覆膜支架腔内修复术与药物保守治疗对Stanford B型主动脉夹层动脉瘤患者肝肾功能、炎性因子以及预后的影响

目的:比较覆膜支架腔内修复术与药物保守治疗对Standford B型主动脉夹层动脉瘤的疗效及对患者肝肾功能、炎性因子及预后的影响。方法:选择2012年1月～2014年8月我院收治的Standford B型主动脉夹层动脉瘤患者68例,按照随机数字表法分为对照组与研究组,各34例。对照组入院后采取药物保守治疗,研究组应用覆膜支架腔内修复术治疗。观察两组住院期间死亡率、再次手术或介入率以及治疗前、治疗2周后肝肾功能、血清炎性因子变化。所有患者随访36个月,比较两组患者预后情况。结果:研究组再次手术或介入率为2.94%,低于对照组的22.58%(P0.05)。治疗2周后,研究组丙氨酸转氨酶(ALT)、天门冬氨酸氨基转移酶(AST)、尿素氮(BUN)、肌酐(Cr)、胱抑素C、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、γ-干扰素(INF-γ)、C反应蛋白(CRP)水平较治疗前降低(P0.05),且研究组低于对照组(P0.05)。两组患者均随访36个月,随访12个月时两组患者生存率分别为100.00%和80.65%,随访36个月时两组患者生存率分别为91.18%和29.03%,经Log Rank分析显示,两组生存率比较差异有统计学意义(P0.05)。结论:覆膜支架腔内修复术治疗Standford B型主动脉夹层动脉瘤的疗效确切,能够改善患者肝肾功能,降低炎症反应,患者近中期随访生存率较高,其效果优于保守治疗。     

Photoluminescence imaging of europium (III)‐doped γ‐Al2O3 nanofiber structures

Aluminium oxide (Al₂O₃) has widely been used for catalysts, insulators, and composite materials for diverse applications. Herein, we demonstrated if γ‐Al₂O₃ was useful as a luminescence support material for europium (Eu) (III) activator ion. The hydrothermal method and post‐thermal treatment at 800°C were employed to synthesize Eu(III)‐doped γ‐Al₂O₃ nanofibre structures. Luminescence characteristics of Eu(III) ions in Al₂O₃ matrix were fully understood by taking 2D and 3D‐photoluminescence imaging profiles. Various sharp emissions between 580 to 720 nm were assigned to the ⁵D₀→⁷F_J (J = 0, 1, 2, 3, 4) transitions of Eu(III) activators. On the basis of X‐ray diffraction crystallography, Auger elemental mapping and the asymmetry ratio, Eu(III) ions were found to be well doped into the γ‐Al₂O₃ matrix at a low (1 mol%) doping level. A broad emission at 460 nm was substantially increased upon higher (2 mol%) Eu(III) doping due to defect creation. The first 3D photoluminescence imaging profiles highlight detailed understanding of emission characteristics of Eu(III) ions in Al oxide‐based phosphor materials and their potential applications.     

Development of a risk scoring system for patients with papillary thyroid cancer

As the importance of personalized therapeutics in aggressive papillary thyroid cancer (PTC) increases, accurate risk stratification is required. To develop a novel prognostic scoring system for patients with PTC (n = 455), we used mRNA expression and clinical data from The Cancer Genome Atlas. We performed variable selection using Network‐Regularized high‐dimensional Cox‐regression with gene network from pathway databases. The risk score was calculated using a linear combination of regression coefficients and mRNA expressions. The risk score and clinical variables were assessed by several survival analyses. The risk score showed high discriminatory power for the prediction of event‐free survival as well as the presence of metastasis. In multivariate analysis, the risk score and presence of metastasis were significant risk factors among the clinical variables that were examined together. In the current study, we developed a risk scoring system that will help to identify suitable therapeutic options for PTC.     

Anticancer activity of paroxetine in human colon cancer cells: Involvement of MET and ERBB3

The concept of drug repositioning has recently received considerable attention in the field of oncology. In the present study, we propose that paroxetine can be used as a potent anticancer drug. Paroxetine, one of the selective serotonin reuptake inhibitors (SSRIs), has been widely prescribed for the treatment of depression and anxiety disorders. Recently, SSRIs have been reported to have anticancer activity in various types of cancer cells; however, the underlying mechanisms of their action are not yet known. In this study, we investigated the potential anticancer effect of paroxetine in human colorectal cancer cells, HCT116 and HT‐29. Treatment with paroxetine reduced cell viability, which was associated with marked increase in apoptosis, in both the cell lines. Also, paroxetine effectively inhibited colony formation and 3D spheroid formation. We speculated that the mode of action of paroxetine might be through the inhibition of two major receptor tyrosine kinases – MET and ERBB3 – leading to the suppression of AKT, ERK and p38 activation and induction of JNK and caspase‐3 pathways. Moreover, in vivo experiments revealed that treatment of athymic nude mice bearing HT‐29 cells with paroxetine remarkably suppressed tumour growth. In conclusion, paroxetine is a potential therapeutic option for patients with colorectal cancer.     

藏区金腰种质资源调查与分析

金腰属植物因富含黄酮醇类化合物而具有显著的药效,通过对我国西藏、云南、四川、青海以及甘肃5个省(自治区)进行金腰属植物种质资源的科学考察,共收集到19种(含2变种)145份野生种质资源。此外四川省发现金腰新分布2种,分别为秦岭金腰(Chrysosplenium biondianum Engl.)、陕甘金腰(Chrysosplenium qinlingense Z.P.Jien&J.T.Pan),均为中国特有种;甘肃省发现金腰新分布3种,分别为毛金腰(Chrysosplenium pilosum Maxim.)、绵毛金腰(Chrysosplenium lanuginosum Hook.f.&Thomson)和蜕叶金腰(Chrysosplenium henryi Franch.),凭证标本存于中南民族大学植物标本馆(HSN)。金腰属植物作为传统藏药长期以来被用于治疗各种疾病,如长梗金腰(Chrysosplenium axillare Maxim.)的75%乙醇提取物具抗炎症、抗流感病毒活性,从灰花金腰(Chrysosplenium grayanum Maxim.)与裸茎金腰(Chrysosplenium nudicaule Bunge)提取的五环三萜对肿瘤细胞有较强抑制效果。本调查丰富了野生藏药金腰属植物种质资源,为深入研究金腰属植物的分类与药理活性提供了基础。     

Structural hybridization of pyrrolidine-based T-type calcium channel inhibitors and exploration of their analgesic effects in a neuropathic pain model

Highly effective and safe drugs for the treatment of neuropathic pain are urgently required and it was shown that blocking T-type calcium channels can be a promising strategy for drug development for neuropathic pain. We have developed pyrrolidine-based T-type calcium channel inhibitors by structural hybridization and subsequent assessment of in vitro activities against Ca_v3.1 and Ca_v3.2 channels. Profiling of in vitro ADME properties of compounds was also carried out. The representative compound 17h showed comparable in vivo efficacy to gabapentin in the SNL model, which indicates T-type calcium channel inhibitors can be developed as effective therapeutics for neuropathic pain.     

SAR optimization studies on a novel series of 2-anilinopyrimidines as selective inhibitors against triple-negative breast cancer cell line MDA-MB-468

Triple-negative breast cancers (TNBCs) account for approximately 15% of breast cancer cases and exhibit an aggressive clinical behavior. In this study, we designed and synthesized two series of 2-anilinopyrimidines based on the structure of our previously reported compound 1 that act as a selective inhibitor of the basal-like TNBC cell line MDA-MB-468. Through the fine-tuning of 1, cyclic and acyclic amines at 4-position of the pyrimidine core were turned out to be crucial for the selectivity. An extensive analysis of structure-activity relationships of the analogs revealed that aminoalkyl groups at the end of the propyl chain are amenable to modification. Among the newly synthesized analogs, compound 38, bearing 4-chloropiperidinyl and cyclohexyl groups, was found to be the most potent and selective, and was about three times more potent and selective than 1 was against the TNBC cells.     

A novel indirubin derivative that increases somatic cell plasticity and inhibits tumorigenicity

Indirubin-based compounds affect diverse biological processes, such as inflammation and angiogenesis. In this study, we tested a novel indirubin derivative, LDD-1819 (2-((((2Z,3E)-5-hydroxy-5′-nitro-2′-oxo-[2,3′-biindolinylidene]-3-ylidene)amino)oxy)ethan-1-aminium chloride) for two major biological activities: cell plasticity and anti-cancer activity. Biological assays indicated that LDD-1819 induced somatic cell plasticity. LDD-1819 potentiated myoblast reprogramming into osteogenic cells and fibroblast reprogramming into adipogenic cells. Interestingly, in an assay of skeletal muscle dedifferentiation, LDD-1819 induced human muscle cellularization and blocked residual proliferative activity to produce a population of mononuclear refractory cells, which is also observed in the early stages of limb regeneration in urodele amphibians. In cancer cell lines, LDD-1819 treatment inhibited cell invasion and selectively induced apoptosis compared to normal cells. In an animal tumor xenograft model, LDD-1819 reduced human cancer cell metastasis in vivo at doses that did not produce toxicity. Biochemical assays showed that LDD-1819 possessed inhibitory activity against glycogen synthase kinase-3β, which is linked to cell plasticity, and aurora kinase, which regulates carcinogenesis. These results indicate that novel indirubin derivative LDD-1819 is a dual inhibitor of glycogen synthase kinase-3β and aurora A kinase, and has potential for development as an anti-cancer drug or as a reprogramming agent for cell-therapy based approaches to treat degenerative diseases.