从肠道菌群角度认识阿尔茨海默病的潜在发病机制

过去10年中,人们逐渐认识到肠道微生物群的多样性及菌群平衡在维护宿主健康中发挥的作用。肠道微生物及其代谢产物通过一系列的生化、免疫和生理功能环节与宿主进行交流,从而影响宿主的稳态和健康。阿尔茨海默病(Alzheimer’s disease,AD)是一种复杂的神经退行性疾病,其易感性和发展过程受年龄、遗传和表观遗传等因素的影响。研究发现,肠道微生物群的紊乱(组成改变和易位)与神经系统疾病(AD)有关,胃肠道通过肠脑轴与中枢神经系统进行沟通,包括对神经的直接作用、内分泌途径和免疫调控方式。动物模型、粪便菌群移植及益生菌干预为肠道菌群与AD的相关性提供了证据。外漏的细菌代谢产物可能直接损害神经元功能,也可能诱发神经炎症,促进AD的发病。本文主要综述了肠道微生物群与AD的关联和作用机制,以期为通过改善肠道菌群结构预防AD的可能干预措施提供依据。     

利用超高效液相色谱和离子色谱法测定注射用磷酸川芎嗪的含量

目的:建立超高效液相色谱法(UPLC)和离子色谱法(IC)测定磷酸川芎嗪中川芎嗪和磷酸的含量,为质量评价提供依据。方法:UPLC测定川芎嗪的色谱柱为Waters Acquity BEH C18 (2.1 mm×50 mm,1.7μm);检测波长:300 nm检测川芎嗪,274 nm检测有关物质邻苯二甲酸二甲酯;流动相为0.1%甲酸水溶液(A)-0.1%甲酸乙腈(B),梯度洗脱(0.0～0.8 min,10%B→90%B;0.8～0.81 min,90%B→10%B;0.81～1.00 min,10%B),流速:0.7 m L/min。IC测定磷酸的离子交换色谱柱为Dionex IonPac AS11-HC-4μm (4×250 mm),流动相为30 mmol/L KOH溶液等度洗脱15 min,流速1.0 m L/min,柱温35℃;电导检测器;抑制器电流为50 m A。结果:川芎嗪和磷酸在10～100 g/m L内具有良好的线性关系,相关系数均为1.0,UPLC法测定川芎嗪的回收率为102.0%。IC测定磷酸的回收率为99.8%。7个公司生产的注射剂中川芎嗪的含量均在药典规定的范围90%～110%内。但是其中3个公司生产的注射剂磷酸超出药典规定范围90%～110%。结论:与常规HPLC/UPLC测定磷酸川芎嗪含量方法比较,本文所用方法测定结果更加准确、全面、且重复性好,能够真实反应注射用磷酸川芎嗪的实际含量,对于注射用磷酸川芎嗪的安全性和有效性评估提供了一定的依据。     

OSAHS风险对患者静脉麻醉术后认知功能障碍的影响

目的:探讨OSAHS风险与静脉麻醉手术患者术后发生认知功能障碍的关系。方法:采用No SAS评分对55例静脉麻醉手术患者进行OSAHS风险评估,并将其分为对照组23例(NoSAS 8分)和OSAHS组32例(No SAS≥8分),以蒙特利尔认知评估量表(MoCA)对两组患者在术前和术后第一天进行认知功能评估,计算每位患者手术前后Mo CA评分的差值△Mo CA(术前MoCA-术后MoCA),比较两组患者手术前后的MoCA评分及△MoCA。结果:OSAHS组术前MoCA评分(25.83±1.80)明显低于对照组术前MoCA评分(28.05±1.31)(P0.05)。OSAHS组术后MoCA评分(25.13±1.64)较术前无明显变化(P0.05),对照组术后Mo CA评分(26.73±1.17)明显低于术前(P0.05)。OSAHS组△MoCA(0.39±1.03)明显低于对照组(1.32±1.08),主要表现为视空间与执行功能[(0.09±0.29) vs.(0.30±0.32)]、注意力[(0.09±0.60) vs.(0.47±0.70)]和延时回忆力[(0.17±0.39) vs.(0.47±0.51)]两方面(P0.05)。结论:OSAHS高风险患者静脉麻醉术后认知功能障碍的程度较OSAHS低风险人群显著降低。     

生物钟基因PER2在结直肠癌中的表达及意义

目的:探讨PER2基因表达水平和结直肠癌发生发展的关系。方法:收集203例在上海市第一人民医院接受根治性肠切除术结直肠癌患者的标本,通过实时定量PCR和免疫组织化学技术检测PER2在肿瘤组织和邻近正常组织中的表达水平,并对PER2的表达与患者的病理资料和临床预后的相关性进行统计学分析。结果:PER2在结直肠患者肿瘤组织的表达较正常组织减少(P0.001)。与PER2阳性患者相比,PER2阴性的结直肠癌患者有远处转移(P=0.026)、AJCC分期为IV期(P=0.011)的比例更高。结论:PER2基因在结直肠癌患者中存在低表达现象,其对于患者的AJCC分期评价以及了解患者有无远处转移有一定的参考价值。     

64排螺旋CT对粗隆间骨折Evans分型的影响研究

目的:探讨64排螺旋CT对粗隆间骨折Evans分型的影响,为临床使用提供参考依据。方法:2015年3月至2017年3月,三甲医院高年资创伤骨科主任医师2名,医师1、医师2分别按照术前X线、术前64排螺旋CT平扫和三位重建结果对128例新鲜闭合单侧粗隆间骨折患者进行Evans分型,分别记为X线分型、CT分型。本院术者依据围术期X线、CT及术中所见骨折情况进行Evans分型(逆粗隆间骨折定义为Ⅴ型)作为最终分型。记录分型结果,计算并对比准确率、误诊率。结果:(1)剔除5例,90.09%(123/128)的患者完成研究。(2)分型结果:X线分型中,3例(最终分型Ⅲ型2例,Ⅳ型1例)无法定型;Ⅰ型正确1例,改为Ⅱ型1例;Ⅱ型正确18例,改为Ⅰ型2例,改为Ⅲ型3例,Ⅳ型2例;Ⅲ型正确45例,改为Ⅱ型7例,改为Ⅳ型1例;Ⅳ型正确19例,改为Ⅱ型3例,改为Ⅲ型15例。CT分型中,Ⅰ型正确3例,Ⅱ型正确29例,Ⅲ型正确64例,改为Ⅳ型1例,Ⅳ型正确22例,Ⅴ型正确3例。(3)CT分型的总准确率、总误诊率优于X线分型(99.19%vs67.48%、0.81%vs30.08%,P0.05)。(4)Ⅰ型、Ⅱ型、Ⅲ型、Ⅳ型骨折进行CT分型,准确率高于X线分型(P0.05),误诊率低于X线分型(P0.05);Ⅴ型骨折,两种分型准确率、误诊率相等。结论:64排螺旋CT平扫及三维重建是粗隆间骨折Evans分型较为可靠的辅助检查,可考虑推广运用。     

丁基苯酞对心力衰竭大鼠心房颤动的影响及作用机制

为探讨丁基苯酞(DL-3-N-butylphthalide,NBP)对心肌梗死诱导的心力衰竭(heart failure,HF)大鼠心房结构重塑和心房颤动形成的影响,本研究将心力衰竭模型大鼠随机分为丁基苯酞组(NBP)、模型组(Model)和假手术组(Sham)。将丁基苯酞用大豆油溶解,制成10 mg/mL的丁基苯酞溶液。丁基苯酞组按照80 mg/kg体重对SD大鼠进行灌胃,模型组和假手术组用等量的大豆油灌胃。假手术组大鼠接受相同手术但未结扎左前降支冠状动脉。分别检测大鼠的超声心动图、心房颤动诱导性试验及心房纤维化,并检测TNF-α、TGF-β1、NF-κB、Nrf2和HO-1的蛋白表达。研究显示,应用丁基苯酞治疗4周后,NBP组大鼠心功能显著改善(p<0.05);NBP组大鼠心房颤动诱导能力和持续时间显著降低(p<0.05);NBP组大鼠心房纤维化程度显著减轻(p<0.05)。丁基苯酞显著抑制TNF-α,NF-κB和TGF-β1的蛋白表达,并上调Nrf2和HO-1的蛋白表达。并且,NBP对TNF-α/NF-κB/TGF-β1和纤维化的抑制作用可能与Nrf2/HO-1信号通路的激活有关。因此,丁基苯酞有望成为预防房颤的上游治疗中的有效药物。     

MiR‐103 inhibiting cardiac hypertrophy through inactivation of myocardial cell autophagy via targeting TRPV3 channel in rat hearts

Cardiac hypertrophy is a common pathological change frequently accompanied by chronic hypertension and myocardial infarction. Nevertheless, the pathophysiological mechanisms of cardiac hypertrophy have never been elucidated. Recent studies indicated that miR‐103 expression was significantly decreased in heart failure patients. However, less is known about the role of miR‐103 in cardiac hypertrophy. The present study was designed to investigate the relationship between miR‐103 and the mechanism of pressure overload‐induced cardiac hypertrophy. TRPV3 protein, cardiac hypertrophy marker proteins (BNP and β‐MHC) and autophagy associated proteins (Beclin‐1 and LC3‐II) were up‐regulated, as well as, miR‐103 expression and autophagy associated proteins (p62) were down‐regulated in cardiac hypertrophy models in vivo and in vitro respectively. Further results indicated that silencing TRPV3 or forcing overexpression of miR‐103 could dramatically inhibit cell surface area, relative fluorescence intensity of Ca²⁺ signal and the expressions of BNP, β‐MHC, Beclin‐1 and LC3‐II, but promote p62 expression. Moreover, TRPV3 protein was decreased in neonatal rat ventricular myocyte transfected with miR‐103, but increased by AMO‐103. Co‐transfection of the miR‐103 with the luciferase reporter vector into HEK293 cells caused a sharp decrease in luciferase activity compared with transfection of the luciferase vector alone. The miR‐103‐induced depression of luciferase activity was rescued by an AMO‐103. These findings suggested that TRPV3 was a direct target of miR‐103. In conclusion, miR‐103 could attenuate cardiomyocyte hypertrophy partly by reducing cardiac autophagy activity through the targeted inhibition of TRPV3 signalling in the pressure‐overloaded rat hearts.     

BAG3‐positive pancreatic stellate cells promote migration and invasion of pancreatic ductal adenocarcinoma

BAG3 is constitutively expressed in multiple types of cancer cells and its high expression is associated with tumour progression and poor prognosis of PDAC . However, little is known about the role of BAG3 in the regulation of stromal microenvironment of PDAC. The current study demonstrated that beside PDAC tumour cells, BAG3 was also expressed in some activated stroma cells in PDAC tissue, as well as in activated PSCs. In addition, the current study demonstrated that BAG3 expression in PSCs was involved in maintenance of PSCs activation and promotion of PDACs invasion via releasing multiple cytokines. The current study demonstrated that BAG3‐positive PSCs promoted invasion of PDACs via IL‐8, MCP1, TGF‐β2 and IGFBP2 in a paracrine manner. Furthermore, BAG3 sustained PSCs activation through IL‐6, TGF‐β2 and IGFBP2 in an autocrine manner. Thereby, the current study provides a new insight into the involvement of BAG3 in remodelling of stromal microenvironment favourable for malignant progression of PDAC, indicating that BAG3 might serve as a potential target for anti‐fibrosis of PDAC.     

Confined Fe2VO4⊂Nitrogen‐Doped Carbon Nanowires with Internal Void Space for High‐Rate and Ultrastable Potassium‐Ion Storage

Developing low‐cost, high‐capacity, high‐rate, and robust earth‐abundant electrode materials for energy storage is critical for the practical and scalable application of advanced battery technologies. Herein, the first example of synthesizing 1D peapod‐like bimetallic Fe₂VO₄ nanorods confined in N‐doped carbon porous nanowires with internal void space (Fe₂VO₄?NC nanopeapods) as a high‐capacity and stable anode material for potassium‐ion batteries (KIBs) is reported. The peapod‐like Fe₂VO₄?NC nanopeapod heterostructures with interior void space and external carbon shell efficiently prevent the aggregation of the active materials, facilitate fast transportation of electrons and ions, and accommodate volume variation during the cycling process, which substantially boosts the rate and cycling performance of Fe₂VO₄. The Fe₂VO₄?NC electrode exhibits high reversible specific depotassiation capacity of 380 mAh g^?1 at 100 mA g^?1 after 60 cycles and remarkable rate capability as well as long cycling stability with a high capacity of 196 mAh g^?1 at 4 A g^?1 after 2300 cycles. The first‐principles calculations reveal that Fe₂VO₄?NC nanopeapods have high ionic/electronic conductivity characteristics and low diffusion barriers for K⁺‐intercalation. This study opens up new way for investigating high‐capacity metal oxide as high‐rate and robust electrode materials for KIBs.