Association between SERPING1 rs2511989 polymorphism and age-related macular degeneration: Meta-analysis

AIM: To investigate the association between SERPING1 rs2511989 (G>A) polymorphism and age-related macular degeneration (AMD). METHODS: A number of electronic databases (up to July 15, 2014) were searched independently by two investigators. A Meta-analysis was performed on the association between SERPING1 rs2511989 polymorphism and AMD. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. RESULTS: Eight studies with 16 cohorts consisting of 9163 cases and 6813 controls were included in this Meta-analysis. There was no significant association between rs2511989 polymorphism and AMD under all genetic models in overall estimates (A vs G: OR= 0.938, 95%CI =0.858-1.025; AA vs GG:OR =0.871, 95%CI =0.719-1.056; AG vs GG: OR =0.944, 95%CI =0.845-1.054; AA+AG vs GG: OR =0.927, 95% CI =0.823-1.044; AA vs AG+GG: OR =0.890, 95%CI =0.780-1.034). Cumulative Meta-analyses also showed a trend of no association between rs2511989 polymorphism and AMD as information accumulated by year. Subgroup analysis and Meta-regression analysis indicated that age-matching status was the main source of heterogeneity. Sensitivity analysis found the results in overall comparisons and subgroup comparisons of white subjects under the allele model were found to have significantly statistical differences after studies deviating from Hardy-Weinberg equilibrium (HWE) were excluded (overall: OR=0.918, 95%CI = 0.844-0.999, P =0.049; whites: OR =0.901, 95%CI = 0.817-0.994, P =0.038). However, the results were not sufficiently robust for further sensitivity analysis and statistical differences disappeared on applying Bonferroni correction (with a significance level set at 0.05/25). CONCLUSION: This Meta-analysis indicates that SERPING1 rs2511989 polymorphism and AMD tend to have no association with each other. Age matching status is a big confounding factor, and more studies with subtle designs are warranted in future.     

HSPA13在ARPE19细胞氧化应激中的作用

目的 探讨HSPA13在ARPE19细胞氧化应激中的作用。 方法 采用CCK8法检测不同浓度H2O2对ARPE19细胞活力的影响;Western印迹法和免疫荧光检测H2O2对HSPA13表达的影响;CCK8法检测HSPA13的表达水平对氧化应激诱导的细胞活力的影响;过表达或siRNA干扰HSPA13后,分别检测氧化应激相关指标和促炎因子的分泌;RNA测序分析空载组和HSPA13干扰组差异表达的基因,并进行GO富集及KEGG信号通路分析。 结果 CCK8法结果显示,与H2O2空白对照组相比,100、200、300、400μmol/L H2O2处理组细胞活力降低（P<0.05）。Western印迹法结果显示,与H2O2空白对照组相比,H2O2处理组HSPA13的表达上升（P<0.05）。CCK8法结果显示,过表达HSPA13可保护细胞活力。氧化应激相关指标和促炎因子检测结果显示,与H2O2处理组相比,过表达HSPA13加H2O2处理组中SOD1和GPX1 mRNA表达上升,MDA含量降低,GSH含量上升,IL-8、IL-2和IL-1β分泌下降;而siRNA干扰HSPA13加H2O2处理组的结果则相反,并且活性氧类含量上升（P<0.05）。RNA测序结果显示,与空载组相比,HSPA13干扰组差异基因表达上调的有64个,下调的有254个。GO富集分析表明,HSPA13与细胞代谢或多种生理过程相关。KEGG分析显示,HSPA13与PI3K-Akt信号通路、TGFβ信号通路相关。 结论 氧化应激诱导ARPE19细胞中HSPA13的表达上调;HSPA13在细胞氧化损伤中发挥保护作用,这为寻找年龄相关性黄斑变性新的治疗靶点提供有益的线索。     

颈椎前路减压融合与人工颈椎椎间盘置换联合对多节段颈椎病的疗效及邻近节段退变的影响分析

目的:探究颈椎前路减压融合术(anterior cervical decompression and fusion,ACDF)联合人工颈椎椎间盘置换术(artificial cervical disc replacement,ACDR)在治疗多节段颈椎病上的临床疗效及对其邻近节段退变的影响。方法:按入院先后将本院收治的57例多节段颈椎病患者分为观察组(32例)和对照组(25例)。对照组患者给予ACDF进行治疗;观察组患者则采用颈椎Hybrid手术方式(ACDF联合ACDR)进行治疗。就两组患者的临床治疗效果以及邻近节段退变情况进行对比性分析。结果:观察组患者的术中出血量、手术时间以及住院时间均明显低于对照组(P<0.05)。在两组患者的腰椎功能改善上,观察组的总有效率为90.63%,与对照组(92.00%)比较并未见明显差异(P<0.05)。在术前、术后3个月、术后6个月和术后12个月,两组患者在JOA评分以及NDI评分均未见显著差异(P>0.05)。术后12个月,观察组患者的颈椎整体活动度明显大于对照组,其上、下位邻近节段活动度则明显低于对照组(P<0.05)。结论:在治疗多节段颈椎病上,ACDF联合ACDR疗效显著,能够减少邻近节段运动的负荷,降低了邻近节段退变的发生,此外还具有创伤小、恢复快、并发症少的特点。     

Acupotomy versus sodium hyaluronate for treatment of knee osteoarthritis in rabbits

Objective

To investigate the possible advantages of acupotomy over sodium hyaluronate injection for the treatment of knee osteoarthritis (KOA).

Blood-retinal barrier as a converging pivot in understanding the initiation and development of retinal diseases

Clinical ophthalmologists consider each retinal disease as a completely unique entity. However, various retinal diseases, such as uveitis, age-related macular degeneration, diabetic retinopathy, and primary open-angle glaucoma, share a number of common pathogenetic pathways. Whether a retinal disease initiates from direct injury to the blood-retinal barrier (BRB) or a defect/injury to retinal neurons or glia that impairs the BRB secondarily, the BRB is a pivotal point in determining the prognosis as self-limiting and recovering, or developing and progressing to a clinical phenotype. The present review summarizes our current knowledge on the physiology and cellular and molecular pathology of the BRB, which underlies its pivotal role in the initiation and development of common retinal diseases.     

Temporo-spatial distribution of blood vessels in human lumbar intervertebral discs

While there is consensus in the literature that blood vessels are confined to the outer anulus fibrosus of normal adult intervertebral disc, debate continues whether there is a vascular in-growths into inner parts of the intervertebral disc during degeneration. We therefore tested the hypothesis that vascular in-growth is not a distinct feature of disc degeneration. The specific endothelial cell marker CD 31 (PECAM) was used to immunohistochemically investigate 42 paraffin-embedded complete mid-sagittal human intervertebral disc sections of various ages (0–86 years) and varying extent of histomorphological degeneration. Additionally, 20 surgical disc samples from individuals (26–69 years) were included in this study. In discs of fetal to infantile age, blood vessels perforated the cartilaginous end plate and extended into the inner and outer anulus fibrosus, but not into the nucleus pulposus. In adolescents and adults, no blood vessels were seen except for the outer zone of the anulus fibrosus adjacent to the insertion to ligaments. The cartilaginous end plate remained free of vessels, except for areas with circumscribed destruction of the end plate. In advanced disc degeneration, no vessels were observed except for those few cases with complete, scar-like disc destruction. However, some rim lesions and occasionally major clefts were surrounded by a small network of capillary blood vessels extending into deeper zones of the anulus fibrosus. A subsequent morphometric analysis, revealed slightly “deeper” blood vessel extension in juvenile/adolescent discs when compared to young, mature and senile adult individuals with significantly “deeper” extension in the posterior than anterior anulus. The analysis of the surgical specimens showed that only sparse capillary blood vessels which did not extend into the nucleus pulposus even in major disc disruption. Our results show that vascular invasion deeper than the periphery was not observed during disc degeneration, which supports the hypothesis that vascular in-growth is not a distinct feature of disc degeneration. This study was supported by a grant from the AO/ASIF Foundation Switzerland (00-B72) and a grant from the AO Spine (SRN 02/103).     

Neutralization of the chemokine CXCL10 reduces apoptosis and increases axon sprouting after spinal cord injury

Spinal cord injury (SCI) is followed by a secondary degenerative process that includes cell death. We have previously demonstrated that the chemokine CXCL10 is up-regulated following SCI and plays a critical role in T-lymphocyte recruitment to sites of injury and inhibition of angiogenesis; antibody-mediated functional blockade of CXCL10 reduced inflammation while enhancing angiogenesis. We hypothesized, based on these findings, that the injury environment established by anti-CXCL10 antibody treatment would support greater survival of neurons and enhance axon sprouting compared with the untreated, injured spinal cord. Here, we document gene array and histopathological data to support our hypothesis. Gene array analysis of treated and untreated tissue from spinal cord-injured animals revealed eight apoptosis-related genes with significant expression changes at 3 days postinjury. In support of these data, quantification of TUNEL-positive cells at 3 days postinjury indicated a 75% reduction in the number of dying cells in treated animals compared with untreated animals. Gene array analysis of treated and untreated tissue also revealed six central nervous system growth-related genes with significant expression changes in the brainstem at 14 days postinjury. In support of these data, quantification of anterograde-labeled corticospinal tract fibers indicated a 60-70% increase in axon sprouting caudal to the injury site in treated animals compared with untreated animals. These findings indicate that anti-CXCL10 antibody treatment provides an environment that reduces apoptosis and increases axon sprouting following injury to the adult spinal cord.     

腰椎融合术后发生邻近节段退行性变的研究进展

随着脊柱手术方法的日趋成熟和内固定器械的日新月异,脊柱融合术的成功率有了明显提高。然而术后长期随访并发症也日益引起脊柱外科医师的关注,尤其是融合内固定术后邻近节段退变（adjacent segment degenera-tion,ASD）的问题变得更为突出,因其可引起临床症状,影响预后,正成为基础和临床研究的热点。本文从ASD发生的机制,影响ASD的因素,ASD的治疗策略,ASD的预防做一综述。     

退变性脊柱侧凸椎间盘-终板退变与骨性结构参数的相关性研究及意义

目的 分析退变性脊柱侧凸椎间盘-终板退变与骨性结构参数的关系,探讨其在退变性脊柱侧凸发病机制中的作用及意义.方法 回顾分析2005年3月至2010年3月诊治的79例退变性脊柱侧凸患者(病例组)的影像学资料,选取41例诊断为特发性脊柱侧凸患者(对照组)的影像学资料做为对照.所有患者以主弯内的椎体及附件为观测对象,分别测量椎体和椎间两侧高度及两侧关节突关节面矢状角角度,分别计算椎体和椎间两侧平均高度及两侧关节突关节面平均矢状角作为骨性结构参数.采用分级评分法对各个椎间盘及邻近终板退变程度进行量化,其分值代表椎间盘-终板退变的程度.组内比较各骨性结构参数,分析骨性结构参数的特点及其与椎间盘-终板退变和侧凸Cobb角的关系.结果 经配对t检验比较,病例组的椎间高度、椎体高度及关节面矢状角凸凹侧差异有统计学意义(t=3.411,2.623和2.085,P＜0.05);对照组的椎间高度凸凹侧差异有统计学意义(t =3.276,P＜0.01),椎体高度及关节面矢状角差异无统计学意义(t=1.572和1.493,P＞0.05).直线相关和多元回归分析显示,各骨性结构参数不对称度与椎间盘-终板退变有显著相关性(-1 ＜r＜1,P ＜0.05),与腰椎侧凸Cobb角呈正相关(0＜r＜1,P＜0.05),且存在直线回归关系(F=427.342,P＜0.01),其回归方程为Cobb角=-8.904+8.136×椎间不对称度+3.274×椎体不对称度-0.713×关节突不对称度.结论 退变性脊柱侧凸两侧骨性结构呈不对称改变,其不对称性与椎间盘-终板退变和脊柱侧凸相互关联;不对称骨性结构改变可能是侧凸渐进性发展的生物力学动力因素,而椎间盘-终板不对称退变可能有病因学意义.