Inhibition of Bacterial Adherence on the Surface of Stents and Bacterial Growth in Bile by Bismuth Dimercaprol

Bacterial infection and biofilm formation on the surface of biliary stents is believed to be one of the main factors in stent occlusion. This study explored the role of the new reagent, bismuth dimercaprol, in preventing bacterial adherence and bacterial biofilm formation on the surface of biliary stents. Sterile porcine bile preparations, infected separately with Escherichia coli, Klebsiella pneumoniae, Enterobacter, and Enterococcus, were used as the perfusion media in an in vitro perfusion system. The bacterial growth in the media and the bacterial adherence on the surface of stents were tested when different concentrations of bismuth dimercaprol were used in the perfusion media. BisBAL (5 μ M) did not inhibit the growth of any of the tested bacterial species. It did, however, significantly decrease the amount of bacteria adhering to the surface of stents for all bacterial strains except Escherichia coli. Bismuth dimercaprol (20 μ M) significantly inhibited the growth of Escherichia coli, Klebsiella pneumoniae, and Enterobacter and, thereby, significantly decreased the amount of these bacteria adhering to the surface of stents. The unique bactericidal and anitbiofilm activities of bismuth thiols might contribute to delaying the process of biliary stent occlusion if the effective concentrations of bismuth thiols could be delivered to the target sites. The feasibility of this application of bismuth thiols deserves further investigation.     

L-3-n-butylphthalide protects against vascular dementia via activation of the Akt kinase pathway

As a neuroprotective drug for the treatment of ischemic stroke, 3-n-butylphthalide, a celery seed ex- tract, has been approved by the State Food and Drug Administration of China as a clinical therapeutic drug for ischemic stroke patients. L-3-n-butylphthalide possesses significant efficacy in the treatment of acute ischemic stroke. The activated Akt kinase pathway can prevent the death of nerve cells and exhibit neuroprotective effects in the brain after stroke. This study provides the hypothesis that I-3-n- butylphthalide has a certain therapeutic effect on vascular dementia, and its mechanism depends on the activation of the Akt kinase pathway. A vascular dementia mouse model was established by cere- bral repetitive ischemia/reperfusion, and intragastrically administered I-3-n-butylphthalide daily for 28 consecutive days after ischemia/repedusion, or 7 consecutive days before ischemia/reperfusion. The Morris water maze test showed significant impairment of spatial learning and memory at 4 weeks after operation, but intragastric administration of I-3-n-butylphthalide, especially pretreatment with I-3-n- butylphthalide, significantly reversed these changes. Thionine staining and western blot analylsis showed that preventive and therapeutic application of I-3-n-butylphthalide can reduce loss of pyrami- dal neurons in the hippocampal CA1 region and alleviate nerve damage in mice with vascular demen- tia. In addition, phosphorylated Akt expression in hippocampal tissue increased significantly after I-3-n- butylphthalide treatment. Experimental findings demonstrate that I-3-n-butylphthalide has preventive and therapeutic effects on vascular dementia, and its mechanism may be mediated by upregulation of phosphorylated Akt in the hippocampus.     

Molecular cloning, characterization and expression profiles of three estrogen receptors in protogynous hermaphroditic orange-spotted grouper (Epinephelus coioides)

Estrogen plays key roles in vertebrate reproductive system via estrogen receptors (ERs) as mediating pathways. In the present study, three full-length ERs cDNA sequences were isolated from a protogynous teleost, the orange-spotted grouper (Epinephelus coioides), and were 2235 bp for gERα, 1967 bp for gERβ1 and 2158 bp for gERβ2, respectively. Phylogenetic and amino acid alignment analyses showed that each gER was clustered in the corresponding taxonomic groups of the perciformes and exhibited high evolutional conservation in functional domains. RT-PCR revealed that gERs expressed at different levels in all the obtained tissues. gERα highly expressed in mature ovaries, gERβ1 mainly expressed in immature ovaries and gERβ2 varied greatly during ovarian development. During female to male sex reversal induced by 17α-methyltestosterone (MT) implantation, gERα decreased gradually, gERβ1 increased gradually, and gERβ2 decreased firstly and recovered subsequently in male stage. The present study speculated the potential roles of gERs during female maturation and female to male sex reversal induced by MT in the protogynous grouper E. coioides.     

Analysis of plasma trough level of imatinib in Chinese CML patients

OBJECTIVE: To evaluate the relationship between plasma trough level of imatinib and clinical outcomes in Chinese CML patients. Methods Plasma trough levels in 416 CML patients who received imatinib orally in six general hospitals were assessed. The correlations of imatinib plasma trough level with baseline characteristics including age, weight and BSA, and clinical response were evaluated. RESULTS: (1) Effects of age, body weight and BSA on imatinib plasma trough levels were not to be clinically significant. (2) Median imatinib plasma trough levels was 1271 (109-4329). Imatinib plasma trough level was related to dose of imatinib administration. Plasma trough levels at imatinib of dose < 400, 400 and > 400 mg were (969 ± 585), (1341 ± 595) and (1740 ± 748) μg/L (P < 0.01), respectively. (3) There was no statistic difference in imatinib plasma trough level with complete cytogenetic response [CCyR (1337 ± 571) μg/L vs no CCyR (1354 ± 689) μg/L, P = 0.255]. (4) Imatinib plasma trough level might be important for a good clinical response in some CML patients. Conclusion There was a large interpatient variability in imatinib plasma concentration in Chinese CML patients. No correlation of imatinib plasma trough level with CCyR was observed. However, higher doses of imatinib were shown to attain greater trough plasma concentration, suggesting that imatinib plasma trough level might be important for a good clinical response in some CML patients.     

基于系统复杂性的中医药临床研究方法学探析

根据中医药临床研究方法存在的问题,从系统复杂性研究视角,提出中医药临床研究相似诊疗环节识别的"案例推理"模式;同时在中医药临床诊疗过程中开展多维度、多信息源关联映射的"中医诊疗小数据"建模研究,探求不同疾病、不同诊疗体系下中医临床疗效评价指标体系的可能性新路径,为后续相关研究作出提示。     

案例推理对中医临床案例研究的认识和启示

中医医案作为专家经验的载体,对指导中医临床实践、提升中医学者临证水平具有重要意义,人工智能领域案例推理技术有望弥补现有中医医案研究情境化特征缺失的遗憾.但由于不同类型的中医医案研究要点不同,因此,本文通过分析中医医案的分类、特点及研究现状,并通过考察案例推理的理论内涵及在中医医案方向的应用现状,探讨案例推理对中医临床案...     

龟羚帕安胶囊治疗帕金森病多中心、随机、双盲、对照临床研究

目的 客观评价中药龟羚帕安胶囊治疗帕金森病的临床疗效。     

黄芩苷金属离子配合物药效学作用概述

近年来，针对中药黄芩的研究持续升温，国内外学者就黄苓的药理作用在整体、系统、器官、细胞、分子、基因水平上作了大量研究，而且多以黄苓活性成分提取为基础，针对某一特定成分及其变体的药理作用进行研究，研究结果显示黄苓活性成分的药效作用主要体现在抗炎、抗菌、抗病毒、抗氧化、清除自由基、调节细胞凋亡等方面。本文拟从黄苓成分中具有代表性的黄苓苷入手，介绍国内外针对其药效学作用的研究概况，为黄芩的进一步研究提供参考。     

Locating a blood pressure quantitative trait locus within 117 kb on the rat genome: substitution mapping and renal expression analysis

Previously, a blood pressure (BP) quantitative trait locus (QTL) on rat chromosome 9 (RNO9) was localized to a <2.4 cM interval using congenic strains generated by introgressing segments of RNO9 from the Dahl salt-resistant (R) rat into the background of the Dahl salt-sensitive (S) rat. Renal gene expression using Affymetrix gene chips was profiled on S and a congenic strain spanning the 2.4-cM BP QTL interval. This analysis identified 20 differentially expressed genes/expressed sequence tags. Of these, the locus with the greatest differential expression (30- to 35-fold) was regulated endocrine-specific protein 18 (Resp18), which also mapped in the 2.4-cM BP QTL interval. Additional substitution mapping located the QTL to <0.4 cM or approximately 493 kb. This newly defined QTL region still included Resp18. Nucleotide variants were identified between S and R genomic DNA of Resp18 in the coding, 5' regulatory and 3' untranslated regions. The coding sequence variation (T/C) occurs in exon 2 and predicts an amino acid change (Ile/Val) in the protein product. Resp18 was considered a differentially expressed positional candidate for the QTL. To fine-map the BP QTL, we constructed a congenic strain with a smaller introgressed region. Compared with the S rat, this strain (1) had significantly lower BP, (2) did not contain the R form of Resp18, and (3) did not retain the rather spectacular differential expression of Resp18. Together, these results demonstrate that a BP QTL independent of Resp18 exists within the newly defined 117-kb QTL region on RNO9.     

miR-194 is a marker of hepatic epithelial cells and suppresses metastasis of liver cancer cells in mice

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by interacting with the 3' untranslated region (3'-UTR) of multiple mRNAs. Recent studies have linked miRNAs to the development of cancer metastasis. In this study, we show that miR-194 is specifically expressed in the human gastrointestinal tract and kidney. Moreover, miR-194 is highly expressed in hepatic epithelial cells, but not in Kupffer cells or hepatic stellate cells, two types of mesenchymal cells in the liver. miR-194 expression was decreased in hepatocytes cultured in vitro, which had undergone a dedifferentiation process. Furthermore, expression of miR-194 was low in liver mesenchymal-like cancer cell lines. The overexpression of miR-194 in liver mesenchymal-like cancer cells reduced the expression of the mesenchymal cell marker N-cadherin and suppressed invasion and migration of the mesenchymal-like cancer cells both in vitro and in vivo. We further demonstrated that miR-194 targeted the 3'-UTRs of several genes that were involved in epithelial-mesenchymal transition and cancer metastasis. Conclusion: These results support a role of miR-194, which is specifically expressed in liver parenchymal cells, in preventing liver cancer cell metastasis.