低温海水浸泡对大鼠血浆蛋白质组的影响研究

目的模拟海难落水所致重度低体温损伤,比较鉴定低温海水浸泡模型动物血浆蛋白质组差异,为研究低体温相关血浆蛋白提供线索。方法将50只雄性健康Wistar大鼠平均分成5组,分别在低温海水中浸泡0、2、4、6、10 h后采集下腔静脉血。分离血浆后,用试剂盒去除Ig G和白蛋白等高丰度蛋白,并经过除盐后采用蛋白质双向凝胶电泳(2-DE)分离。对差异1.5倍以上的蛋白斑点,用基质辅助激光解析电离飞行时间质谱(MALDI-TOF-MS)进行肽质量指纹图谱分析,应用NCBI或Swiss-prot数据库鉴定差异蛋白质。结果大鼠浸泡在15℃海水中,中心体温(肛温)迅速下降,浸泡30 min降至19℃,浸泡120 min降至16℃左右,体温维持不变,说明进入重度低体温状态。初步鉴定出3个与低温相关差异蛋白,肺表面相关蛋白A(SP-A)、丝氨酸蛋白酶抑制剂A3K(SPA3K)和抑制物组织基质金属蛋白酶抑制剂-3(TIMP-3)。与正常大鼠相比,这3个蛋白的表达水平均随着低温海水浸泡时间的延长明显上调。结论低温海水浸泡后的大鼠血浆蛋白质组相对正常大鼠血浆蛋白质组有改变。研究差异蛋白有助于阐明低温损伤的分子机制,为研究和治疗低体温症提供靶标。     

生物等效性试验中受试者食用高脂餐的调查研究

目的评价餐后生物等效性试验中受试者食用高脂餐的情况,总结高脂餐食谱制订的考虑因素。方法对完成首都医科大学附属北京朝阳医院Ⅰ期临床试验研究室(以下简称"本中心")两周期、双交叉、餐后生物等效性试验的33例健康受试者的高脂餐食谱、就餐时间、进食量进行分析,对食用西式高脂餐的21例受试者进行就餐感受的问卷调查,调查内容包括食用高脂餐的感受、餐后饱腹感、餐后有无不适、对于中西式高脂餐的选择和对西式高脂餐中接受度不高的成分。结果本中心选择的中式、西式高脂餐对于受试者的进食量均无影响;57. 14%的受试者倾向于食用西式高脂餐,42. 86%的受试者倾向于食用中式高脂餐;西式高脂餐中接受度不高的成分主要有黄油(33. 33%)、纯牛奶(14. 29%)、沙拉酱(14. 29%)、美式培根(9. 52%)。结论本中心选择的中西式高脂餐基本满足试验需要。综合考虑指导原则要求、受试者就餐感受、避免接受度不高的食物成分等因素,制订更为合理的高脂餐食谱,从而提高临床试验质量。     

A visible fluorescent nanovaccine based on functional genipin crosslinked ovalbumin protein nanoparticles

Accurate and efficient antigen delivery is crucial for inducing a strong and long-term immune response. A visible protein nanovaccine made from antigen could provide a novel and promising technology for secure and efficient delivery of the antigen with imaging visualization. In this study, a functional nanovaccine based on genipin crosslinked ovalbumin (OVA) fluorescent nanoparticles with chitosan (CS-OVA-NPs) was developed. The nanovaccine can carry abundant antigens by self-crosslinking without additional carriers. The fluorescence imaging technique was applied to monitor and reveal the process of antigen delivery in vivo based on the fluorescence of genipin with a non-invasive and real-time manner. This functional OVA nanovaccine can enhance the uptake of OVA in Dendritic Cells (DCs) and further promote DCs to maturate in vitro. In vivo study further indicated CS-OVA-NPs could trigger antigen-specific immune responses, which demonstrated that this fluorescent nanovaccine provided a novel design approach for accurate and efficient vaccine delivery.     

高效液相色谱法测定二乙酰氨乙酸乙二胺注射液的有关物质

目的建立一种高效液相色谱法测定二乙酰氨乙酸乙二胺注射液有关物质.方法以ODS-C18为固定相,磷酸盐缓冲液(pH5.8)-乙腈-四氢呋喃(978:20:2)为流动相,检测波长为210 nm.结果该方法灵敏度高,精密度好.结论该法能有效检测二乙酰氨乙酸乙二胺有关物质.     

ARL4C stabilized by AKT/mTOR pathway promotes the invasion of PTEN-deficient primary human glioblastoma

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) deficiency in primary human glioblastoma (GBM) is associated with increased invasiveness and poor prognosis with unknown mechanisms. Therefore, how loss of PTEN promotes GBM progression remains to be elucidated. Herein, we identified that ADP-ribosylation factor like-4C (ARL4C) was highly expressed in PTEN-deficient human GBM cells and tissues. Mechanistically, loss of PTEN stabilized ARL4C protein due to AKT/mTOR pathway-mediated inhibition of ARL4C ubiquitination. Functionally, ARL4C enhanced the progression of GBM cells in vitro and in vivo. Moreover, microarray profiling and GST pull-down assay identified that ARL4C accelerated tumor progression via RAC1-mediated filopodium formation. Importantly, targeting PTEN potently inhibited GBM tumor progression in vitro and in vivo, whereas overexpression of ARL4C reversed the tumor progression impaired by PTEN overexpression. Clinically, analyses with patients' specimens validated a negative correlation between PTEN and ARL4C expression. Elevated ARL4C expression but PTEN deficiency in tumor was associated with poorer disease-free survival and overall survival of GBM patients. Taken together, ARL4C is critical for PTEN-deficient GBM progression and acts as a novel prognostic biomarker and a potential therapeutic candidate. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

A cross-sectional serum investigation of a clustering hepatitis C virus infection in Southwest China

Serum samples were collected in a village with a clustering hepatitis C virus (HCV) infection. HCV antibody, HCV RNA loads, liver function indexes, HCV envelope antibody, and neutralizing activity were assessed. Among 851 adult sera, 342 samples were positive for anti-HCV. Of these positive samples, 254 (74.3%) were HCV RNA positive (≥800 copies/mL). None of the 69 children's sera were positive for HCV antibody or RNA. Among the HCV antibody positive sera, alanine aminotransferase, and aspartate aminotransferase levels increased with the higher virus loads, but decreased when virus loads were higher than 1 × 10 ⁶ copies/mL. HCV envelope antibody and neutralizing antibody levels increased with viral load.