国产吸附破伤风疫苗用于成人加强免疫的安全性及免疫原性观察

目的:评价成都欧林生物科技股份有限公司研制的吸附破伤风疫苗用于成人加强免疫的临床安全性与免疫原性。方法:分两阶段开展:第一阶段采用开放性设计,评价试验疫苗的安全性,在确认安全性的情况下开展第二阶段试验;第二阶段采用单中心、随机、盲法、同类制品平行对照的试验设计,选择18~30岁的常住健康人群,按1∶1的比例随机接种试验疫苗和阳性对照疫苗,使用日记卡记录接种后28 d内的不良反应/事件发生情况。采集免疫前和免疫后28 d的血液标本,使用标准酶联免疫吸附试验方法进行破伤风类毒素抗体浓度检测。结果:第一阶段招募30名受试者,试验疫苗接种后7 d内总体不良反应为33.3%;第二阶段试验组和阳性对照组各入组600人,总体不良反应发生率分别为30.7%和31.5%,以轻中度不良反应为主,最常见接种局部和全身不良反应分别为疼痛和发热,不良反应的发生在组间差异无统计学意义(P≥0.05)。加强免疫后试验组与阳性对照组均诱导较强的免疫反应:破伤风抗体浓度达到保护性水平的受试者比例均达到100%,GMC分别为3.38、3.16 U/ml。结论:成都欧林生物科技股份有限公司研制的吸附破伤风疫苗具有良好的安全性和免疫原性,适用于成人进行加强免疫和进一步进行联合疫苗的研制。     

Usefulness of optical coherence tomography to detect central serous chorioretinopathy in monkeys

Many systemic drugs can induce ocular toxicity and several ocular side‐effects have been identified in clinical studies. However, it is difficult to detect ocular toxicity in preclinical studies because of the lack of appropriate evaluation methods. Optical coherence tomography (OCT) is useful because it can provide real‐time images throughout a study period, whereas histopathology only provides images of sacrificed animals. Using OCT alongside histopathology, attempts were made to find effective approaches for screening of drug‐induced ocular toxicity in monkeys. Such approaches could be used in preclinical studies prior to human trials. Six male cynomolgus monkeys (Macaca fascicularis Raffles) were orally administered one of six candidate MAPK/ERK kinase (MEK) inhibitors. Central serous chorioretinopathy, a known side‐effect of such inhibitors, was identified in four monkeys by OCT. Artifacts generated during tissue processing meant that histopathology could not detect edematous changes. Thus, OCT is a useful tool to detect ocular toxicity which cannot be detected by histopathology in preclinical studies. Copyright © 2014 John Wiley & Sons, Ltd.     

ICP-AES测定玛咖中微量元素的含量

采用ICP-AES电感耦合等离子体发射光谱仪,对药材玛咖中的微量元素进行测定和分析。实验结果表明玛咖中含有Ca、Mg、P、Cu、Zn、Mn、Fe等多种元素,为进一步探讨金属元素与药效的关系提供数据。     

HPLC波长切换法同时测定杜仲双降袋泡剂中7种成分的含量

目的建立高效液相(HPLC)波长切换法同时测定杜仲双降袋泡剂中桃叶珊瑚苷、京尼平苷酸、绿原酸、京尼平苷、松脂醇二葡萄糖苷、芦丁及槲皮素7种成分含量的方法。方法以80%甲醇为溶剂,加热回流提取;色谱柱:Hydrosphere C18(4.6 mm×200 mm,5μm);柱温:30℃;流动相:乙腈-0.1%磷酸溶液,梯度洗脱;检测波长:208 nm(桃叶珊瑚苷)、235 nm(京尼平苷酸、绿原酸、京尼平苷、松脂醇二葡萄糖苷)、270 nm(芦丁、槲皮素);流速:0.9 ml/min。结果桃叶珊瑚苷、京尼平苷酸、绿原酸、京尼平苷、松脂醇二葡萄糖苷、芦丁、槲皮素的质量浓度分别在10.97~274.25μg/ml(r=0.999 7)、9.78~244.50μg/ml(r=0.999 8)、6.86~171.50μg/ml(r=0.999 6)、2.47~61.75μg/ml(r=0.999 7)、8.11~202.75μg/ml(r=0.999 1)、4.59~114.75μg/ml(r=0.999 9)、1.85~46.25μg/ml(r=0.999 5)范围内线性关系良好;平均加样回收率分别为99.85%、98.92%、97.52%、97.08%、98.51%、97.10%、96.91%,RSD分别为0.93%、0.74%、1.26%、1.37%、0.88%、1.05%、1.33%。结论所建立的HPLC波长切换法可以同时测定杜仲双降袋泡剂中桃叶珊瑚苷、京尼平苷酸、绿原酸、京尼平苷、松脂醇二葡萄糖苷、芦丁和槲皮素的含量,方法简便准确、灵敏度高,可用于杜仲双降袋泡剂的质量控制。     

基于一测多评法对丁蔻理中丸中6种成分的质量控制研究

目的:建立一测多评法同时测定丁蔻理中丸中白术内酯Ⅲ、白术内酯Ⅰ、丁香酚、6-姜辣素、8-姜酚、10-姜酚6种成分的含量。方法:以白术内酯Ⅰ为内标物,建立白术内酯Ⅰ与白术内酯Ⅲ、丁香酚、6-姜辣素、8-姜酚、10-姜酚之间的校正因子,计算待测成分含量,并将外标法测定值与一测多评法计算值进行对比,验证所建立一测多评法的准确性。结果:白术内酯Ⅲ、白术内酯Ⅰ、丁香酚、6-姜辣素、8-姜酚和10-姜酚分别在1.09~21.80μg·mL-1、0.71~14.20μg·mL-1、13.67~273.40μg·mL-1、6.04~120.80μg·mL-1、1.46~29.20μg·mL-1、1.78~35.60μg·mL-1范围内线性关系良好;各成分一测多评法计算值与外标法实测值无显著性差异。结论:利用校正因子对丁蔻理中丸中6种成分的含量测定是可行的,一测多评法可以用于丁蔻理中丸的质量评价研究。     

Identification of a novel DRB1 allele through intergenic recombination between HLA-DRB1 and HLA-DRB302 in a Chinese family

In this study, a novel DRB1 allele was revealed by routine HLA-SBT typing noted for its extensive mismatches to any known DRB1 alleles within the exon 2. Sequences containing the exons 2, 3 of HLA-DRB1, their surrounding introns, and the full-length cDNA of DRB1 were analyzed to determine a possible recombination event. Interestingly, the sequences of entire exon 2 were characterized as DRB3^∗02:02:01:01/02; while exon 3 were characterized as DRB1^∗14 like alleles. Further analysis of the sequences using Simplot software suggested that an intergenic recombinant event (i.e. exchange of sequence between non-allelic genes) may have occurred between DRB3^∗02 allele and DRB1^∗14 like allele, and the recombination sites are located at intron 1 and the boundary of exon 2 and intron 2 of DRB1. There are 5 CGGGG sequences flanking each side of exon 2 could serve as potential recombination site. Moreover, the full-length cDNA of the novel allele has been identified. The exon 1 and exon 3 to exon 6 share the same sequence as DRB1^∗14 like alleles. At the mRNA level, the new allele has no significant difference when compared with the other DRB1 allele. This novel recombinant allele is also found to be paternally inherited. In conclusion, this is the first report of a DRB1 and DRB3 intergenic recombination event involving whole exon 2, which generate a new DRB1^∗14:141.     

新型腰椎后路动态稳定系统的三维有限元分析

目的对新型腰椎后路动态稳定系统进行三维有限元分析,研究其在稳定节段及邻近节段的生物力学影响,为下腰痛的脊柱内植物的设计和应用提供参考。方法基于正常腰椎有限元模型,构建腰椎不稳损伤模型,即腰椎切除腰4和腰5之间的双侧小关节、腰4椎板下1/2、后纵韧带,形成脊柱失稳模型,分别在失稳模型上进行坚强内固定系统和后路动态稳定系统,比较两种术式对手术节段和临近阶段的活动度、各个节段的弯曲刚度、椎间盘应力水平、前纵韧带应力水平及小关节韧带拉力的变化情况。结果对内固定桥接节段(腰4/腰5)应用新型腰椎后路动态稳定系统和坚强内固定系统后,在屈伸、侧屈、轴向旋转方向上的活动度均明显减小,但坚强固定后活动度减小更明显,应用动态稳定系统活动度更接近于正常腰椎节段;腰4/腰5椎间盘最大应力均减小,但坚强固定后活动度减小更明显,应用动态稳定系统活动度更接近于正常腰椎节段;对邻近节段(腰3/腰4、腰5/S1)应用新型腰椎后路动态稳定系统和坚强内固定系统后,在屈伸、侧屈、轴向旋转方向上的活动度均有所增大,但坚强固定后活动度增加更明显,应用动态稳定系统邻近节段活动度更接近于正常腰椎节段;邻近节段椎间盘最大应力均增大,但坚强固定后增大更明显,应用动态稳定系统更接近于正常腰椎节段;应用腰椎内固定后,邻近节段的小关节应力峰值增大,并且应用腰椎坚强内固定模型的小关节应力增大更多;应用腰椎动态固定的模型邻近关节应力峰值更加接近完整腰椎模型。结论新型腰椎后路动态稳定系统对比坚强内固定系统能够使失稳节段的活动更加接近于正常,减小邻近节段的活动度增加,减小邻近节段椎间盘及小关节压力,说明新型腰椎动态稳定系统达到设计要求。     

妊娠高血压综合征患者血清IL-12、TNF-α和CRP的变化及其意义

目的测定妊高征患者血清中TNF-α、IL-12和CRP的表达情况,来初步探讨炎性细胞因子及参与炎症反应表达的CRP,在妊高征患者母体免疫系统中的功能,以及与妊高征发病的关系。方法选取妊高征患者76例作为研究对象,随机选取正常晚期妊娠妇女62例作为对照组。检测以上两组孕妇血清TNF-α、IL-12和CRP水平。结果妊高征组与正常妊娠组相比,TNF-α、IL-12、CRP差异有统计学意义（P〈0．01）。轻度予痫前期组与重度子痫前期组相比,TNF-α、IL-12、CRP差异有统计学意义（P〈0．05）。妊高征组血清IL-12与TNF-α呈正相关关系（P〈0．01）,轻度子痫前期组、重度子痫前期组和正常晚期妊娠组血清IL-12与TNF-α呈正相关关系（P〈0．01）。妊高征组血清CRP与IL—12和TNF-α呈正相关关系（P〈0．01）;轻度子痫前期纽、重度子痫前期组、正常晚期妊娠组血清CRP与IL-12和TNF-α呈正相关关系（P〈0．05）。结论妊高征患者体内IL-12、TNF-α及CRP浓度较正常晚期妊娠妇女体内升高,炎性细胞因子的升高与妊高征的发生密切相关。