原发性高血压患者血浆同型半胱氨酸水平与脉搏波传导速度的相关性

目的通过分析原发性高血压患者血浆同型半胱氨酸(Hcy)水平与臂踝脉搏波传导速度(BaPWV)的相关性,探讨原发性高血压患者血浆Hcy水平与动脉僵硬度的关系。方法高血压病患者共146例,根据Hcy的四分位间距水平分成四组,同时根据BaPWV≥1400 cm/s为异常界值,分成BaPWV正常组和异常组。测定空腹血糖、血脂及Hcy,测定双侧BaPWV。结果 Hcy与年龄、吸烟史、收缩压(SBP)、脉压(PP)、脉压指数(PPI)及BaP-WV呈正相关(r分别为0.278、0.272、0.608、0.575、0.460及0.351,P<0.05),BaPWV与Hcy、SBP、PP及PPI呈正相关(r分别为0.351、0.322、0.322及0.253,P<0.01)。以BaPWV为因变量,进行Logistic回归方程分析,结果显示PP和Hcy是高血压病患者BaPWV升高的独立危险因素。结论 Hcy水平升高与高血压病患者动脉僵硬度的发生发展密切相关。     

Mesenchymal stem cell-derived exosomes inhibit the VEGF-A expression in human retinal vascular endothelial cells induced by high glucose

AIM: To determine the effect of exosomes derived from human umbilical cord blood mesenchymal stem cells (hUCMSCs) on the expression of vascular endothelial growth factor A (VEGF-A) in human retinal vascular endothelial cells (HRECs). METHODS: Exosomes were isolated from hUCMSCs using cryogenic ultracentrifugation and characterized by transmission electron microscopy, Western blotting and nanoparticle tracking analysis. HRECs were randomly divided into a normal control group (group A), a high glucose model group (group B), a high glucose group with 25 μg/mL (group C), 50 μg/mL (group D), and 100 μg/mL exosomes (group E). Twenty-four hours after coculture, the cell proliferation rate was detected using flow cytometry, and the VEGF-A level was detected using immunofluorescence. After coculture 8, 16, and 24h, the expression levels of VEGF-A in each group were detected using PCR and Western blots. RESULTS: The characteristic morphology (membrane structured vesicles) and size (diameter between 50 and 200 nm) were observed under transmission electron microscopy. The average diameter of 122.7 nm was discovered by nanoparticle tracking analysis (NTA). The exosomal markers CD9, CD63, and HSP70 were strongly detected. The proliferation rate of the cells in group B increased after 24h of coculture. Immunofluorescence analyses revealed that the upregulation of VEGF-A expression in HRECs stimulated by high glucose could be downregulated by cocultured hUCMSC-derived exosomes (F=39.03, P<0.01). The upregulation of VEGF-A protein (group C: F=7.96; group D: F=17.29; group E: F=11.89; 8h: F=9.45; 16h: F=12.86; 24h: F=42.28, P<0.05) and mRNA (group C: F=4.137; group D: F=13.64; group E: F=22.19; 8h: F=7.253; 16h: F=16.98; 24h: F=22.62, P<0.05) in HRECs stimulated by high glucose was downregulated by cocultured hUCMSC-derived exosomes (P<0.05). CONCLUSION: hUCMSC-derived exosomes downregulate VEGF-A expression in HRECs stimulated by high glucose in time and concentration dependent manner.     

鲍曼不动杆菌生物膜形成与耐药的相关性初探

目的探索鲍曼不动杆菌生物膜的形成与耐药的相关性。方法采用96孔板培养法模拟体内生物膜形成,结晶紫染色法鉴定各菌株生物膜生长情况。将鲍曼不动杆菌于黑色聚碳酸酯膜上形成生物膜,其上覆盖药敏纸片,然后将此结构置于涂有大肠埃希菌ATCC25922菌株的M-H平板上,通过测量抑菌圈直径观察生物膜对氯霉素和氧氟沙星的渗透限制作用。结果结晶紫染色测定各菌株均能于体外形成生物膜。除85号菌株外,各菌株与对照组相比,对氯霉素均有明显渗透限制作用,而对氧氟沙星无明显作用。结论生物膜对某些药物的渗透限制作用是细菌耐药的重要机制之一。     

DNA去甲基化药物的研究进展

DNA甲基化是调节基因表达而不改变DNA碱基序列的表观遗传修饰,通过沉默肿瘤抑制基因在癌症发展中发挥关键作用。DNA去甲基化药物在临床上已经显示出疗效,然而,高效性和特异性的DNA去甲基化药物尚未出现。目前,在市场上已有2种药物阿扎胞苷和地西他滨用于治疗骨髓增生异常综合征。寻找直接结合靶点新的抑制剂是未来的方向。从抗肿瘤活性和临床研究方面介绍了DNA去甲基化药物的研究进展。     

蒺藜果实的化学成分研究

目的研究蒺藜科植物蒺藜Tribulus terrester的干燥成熟果实的化学成分。方法利用硅胶柱色谱、Sephadex LH-20凝胶柱色谱、制备HPLC和薄层色谱等方法进行分离、纯化,并结合HR-ESI-MS与现代波谱学技术鉴定化合物结构。结果从蒺藜果实中分离得到14个化合物,分别鉴定为N-p-阿魏酰酪胺(1)、N-trans-p-coumaroyl-3-O-methyldopamine(2)、甲基阿魏酸(3)、咖啡酸甲酯(4)、原儿茶酸甲酯(5)、trifilines A(6)、5β-spirost-25(27)-en-3β-ol-12-one 3-O-{β-D-glucopyranosyl-(1→2)-O-[β-D-glucopyranosyl-(1→3)]-β-D-glucopyranoside}(7)、tribulosaponin B(8)、isoterrestrosin B(9)、25(R)-螺甾烷-3,5-二烯-12-酮(10)、25(R)-螺甾烷-24β-羟基-4-烯-3,12-酮(11)、26-O-β-D-glucopyranosyl-(25S)-5α-furostane-20(22)-en-12-one-3β,26-diol-3-O-α-L-rhamnopyranosyl-(1→2)-[β-D-glucopyranosyl-(1→4)]-β-D-galactopyranoside(12)、terrestrinone A1(13)和terrestrinone A2(14)。结论化合物1～7为首次从蒺藜科植物中分离得到。     

Higenamine as a Potential Pharmacologic Stress Agent in the Detection of Coronary Artery Disease

Myocardial perfusion imaging (MPI) is valuable for the diagnosis, prognosis, and management of coronary artery disease (CAD). The most commonly used pharmacologic stress agents at present are vasodilators and adrenergic agents. However, these agents have contraindications and may cause adverse effects in some patients. Thus, other stress agents feasible for more patients are required. Higenamine (HG) is a β-adrenergic receptor agonist currently approved for clinical trials as a stress agent for myocardial infarction. It also has a promising value in MPI for the detection of CAD in preclinical and clinical studies. This review summarizes the application of HG on MPI, including its mechanism of action, stress protocol, efficacy, and safety.     

三例典型无功能胰腺神经内分泌瘤诊疗分析

无功能胰腺神经内分泌瘤（NF-PNETs）临床罕见,本文回顾性分析天津市第一中心医院 2012 年 7 月— 2017年2月收治的3例病理诊断明确的典型NF-PNETs患者的相关资料,探讨NF-PNETs的临床表现、病理及免疫组 化特点、诊疗及预后情况。     

头颈鳞癌与中心碳代谢通路研究

目的:探究头颈鳞癌代谢重编程机制。方法:通过对头颈鳞癌和癌旁组织进行真核有参转录组学、TMT标记定量蛋白质组学和非靶向代谢组学分析,找到差异表达基因、蛋白质和代谢物,进行基因本体（GO）富集分析和京都基因和基因组百科全书（KEGG）富集分析等生物信息学分析,两两组学联合分析预测参与头颈鳞癌代谢重编程的重要代谢通路。然后进行平行反应监测（PRM）验证通路重要蛋白,找到差异表达蛋白及代谢通路。结果:联合分析结果提示,肿瘤中心碳代谢和蛋白质消化吸收途径可能与肿瘤有关。PRM结果表明,表皮生长因子受体（EGFR）、乳酸脱氢酶A（LDHA）、磷酸甘油酸酯转位酶1（PGAM1）、己糖激酶3（HK3）和磷酸果糖激酶（PFKP）在肿瘤中表达升高并参与肿瘤中心碳代谢途径。结论:肿瘤中心碳代谢通路及相关蛋白EGFR、 PGAM1、 LDHA、 HK3、 PFKP在头颈鳞癌发生、发展中起关键作用。     

FTY720 attenuates paraquat-induced lung injury in mice

Paraquat (PQ) poisoning, with the lung as a primary target organ, is a devastating disease which irreversibly progresses to diffuse alveolitis followed by extensive lung fibrosis. In the present study, we aimed to investigate the effect of FTY720, an immune modulator, on PQ-induced lung injury in mice. C57BL/6 mice were randomized into four groups: 1) PQ group (n = 12): mice was instilled with PQ (30 mg/kg, ip); 2) PQ + FTY720 group (n = 12): animals received FTY720 (0.1 mg/kg, ip) solution 2 h after PQ exposure and twice a week for 4 consecutive weeks; 3) FTY720 group (n = 5): FTY720 (0.1 mg/kg, ip) was administrated twice a week for 4 consecutive weeks; and 4) Control group (n = 10): same volumes of saline were injected. Mice were sacrificed on either day 3 or day 28 for histopathological, biochemical and immunohistochemical analyses of lung damage indicators. We found that FTY720 treatment attenuated PQ-induced acute lung injury and lung fibrosis as evaluated by histopathological changes and Ashcroft score. On day 3, FTY720 administration reduced PQ-induced increases in lung wet weight/body weight (LW/BW), total protein and cytokine levels including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in bronchoalceolar lavage fluid (BALF). On day 28, the expressions of alpha-smooth muscle actin (α-SMA), transforming growth factor-beta (TGF-β) and vascular endothelial growth factor (VEGF) detected by immunohistochemistry, as well as the mRNA levels of α-SMA, Type-I Collagen and Type-III Collagen examined by Real-time PCR were down-regulated after FTY720 treatment. These results indicate that FTY720 could attenuate PQ-induced lung injury, but further investigation is necessary.     

Magnetic Targeting of Novel Heparinized Iron Oxide Nanoparticles Evaluated in a 9L-glioma Mouse Model

Purpose

A novel PEGylated and heparinized magnetic iron oxide nano-platform (DNPH) was synthesized for simultaneous magnetic resonance imaging (MRI) and tumor targeting.

Methods

Starch-coated magnetic iron oxide nanoparticles (“D”) were crosslinked, aminated (DN) and then simultaneously PEGylated and heparinized with different feed ratios of PEG and heparin (DNPH1-4). DNPH products were characterized by Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and superconducting quantum interference device (SQUID). The magentic targeting of DNPH3, with appropriate amounts of conjugated PEG and heparin, in a mouse 9L-glioma subcutaneous tumor model was confirmed by magnetic resonance imaging (MRI)/electron spin resonance (ESR).

Results

DNPH3 showed long circulating properties in vivo (half-life >8 h, more than 60-fold longer than that of parent D) and low reticuloendothelial system (RES) recognition in liver and spleen. Protamine, a model cationic protein, was efficiently loaded onto DNPH3 with a maximum loading content of 26.4 μg/mg Fe. Magnetic capture of DNPH3 in tumor site with optimized conditions (I.D. of 12 mg/kg, targeting time of 45 min) was up to 29.42 μg Fe/g tissue (12.26% I.D./g tissue).

Conclusion

DNPH3 showed the potential to be used as a platform for cationic proteins for simultaneous tumor targeting and imaging.