Stilbenes and oligostilbenes from leaf and stem of <Emphasis Type="Italic">Vitis amurensis</Emphasis> and their cytotoxic activity

Chromatographic separation of the EtOAc fraction from the leaf and stem of Vitis amurensis led to the isolation of six oligostilbenoids (i.e., r-2-viniferin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), gnetin H (4), amurensin G (5), (+)-ampelopsin A (8)) and four stilbenoids (i.e., trans-resveratrol (6), (+)-ampelopsin F (7), piceatannol (9), and trans-piceid (10)). The structures have been identified on the basis of spectroscopic evidence and physicochemical properties. The isolates were investigated for cytotoxic activity against three cancer cell lines in vitro using the MTT assay method. Amurensin G (5) and trans-resveratrol (6) showed significant cytotoxic activity against L1210, K562 and HTC116 cancer cell lines with IC₅₀ values ranging from 15.7 ± 2.1 to 30.9 ± 1.8 μM. (+)-Ampelopsin A (8) and trans-piceid (10) exhibited considerable cytotoxic activity against L1210 (IC₅₀ values of 30.6 ± 4.1 and 28.7 ± 2.81 μM, respectively) and K562 (IC₅₀ values of 38.6 ± 0.82 and 24.6 ± 0.76 μM, respectively). Gnetin H (4) showed only weak cytotoxic activity against L1210 with an IC₅₀ value of 40.1 ± 4.23 μM. On the other hand, r-2-viniverin (1), trans-amurensin B (2), trans-ɛ-viniferin (3), (+)-ampelopsin F (7), and piceatannol (9) exhibited no activity on three cancer cell lines.     

Avermectins菌丝提取液的分析与主要成分的分离富集

采用高效液相色谱（HPLC）-紫外检测（UVD）／蒸发光散射检测（ELSD）的方法分析avermectins菌丝提取液，发现主要成分为具有紫外吸收和无紫外吸收的物质。利用硅胶吸附柱层析方法分离富集了其中的主要成分。对几种有紫外吸收的组分（A1a、A2a、B1a、B2a）进行了核磁共振（NMR）分析，根据异核单量子相干谱（HSQC）对所有的^13C—NMR和^1H—NMR谱带进行了归属。鉴定了无紫外吸收的物质中含有糖类物质。     

Puerarin activates endothelial nitric oxide synthase through estrogen receptor-dependent PI3-kinase and calcium-dependent AMP-activated protein kinase

The cardioprotective properties of puerarin, a natural product, have been attributed to the endothelial nitric oxide synthase (eNOS)-mediated production of nitric oxide (NO) in EA.hy926 endothelial cells. However, the mechanism by which puerarin activates eNOS remains unclear. In this study, we sought to identify the intracellular pathways underlying eNOS activation by puerarin. Puerarin induced the activating phosphorylation of eNOS on Ser1177 and the production of NO in EA.hy926 cells. Puerarin-induced eNOS phosphorylation required estrogen receptor (ER)-mediated phosphatidylinositol 3-kinase (PI3K)/Akt signaling and was reversed by AMP-activated protein kinase (AMPK) and calcium/calmodulin-dependent kinase II (CaMKII) inhibition. Importantly, puerarin inhibited the adhesion of tumor necrosis factor (TNF)-α-stimulated monocytes to endothelial cells and suppressed the TNF-α induced expression of intercellular cell adhesion molecule-1. Puerarin also inhibited the TNF-α-induced nuclear factor-κB activation, which was attenuated by pretreatment with N^G-nitro-l-arginine methyl ester, a NOS inhibitor. These results indicate that puerarin stimulates eNOS phosphorylation and NO production via activation of an estrogen receptor-mediated PI3K/Akt- and CaMKII/AMPK-dependent pathway. Puerarin may be useful for the treatment or prevention of endothelial dysfunction associated with diabetes and cardiovascular disease.     

Effects of hypocrellin A on expression of vascular endothelial growth factor and endothelin-1 in human umbilical endothelial cells

Increased endothelin-1 (ET-1), vascular endothelial growth factor (VEGF) and activation of protein kinase C (PKC) are co-contributors to endothelial hyperpermeability in diabetes. Several lines of evidence have suggested a hypothesis that activation of specific PKC isoforms are the causative factor in ET-1 and VEGF mediated endothelial dysfunction. In the present study, we tested this hypothesis with hypocrellin A, a naturally occurring PKC inhibitor from a Chinese plant. Human umbilical vein endothelial cells (HUVECs) were incubated with 20 mM glucose in both the presence and absence of hypocrellin A, after which, the protein expression and release of VEGF and mRNA expression and release of ET-1 were measured. VEGF and ET-1 were released into the medium and expressions of VEGF protein and ET-1 mRNA were significantly increased in HUVECs incubated with 20 mM glucose. Hypocrellin A (150 nM) significantly decreased VEGF release (117 +/- 3 vs. 180 +/- 11 pg/mg, p < 0.05) and VEGF protein expression (from 130 +/- 14% to 88 +/- 18.5%, p < 0.05). ET-1 release was also reduced in hypocrellin A treated HUVECs (63.3 +/- 9.9 vs. 75.2 +/- 12.6 ng/mg). Hypocrellin A significantly reversed the effect of high glucose on ET-1 mRNA expression (p < 0.05). The results revealed that PKC activation plays a pivotal role in VEGF and ET-1 mediated endothelial permeability. The naturally occurring compound hypocrellin A may be a potentially novel treatment for endothelial dysfunction in diabetes.     

右美托咪定对正颌患者术后恢复的影响

目的 观察应用右美托咪定对正颌患者术后恢复的影响.方法 选择40例正颌患者,随机分成右美托咪定组（A组）和安慰剂组（B组）,A组给予负荷剂量1 μg/kg（20 min）的右美托咪定,后0.5μg/（kg·h）泵注,B组则给予容量和外形相似的0.9％氯化钠注射液.手术结束前20 min左右停药,观察患者的术后恢复情况及血气分析结果变化.结果 A组的睁眼、气管拔管时间均比B组相比明显缩短（P＜0.05）;与术前相比两组患者在气管拔管后,PaO2和pH明显降低（P＜0.05）,PaCO2明显升高（P＜0.05）,B组PaO2下降更显著（P＜0.05）.结论 联合应用右美托咪定可缩短正颌患者的术后恢复时间,并改善氧合功能.     

某三甲医院实施抗菌药物临床应用专项整治前后应用情况比较

目的 评价专项整治活动开展前后抗菌药物临床应用情况.方法 收集该院抗菌药物专项整治前,即2010年1月至2011年6月抗菌药物使用相关数据;与整治后2011年7月至2013年8月抗菌药物使用相关数据进行统计分析.结果 （1）实施专项整治后,该院抗菌药物使用日趋合理.监测指标中,住院患者抗菌药物使用率、抗菌药物使用强度、Ⅰ类切口抗菌药物预防使用率、外科手术预防使用抗菌药物时间在0.5～2h符合率及Ⅰ类切口手术预防用药疗程符合率整治前后差异有统计学意义（P＜0.05）.（2）该院铜绿假单胞菌和金黄色葡萄球菌耐药率在抗菌药物专项整治前后,经W检验差异有统计学意义（P＜0.05）.结论 抗菌药物专项整治非常有必要,通过专项整治,抗菌药物的使用更加合理.     

HPLC方法研究葛根素混合胶束在Beagle犬体内的药代动力学(英文)

采用高效液相色谱法测定Beagle犬口服葛根素原料药及自制葛根素混合胶束后葛根素的血药浓度, 并计算其药代动力学参数, 比较两者的生物利用度。Beagle犬随机分为两组, 采用单剂量灌胃给予葛根素原料药与葛根素混合胶束, 于不同的时间点取血并用HPLC法测定葛根素的血浆药物浓度。HPLC条件: 色谱柱为DIKMA ODS C18柱 (150 mm×4.6 mm, 5 μm), 保护柱为DIKMA ODS C18柱 (8 mm×4 mm); 流动相甲醇-水 (25:75, v/v); 柱温30 °C; 流速1 mL/min; 检测波长250 nm, 内标物为茶碱。采用WinNonlin 6.1软件求算药代动力学参数。葛根素原料药与葛根素混合胶束在Beagle犬体内的药物动力学参数Tmax分别为61.48和202.91 min, AUC分别为515.96和2796.43 min·μg/mL, CL/F分别为232.58和42.91 mL/min/kg。Beagle犬口服葛根素混合胶束与葛根素原料药的相对生物利用度为542.0%。混合胶束制剂明显提高了葛根素在Beagle犬体内的生物利用度, 且减缓消除速率, 延长达峰时间, 起到了长效、缓效的作用。     

卡培他滨联合顺铂治疗晚期乳腺癌的临床研究

目的 探讨卡培他滨联合顺铂治疗蒽环类及紫杉类耐药的晚期乳腺癌的临床效果.方法 选取解放军第三二三医院肿瘤中心的19例蒽环类及紫杉类耐药的晚期乳腺癌患者,给予卡培他滨联合顺铂治疗,21 d为1个周期,所有患者均治疗2个周期以上,观察临床疗效及不良反应.结果 19例患者中完全缓解1例,部分缓解9例,稳定6例,进展3例,总有效率为52.6％.中位无疾病进展生存期6.0个月（95％CI：4.4 ～7.6个月）,中位生存期15.0个月（95％ CI：13.0 ～ 16.9个月）.主要的毒性反应有骨髓抑制、乏力、胃肠道反应及手足综合征等,为可逆性,无治疗相关死亡.结论 卡培他滨联合顺铂疗效较好,毒性反应可耐受,可作为蒽环类及紫杉类耐药的晚期乳腺癌患者的治疗选择.     

DRR1对小鼠神经干细胞分化以及神经元突起形成的影响

目的:本研究旨在阐明肾细胞癌下调蛋白1(DRR1)在小鼠大脑组织中的表达谱及相关生物学功能.方法:首先,通过real time RT-PCR的方法明确在不同发育阶段的小鼠大脑组织中DRR1的表达水平;利用免疫荧光染色法检测DRR1在原代培养的神经干细胞以及神经元中的表达情况.其次,采用real time RT-PCR的...