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Relationship between polymorphisms in -572G/C interleukin 6 promoter gene polymorphisms (rs1800796) and risk of rheumatoid arthritis: A meta-analysis.
Get PDFAIMS(#br)This meta-analysis was aimed to investigate the association between -572G/C interleukin (IL)-6 gene polymorphism and occurrence risk of rheumatoid arthritis (RA).(#br)METHODS(#br)Literature search was conducted in PubMed, Embase, Springer and Google Scholar up to November 2018. The pooled odds ratios (ORs) and 95% confidence interval (CI) were calculated by Revman 5.3.(#br)RESULTS(#br)A total of six case-control studies were included in this meta-analysis. In the allele model (G vs C), homozygous gene model (GG vs CC), recessive gene model (GG vs GC + CC), and dominant gene model (GG + GC vs CC), the pooled estimate indicated there was significant association between -572G/C IL-6 gene polymorphism and risk of RA. However, no significant statistical results were found in meta-analyses of heterozygote gene models.(#br)CONCLUSIONS(#br)The -572G/C IL-6 gene polymorphism is associated with the risk of RA. The GG genotype may be the main contributor in increasing susceptibility to RA
The Modulatory Properties of Astragalus membranaceus Treatment on Triple-Negative Breast Cancer: An Integrated Pharmacological Method.
Get PDFBackground: Studies have shown that the natural products of Astragalus membranaceus (AM) can effectively interfere with a variety of cancers, but their mechanism of action on breast cancer remains unclear. Triple-negative breast cancer (TNBC) is associated with a severely poor prognosis due to its invasive phenotype and lack of biomarker-driven-targeted therapies. In this study, the potential mechanism of the target composition acting on TNBC was explored by integrated pharmacological models and in vitro experiments. Materials and Methods: Based on the Gene Expression Omnibus (GEO) database and the relational database of Traditional Chinese Medicines (TCMs), the drug and target components were initially screened to construct a common network module, and multiattribute analysis was then used to characterize the network and obtain key drug-target information. Furthermore, network topology analysis was used to characterize the betweenness and closeness of key hubs in the network. Molecular docking was used to evaluate the affinity between compounds and targets and obtain accurate combination models. Finally, in vitro experiments verified the key component targets. The cell counting kit-8 (CCK-8) assay, invasion assay, and flow cytometric analysis were used to assess cell viability, invasiveness, and apoptosis, respectively, after Astragalus polysaccharides (APS) intervention. We also performed western blot analysis of key proteins to probe the mechanisms of correlated signaling pathways. Results: We constructed "compound-target" (339 nodes and 695 edges) and "compound-disease" (414 nodes and 6458 edges) networks using interaction data. Topology analysis and molecular docking were used as secondary screens to identify key hubs of the network. Finally, the key component APS and biomarkers PIK3CG, AKT, and BCL2 were identified. The in vitro experimental results confirmed that APS can effectively inhibit TNBC cell activity, reduce invasion, promote apoptosis, and then counteract TNBC symptoms in a dose-dependent manner, most likely by inhibiting the PIK3CG/AKT/BCL2 pathway. Conclusion: This study provides a rational approach to discovering compounds with a polypharmacology-based therapeutic value. Our data established that APS intervenes with TNBC cell invasion, proliferation, and apoptosis via the PIK3CG/AKT/BCL2 pathway and could thus offer a promising therapeutic strategy for TNBC
Microarray‑based analysis of COL11A1 and TWIST1 as important differentially‑expressed pathogenic genes between left and right‑sided colon cancer.
Get PDFColonic cancer has become a main reason of mortality associated with cancer; however, left and right‑sided colonic cancer have diverse outcomes in terms of epidemiological, histological, clinical parameters and prognosis. We aimed to examine the discrepancies between these two types of colon cancers to identify potential therapeutic targets. In the present study, three gene expression profiles (GSE44076, GSE31595, GSE26906) from Gene Expression Omnibus (GEO) database were downloaded and further analyzed. A PPI (protein‑protein interaction) network of the differentially‑expressed genes (DEGs) of GSE44076 between tumor and normal was established with the Search Tool for the Retrieval of Interacting Genes database. Then, the DEGs of these two colon cancers (left, right) samples were identified. Subsequently, the intersection of DEGs of left and right‑sided colon cancer samples obtained from three databases, and DEGs of tumor and normal samples were analyzed. Collagen type XI α1 chain (COL11A1), Twist family bHLH transcription factor 1 (TWIST1), insulin‑like 5 and chromogranin A were upregulated proteins, while 3β‑hydroxysteroid dehydrogenase was downregulated protein in right colon cancer than in left‑sided tumor samples. Through further experimental verification, we revealed that COL11A1 and TWIST1 were significantly upregulated at the mRNA and protein levels within right‑sided colon cancer compared with in left‑sided colon cancer samples (P<0.05), consistent with bioinformatical analysis. Furthermore, a positive correlation between COL11A1 and TWIST1 protein expression was observed (P<0.0276). Collectively, our data showed that COL11A1 and TWIST1 may be potential prognostic indicators and molecular targets for the treatment of right‑sided colon cancer
Rapid detection and structural characterization of verapamil metabolites in rats by UPLC-MSE and UNIFI platform.
Get PDFHigh-resolution mass spectrometry (HRMS) is an important technology for studying biotransformations of drugs in biological systems. In order to process complex HRMS data, bioinformatics, including data-mining techniques for identifying drug metabolites from liquid chromatography/high-resolution mass spectrometry (LC/HRMS) or multistage mass spectrometry (MSn ) datasets as well as elucidating the detected metabolites’ structure by spectral interpretation software, are important tools. Data-mining technologies have widely been used in drug metabolite identification, including mass defect filters, product ion filters, neutral-loss filters, control sample comparisons and extracted ion chromatographic analysis. However, the metabolites identified by current different technologies are not the same, indicating the importance of technique integration for efficient and complete identification of metabolic products. In this study, a universal, high-throughput workflow for identifying and verifying metabolites by applying the drug metabolite identification software UNIFI is reported, to study the biotransformation of verapamil in rats. A total of 71 verapamil metabolites were found in rat plasma, urine and faeces, including two metabolites that have not been reported in the literature. Phase I metabolites of verapamil were identified as N-demethylation, O-demethylation, N-dealkylation and oxidation and dehydrogenation metabolites; phase II metabolites were mainly glucuronidation and sulfate conjugates, indicating that UNIFI software could be effective and valuable in identifying drug metabolites
86例静脉营养药物不良反应的临床分析
No full text静脉营养药物是为人体提供必须的营养支持,在维持患者生命体征及促进患者康复方面具有重要作用的一类药物。该类药物主要有葡萄糖、蛋白质、脂肪、维生素、微量元素等,不仅可提供饮食不足时的营养补充,也可作为唯一的营养来源,临床应用广泛[1]。由于成分复杂、稳定性差及配制难度大等原因,该类药物的药品不良反应（adverse drug reactions,ADRs）报道逐年增加。本研究回顾性分析联勤保障
大陆惠台政策成效评估的理论模型构建——以2009—2012年扩大对台采购政策为例
Get PDF惠台政策管理亟待实现由粗放到集约、由经验到科学的转变,政策成效的科学评估和针对问题治理的政策调整是促进这一转变的关键因素。本文在惠台政策目标特性及其关联因素分析基础上,借鉴弗兰克·费希尔(Frank Fischer)政策评估分析框架,并纳入侧面影响模型、用户导向模型、利益相关人模型等政策评估理论模型的核心思想,建构惠台政策评估的适用理论模型;进而运用该理论模型所提供的方法论工具,针对2009-2012年集中实施的扩大对台采购政策展开应用案例分析;最后引申探讨惠台政策运行的机制性问题。本文侧重相关理论和方法论探讨,旨在为惠台政策评估研究提供思路参照。2015年度国家社会科学基金一般项目“大陆惠台政策成效评估及策略调整研究”(15BJL102
SNX8 Enhances Non-amyloidogenic APP Trafficking and Attenuates Aβ Accumulation and Memory Deficits in an AD Mouse.
Get PDFDysregulation of various APP trafficking components in the endosome has been previously implicated in Alzheimer’s disease (AD). Although single nucleotide polymorphisms within the gene locus encoding the endosomal component, SNX8 have been previously associated with AD, how SNX8 levels are altered and its contribution to AD onset is currently unknown. Here, we observe decreased expression of SNX8 in human AD and AD mouse brain. SNX8 predominantly localized to early and late endosomes, where SNX8 overexpression enhanced total APP levels, cell surface APP distribution and consequent soluble APPα cleavage. SNX8 depletion resulted in elevated β-amyloid (Aβ) levels, while SNX8 overexpression reduced Aβ levels in cells and in an APP/PS1 AD mouse model. Importantly, SNX8 overexpression rescued cognitive impairment in APP/PS1 mice. Together, these results implicate a neuroprotective role for SNX8 in enhancing non-amyloidogenic APP trafficking and processing pathways. Given that endosomal dysfunction is an early event in AD, restoration of dysfunctional endosomal components such as SNX8 may be beneficial in future therapeutic strategies
Pharmacokinetics and Tissue Distribution of DVDMS-2 in Tumor-bearing Mice.
Get PDFDVDMS-2 is a novel candidate for photodynamic therapy of tumors. The purpose of the present study was to assess the distribution and elimination of DVDMS-2 in mice bearing hepatoma 22 tumors. DVDMS-2 (1, 2 and 4 mg kg-1 ) was injected intravenously into the mice, extracted from biological tissues and quantified using a fluorescence assay. The data obtained were processed with WinNonlin pharmacokinetic software. The fluorescence assay established for DVDMS-2 quantification was a rapid, reproducible, sensitive and specific method with good linearity. The pharmacokinetics of DVDMS-2 in tumor-bearing mice conformed to a two-compartment model. DVDMS-2 accumulated in tumor tissue to a greater extent than adjacent tissues (skin, muscle) and sustained a relatively high-level concentration 12 to 24 h following administration, which may be the optimal treatment time point. In conclusion, DVDMS-2 selectively accumulated in tumor tissue and was eliminated at a rapid rate in tumor-bearing mice, suggesting that DVDMS-2 may have few side effects, including skin phototoxicity. The present study established the pharmacokinetic characteristics of DVDMS-2, which may be beneficial in future clinical study
临床药师干预对提高辅助用药应用合理性的作用研究
Get PDF目的分析临床药师干预对提高辅助用药应用合理性的作用。方法回顾分析2018年1-12月医院普外科、骨外科、内科、产科、妇科等所收治470例患者的辅助用药资料,由医院临床药师对于辅助用药资料进行专项点评以及巡查,分析临床药师干预对提高辅助用药应用合理性的作用。结果经研究统计发现,470例患者的辅助用药医嘱数量为864份,依据《新编药物学》的分类方法统计分析辅助用药情况发现:医院所应用范围最为广泛的药物包括肠内营养乳剂、脂肪乳(10%)氨基酸(15)葡萄糖(20%)注射液、脂肪乳氨基酸(17)葡萄糖(11%)注射液、多种微量元素注射液(Ⅱ)、脂溶性维生素注射液(Ⅱ)、注射用水溶性维生素、匹多莫德颗粒、奥拉西坦注射液、丹参川芎嗪注射液、参芎葡萄糖注射液、丹红注射液、参麦注射液、丹参注射液、依达拉奉注射液以及注射用鼠神经生长因子。依据数据统计发现,不合理用药的情况主要包括超说明书用法用量、适应证不适宜、联合用药不适宜、溶媒选择不适宜、用药疗程延长、药物配伍不当以及使用未注意用药禁忌证。经临床药师干预后,医院不合理用药情况均有所降低,有效提高了辅助用药的合理性。864份辅助用药数量分别来自普外科、骨外科、神经外科、内科、妇科、产科、儿科、新生儿科。结论在临床辅助用药中,对于辅助用药实施审核评价,应保持客观依据,通过对临床药师进行干预,可提高辅助用药应用合理性,有利于辅助用药风险性的降低
当前台湾岛内“台独”势力的组织发展研究
Get PDF台独是影响祖国和平统一的主要障碍,"台独"组织是其组织化的表现形式,"台独"组织的发展现状和趋势也影响着祖国和平统一进程的走向。"台独"组织历经了起源、海外和"解严"后三个时期的发展,形成了一种多样化多面向的发展格局。当前岛内各"台独"组织之间围绕着特定的政党、特定的个人和特定的活动及议题形成了不同的组织群体,呈现出形式多样、相互整合;人员混杂、重叠交错;内部无援、外部勾连的特点。但是受到岛内外各种因素的影响,"台独"组织的发展陷入了困境,最终走向衰落的趋势难以避免。厦门市人文社科基地调研课题资助重点项目“民进党重返执政后‘台独风险’研究”(项目号:K5419001)的阶段性成