A family harboring homozygous FZD4 deletion supports the existence of recessive FZD4-related familial exudative vitreoretinopathy

Purpose: To document recessive FZD4-related familial exudative vitreoretinopathy.

Methods: Retrospective case series.

Results: Two brothers, the only two males among five siblings, had bilateral infantile retinal detachments and were referred for genetic counseling. Next-generation sequencing uncovered a homozygous FZD4 frameshift deletion in both affected brothers (c.40_49delCCCGGGGGCG; p.Pro14Serfs*44). None of the other immediate family members had clinical evidence for retinal disease, including the three family members who underwent confirmatory genetic testing and were found to be heterozygous for the mutation (both parents and one sister).

Conclusions: The findings in this family support the concept that some mutated FZD4 alleles can be associated with recessive rather than dominant disease.     

重硅油填充治疗极重度增生性玻璃体视网膜病变

目的:研究玻璃体切割联合重硅油填充治疗极重度增生性玻璃体视网膜病变(proliferative vitreous retinopathy,PVR)的临床疗效. 方法:回顾性筛选2012-06/2015-12我科收治的极重度PVR患者13例13眼,分析对其行玻璃体切割联合重硅油填充术及后期重硅油取出联合C3F8填充术的临床疗效.13眼于重硅油填充术后10~17wk行重硅油取出联合C3F8填充术.13眼观察随访时间为玻璃体切割联合重硅油填充术后第1~7d、出院后1、2、4~17wk,重硅油取出术后第 1~7d、出院后1、2、4、8、12、24wk复查,取油术后随诊时间不少于24wk.观察指标包括视网膜复位、最佳矫正视力、眼压、人工晶状体及并发症等.结果:患者13眼于重硅油填充术后随诊期间,下方裂孔均封闭、视网膜均平复;13眼分别于重硅油填充术后10~17wk行重硅油取出联合C3F8填充术,其中第5例患者于取油术后4wk因黄斑裂孔再次视网膜脱离,第8例患者于取油术后8wk因颞上方新的裂孔再次视网膜脱离,余11眼于取油术后随诊24wk,下方视网膜裂孔均封闭、视网膜平复.患者13眼于重硅油填充术前最佳矫正视力为光感~手动,于重硅油取出术后24wk随诊时最佳矫正视力为手动~20/250,其中重硅油取出术后再出现视网膜脱离的第5例及第8例患者于末次随诊时视力为指数和手动.4眼于重硅油填充术后1wk内出现高眼压,经抗炎和降眼压药物治疗后,眼压降至10~21mmHg,后期因重硅油乳化5眼出现药物难以控制的高眼压,对其及时行重硅油取出术,取油术后3眼曾出现一过性高眼压,经降眼压药物治疗后控制在10~21mmHg,后期3眼停用降眼压药物未再出现眼压升高情况.13眼于治疗期间未出现严重前房炎症反应、眼内炎等并发症.结论:对极重度PVR行玻璃体切割联合重硅油填充及后期重硅油取出联合C3F8填充术,可获得满意的视网膜复位率,并最大限度地提高患者的预后视力.     

玻璃体切除术前注射抗VEGF类药物治疗PDF的疗效及安全性的Meta分析

目的:探究增殖性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)患者行玻璃体切除术治疗前玻璃体腔内注射抗VEGF类药物的有效性与安全性.方法:全面检索EMbase、The Cochrane Library、Pubmed、中国生物医学文摘数据库(CBM)、万方数据库(WanFang Database)、中国期刊全文数据库(CNKI)等数据库,检索时限均从建库至2017-01,语种不限,检索文献类型为随机对照试验;采用Jadad量表及Cochrane协作网提供的风险偏倚评估工具评价所纳入研究的质量,采用GRADEpro软件对各评价指标的参数进行循证医学质量评价;采用漏斗图检测所纳入文献的发表偏倚;最后采用Review Manager 5.3软件行Meta分析.结果:最终纳入发表时间介于2008/2016的16篇随机对照试验文献.共包含923例患眼,其中493例患眼进入PPV联合术前玻璃体腔内注射anti-VEGF组(试验组),430例患眼进入单纯行PPV组(对照组).Meta分析结果显示:(1)试验组术中出血的发生概率明显低于对照组[OR=0.06,95%CI(0.02~0.15),P<0.01],两组之间的差异具有统计学意义.(2)试验组手术持续时间明显短于对照组[WMD=-29.13,95%CI(-36.95~-21.30),P<0.01],两组之间的差异具有统计学意义.(3)试验组术后早期[OR=0.29,95%CI(0.19~0.44),P<0.01]及晚期[OR=0.34,95%CI(0.20~0.58),P<0.01]玻璃体出血的概率均低于对照组,两组之间的差异均具有统计学意义.(4)试验组术后最佳矫正视力水平不优于对照组[WMD=-0.51(LogMAR),95%CI(-1.10~0.08),P=0.09],两组之间的差异无统计学意义.(5)试验组术中医源性视网膜破裂发生概率低于对照组[OR=0.24,95%CI(0.14,0.40),P<0.01],两组之间的差异具有统计学意义.(6)在纳入的16篇文献共493例试验组患眼中,无1例报道出现与注射anti-VEGF类药物相关的明显眼内及全身不良反应.结论:PDR患者行玻璃体切除术治疗前玻璃体腔内注射抗VEGF类药物是安全、有效的治疗措施,能够显著减少术中及术后并发症的发生概率,改善患者的整体治疗效果.其具体的实施方案,如注射药物的剂量、玻璃体腔内注射与手术的间隔时间等,还有待进一步的探索与完善.     

25G+玻璃体切割联合玻璃体腔注射康柏西普治疗严重PDR

目的:对比25 G+玻璃体切割联合玻璃体腔注射康柏西普及单纯行25 G+玻璃体切割术治疗严重增生性糖尿病视网膜病变(PDR)的临床疗效.方法:回顾性临床病例对照研究.选取2014-10/2016-08在我院行25 G+玻璃体切割术的严重PDR患者35例42眼,其中行25 G+玻璃体切割术前玻璃体腔注射康柏西普眼用注射液18例22眼为A组;仅行25 G+玻璃体切割术患者17例20眼为B组,比较两组患者手术时间、术中并发症的发生情况、观察两组患者术后3 mo时玻璃体再积血(RVH)发生率、黄斑中心凹厚度(CFT),术后6 mo时BCVA(LogMAR)、CFT.结果:术中A、B两组患者的手术时间分别为58.23±8.18和72.41±10.31min,差异有统计学意义(t=2.9,P=0.002).术中主要并发症为医源性裂孔和术中撕膜时较大量出血,A组分别为2眼、1眼,B组为7眼、6眼,差异均有统计学意义(P=0.041、0.027).RVH发生率:术后3 mo时A组为2眼、B组为8眼,两组RVH发生率比较差异有统计学意义(P=0.030).BCVA(LogMAR):术后6mo时A组为0.92±0.35,B组为1.04±0.43,两者比较差异无统计学意义(t=0.241,P=0.212),但均较术前(A组为1.86±0.64,B组为1.73±0.82)明显提高,差异有统计学意义(t=4.614、7.355,均P<0.01).CFT:术后3 mo时,A组为273.42±25.21μm、B组为284.58±27.44μm,两者比较差异无统计学意义(t=0.488,P=0.179),但均较术前(A组为351.6±34.4μm、B组为358.2±37.1μm)明显下降,差异有统计学意义(t=3.152、4.933,均P<0.01);术后6mo时A组为238.16±16.35μm,B组为247.04±17.43μm,两者比较差异无统计学意义(t=0.571,P=0.133),但均较术前明显下降,差异有统计学意义(t=2.474、4.802,均P<0.01).结论:严重PDR患者行25 G+玻璃体切割联合术前玻璃体腔注射康柏西普治疗可有效改善视力,减轻黄斑水肿症状,相比较单纯玻璃体切割术还可缩短手术时间,减少术中并发症的发生,显著降低术后3 mo的RVH发生率.     

家族性渗出性玻璃体视网膜病变研究进展

家族性渗出性玻璃体视网膜病变(familial exudative vitreoretinopathy,FEVR)是一种罕见的先天性视网膜血管发育异常性疾病,主要表现为周边部视网膜无血管灌注区.其临床表现多样,轻者可无明显症状而漏诊;中重度者视力极差或失明,可表现为视网膜周边无灌注区伴新生血管形成,视网膜渗出,镰状皱褶,黄斑异位和视网膜脱离等.已发现FEVR相关的突变基因包括FZD4、LRP5、NDP、TSPAN12、ZNF408和KIF11基因,涉及常染色体显性遗传、常染色体隐性遗传、X连锁遗传等多种遗传方式.本文就该病的发病机制、临床特点和分期、致病基因研究进展和鉴别诊断与治疗等方面进行综述.     

PKCα对人视网膜色素上皮细胞移行作用的影响

目的 通过体外实验探讨蛋白激酶Cα(PKCα)对人视网膜色素上皮(RPE)细胞移行的影响.方法 实验研究.培养正常人PKCαRPE细胞,将实验分为Control组、Thymeleatoxin (PKCα激动剂)组、siRNA-PKCα(PKCα抑制剂)组和Nonsilencing siRNA (Non-siRNA)组,应用RT-PCR检测RPE细胞内PKCαmRNA的表达.细胞划痕实验观察RPE细胞的移行速度,Transwell实验观察RPE细胞的跨膜细胞数,活细胞动态实验观察RPE细胞的细胞活力.组间数据比较采用独立样本t检验.结果 通过光镜和免疫荧光方法计数成功培养获得RPE细胞.Thymeleatoxin组的RPE细胞内PKCαmRNA的含量明显高于Control组(t=3.712,P=.034),siRNA-PKCα组的PKCαmRNA的含量明显低于Non-siRNA组(t=3.274,P=0.031).Thymeleatoxin组RPE细胞的移行速度、跨膜细胞数、细胞活力等均明显优于Control组(t=9.743、5.616、2.300,均P＜0.05),siRNA-PKCα组的移行速度、跨膜细胞数、细胞活力等均明显弱于Non-siRNA组(t=3.643,P＜0.001;t=7.202,P=0.002;t=2.418,P=0.042).结论 PKCα对人RPE细胞的移行有上调作用,提示PKCα可为增生性玻璃体视网膜病变的防治提供新的药物靶点.     

增生性玻璃体视网膜病变中水通道蛋白-1表达的实验研究

目的　检测水通道蛋白-１（ａｑｕａｐｏｒｉｎ-１,ＡＱＰ-１）在增生性玻璃体视网膜病变（ｐｒｏ-ｌｉｆｅｒａｔｉｖｅｖｉｔｒｅｏｒｅｔｉｎｏｐａｔｈｙ,ＰＶＲ）中的表达,以确定其在ＰＶＲ细胞迁移和增殖中可能的作用。方法　从１０例ＰＶＲ患者的眼科手术中收集１０例ＰＶＲ增生膜。采用实时定量聚合酶链反应（ＲＴ-ｑＰＣＲ）和免疫荧光法分别确定ＰＶＲ增生膜中ＡＱＰ-１ｍＲＮＡ和蛋白的表达。结果　ＲＴ-ｑＰＣＲ检测发现,ＡＱＰ-１ｍＲＮＡ在所有ＰＶＲ增生膜中均出现了显著表达,其扩增的Ｃｑ值为２７～２９（２８．１０±０．５４）;免疫荧光检测发现,ＡＱＰ-１标记细胞所总细胞数的比例为（２５．３６ ±２．３５）％,且ＡＱＰ-１蛋白主要表达在增生膜的边缘细胞中。同时１０例ＰＶＲ增生膜ＡＱＰ-１ｍＲＮＡ和蛋白质的表达非常接近,并无明显差别,与患者年龄、性别和之前是否接受过手术等无关。结论　ＡＱＰ-１可能在ＰＶＲ细胞迁移和增殖过程中起到了潜在的作用。     

Hyperinsulinemia is associated with endometrial hyperplasia and disordered proliferative endometrium: A prospective cross-sectional study

Objective

To explore the relationship between metabolic abnormalities and DPE (disordered proliferative endometrium), EH (endometrial hyperplasia) and type I EC (endometrial cancer).

Methods

We conducted a prospective cross-sectional study that lasted from September 2011 to September 2012 at the Obstetrics and Gynecology Hospital of Fudan University. 314 cases were enrolled, including 56 cases of DPE, 194 cases of EH and 25 cases of type I EC. 39 healthy female cases were collected as a control group. General information was collected, and blood tests, including blood lipids, OGTT (75-g oral glucose tolerance test) and insulin release tests were examined. Statistical analysis was performed using SPSS 19.0 (Chicago, USA), and 0.05 was chosen as the significance test level.

Results

The median (inter-quartile) age of the 314 study subjects was 44 (12) years, with the ages ranging from 21 to 75 years. Elevated insulin level was correlated with DPE, EH without/with atypia and EC. The risk increased when HOMA-IR (homeostasis model assessment-insulin resistance) ≥ 2.95 (the lower limit of the top quartile of HOMA-IR distribution in non-diabetic patients); the OR (odds ratio) for DPE was 9.973 (95% CI (coefficient interval): 2.038–48.789, P = 0.005), that for EH without atypia was 8.481 (95% CI:1.860–38.672, P = 0.006), that for EH with atypia was 18.716 (95% CI: 3.091–113.335, P = 0.001) and that for type I EC was 45.199 (95% CI: 5.886–347.065, P < 0.001). Opposite trends were observed for the QUICKI (Quantitative Insulin Sensitivity Check Index).

Conclusions

Hyperinsulinemia is associated with DPE and EH without/with atypia, not only with type I EC, and it might be a key factor that initiates and promotes endometrial hyperplastic lesions.     

Distribution of Ki67 Proliferative Indices among WHO Subtypes of Non-Hodgkin’s Lymphoma: Association with other Clinical Parameters

Background: Non-hodgkin lymphoma (NHL) is a diverse group of disease encompassing divergent tumortypes with contrasting clinical behaviors. We aimed to evaluate the usefulness of Ki67 index in segregatingindolent from aggressive NHL and its association with clinical parameters. Materials and Methods: Duringa study period of 4.5 years, a total of 215 cases of lymphomas were diagnosed among of which 172 cases wereNHL. Ki67 immunohistochemical staining was performed by the DAKO envision method. Average proportion oftumor cells stained was calculated to determine the proliferative index. Results: The mean age at diagnosis was46.2 years +19.8 (3-81) with a male to female ratio of 1.5:1. Mean Ki67 index for indolent NHL included 23%for small cell, 25% for mantle cell, 28.5% for marginal zone and 34.6% for follicular lymphoma. On the otherhand, mean Ki67 index for aggressive lymphomas were 66.4%, 66.9%, 80.3%, 83.3% and 94.4% for diffuselarge B cell, T cell (NOS), anaplastic large cell, lymphoblastic and burkitts lymphoma respectively. No significantcorrelation was found between Ki67 index and other clinical parameters like age and extra nodal involvement.Conclusions: Ki67 index is a valuable IHC marker to distinguish indolent from aggressive lymphomas especiallyin small needle biopsies where exact typing may not be possible.     

术前新辅助化疗结合肠内营养对胃癌患者肿瘤细胞增殖活性的影响分析

目的探讨术前新辅助化疗结合肠内营养对胃癌患者肿瘤细胞增殖活性的影响效果。 方法将2012年7月至2014年7月收治的132例进展期胃癌患者,随机分为观察组（术前新辅助化疗联合肠内营养）和对照组（单纯予以新辅助化疗）,各66例,采用流式细胞仪检测两组患者肿瘤标本的细胞增殖情况,通过CD4、CD8、CD4/CD8、NK细胞的检测评价两组患者的免疫功能,检测血清学指标以及营养风险筛查（NRS评分）进行营养评价。 结果治疗前,两组患者的肿瘤细胞增殖活性、免疫指标、营养状况均差异无统计学意义。治疗后,观察组患者的CD4、CD4/CD8、NK、总蛋白、白蛋白、前白蛋白、转铁蛋白、血红蛋白均较对照组增加明显,DI、SPF、PI、CD8、NRS评分降低明显,差异有统计学意义（P<0.05）。 结论术前新辅助化疗结合肠内营养可较好地降低肿瘤细胞的增殖活性,改善其免疫水平及营养状况。