造血干细胞移植病人极期阴囊处皮肤损伤的护理

白细胞是人体防御细菌入侵的重要防线,中性粒细胞占白细胞总数50%～70%,机体抵御病原体,特别是处于化脓性细菌入侵的第一线,是一道天然免疫屏障。病人极期白细胞及中性粒细胞计数持续下降,一般有头晕、乏力、四肢酸软、食欲减退、低热、失眠或极度衰弱等非特异性症状[1,2]。尤其是病人虚弱多汗,阴囊处皮肤的特性及经钴60全身照射对皮肤的特异性损害,导致阴囊处发生皮肤损伤的几率增加。此期病人易发生     

阿德福韦酯对慢性乙肝患者白细胞介素-8及其mRNA表达的影响

目的探讨阿德福韦酯对慢性乙肝患者白细胞介素-8（IL--8）及其mRNA表达的影响。方法随机选择（信封法）典型HBV感染患者，以ELISA法检测患者血清IL-8水平；Real-timePCR检测PBMC中IL．8mRNA含量，以lgcDNA／lgGAPDH代表其mRNA水平。结果慢性乙肝患者外周血IL-8水平为（3．536±O．383）×105pg／L，IL-8mRNA为（1．1045±0．2267），其中“大三阳”组为（4．702±0．572）×105pg／L，治疗24周为（4．503±0．473）×105pg／L、48周IL-8水平为（4．114±0．420）×105pg／L，其IL-8mRNA分别为（1．1645±0．1340）lgcDNA／lgGAPDH、（1．0267±0．1344）lgcDNA／lgGAPDH、（0．8223±0．1643）lgcDNA／lgGAP·DH，与“小三阳”组相比差异有统计学意义（P〈0．05）。结论阿德福韦酯除发挥抗病毒作用外，还能间接下调因IL-8过度表达所致的炎性反应。     

缺氧条件下白花丹醌对肝癌HepG2细胞增殖、凋亡与侵袭及HIF-1α表达的影响

目的 研究白花丹醌在缺氧条件下对人肝癌细胞HepG2增殖、凋亡、侵袭和低氧诱导因子1α(hypoxia induced factor1α，HIF-1α)及其下游基因表达的影响。方法 采用二氯化钴(CoCl₂)化学诱导法建立HepG2细胞体外缺氧模型，经不同浓度(2，4，8 μmol·L^–1)白花丹醌处理24 h后，MTT、平板克隆形成试验观察HepG2细胞增殖水平变化；使用Annexin V/PI双染流式细胞术检测HepG2细胞凋亡情况；使用Transwell试验观察HepG2细胞侵袭能力的变化；使用qRT-PCR检测HepG2细胞内HIF-1A mRNA转录水平变化；使用Western blotting检测细胞内HIF-1α及其下游基因c-Myc、VEGFA、MMP9和TWIST1的蛋白表达水平。结果 当CoCl₂处理浓度为150 μmol·L^–1时，HepG2细胞增殖水平未见显著变化，而HIF-1α蛋白表达水平显著升高(P<0.01)，提示体外缺氧模型建立成功。与常氧对照组相比，MTT、平板克隆形成试验结果显示不同浓度白花丹醌作用HepG2细胞后，其增殖水平受到显著抑制(P<0.05或P<0.01)； Transwell试验结果显示白花丹醌可显著抑制HepG2细胞侵袭(P<0.05或P<0.01)；流式细胞术结果表明白花丹醌能显著诱导HepG2细胞凋亡(P<0.05或P<0.01)；Western blotting及qRT-PCR检测结果显示，白花丹醌能显著下调HIF-1α蛋白及HIF-1A mRNA表达水平(P<0.05或P<0.01)。Western blotting检测结果显示HIF-1α及其下游基因c-Myc、VEGFA、MMP9和TWIST1的蛋白表达水平均显著下调(P<0.05或P<0.01)。结论 CoCl₂体外模拟肝癌HepG2细胞缺氧的适宜浓度为150 μmol·L^–1；在缺氧条件下，白花丹醌可显著抑制肝癌HepG2细胞的增殖与侵袭，同时诱导细胞凋亡，其作用机制可能与下调HIF-1α蛋白及其下游靶基因蛋白表达有关。     

基于重水拉曼技术评价口腔抑菌剂对粪肠球菌抑菌效能的研究

目的:开发有效且对患者副作用小的口腔抑菌剂配方,系统评价过氧化氢(hydrogen peroxide,H2O2)、次氯酸钠(Sodium hypochlorite,NaClO)对粪肠球菌(Enterococcus faecalis ATCC29212)的抑菌效能.方法:分别采用肉汤稀释法和重水拉曼技术(D2O-labeled single-cell Raman micro-spectroscopy),通过最小抑菌浓度(minimum inhibitory concentration,MIC)和最低抑制代谢浓度(minimum inhibitory concentration based on metabolic activity,MIC-MA)定量评价了抑菌剂对粪肠球菌的生长和代谢抑制作用.结果:对于过氧化氢和次氯酸钠,MIC分别为110 mg/L和0.45 g/L,尽管生长完全停止,但细菌细胞的代谢活性在8 h平均降低了71％、70％,显示出一种"非生长但代谢活跃"(NGMA)的状态,这种状态可能导致潜在的难治性反复感染.而MIC-MA分别为220 mg/L和0.9 g/L时,所有细胞的代谢活动在暴露8 h后完全停止.此外,NaClO+H2O2的组合使用优于单独使用次氯酸钠、过氧化氢.结论:MIC-MA有利于严格评估抗细菌疗效,NaClO+H2O2可作为细菌病原体更有效的抑菌剂方案.     

天麻钩藤饮加减对妊娠期高血压疾病患者RSS系统的影响

目的观察天麻钩藤饮加减对妊娠期高血压疾病(HDCP)患者RSS系统的影响。方法将160例HDCP患者随机分为治疗组和对照组各80例。对照组给予硫酸镁注射液静脉滴注;治疗组在硫酸镁注射液治疗基础上加用天麻钩藤饮加减治疗。于两组治疗前和治疗72 h后比较血压、24 h尿蛋白定量及血清肾素活性(PRA)、血管紧张素Ⅱ(AngⅡ)水平变化。结果两组治疗后收缩压和舒张压与治疗前比较均明显下降,差异均有统计学意义(P0.01)。治疗后,治疗组收缩压和舒张压显著优于对照组,与对照组比较差异具有统计学意义(P0.01)。两组治疗后24 h尿蛋白定量与治疗前比较均明显下降,差异均有统计学意义(P0.01)。治疗后,治疗组24 h尿蛋白定量显著优于对照组(P0.01)。治疗后,治疗组血清肾素活性(PRA)和血管紧张素Ⅱ(AngⅡ)下降明显(P0.01)。结论在硫酸镁解痉药物治疗基础上应用天麻钩藤饮加减治疗HDCP能够显著改善患者血压和24 h尿蛋白定量,其作用可能与降低血清PRA和AngⅡ水平有关。     

Quantitative Estimation of Plasma Free Drug Fraction in Patients With Varying Degrees of Hepatic Impairment: A Methodological Evaluation

Quantitative prediction of unbound drug fraction (f_u) is essential for scaling pharmacokinetics through physiologically based approaches. However, few attempts have been made to evaluate the projection of f_u values under pathological conditions. The primary objective of this study was to predict f_u values (n = 105) of 56 compounds with or without the information of predominant binding protein in patients with varying degrees of hepatic insufficiency by accounting for quantitative changes in molar concentrations of either the major binding protein or albumin plus alpha 1-acid glycoprotein associated with differing levels of hepatic dysfunction. For the purpose of scaling, data pertaining to albumin and α1-acid glycoprotein levels in response to differing degrees of hepatic impairment were systematically collected from 919 adult donors. The results of the present study demonstrate for the first time the feasibility of physiologically based scaling f_u in hepatic dysfunction after verifying with experimentally measured data of a wide variety of compounds from individuals with varying degrees of hepatic insufficiency. Furthermore, the high level of predictive accuracy indicates that the inter-relation between the severity of hepatic impairment and these plasma protein levels are physiologically accurate. The present study enhances the confidence in predicting f_u in hepatic insufficiency, particularly for albumin-bound drugs.     

Discovery of acylphloroglucinol-based meroterpenoid enantiomers as KSHV inhibitors from Hypericum japonicum

Kaposi''s sarcoma associated herpesvirus (KSHV) has gained considerable attention as a type of carcinogenic pathogen. Recent research suggests that KSHV has participated in the pathogenesis of Kaposi''s sarcoma-related malignant neoplastic diseases. Viral lytic infection might be pivotal for the etiopathogenesis of KSHV-induced diseases; however, most clinical KSHV lytic replication inhibitors like ganciclovir, nelfinavir, or cidofovir do not restrain virus replication effectively enough to achieve clinical efficacy. In our continued pharmaceutical studies on Chinese herbal medicines, new acylphloroglucinol-based meroterpenoid enantiomers have been discovered from Hypericum japonicum. Most of these metabolites have potential inhibitory activities that target KSHV lytic replication. Amongst these analogues, compounds 1a and 1b possess an unreported ring system cyclopenta[b]chromene. Compounds 1a with 4a exhibit stronger inhibitory activities towards the lytic replication of KSHV in Vero cells. In addition, 1a and 4a have IC₅₀ values of 8.30 and 4.90 μM and selectivity indexes of 23.49 and 25.70, respectively. Qualitative and quantitative SAR and molecular docking studies for acylphloroglucinol-based meroterpenoids with regard to anti-KSHV activity were conducted. An explanation for the variation in the activity and selectivity indexes was proposed in accordance with the predicted binding pose found with molecular docking to a putative target, thymidylate synthase (kTS). Compounds 1a and 4a have potential for further development and optimization of their anti-KSHV activities which could lead to new candidate drugs.

New enantiomers (1a/1b–4a/4b) were discovered from Hypericum japonicum. 1a/1b possessed a novel ring system cyclopenta[b]chromene. 1a and 4a exhibited promising anti-KSHV activities. QSAR studies for enantiomers on anti-KSHV activity were conducted.