(xué)位論文 前1條

1 龐向華;骨質(zhì)疏松患者成骨細(xì)胞相關(guān)細(xì)胞因子蛋白表達(dá)與證型的相關(guān)性研究[D];廣州中醫(yī)藥大學(xué);2008年

，

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