Diagnostic value of RASSF1A hypermethylation in colorectal cancer: a meta-analysis

Purpose

Ras association domain family 1 isoform A (RASSF1A), a member of Ras association domain family, plays an important role in tumorigenesis. The goal of our meta-analysis was to assess the diagnostic value of RASSF1A hypermethylation in colorectal cancer (CRC).

双抗夹心化学发光免疫分析定量检测Ⅳ型胶原方法的建立

目的 建立基于双抗夹心微孔板化学发光酶免疫分析的人血清Ⅳ型胶原定量检测方法.方法 应用Ⅳ型胶原多抗进行包被,辣根过氧化物酶标记Ⅳ型胶原单抗,以鲁米诺化学发光体系检测,调整优化各种反应液的工作浓度和各类反应条件后建立双抗体夹心的检测方法;评价所建立方法的线性范围、特异性、灵敏度、稳定性等性能指标;应用肝纤维化患者血清与进口试剂进行比对实验.结果 所建立方法的灵敏度为15.5 ng/ml,线性范围25 ～ 850 ng/ml,批内、批间变异均小于8％.检测Ⅳ型胶原的临床高、中、低值血清回收率分别为98.5％、94.3％和102.6％;在4℃和37℃条件下分别进行了3、5、7d的稳定性考察,线性相关系数均＞0.99,标准偏差＜7％;比对实验分析显示与进口试剂相关性具有统计学意义.结论 成功建立了定量Ⅳ型胶原化学发光酶免疫分析方法,该方法有较好的准确性、灵敏度、重复性,与进口试剂检测结果等效.     

Targeting efficiency of RGD-modified nanocarriers with different ligand intervals in response to integrin αvβ3 clustering

Receptor change induced by ligand binding is a new issue to face in the field of targeted delivery. Receptor clustering, the main pattern of receptor changes, decreases the affinity between ligand and receptor due to the redistribution of receptor position. In an attempt to respond to such challenge, we designed and constructed three RGD-modified nanocarriers with different ligand intervals: stealth liposomes modified with the monomeric RGD (moRGD-LP), dimeric RGD (diRGD-LP) and a special dimeric RGD with a linker between two cyclic RGD motifs (P-diRGD-LP). The αvβ3-positive and -negative tumor cells (Melanoma B16 and MCF-7) were used as the cell models. As a result, P-diRGD-LP demonstrated strongest interaction with B16 cells in surface plasmon resonance study and highest cellular uptake in B16 cells in real-time confocal analysis. The enhanced endocytosis of P-diRGD-LP was found to be αvβ3-mediated and P-diRGD-LP increased the involvement of the clathrin-dependent pathway. Importantly, P-diRGD-LP demonstrated the best targeting effect in B16-tumor bearing mice in both in vivo and ex vivo near-infrared fluorescent images, about 2.4-fold that of moRGD-LP and 2.8-fold that of diRGD-LP at 3 h. Further, we validated integrin αvβ3 clustering on B16 cells via a single-molecule imaging by a total internal reflection fluorescence microscopy. Finally, the 3D models of αvβ3 clustering suggested a receptor interval within 41.916–65.779 Å, while the molecular computation revealed an RGD ligand interval of 20.944 Å, 42.753 Å and 78.196 Å for diRGD-LP, P-diRGD-LP and moRGD-LP, respectively, confirming the best matching between clustered αvβ3 and P-diRGD-LP. In conclusion, P-diRGD-LP could achieve higher targeting to αvβ3-positive tumor via the enhanced interaction based on the better ligand-receptor compatibility. The design of targeted nanocarriers against receptor clustering might provide new insight into the nanotechnology-based anticancer therapy.     

Replication of the association of the aspartic acid repeat polymorphism in the asporin gene with knee-osteoarthritis susceptibility in Han Chinese

A genetic association of osteoarthritis (OA) and functional polymorphisms in the aspartic acid (D) repeat of the asporin gene was reported in Japanese and European Caucasians; however, the results were controversial. Our objective was to evaluate whether the D repeat polymorphism was associated with knee OA in Han Chinese. The D repeat polymorphism was genotyped in 218 patients who suffered from primary symptomatic knee OA with radiographic confirmation and in 454 age-matched controls, and the allelic association of the repeat was examined. Frequencies of the D13 and D14 alleles were similar to those of Japanese, but different from those of European Caucasians. The D14 allele was significantly over-represented in knee OA patients (P=0.0013; odds ratio 2.04; 95% confidence interval 1.32–3.15). D14 was more frequent in early-onset patients than in late-onset patients (P=0.043) and the age at onset in patients with D14 was earlier (P=0.028; log-rank test). Thus, the association of the D14 allele with knee OA susceptibility was replicated in Han Chinese. This was the first instance that association of the OA susceptibility gene was definitely replicated between different ethnic groups.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

基于正则化的磁共振相控阵线圈图像均匀性校正算法

由于能提供更大的扫描视野,更高的信噪比和缩短扫描时间,相控阵线圈已经被广泛使用在磁共振成像(MRI)设备中。相控阵线圈的图像重建合成最常用的是SOS算法,但是SOS算法通常会造成图像的灰度不均匀。这样不仅会直接影响医生诊断的准确性,同时对图像自动分割等后处理技术的使用也会产生不良影响。本文提出一种改进的基于正则化的最小二乘化方法,用于MRI相控阵图像的合成。在该方法中利用均匀的大体线圈和相控阵线圈进行预扫描获得线圈敏感图,通过引入正则函数来控制重建图像的噪声。此外,在正则函数中还使用大体线圈的预扫描图像作为参考图像。使用水模和志愿者成像数据验证,该方法能够有效提高相控阵线圈重建图像的均匀性。     

The lysogenic cycle of the filamentous phage Cflt from Xanthomonas campestris pv. citri

A phage, Cflt, forming turbid plaques, was isolated from Xanthomonas campestris pv. citri. After infection, infected sensitive cells become immune to Cflt and produce very few phages. These properties were genetically rather stable. The phage was purified and shown to be filamentous with a size of 1157 +/- 73 nm. The genome size is about 7.62 kb. The phage does not affect the growth of host bacteria. Under natural cultivation conditions Cflt-lysogenized cells could be induced spontaneously to give high phage yields, or cured to give phage-free cells. The integration of Cflt DNA into host DNA was proved by Southern blot hybridization. The lysogenic phage was genetically stable in log phase cells and persisted in stationary phase cells through many cell generations in the absence of extracellular phage reinfection.     

LPS诱导小鼠脑小胶质细胞的激活及Tomato lectin的表达变化

探讨小胶质细胞对侧脑室注射内毒素脂多糖(lipopolysaccharide,LPS)刺激的反应及时程变化。采用组织化学方法,观察小鼠单次注射LPS入侧脑室后,Tomatolectin阳性的小胶质细胞于不同时间点在脑内的分布及表达的时程变化。LPS注射24h后,Tomatolectin组织化学染色显示血管内皮细胞、静息的和不同激活状态的小胶质细胞均呈阳性反应,其中Tomatolectin阳性的小胶质细胞明显被激活,2d时达表达高峰,巨噬细胞样的细胞和小胶质细胞呈现出肥大的、阿米巴样或杆状细胞等不同激活状态下的形态特征。这些激活的小胶质细胞主要分布于侧脑室周围的脑实质结构,如海马、隔区、胼胝体、纹状体,第三脑室周围的下丘脑及其它间脑结构。本结果提示:LPS能诱导小鼠脑室周围的脑实质内的小胶质细胞被激活,并上调小胶质细胞内Toma-tolectin的表达,这些细胞可能参与脑内刺激的免疫调节。     

胸腰椎爆裂性骨折形态学异常的放射学测量及其与脊髓损伤的关系

目的：探讨胸腰椎爆裂性骨折形态学异常与脊髓损伤的关系。方法：回顾性分析７８例胸腰裂性骨的,根据椎管正中矢状状径计算椎管狭窄率,并按Ｃｏｂｂ法测量后凸畸形角度,同时记录ＡＳＩＡ下肢运动评分结果：无脊髓损伤、不完全脊髓损伤及完全脊髓损伤三组的椎管狭窄率及后凸畸形角度相差无显著统计撑意义（Ｐ〉０．０５）,椎管狭窄率及后凸畸形角度与ＡＳＩＡ评分相关笥无显著统计学意义（ＰＭ〉０．０５）。结论：胸腰椎爆裂性骨     

骨形态发生蛋白2对成牙骨质细胞中硬化蛋白表达调控机理的研究

目的 探索成牙骨质细胞OCCM-30中骨形态发生蛋白2（BMP2）对硬化蛋白（SOST）表达的调控机制。方法 用2种质量浓度的BMP2（50、100 ng·mL^-1）处理成牙骨质OCCM-30细胞3、5、7 d,相同体积的PBS液为对照组,采用实时荧光定量聚合酶链反应（RT-PCR）、免疫印迹法检测SOST mRNA和蛋白的表达情况。将OCCM-30细胞分为5组：空白对照组、BMP2组、BMP2+dorsomorphin组、BMP2+SB202190组、BMP2+PD98059组,根据分组分别加入100 ng·mL^-1的BMP2和相应的试剂共培养,于3、5 d时检测SOST mRNA和蛋白的表达情况。结果 100 ng·mL^-1 BMP2对SOST表达的上调作用强于50 ng·mL^-1 BMP2,且有时间依赖性（P<0.05）。BMP2+dorsomorphin组、BMP2+ SB202190组、BMP2+ PD98059组的SOST mRNA水平和蛋白质水平均降低,其中BMP2+dorsomorphin组降低最明显（P<0.05）。结论 成牙骨质细胞中BMP2主要是通过Smad信号通路介导上调SOST的表达。     

心脏电机械标测与核素心肌显像评估急性心肌梗死患者存活心肌的比较

目的:比较心脏电机械标测系统(electromechanicalmapping,NOGA)、TM核素心肌显像和超声心动图在评估急性心肌梗死患者存活心肌状况的作用。方法:选择2003-01/04南京医科大学附属南京第一医院心内科住院并符合纳入标准的急性心肌梗死患者5例,均为男性,平均年龄(56±3)岁。急诊经皮冠状动脉腔内成形术后第7天分别进行NOGATM系统、心脏超声及核素心肌显像测定。结果:NOGA系统测定出梗死区域的单极电压(unipolarvoltagepoten-TMtials,UVP)犤(5.8±2)mV犦显著低于非梗死区域的心肌犤(11.9±3)mV,P<0.01犦,同时测得梗死区域心肌的内膜下心肌短缩率(linearlocalshortening,LLS)犤(0.7±0.2)%犦明显小于非梗死区域心肌犤(11.2±4)%,P<0.01犦。特征性曲线分析NOGATM判断心肌存活状态的UVP界定值为8.0mV敏感性及特异性均为88%。()结论:LLS与心脏超声相关性良好,当UVP≥8.0mV时提示心肌处于存活状态。