MicroRNA‐375‐3p enhances chemosensitivity to 5‐fluorouracil by targeting thymidylate synthase in colorectal cancer

Resistance to chemotherapy is a major challenge for the treatment of patients with colorectal cancer (CRC). Previous studies have found that microRNAs (miRNAs) play key roles in drug resistance; however, the role of miRNA‐373‐3p (miR‐375‐3p) in CRC remains unclear. The current study aimed to explore the potential function of miR‐375‐3p in 5‐fluorouracil (5‐FU) resistance. MicroRNA‐375‐3p was found to be widely downregulated in human CRC cell lines and tissues and to promote the sensitivity of CRC cells to 5‐FU by inducing colon cancer cell apoptosis and cycle arrest and by inhibiting cell growth, migration, and invasion in vitro. Thymidylate synthase (TYMS) was found to be a direct target of miR‐375‐3p, and TYMS knockdown exerted similar effects as miR‐375‐3p overexpression on the CRC cellular response to 5‐FU. Lipid‐coated calcium carbonate nanoparticles (NPs) were designed to cotransport 5‐FU and miR‐375‐3p into cells efficiently and rapidly and to release the drugs in a weakly acidic tumor microenvironment. The therapeutic effect of combined miR‐375 + 5‐FU/NPs was significantly higher than that of the individual treatments in mouse s.c. xenografts derived from HCT116 cells. Our results suggest that restoring miR‐375‐3p levels could be a future novel therapeutic strategy to enhance chemosensitivity to 5‐FU.     

Helicobacter pylori induces epithelial-mesenchymal transition in gastric carcinogenesis via the AKT/GSK3β signaling pathway

Helicobacter pylori (H. pylori) is a main risk factor for gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is involved in the development and progression of H. pylori-associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3β signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether H. pylori infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT-associated proteins, including E-cadherin and N-cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E-cadherin, N-cadherin, AKT, phosphorylated (p-)AKT (Ser473), GSK3β and p-GSK3β (Ser9) were further determined in H. pylori-infected Mongolian gerbil gastric tissues and cells co-cultured with H. pylori by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E-cadherin were decreased, whereas the expression levels of the mesenchymal marker N-cadherin were increased during gastric carcinogenesis. Their expression levels were associated with H. pylori infection. Furthermore, H. pylori infection resulted in downregulation of E-cadherin expression and upregulation of N-cadherin expression in Mongolian gerbils and GES-1 cells. In addition, an investigation of the associated mechanism of action revealed that p-AKT (Ser473) and p-GSK3β (Ser9) were activated in GES-1 cells following co-culture with H. pylori. Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E-cadherin, N-cadherin, p-AKT and p-GSK3β did not show significant differences between GES-1 cells that were co-cultured with or without H. pylori. The levels of p-AKT and p-GSK3β were increased in H. pylori-infected Mongolian gerbils. In conclusion, the present study demonstrated that H. pylori infection activated AKT and resulted in the phosphorylation and inactivation of GSK3β, which in turn promoted early stage EMT. These effects were AKT-dependent. This mechanism may serve as a prerequisite for GC development.     

Ethyl lactate as a potential green solvent to extract hydrophilic (polar) and lipophilic (non-polar) phytonutrients simultaneously from fruit and vegetable by-products

Phytonutrients extracted from natural resources are receiving much attention among researchers due to their highly antioxidative characteristics which prevent several degenerative diseases including cardiovascular diseases and cancers. These nutraceutical compounds can be used in food, pharmaceutical and cosmetic products as natural antioxidants, preservatives, colourants and functional foods. Huge volume of food wastes are generated from the processing industry and these low-value food residues are rich in various phytonutrients worth recovering. This approach of valorisation reduces the generation of food wastes and is cost-effective considering the cheap feedstock, reduced waste management expenses and high market value of extracted compounds. In light of the health and safety risks posed by commonly used organic extraction solvents derived from the petrochemical industry, there is a need to recover the phytonutrients using green, sustainable and efficient solvents that are safe for human consumption. This work discusses ethyl lactate as a safe, green, efficient and potentially cheap solvent to recover phytonutrients from fruit and vegetable by-products. Ethyl lactate is compared with other organic solvents commonly used from the aspects of safety, environmental impacts and efficiency. Current challenges when employing ethyl lactate are also discussed.     

珠海地区NRXN1和NLGN1基因多态性与儿童孤独症的关联性研究

目的 探索珠海地区NRXN1和NLGN1基因多态性与儿童孤独症易感性的关系,为孤独症的防治提供科学依据。方法 采用病例对照的研究方法,选取2011－2016年就诊于珠海市妇幼保健院的123例珠海地区的孤独症患儿和506例健康对照。采用口腔拭子采集口腔上皮细胞以提取DNA,采用Sequenom Mass Array platform分型技术对NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544进行基因分型。结果 NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544位点基因型分布在孤独症组和健康对照组比较,差异无统计学意义;但NLGN1基因上的rs9855544与NRXN1基因上的rs11885824存在基因与基因间的交互作用(预测准确率为0.480,交叉验证一致性为10/10,P=0.040)。结论 NRXN1基因上的rs1045881和rs11885824以及NLGN1上的rs9855544位点基因多态性可能与孤独症易感性没有关联,但NLGN1基因上的rs9855544与NRXN1基因上的rs11885824之间的交互作用可能是孤独症易感性的影响因素。     

我国类鼻疽病的流行病学特征及诊疗的研究进展

类鼻疽病是由类鼻疽伯克霍尔德菌(Burkholderia pseudomallei)感染引起的一类人畜共患病,主要流行于全球热带及亚热带地区。在我国主要流行于南部地区,疫源地为海南、广东、广西、台湾等。伴随着旅游业和贸易业的发展,我国其他非疫区出现了输入性病例。类鼻疽病的感染途径主要为经伤口、粘膜、呼吸道、消化道等,其病变可涉及机体所有器官,易造成较高的误诊率和病死率。然而我国目前类鼻疽病的流行病筛查技术存在一定的局限性,在防控方面未实行有效的疾病监测和疾病报告制度,对基层医师和民众疾病知识普及的力度不够。因此,本文旨在提高我国医务工作者对类鼻疽病的重视程度,从类鼻疽病的病原学特征、流行病学特征、临床特征、诊断与治疗、防控措施这五个方面进行详细综述。     

临床医学专业“5+3”一体化本科全程导师制创新人才培养的实践与探索

以培养创新型人才为目标，大连医科大学制定实施了“5+3”创新人才培养改革方案，以导师制培养为载体，在医学本科教育全过程中，制定分阶段创新能力培养体系，涵盖课程、讲座、实验设计、论文等基本科研能力训练，强化本科生科研能力培养。通过对首届“5+3”学生阶段性培养成果的统计学分析发现，“5+3”学生发表中文期刊、SCI，主持国家级创新项目、省级创新项目的比例均显著高于普通5年制学生，差异具有统计学意义（P<0.05）。虽然实施过程中存在一些问题和不足，但以导师制为核心的科研基础训练对提高学生科研思维和创新能力效果显著，对培养医学创新型人才具有可实施性。     

硬膜外麻醉与椎旁神经阻滞非气管插管单孔胸腔镜手术效果比较

目的比较硬膜外麻醉与椎旁神经阻滞非气管插管单孔胸腔镜手术的效果。方法选择2017年11月至2019年6月锦州医科大学附属第一医院收治的45例采用非气管插管麻醉单孔胸腔镜手术的肺部良恶性肿瘤患者,采用随机数字表法分为椎旁神经阻滞组(22例)与硬膜外麻醉组(23例)。麻醉诱导前,椎旁神经阻滞组均于超声引导下阻滞胸3~6棘突旁神经根;硬膜外麻醉组均于胸6~7或7~8间隙行硬膜外穿刺置管麻醉。比较两组手术时间、术中出血量、术后定向力恢复时间、下床活动时间、带管时间、出院时间及相关并发症。结果两组患者手术时间、术中出血量差异均无统计学意义(均P>0.05)。与硬膜外麻醉组相比,椎旁神经阻滞组术后定向力恢复时间[(7.22±2.20)min比(18.80±5.06)min]、下床活动时间[(11.45±3.01)h比(21.90±4.61)h]、带管时间[(2.77±0.81)d比(5.47±1.31)d]、出院时间[(3.68±0.84)d比(6.17±1.03)d]均缩短,两组差异均有统计学意义(t值分别为-9.874、-8.763、-8.282、-7.594,均P<0.05)。椎旁神经阻滞组术后未发生低氧血症、低血压、肺部并发症、恶心、呕吐、尿潴留等相关并发症。结论非气管插管单孔胸腔镜手术中采用椎旁神经阻滞术后恢复快、并发症少,临床上可优先选择,有助于快速康复。