人工智能在临床基因组学中的应用进展

临床基因组学主要研究基因组信息在临床中的应用,包括诊断、治疗决策、预测预后。在传统的算法和技术难以处理基因组学中复杂又庞大的数据时,人工智能的应用带来新的希望。目前,人工智能已参与到临床基因组学的多种任务中,如识别变异、变异分类、影像-遗传诊断、电子病历-基因诊断、药物作用及不良反应预测等。本文主要综述临床基因组中不同方面的人工智能应用。     

玻璃体腔注射Ranibizumab联合视网膜光凝治疗视网膜分支静脉阻塞继发黄斑水肿

目的：观察玻璃体腔注射Ranibizumab(雷珠单抗)联合视网膜光凝术对视网膜分支静脉阻塞( branch retinal vein occlusion,BRVO)继发黄斑水肿的治疗效果。
　　方法：确诊为视网膜分支静脉阻塞继发性黄斑水肿的患者42例42眼,随机分为三组,每组14眼。单纯注药组给予玻璃体腔注射Ranibizumab 0.05 mL;单纯光凝组行黄斑格栅样光凝;联合治疗组先行玻璃体腔内注射Ranibizumab,再于注药1wk 后行黄斑格栅样光凝。观察三组治疗前和治疗后1,3,6 mo时患者的最佳矫正视力( BCVA)、黄斑区中心凹厚度( CMT)。
　　结果：三组在治疗前BCVA和CMT组间差异无显著性( P>0.05)。各组在治疗后1,3,6 mo的BCVA和CMT均优于治疗前,差异有统计学意义(P<0.05)。单纯注药组治疗后1,3,6mo 的 BCVA 和 CMT 变化有显著性差异( P<0.05),BCVA呈下降趋势,CMT呈增厚趋势;单纯光凝组和联合治疗组治疗后1,3,6 mo BCVA及CMT变化无显著性差异(P>0.05)。治疗后1,3,6mo,联合治疗组BCVA和CMT优于单纯注药组和单纯光凝组(P<0.05),治疗后3,6 mo,单纯光凝组BCVA和CMT优于单纯注药组(P<0.05)。
　　结论：玻璃体腔注射Ranibizumab联合视网膜光凝可以有效治疗视网膜分支静脉阻塞继发黄斑水肿,提高视力,相比单纯注药或者单纯光凝效果更稳定可靠。     

冠脉斑块类型及冠脉狭窄程度与脑梗塞的相关性研究

目的 探讨脑梗死患者与非脑梗死患者冠脉斑块类型及冠脉狭窄程度的差异.方法 选取2013年3～7月我院心内科收治的172例可疑冠心病患者,根据有无脑梗死病史,分为脑梗死组(46例)和非脑梗死组(126例).所有患者均行冠脉双源CT,并对冠脉血管斑块节段(混合斑块节段、钙化斑块节段和非钙化斑块节段)计数.对两组患者冠脉斑块的类型及冠脉狭窄程度分析比较.结果 脑梗死组冠脉病变支数明显多于非脑梗死组(P=0.019);脑梗死组冠脉斑块节段总数和混合斑块节段数明显多于非脑梗死组(P＜0.01);脑梗死组与非脑梗死组相比,LM P=0.016,LAD P＜0.01,LCX P=0.003,RCA P=0.037,且混合斑块节段数明显多于非脑梗死组.结论 ①与无脑梗死病史的患者相比,有脑梗病史且合并疑似冠心病的患者,冠脉受累节段数明显较多;②冠脉混合斑块有可能是脑梗死的一个重要危险因素,但尚需进一步大样本研究.     

DOC-1R基因表达载体的构建及其重组蛋白的表达纯化

目的 构建DOC-1R(deleted in oral cancer-1 related)的原核表达载体并且纯化其重组蛋白,用于进一步研究DOC-1R蛋白的结构与功能.方法 采用基因重组技术构建原核表达载体pGEX-DOC-1R,经DNA测序鉴定后,转化E.coli BL21,IPTG诱导表达并纯化融合蛋白.结果 以菌落PCR及限制性内切酶酶切鉴定得到候选阳性克隆,测序结果表明所得到的克隆序列及开放阅读框架完全正确,IPTG诱导后SDS-PAGE电泳分析表明在40 kD处出现特征蛋白表达带,经磁珠亲合层析后Western印迹检测证实得到较高纯度的GST-p14DOC-1R融合蛋白.结论 成功构建了pGEX-DOC-1R的原核表达载体,表达并纯化出GST-p14DOC-1R融合蛋白,为DOC-1R抗体制备及研究DOC-1R蛋白结合蛋白及其在细胞周期调控中的生物学功能奠定了基础.     

改良显微小梁切除术治疗葡萄膜炎继发性青光眼

目的 探讨小梁切除术中采用虹膜节段切除联合应用丝裂霉素C(MMC)及粘弹剂治疗葡萄膜炎继发性青光眼的临床疗效.方法 术中根据患者的年龄、炎症和结膜Tenon囊情况选用不同浓度的MMC(0.25～0.33 mg/ml),应用粘弹剂分离虹膜前后粘连和瞳孔区机化膜并剪除机化膜,节段切除虹膜,可控缝线缝合巩膜瓣.观察手术前后视力、眼压、炎症和术后并发症情况.结果 葡萄膜炎继发性青光眼共38例42眼,平均随访时间(12.01±3.56)月.术后末次复查与术前比较,视力提高14眼,不变28眼;前房炎症消失35眼,减轻7眼;平均眼压(15.20±4.64)mmHg与术前(38.37±12.93)mmHg比较差异有统计学意义(t=8.255,P=0.000).手术总成功率92.9%,无严重并发症发生.结论 小梁切除术术中联合应用MMC、粘弹剂、虹膜前后粘连分离、虹膜节段切除及可控缝线技术能够提高较严重葡萄膜炎继发性青光眼的手术成功率,减少手术并发症及术后炎症反应,减少葡萄膜炎复发.     

糖尿病性黄斑水肿的光学相干断层成像

目的:观察糠尿病性黄斑水肿(diabetic macular edema,DME)的光学相干断层成像(optical coherence tomography,OCT)图像特征,分析其黄斑视网膜厚度与视力的关系.方法:对50例80眼经检眼镜或荧光素眼底血管造影(fundus fluorescein angiography,FFA)检查确诊为糖尿病视网膜病变伴黄斑水肿的患者进行经黄斑中心凹水平和垂直线性扫描的OCT检查.结果:10眼表现为黄斑中心凹局限性水肿改变,21眼表现为黄斑中心凹囊样改变伴神经上皮层浆液性脱离,49眼表现为黄斑区视网膜神经上皮层弥漫性增厚.DME患者黄斑视网膜厚度与视力呈负相关关系(r=-0.60,P=0.000).结论:DME的主要OCT图像特征为黄斑视网膜弥漫性水肿、黄斑囊样水肿伴神经上皮层脱离和黄斑局限性水肿改变;DME患者黄斑水肿越严重,视力越差.     

内界膜剥离治疗特发性黄斑裂孔的早期愈合观察

目的：探讨玻璃体切除联合内界膜剥离治疗特发性黄斑裂孔的早期愈合情况。方法：回顾分析了2001年1月～2003年10月在我院行手术治疗的特发性黄斑裂孔25例(25只限),所有病人均采用经平坦部玻璃体切除联合黄斑前膜和(或)内界膜剥离,气-液交换和16％全氟丙烷(C3F8)充填。术后保持面朝下体位至少2周。采用裂隙灯、前置镜,光学相干断层扫描(OCT)检查观察手术后1个月内的黄斑裂孔的关闭情况。手术后第1周内每天检查,14、21和28d行常规裂隙灯前置镜检查;根据手术后玻璃体腔气体吸收的情况行OCT检查,当气体吸收超过50％,黄斑部露出时即行OCT检查。结果：25只眼中23只眼术中完整的撕除黄斑裂孔周围内界膜,2只眼未能完整撕除裂孔旁的内界膜。在手术后24—48h,23只眼裂隙灯及裂隙灯前置镜检查未发现黄斑裂孔的形态,1个月内的OCT检查证实23只眼黄斑裂孔均闭合．裂孔闭合率为92％,随访期间未发现裂孔再裂开现象。未闭合的2只眼均为手术中未能完整撕除内界膜眼,其中1只眼为3期黄斑裂孔,1只眼为4期黄斑裂孔,在随访期间未见裂孔关闭。术后早期黄斑裂孔关闭的23只眼的OCT形态主要表现为：正常的中心凹形态(简单闭合)15只眼(65,2％),桥样结构8只眼(34．8％)。结论：大部分特发性黄斑裂孔在手术后早期即已关闭,提示特发性黄斑裂孔在形成过程中不伴局部的视网膜组织缺损或缺损极少,手术解除玻璃体,特别是内界膜的机械牵拉后视网膜可复位,裂孔闭合。     

中心性浆液性脉络膜视网膜病变频域光相干断层扫描与时域光相干断层扫描图像比较

Objective To compare difference of the cross-sectional pathological imaging and quantitative measurement of central serous chorioretinopathy (CSC) between time-and fourier-domain optical coherence tomography (OCT). Methods Consecutive 26 patients (26 eyes) with unilaterial CSC were subsumed. Bilateral eyes of all the patients underwent time-and fourier-domain OCT. Horizontal and vertical line scanning and radial six-line scanning protocols were used for time-domain OCT examination; horizontal and vertical high resolution five-line scanning and macular cube scanning protocols were used for fourier-domain OCT examination. The characteristics of OCT images, retinal segmentation and the quantitative measurement were compared between these two methods. Results Fourier-domain OCT could yield the three-dimensional images of surface of inner limiting membrane (ILM) and RPE. The band of external limiting membrane (ELM) of normal subjects and CSC patients, and the inner segment and outer segment (IS/OS) of normal subjects could be clearly shown by fourier-domain OCT. However, the band of IS/OS disappeared in 65.4 % of the CSC patients. The outer boundary of retina was defined in front of the retinal pigmental epithelia (RPE) by fourier-domain OCT. The foveal thickness of normal subjects and CSC patients was (180. 50 ±12.69) and (158. 41 ± 34.20) μm, respevtively. The height of detachment of neuralepithelial layer was (245.84± 154.61) μm measured by fourier-domain OCT. The band of IS/OS of normalsubjects could be clearly shown by time-domain OCT. However, the band of IS/OS disappeared in 73.4%of the CSC patients, which showed no difference with fourier-domain OCT (Z=-0. 108, P=0. 914). Theouter boundary of retina was defined in front of the IS/OS band by OCT. The foveal thickness of normal subjects was (141.16±12.75) μm, which was thinner than that measured by fourier-domain OCT (t= 20. 671,P= 0. 000). The foveal thickness and the height of detachment of neural epithelial layer was (146.40± 36.28) μm and (240. 32±156. 82) μm measured by time-domain OCT, respectively, which showed no significant difference with which measured by fourier-domain OCT (t value was from 0. 026 to 1. 517, P value was from 0. 144 to 0. 980). Conclusions Fourier-domain OCT yields better visualization of intraretinal layers and more accurate definition of outer boundary of retina than time-domain OCT. Thus the measurements by fourier-domain OCT were more accurate. Moreover, three-dimensional images of CSC shown by fourier-domain OCT enable the comprehensive observation of pathological morphology and location.     

闭合性眼外伤致黄斑裂孔的光相干断层扫描图像分析

Objective To observe the features of the images of optical coherence tomograpy (OCT) in patients with traumatic macular hole (TMH), and detect the clinical significance of OCT. Methods Consecutive 74 patients (74 eyes) diagnosed with TMH by examinations of visual acuity, slit lamp, and direct or indirect ophthalmoscopy underwent optical coherence tomography (OCT), The analysis software of OCT was used to make the quantitative measurements of TMH. And the TMH were classified according to the morphological characteristics of the images of OCT. 50°color fundus photography was performed on the patients after OCT. The relationship of TMH with the average visual acuity, disease duration, average neuroepithelial thickness on the margin of hole, and the base diameter and the apex diameter of macular hole were retrospectively analyzed. Results The characterisctics of the images of 74 cases (74 eyes) of TMH were classified into 5 types: macular holes with symmetric edema of the neurosensory retina at the margin in 27 eyes (36.5%), macular holes with asymmetric edema of the neurosensory retina at the margin in 12 eyes (16.2%), macular hole with full-thickness defect of neurosensory retina without edema or detachment at the margin in 14 eyes (18.9 %), macular hole with localized detachment of the neurosensory retina at the margin without edema in 17 eyes (23.0 %), and macular hole with thinning neurosensory retina in 4 eyes (5. 4 %).There was no significant difference of visual acuity among different types of TMH (F=1. 574, P=0. 191).The visual acuity was positively related with the marginal retinal thickness (r=0. 342, P=0. 003), but not related to age, diameter of macular hole or the disease duration(r value was from-0. 022 to-0. 134, P value was from 0. 863 to 0. 261). The disease duration of Type IV TMH was shorter than that of other TMH types. In the patients with the disease duration over 90 days, Type I TMH was predominant. The average retinal thicknesses at the margin of the hole showed significant differences among different TMH types (F= 13.921, P= 0.000). Conclusions TMH could be divided into 5 types according to the characteristics of images of OCT; the clinical characteristics of different types of TMH varies.     

闭合性眼外伤致黄斑裂孔的光相干断层扫描图像分析

Objective To observe the features of the images of optical coherence tomograpy (OCT) in patients with traumatic macular hole (TMH), and detect the clinical significance of OCT. Methods Consecutive 74 patients (74 eyes) diagnosed with TMH by examinations of visual acuity, slit lamp, and direct or indirect ophthalmoscopy underwent optical coherence tomography (OCT), The analysis software of OCT was used to make the quantitative measurements of TMH. And the TMH were classified according to the morphological characteristics of the images of OCT. 50°color fundus photography was performed on the patients after OCT. The relationship of TMH with the average visual acuity, disease duration, average neuroepithelial thickness on the margin of hole, and the base diameter and the apex diameter of macular hole were retrospectively analyzed. Results The characterisctics of the images of 74 cases (74 eyes) of TMH were classified into 5 types: macular holes with symmetric edema of the neurosensory retina at the margin in 27 eyes (36.5%), macular holes with asymmetric edema of the neurosensory retina at the margin in 12 eyes (16.2%), macular hole with full-thickness defect of neurosensory retina without edema or detachment at the margin in 14 eyes (18.9 %), macular hole with localized detachment of the neurosensory retina at the margin without edema in 17 eyes (23.0 %), and macular hole with thinning neurosensory retina in 4 eyes (5. 4 %).There was no significant difference of visual acuity among different types of TMH (F=1. 574, P=0. 191).The visual acuity was positively related with the marginal retinal thickness (r=0. 342, P=0. 003), but not related to age, diameter of macular hole or the disease duration(r value was from-0. 022 to-0. 134, P value was from 0. 863 to 0. 261). The disease duration of Type IV TMH was shorter than that of other TMH types. In the patients with the disease duration over 90 days, Type I TMH was predominant. The average retinal thicknesses at the margin of the hole showed significant differences among different TMH types (F= 13.921, P= 0.000). Conclusions TMH could be divided into 5 types according to the characteristics of images of OCT; the clinical characteristics of different types of TMH varies.