γ-闪烁示踪法确定单硝酸异山梨酯脉冲片在人体内崩解释药情况的研究

目的:研究单硝酸异山梨酯脉冲片的体内过程.方法:以99mT为标记物,利用γ-闪烁示踪显像技术(γ-sicintigraphy)对单硝酸异山梨酯脉冲片在人体消化道不同释药部位进行跟踪检测.结果:单硝酸异山梨酯脉冲片在3名健康志愿者胃肠道内的起崩部位为胃或小肠,起崩时间为3～4 h,完全崩解部位均在升结肠或横结肠,时间约为6～8 h.结论:单硝酸异山梨酯脉冲片在人体胃肠道内具有定时定位的释药效果,达到预期的设计目的.     

鹅掌藤中三萜类化合物的分离与鉴定

目的研究五加科鹅掌柴属植物鹅掌藤(Schefflera arboricola)枝茎的化学成分.方法采用柱色谱分离,通过理化数据和光谱分析确定化合物的结构.结果从鹅掌藤乙酸乙酯提取物中分离得到7个三萜化合物,分别鉴定为羽扇醇(1)、桦木酸(2)、3-epi-betulinic acid(3)、齐墩果酸(4)、3-乙酰齐墩果酸(5)、mesembryanthemoidigenic acid(6)、quinatic acid(7).结论化合物1、5、6、7为首次从该属植物中分得.     

Gatifloxacin inducing apoptosis of stromal fibroblasts through cross-talk between caspase-dependent extrinsic and intrinsic pathways

AIM: To reveal the cytotoxicity and related mechanisms of gatifloxacin (GFX) to stromal fibroblasts (SFs) in vitro. METHODS: SFs were treated with GFX at different concentrations (0.009375%-0.3%), and their viability was detected by MTT method. The cell morphology was observed using light/transmission electron microscope. The plasma membrane permeability was measured by AO/EB double-staining. Then cell cycle, phosphatidylserine (PS) externalization, and mitochondrial transmembrane potential (MTP) were analyzed by flow cytometry. DNA damage was analyzed by electrophoresis and immunostaining. ELISA was used to evaluate the caspase-3/-8/-9 activation. Finally, Western blotting was applied for detecting the expressions of apoptosis-related proteins. RESULTS: Morphological changes and reduced viability of GFX-treated SFs demonstrated that GFX above 0.009375% had cytotoxicity to SFs with dependence of concentration and time. GFX-treating cells also showed G1 phase arrest, increased membrane permeability, PS externalization and DNA damage, which indicated that GFX induced apoptosis of SFs. Additionally, GFX could activate the caspase-8, caspase-9, and caspase-3, induce MTP disruption, downregulate B-cell leukemia-2 (Bcl-2) and B-cell leukemia-XL (Bcl-XL), and upregulate Bcl-2 assaciated X protein (Bax), Bcl-2-associated death promoter (Bad), Bcl-2 interacting domain (Bid) and cytoplasmic cytochrome C in SFs, suggesting that caspase-dependent extrinsic and intrinsic pathways were related to GFX-contributed apoptosis of SFs. CONCLUSION: The cytotoxicity of GFX induces apoptosis of SFs through triggering the caspase-dependent extrinsic and intrinsic pathways.     

补虚逐瘀法联合针灸对冠心病便秘患者心脏不良事件的影响

目的:观察补虚逐瘀法联合针灸对冠心病便秘患者心脏不良事件的影响。方法:选取2014年9月至2016年10月辽宁中医药大学附属第三医院收治的冠心病便秘患者100例,进行回顾性研究,按治疗方式的不同分成联合组(n=56)和单针组(n=44),2组均给予冠心病常规治疗药物,单针组仅给予穴位针灸,联合组在单针组的基础加服补虚逐瘀汤,记录和比较2组的患者便秘情况的临床疗效、心电图疗效及心脏不良事件次数。结果:治疗后,联合组在心脏不良事件发生率(1.79%)的比较明显少于单针组(15.90%)(P0.05),联合组的心电图疗效(92.86%)优于单针组(68.18%)(P0.05)但2组在便秘情况临床疗效的差异无统计学意义(P0.05).结论:实施补虚逐瘀法联合针灸对冠心病便秘患者的治疗上,可明显改善患者心功能,有效减少患者排便时心脏不良事件的发生率,值得临床推广。     

Hyperpolarized [1,4‐13C]‐diethylsuccinate: a potential DNP substrate for in vivo metabolic imaging

The tricarboxylic acid (TCA) cycle performs an essential role in the regulation of energy and metabolism, and deficiencies in this pathway are commonly correlated with various diseases. However, the development of non‐invasive techniques for the assessment of the cycle in vivo has remained challenging. In this work, the applicability of a novel imaging agent, [1,4‐¹³C]‐diethylsuccinate, for hyperpolarized ¹³C metabolic imaging of the TCA cycle was explored. In vivo spectroscopic studies were conducted in conjunction with in vitro analyses to determine the metabolic fate of the imaging agent. Contrary to previous reports (Zacharias NM et al. J. Am. Chem. Soc. 2012; 134: 934–943), [¹³C]‐labeled diethylsuccinate was primarily metabolized to succinate‐derived products not originating from TCA cycle metabolism. These results illustrate potential issues of utilizing dialkyl ester analogs of TCA cycle intermediates as molecular probes for hyperpolarized ¹³C metabolic imaging. Copyright © 2014 John Wiley & Sons, Ltd.     

Determination of plasma antiglycan autoantibodies in patients with IgA nephropathy and the correlation with clinical characteristics

Objective To establish the measurement of IgA1 O-glycan-specific antiglycan autoantibodies in patients with IgA nephropathy (IgAN), and evaluate their role in the development and progression of IgAN. Methods In the IgAN regular follow-up cohort of Peking University Institute of Nephrology from January 2006 to December 2015, 170 patients drawn by stratified randomization were enrolled in this study. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of plasma galactose-deficient IgA1 (Gd-IgA1) and antiglycan autoantibody (IgG and IgA1). The correlation between antiglycan autoantibodies and clinicopathological parameters was analyzed by linear correlation and multiple linear regression analysis. The receiver operating characteristic curve (ROC) was used to evaluate the value of plasma anti glycide antibodies in the diagnosis of IgAN. Results IgG and IgA1 antiglycan autoantibodies that specifically recognized Fab-hinge region (Fab-HR) antigens could be detected in both IgAN and healthy control group. Agglutinin inhibition test showed that the specific antigen epitope was N-acetylgalactosamine (GalNAc) residue exposed to galactose deficiency in IgA1 hinged region. There was no significant difference in the absolute levels of plasma IgG antiglycan autoantibodies between IgAN and healthy controls (P=0.963). After adjustment of the plasma level of IgG, the normalized antiglycan autoantibody (ln[IgG antiglycan antibody/IgG]) in patients with IgAN was significantly higher than that in healthy controls (0.58±0.31 vs 0.37±0.11, P﹤0.01). The normalized level of IgG antiglycan autoantibody in IgAN patients was positively correlated with 24 h urine protein level during renal biopsy (Spearman r=0.183, P﹤0.05), and was also significantly correlated with 24 h urinary protein level after adjusting for baseline clinical and pathological factors (β=0.713, 95%CI 0.323-1.102, P﹤0.01). The area under ROC curve (AUC) of normalized IgG antiglycan autoantibody in the diagnosis of IgAN was 0.764 (95% CI 0.682-0.845, P﹤0.05). Using the cut-off value of 0.396, the sensitivity and specificity of normalized IgG antiglycan autoantibody for IgAN were 0.729 and 0.700 respectively. There was no significant difference in the absolute or normalized levels of IgA1 antiglycan autoantibodies between IgAN patients and healthy controls. Conclusions Gd-IgA1-specific antiglycan autoantibodies can be detected both in IgAN patients and healthy controls. They are elevated in some patients with IgAN and possibly involved in the development of IgAN.