Dissected Aorta Repair Through Stent Implantation trial: Canadian results

Objectives

We describe the Canadian results of the Ascyrus Medical Dissection Stent (AMDS), a novel partially uncovered aortic arch hybrid graft implanted antegrade during hypothermic circulatory arrest to promote true lumen expansion and enhance aortic remodeling.

Effects of topical tranexamic acid during open reduction and internal fixation of acetabular fractures: A retrospective study

ObjectiveThe aim of this study was to assess the effect of topical tranexamic acid on blood loss and transfusion rates in acetabular fracture surgery.MethodsThe medical records of 61 patients who underwent open reduction and internal fixation for acetabular fracture between 2012 and 2015 were retrospectively reviewed. The patients were divided into two groups: Group I consisted of 31 patients (19 men and 12 women, mean age: 52 ± 19 years) who received intraoperatively a topical tranexamic acid solution of 3 g and Group 2 consisted of 30 control patients (17 men and 13 women, mean age: 48 ± 24 years) who received only 0.9% saline solution. The groups were compared based on their intraoperative blood loss, Postoperative drain output at 24 and 48 h, and postoperative hemoglobin levels, and transfusion rates.ResultsThe mean intraoperative blood loss was 410 ± 100 ml in Group 1, compared to 570 ml ± 160 ml of the control group (p < 0.05). The postoperative drain output after 24 h was 210 ± 70 ml in Group 1 compared to 330 ± 90 ml of the control group (p < 0.05). The drain output at 48 h was (50 ± 20 ml) in group 1 compared to 90 ± 40 ml of the control group (p < 0.05). The transfusion rate was significantly low group 1 (42%) than the control group (97%). Hemoglobin drop was again significantly less in tranexamic acid group (2.1 ± 1.1) than the control group (3.2 ± 1.3). The nadir postoperative hemoglobin was higher in the Group 1 (10.4 ± 1.5) than the control group (9.2 ± 1.3).ConclusionTopical administration of tranexamic acid reduces intraoperative and postoperative blood loss in acetabular fracture surgery, decreasing transfusion rates.Level of EvidenceLevel III, Therapeutic Study.     

Nutraceuticals use and type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a complicated metabolic disease and has become one of the significant medical problems worldwide. Researchers aim to provide fine-tuned treatment for T2DM with minimal exposed side effects. Nutraceuticals are compounds or materials and emerging evidence suggests that the use of nutraceuticals has recently been recognized as a promising option for the prevention and management of T2DM, such as probiotics and prebiotics, Vitamin D, n-3 long-chain polyunsaturated fatty acids, and Plant-derived nutraceuticals. This review attempts to show the most popular nutraceuticals and review their effects and possible mechanisms in the prevention or glycemic control of T2DM.     

Recent advances in lipid nanoparticles for delivery of nucleic acid,mRNA, and gene editing-based therapeutics

Lipid nanoparticles (LNPs) are becoming popular as a means of delivering therapeutics, including those based on nucleic acids and mRNA. The mRNA-based coronavirus disease 2019 vaccines are perfect examples to highlight the role played by drug delivery systems in advancing human health. The fundamentals of LNPs for the delivery of nucleic acid- and mRNA-based therapeutics, are well established. Thus, future research on LNPs will focus on addressing the following: expanding the scope of drug delivery to different constituents of the human body, expanding the number of diseases that can be targeted, and studying the change in the pharmacokinetics of LNPs under physiological and pathological conditions. This review article provides an overview of recent advances aimed at expanding the application of LNPs, focusing on the pharmacokinetics and advantages of LNPs. In addition, analytical techniques, library construction and screening, rational design, active targeting, and applicability to gene editing therapy have also been discussed.     

Germline gain-of-function MMP11 variant results in an aggressive form of colorectal cancer

Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.     

基于网络药理学和分子对接探讨补肾活血方治疗尿酸性肾病的作用机制＊

目的 基于网络药理学和分子对接技术探讨补肾活血方治疗尿酸性肾病（uric acid nephropathy， UAN）的分子作用机制。方法 采用中药系统药理学数据库TCMSP筛选出补肾活血方的有效活性成分。通过PubChem、DrugBank、SymMap和SwissTargetPrediction数据库筛选出中药各成分作用靶点。借助GeneCards、DisGenet、malaCards和OMIN数据库获取尿酸性肾病的靶点基因。David绘图工具筛选出中药与疾病的交集靶点，利用Cytoscape3.9.0软件构建“中药-活性成分-疾病-靶点”网络关系图，并通过CytoNCA插件构建蛋白质相互作用网络（PPI），筛选得到核心靶点蛋白。采用AutoDock Vina 1.1.2软件将补肾活血方关键有效成分和核心靶点进行分子对接。最后运用乙胺丁醇和腺嘌呤诱导的尿酸性肾病模型对网络药理学预测的结果进行基础实验验证。结果 本研究共筛选得到补肾活血方治疗UAN的作用靶点234个，其中核心靶点19个，对应5种中药的113种有效成分。GO富集分析共得到925条基因功能信息，KEGG富集分析发现112条信号通路，涉及Toll样受体、NF-κB、PI3K-Akt、p53、TNF等信号通路治疗尿酸性肾病。分子对接结果显示，双脱甲氧基姜黄素、异黄酮等关键活性成分与ALB、MMP9、TLR4等关键核心靶点有较好的结合活性。动物实验结果显示，与模型组相比，补肾活血方组、非布司他组大鼠肾组织TLR4和NF-κB蛋白表达量和血清MMP-9水平明显降低（P<0.05）；血清ALB水平明升高（P<0.05）。结论 本研究提示，补肾活血方中关键活性成分可能通过抑制TLR4/NF-κB信号通路降低TLR4、NF-κB和MMP-9水平，减轻炎症反应，进而减少ALB漏出，发挥保护肾脏治疗尿酸性肾病的作用。     

外周血单个核细胞内人类免疫缺陷病毒DNA和RNA定量对病毒转录活性的区分

目的基于人类免疫缺陷病毒Ⅰ型(HIV-1)感染者外周血单个核细胞(PBMCs)中HIV-1总DNA和RNA定量检测结果对感染细胞内病毒的转录活性进行区分。方法采集2017年10月至2018年12月于哈尔滨医科大学附属第四医院感染科就诊的HIV-1感染者血液样本,分离PBMCs细胞,采用PCR荧光探针法对PBMCs细胞内HIV-1总DNA和RNA进行定量检测,并计算两者比值(Ratio)。根据Ratio值筛选出HIV-1转录活跃组样本和相对非活跃组样本,另外选择健康人PBMCs样本作为对照组。对3组样本进行基因转录组表达谱检测以及人口特征差异性检验,并对基因表达谱检测结果进行主成分分析以验证对3组样本病毒转录活性区分的准确性。结果从60例感染HIV-1患者的PBMCs样本中筛选出HIV-1转录活跃组样本(10例)和相对非活跃组样本(11例),另外选择6例健康人PBMCs样本作为对照组。其中转录活跃组样本Ratio值为165.2~738.93,平均为(339.27±189.68);相对非活跃组Ratio值为4.67~42.39,平均为(17.65±11.78)。转录活跃组和相对非活跃组样本间的CD4+T细胞计数(P=0.049)和Ratio值(P<0.001)差异均具有统计学意义;3组样本年龄(P=0.989)和性别(P=0.650)分布差异无统计学意义。对3组样本的PBMCs基因表达谱主成分分析结果显示:对照组与HIV-1感染者(包括转录活跃组和相对非活跃组)间区分明显。转录活跃组和相对非活跃组间有部分样本重合,同时结果也显示当HIV-1感染者的CD4+T淋巴细胞计数与健康人无显著差异时,其细胞内的基因表达与健康人接近。结论基于HIV-1总DNA和RNA定量检测结果及两者间比值可以较好地区分PBMCs内病毒转录活性。HIV-1感染细胞内部病毒的不同转录激活状况可导致其基因表达谱的异质性。