关于802.1X认证技术在校园网应用中问题的探讨

介绍了802.1X认证技术的体系结构和工作原理,分析了802.1X认证技术在校园网中应用的优势与不足.     

Metabolic activation of fluoropyrrolidine dipeptidyl peptidase-IV inhibitors by rat liver microsomes.

The current study evaluated the potential for two dipeptidyl peptidase-IV (DPP-IV) inhibitor analogs (1S)-1-(trans-4-([(4-trifluoromethoxyphenyl)sulfonyl]amino)cyclohexyl)-2-[(3S)-3-fluoropyrrolidin-1-yl]-2-oxoethanaminium chloride and (1S)-1-(trans-4-([(2,4-difluorophenyl)sulfonyl]amino)cyclohexyl)-2-[(3S)-3-fluoropyrrolidin-1-yl]-2-oxoethanaminium chloride (MRL-A and MRL-B), containing a fluoropyrrolidine moiety in the structure, to undergo metabolic activation. The irreversible binding of these tritium-labeled compounds to rat liver microsomal protein was time- and NADPH-dependent and was attenuated by the addition of reduced glutathione (GSH) or N-acetylcysteine (NAC) to the incubation, indicating that chemically reactive intermediates were formed and trapped by these nucleophiles. Mass spectrometric analyses and further trapping experiments with semicarbazide indicated that the fluoropyrrolidine ring had undergone sequential oxidation and defluorination events resulting in the formation of GSH or NAC conjugates of the pyrrolidine moiety. The bioactivation of MRL-A was catalyzed primarily by rat recombinant CYP3A1 and CYP3A2. Pretreatment of rats with prototypic CYP3A1 and 3A2 inducers (pregnenolone-16alpha-carbonitrile and dexamethasone) enhanced the extent of bioactivation which, in turn, led to a higher degree of in vitro irreversible binding to microsomal proteins (5- and 9-fold increase, respectively). Herein, we describe studies that demonstrate that the fluoropyrrolidine ring is prone to metabolic activation and that GSH or NAC can trap the reactive intermediates to form adducts that provide insight into the mechanisms of bioactivation.     

Enhancement of manumycin A-induced apoptosis by methoxyamine in myeloid leukemia cells.

Farnesyltransferase inhibitors (FTIs) are currently under investigation for leukemia treatment. We evaluated the FTI manumycin A (manumycin) in two myeloid leukemia cell lines (U937 and HL-60). Manumycin induced nitric oxide production and apoptosis of the leukemia cells. Nitric oxide or other reactive oxygen species may induce oxidative DNA damage, and the number of apurinic sites increased after manumycin treatment, which was reversed by concurrent treatment with N-acetyl-L-cysteine. Since repair of DNA damage is important to cell survival, we hypothesized that methoxyamine, an inhibitor of base-excision repair, would enhance the antineoplastic effect of manumycin. The combination of manumycin and methoxyamine resulted in enhanced apoptosis by six criteria increased annexin V binding, release of mitochondrial cytochrome c into the cytosol, activation of caspase-9, activation of caspase-3, specific cleavage of poly-adenosyl ribose polymerase, and increase in the sub-G1 cell cycle fraction. The drug combination enhanced inhibition on the soft agar clonogenic assay and on the formazan dye cell viability assay. The effects of manumycin or manumycin plus methoxyamine on apoptosis were blocked by N-acetyl-L-cysteine, and partially by nitric oxide synthase inhibitors or scavenger of peroxide. We conclude that methoxyamine enhances manumycin-induced apoptosis in myeloid leukemia cells.     

The association of XRCC1 haplotypes and chromosomal damage levels in peripheral blood lymphocyte among coke-oven workers.

Theoretically, a haplotype has a higher level of heterozygosity than individual single nucleotide polymorphism (SNP) and the association study based on the haplotype may have an increased power for detecting disease associations compared with SNP-based analysis. In this study, we investigated the effects of four haplotype-tagging SNPs (htSNP) and the inferred haplotype pairs of the X-ray cross-complementing group 1 (XRCC1) gene on chromosome damage detected by the cytokinesis-block micronucleus assay. The study included 141 coke-oven workers with exposure to a high level of polycyclic aromatic hydrocarbons and 66 nonexposed controls. The frequencies of total MN and MNed cells were borderline associated with the Arg(194)Trp polymorphism (P = 0.053 and P = 0.050, respectively) but not associated with the Arg(280)His, Arg(399)Gln and Gln(632)Gln polymorphisms among coke-oven workers. Five haplotypes, including CGGG, TGGG, CAGG, CGAG, and CGGA, were inferred based on the four htSNPs of XRCC1 gene. The haplotype CGGG was associated with the decreased frequencies of total MN and MNed cells, and the haplotypes TGGG and CGAG were associated with the increased frequencies of total MN and MNed cells with adjustment for covariates among coke-oven workers. This study showed that the haplotypes derived from htSNPs in the XRCC1 gene were more likely than single SNPs to correlate with the polycyclic aromatic hydrocarbon-induced chromosome damage among coke-oven workers.     

黄芪注射液对刀豆蛋白诱导的小鼠肝脏损伤的保护作用

目的：观察免疫损伤模型组与实验组小鼠外周血中T细胞亚群的变化情况，探讨黄芪注射液对小鼠肝脏损伤的保护作用。方法实验组小鼠每天腹腔注射黄芪注射液400μl，正常组与模型组小鼠每天给予等剂量的生理盐水。第7天在给药1小时后，模型组与实验组小鼠分别经尾静脉注射刀豆蛋白，正常组小鼠则给予等剂量的生理盐水。8小时后检测各组动物外周血中CD4^＋T、CD8^＋T细胞以及CD4^＋／CD25^＋T细胞所占比例，检测血浆转氨酶水平，制备肝脏病理标本，进行HE染色。结果尾静脉注射8小时后，实验组小鼠外周血的CD4^＋所占T细胞比例较模型组有所升高（P〈0．05），但仍低于正常组水平（P〉0．05）：而CD8^＋T细胞的比例则无明显变化（P〉0．05）。实验组ALT、AST水平明显低于模型组（P〈0．05）。实验组汇管区淋巴细胞浸润明显减少。结论黄芪注射液对刀豆蛋白诱导的小鼠肝损伤有确切的保护作用。     

药物警戒论-更有效的沟通(六)

医生、药剂师、护士和所有其他直接与医院的病人或社区的药品使用者接触的专业人员都处于一个关键的位置，他们有可能会传播与治疗有关的信息，也可能被人问及有关治疗的各种问题。包括药物的受益和风险问题。遗憾的是，大学本科教育和研究生教育一般很少为这些专业人员进行这方面的基础教育，而这些人却要担负起教育者的职责，向其他人介绍药物最安全和最有效使用的知识。并且，他们对药理学和临床药理学的某些知识缺少认识，有关药物研究和开发过程的知识则更是缺乏。因此他们对于药物的看法可能只是根据早期的疗效和安全性资料。以及受益和风险特点，他们把这些资料看作药物固定的特征。而不是作为某种可以随着时间延长，资料增多而发生改变的东西。     

闭角型青光眼患者红细胞免疫功能与EPO和ET-1的相关性

目的：探讨闭角型青光眼患者红细胞免疫功能与血清促红细胞生成素(EPO)和血浆内皮素-1(ET-1)的相关性。

方法：选取2017-06/10期间我院收治的闭角型青光眼患者30例(病例组)与眼部正常者30例(对照组)为研究对象。测定并比较两组受试者红细胞免疫功能、血清EPO和血浆ET-1浓度,分析之间的相关性。

结果：病例组受试者红细胞C3b受体花环率明显低于对照组(10.81%±2.01% vs 18.06%±3.44%),红细胞免疫复合物花环率明显高于对照组(17.21±3.49% vs 11.74±2.14%),血清EPO浓度明显高于对照组(26.10±5.22 mU/mL vs 22.68±4.06mU/mL),血浆ET-1浓度明显高于对照组(70.85±7.16ng/L vs 58.43±5.09ng/L)。闭角型青光眼患者红细胞C3b受体花环率与血清EPO浓度呈显著正相关(r=0.271,P<0.05),与血浆ET-1浓度无明显相关性。

结论：闭角型青光眼患者红细胞免疫功能与血清EPO浓度呈正相关。     

O-GlcNAc修饰在糖尿病心肌病中的作用及机制研究进展

<正>糖尿病是一种慢性代谢性紊乱疾病。据统计,我国2021年糖尿病患者数量已高达1.41亿[1]。糖尿病引发的心血管意外已成为患者死亡的主要原因,且死亡率明显高于非糖尿病患者[2]。糖尿病心肌病(diabetic cardiomyopathy, DCM)是一种因长期高血糖引起的心脏结构和功能异常的疾病,与多种信号通路有关。     

一种小鼠肠道纤维化模型建造的方法及评价

目的 探究一种使用酒精建造C57BL/6小鼠肠道纤维化模型的方法。方法 将6周龄C57BL/6小鼠根据不同酒精浓度分为正常对照组、50%乙醇组、三硝基苯磺酸(TNBS)/30%乙醇组、TNBS/50%乙醇组,采用灌肠液灌肠方式造模,每周灌肠1次,持续5周,第6周处死后取结直肠。整个实验期间观察小鼠生存状态、体重变化及生存率,每天进行小鼠疾病活跃指数(DAI)评价。固定包埋后,采用苏木精-伊红染色检测肠道黏膜以及腺体结构完整性;马森三色染色法检测小鼠肠道胶原沉积情况;免疫组织化学染色检测纤维化蛋白α-平滑肌肌动蛋白(α-SMA)的表达量。结果 与正常对照组比较,50%乙醇组、TNBS/30%乙醇组、TNBS/50%乙醇组的黏膜破损、腺体丢失比例、纤维化蛋白α-SMA表达明显高于正常对照组,并且50%乙醇组、TNBS/30%乙醇组、TNBS/50%乙醇组的DAI评分更高、胶原沉积更多,且TNBS/50%乙醇组高于TNBS/30%乙醇组,50%乙醇组与TNBS/30%乙醇组相近。结论 与正常组比较,50%乙醇组小鼠各时间点DAI评分均明显增高,整体纤维化程度与TNBS/30%乙醇组类似,单纯使用乙醇可以建造小鼠肠道的纤维化模型。