分子吸附循环人工肝治疗重型肝炎肝脏功能衰竭的临床研究

目的　探讨分子吸附循环 (MARS)人工肝治疗重型肝炎肝脏功能衰竭的临床疗效、不良反应、机制及预后评估。方法　对 86例重型肝炎肝脏功能衰竭患者进行MARS人工肝治疗 ,通过比较治疗前后患者临床症状、肝功能、内毒素、中分子物质及细胞因子等指标 ,判断临床效果和相关的不良反应 ,并将血浆置换 (PE)及内科综合治疗作为对照。通过对比治愈好转率及住院时间评价其疗效。结果　MARS治疗组临床症状改善显效率 6 6 .2 8% ,对照组为2 0 % ;MARS人工肝治疗后血清总胆红素、尿素氮 (BUN)、肌酐 (Cr)、内毒素 (ET)、中分子物质、肿瘤坏死因子 (TNF α)、白细胞介素 (IL 1、IL 10、IL 6 )及血氨明显降低 ,治疗前后统计学检验差异有显著性意义 (P <0 .0 5 )。MARS治疗组与血浆置换 (PE)治疗组在过敏、发热、治疗后水肿等不良反应的发生率比较差异有统计学意义 (P <0 .0 5 ) ;局部血肿及血压下降差异无统计学意义 (P >0 .0 5 ) ;MARS治疗组治愈好转率 89.5 3% ,对照组为 2 8.89% ,差异有统计学意义 (P <0 .0 1) ;住院时间MARS治疗组较对照组短 ,亦有统计学意义 (P <0 .0 1)。结论　MARS人工肝治疗可显著改善重型肝炎患者的临床症状 ,对血清总胆红素、尿素氮、肌酐、内毒素、血氨、中分子物质及细胞因子有明显降低作     

Regulation of CTLA‐4 recycling by LRBA and Rab11

CTLA‐4 is an essential regulator of T‐cell immune responses whose intracellular trafficking is a hallmark of its expression. Defects in CTLA‐4 trafficking due to LRBA deficiency cause profound autoimmunity in humans. CTLA‐4 rapidly internalizes via a clathrin‐dependent pathway followed by poorly characterized recycling and degradation fates. Here, we explore the impact of manipulating Rab GTPases and LRBA on CTLA‐4 expression to determine how these proteins affect CTLA‐4 trafficking. We observe that CTLA‐4 is distributed across several compartments marked by Rab5, Rab7 and Rab11 in both HeLa and Jurkat cells. Dominant negative (DN) inhibition of Rab5 resulted in increased surface CTLA‐4 expression and reduced internalization and degradation. We also observed that constitutively active (CA) Rab11 increased, whereas DN Rab11 decreased CTLA‐4 surface expression via an impact on CTLA‐4 recycling, indicating CTLA‐4 shares similarities with other recycling receptors such as EGFR. Additionally, we studied the impact of manipulating both LRBA and Rab11 on CTLA‐4 trafficking. In Jurkat cells, LRBA deficiency was associated with markedly impaired CTLA‐4 recycling and increased degradation that could not be corrected by expressing CA Rab11. Moreover LRBA deficiency reduced CTLA‐4 colocalization with Rab11, suggesting that LRBA is upstream of Rab11. These results show that LRBA is required for effective CTLA‐4 recycling by delivering CTLA‐4 to Rab11 recycling compartments, and in its absence, CTLA‐4 fails to recycle and undergoes degradation.     

Endosomal trafficking of AMPA-type glutamate receptors

Many different forms of synaptic plasticity have been shown to ultimately modulate the number of AMPA-type glutamate receptors at the synapse. This trafficking involves lateral movements between synaptic and extrasynaptic sites at the neuron surface, as well as vesicular transport between the plasma membrane and intracellular compartments. Several new studies have shed light on the location and regulation of AMPA-type receptor (AMPAR) endocytosis, their intracellular sorting to divergent pathways at the level of endosomes, and the mechanism and sites of receptor recycling. This review summarizes this recent data on the trafficking along the endocytic pathway, and follows the path of internalized AMPAR from endocytosis up to sites of recycling.     

Rapid turnover of spinules at synaptic terminals

Spinules found in brain consist of small invaginations of plasma membranes which enclose membrane evaginations from adjacent cells. Here, we focus on the dynamic properties of the most common type, synaptic spinules, which reside in synaptic terminals. In order to test whether depolarization triggers synaptic spinule formation, hippocampal slice cultures (7-day-old rats, 10–14 days in culture) were exposed to high K⁺ for 0.5–5 min, and examined by electron microscopy. Virtually no synaptic spinules were found in control slices representing a basal state, but numerous spinules appeared at both excitatory and inhibitory synapses after treatment with high K⁺. Spinule formation peaked with ∼1 min treatment at 37 °C, decreased with prolonged treatment, and disappeared after 1–2 min of washout in normal medium. The rate of disappearance of spinules was substantially slower at 4 °C. N-methyl-d-aspartic acid (NMDA) treatment also induced synaptic spinule formation, but to a lesser extent than high K⁺ depolarization. In acute brain slices prepared from adult mice, synaptic spinules were abundant immediately after dissection at 4 °C, extremely rare in slices allowed to recover at 28 °C, but frequent after high K⁺ depolarization. High pressure freezing of acute brain slices followed by freeze-substitution demonstrated that synaptic spinules are not induced by chemical fixation. These results indicate that spinules are absent in synapses at low levels of activity, but form and disappear quickly during sustained synaptic activity. The rapid turnover of synaptic spinules may represent an aspect of membrane retrieval during synaptic activity.     

Analysis of Gene Polymorphisms Associated with K+ Ion Circulation in the Inner Ear of Patients Susceptible and Resistant to Noise-induced Hearing Loss

Noise-induced hearing loss (NIHL) is one of the leading occupational health risks in industrialized countries. It results from an interaction between environmental and genetic factors, however the nature of the genetic factors contributing to NIHL has not yet been clarified. Here, we investigated whether genetic variations in 10 genes putatively involved in the potassium recycling pathway in the inner ear may influence susceptibility to noise. 99 SNPs were genotyped in Polish noise-exposed workers, categorized into susceptible and resistant subjects. The most interesting results were obtained for KCNE1 and KCNQ4 as we replicated associations that were previously reported in a Swedish sample set, hence confirming that they are NIHL susceptibility genes. Additionally we report significant associations in GJB1 , GJB2 , GJB4 , KCNJ10 and KCNQ1 , however due to the lack of replication in the Swedish sample set, these results should be seen as suggestive.     

上海市静脉产业发展现状与对策

通过对上海市工业固体废物、危险废物、电子废物、医疗废物和城市生活垃圾等重要固体废物近几年来的产生量,以及这些固体废物以其资源化、回收和再利用为特征的静脉产业发展现状的调查,表明上海市防治固体废物污染,发展静脉产业方面已作出了相当大的努力,初步形成了静脉产业群,但仍与上海社会经济快速的发展不相适应。文章分析了制约上海静脉产业快速发展的重要问题,包括推进静脉产业发展的配套政策还不到位,缺乏有实力的大企业参与静脉产业的发展和缺乏社会广泛的参与和支持等。针对静脉产业发展所面临的问题,提出了包括提供专项法规和配套政策的支持,积极推进静脉产业园区建设,制定发展静脉产业的专项规划,加大静脉产业关键技术研发力度和争取社会的大力支持等相关对策建议。     

Involvement of glypican-1 autoprocessing in scrapie infection

The copper-binding cellular prion protein (PrP^C) and the heparan sulphate (HS)-containing proteoglycan glypican-1 (Gpc-1) can both be attached to lipid rafts via their glycosylphosphatidylinositol anchors, and copper ions stimulate their cointernalization from the cell surface to endosomes. The prion protein controls cointernalization and delivers copper necessary for S-nitrosylation of conserved cysteines in the Gpc-1 core protein. Later, during recycling through endosomal compartments, nitric oxide can be released from the S-nitroso groups and catalyses deaminative degradation and release of the HS substituents. Here, by using confocal immunofluorescence microscopy, we show that normal PrP^C and Gpc-1 colocalize inside GT1-1 cells. However, in scrapie-infected cells (ScGT1-1), Gpc-1 protein remained at the cell surface separate from the cellular prion protein. Scrapie infection stimulated Gpc-1 autoprocessing and the generated HS degradation products colocalized with intracellular aggregates of the disease-related scrapie prion protein isoform (PrP^Sc). Coimmunoprecipitation experiments demonstrated an association between Gpc-1 and PrP^C in uninfected cells, and between HS degradation products and PrP^Sc in infected cells. Silencing of Gpc-1 expression or prevention of Gpc-1 autoprocessing elevated the levels of intracellular PrP^Sc aggregates in infected cells. These results suggest a role for Gpc-1 autoprocessing in the clearance of PrP^Sc from infected cells.     

Functional selectivity of dopamine D1 receptor agonists in regulating the fate of internalized receptors

Recently, we demonstrated that D(1) agonists can cause functionally selective effects when the endpoints of receptor internalization and adenylate cyclase activation are compared. The present study was designed to probe the phenomenon of functional selectivity at the D(1) receptor further by testing the hypothesis that structurally dissimilar agonists with efficacies at these endpoints that equal or exceed those of dopamine would differ in ability to influence receptor fate after internalization, a functional endpoint largely unexplored for the D(1) receptor. We selected two novel agonists of therapeutic interest that meet these criteria (the isochroman A-77636, and the isoquinoline dinapsoline), and compared the fates of the D(1) receptor after internalization in response to these two compounds with that of dopamine. We found that dopamine caused the receptor to be rapidly recycled to the cell surface within 1h of removal. Conversely, A-77636 caused the receptor to be retained intracellularly up to 48 h after agonist removal. Most surprisingly, the D(1) receptor recovered to the cell surface 48 h after removal of dinapsoline. Taken together, these data indicate that these agonists target the D(1) receptor to different intracellular trafficking pathways, demonstrating that the phenomenon of functional selectivity at the D(1) receptor is operative for cellular events that are temporally downstream of immediate receptor activation. We hypothesize that these differential effects result from interactions of the synthetic ligands with aspects of the D(1) receptor that are distal from the ligand binding domain.     

Feasibility study of chitosan extraction from waste leaves of Luffa cylindrica for bioresource recycling

Chitosan as natural, biocompatible and biodegradable biopolymer has been widely considered to own the characteristics of moisturizing, antibacterial and several biological activities for clinical purposes. Chitosan could be obtained from chitins via deacetylation. As known, chitin is typically derived from the exoskeletons crustaceans and fungal cell wall, but this biopolymer can also be found in other sources, such as plants. In fact, Luffa spp. is popularly utilized as Asian edible plants abundant in chitin/chitosan. This first-attempt study tended to reveal chitosan extracted from renewable agricultural waste (i.e., Luffa leaf waste), through comparative analysis upon the contents of the different portions of Luffa. However, studies that discuss the harvest of chitosan from plant sources are rare. Thus, this study explored the most promising strategy to extract chitosan from the waste-Luffa cylindrica leaves. Meanwhile, comparative analysis clearly exhibited the contents of chitosan from different portions of L. cylindrica. The different chitosan-extracting methods would be implemented to obtain the maximal recovery of chitosan. The maximal amount of plant-based chitosan was extracted from L. cylindrica leaves waste through a promising method (i.e., hydrochloric acid under high pressure and high temperature through moist-heating sterilization). Moreover, it was found that the peel of L. cylindrica contained the highest amount of chitosan. Hence, this study showed that L. cylindrica leaves and peel waste would be the most appropriate sources of chitosan. This first-attempt study developed value-added production from edible plant waste for carbon neutrality and circular economy.     

基于RFID的再生医疗器械管理信息系统设计与实现

目的:对再生医疗器械进行完整、灵活和实时的可追溯管理。方法:利用无线射频识别技术(RFID)设计管理信息系统,对再生医疗器械的回收、清洗、打包到最后的术后清点,实行全程监控。结果:该系统提供了与HIS系统接口,可实现全院系统数据共享,系统的设计与实现是有效的,具有操作简便、灵活、安全性好、便于扩充等优点。结论:该系统方便了器械成本核算、审计和工作量统计,确保了再生医疗器械使用的安全,健全了医院安全管理机制。