The Cellular Toxicity of PM2.5 Emitted from Coal Combustion in Human Umbilical Vein Endothelial Cells

ObjectiveTo explore the relationship between different components offineparticulate matter (PM2.5) emitted from coal combustion and their cytotoxic effect in the vascular endothelial cells. MethodsCoal-fired PM2.5was sampled using a fixed-source dilution channel and flow sampler. The sample components were analyzed by ion chromatography and inductively coupled plasma atomic emission spectroscopy(ICP-AES). The PM2.5suspension was extracted using an ultrasonic water-bath method and thenhuman umbilical vein endothelial cells (EA.hy926) were treated withvarious concentrations of the PM2.5 suspension. Cell proliferation,oxidativeDNA damage, and global DNA methylation levelswere used to measurethe cellulartoxicity of PM2.5emitted fromcoalcombustion. ResultsComparedtoothertypesof coal-fired PM2.5preparations,thePM2.5 suspension from Yinchuan coal had the highest cytotoxicity.PM2.5 suspension from Datong coal hadthe highest toxic effectwhile that fromYinchuan coal had the lowest.Exposure to coal-fired PM2.5 from Jingxi coalresulted inlower 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. At the same dose, PM2.5 emitted from coal combustion could produce more severeDNAimpairmentcompared to that produced by carbon black.Cell survival rate was negatively correlated with chloride and potassiumionscontent.The5-methylcytosine(5-mC) level waspositively correlated withMnandnegatively correlated withZn levels.The 8-OHdG% level was positively correlated withboth MnandFe. ConclusionPM2.5 emitted from coal combustion can decrease cell viability, increase global DNA methylation, and causeoxidativeDNA damage inEA.hy926 cells. Metalcomponentsmay be important factors that influence cellular toxicity.     

Resveratrol relieves particulate matter (mean diameter < 2.5 μm)‐induced oxidative injury of lung cells through attenuation of autophagy deregulation

Oxidative stress and inflammation are critically implicated in ambient fine particulate matter (mean diameter < 2.5 μm; PM_2.5)‐induced lung injury. Autophagy, playing a crucial role in various physiopathological conditions, modulates cellular homeostasis and stress adaptation. Resveratrol is a phytoalexin that exerts potent antioxidant effects on cardiopulmonary diseases. To date, the mechanisms by which resveratrol protects against PM_2.5 remain to be elucidated. In the present study, we investigated the effect of resveratrol on PM_2.5‐induced oxidative injury. The potential role of nuclear factor erythroid‐2‐related factor 2 and autophagy in this progress was explored. Human bronchial epithelial cells were treated with PM_2.5 and the cytotoxicity and oxidative stress markers were determined. The results showed that PM_2.5 decreased cell viability and elevated the level of lactate dehydrogenase. The levels of malondialdehyde and reactive oxygen species were increased by PM_2.5 exposure. PM_2.5 also induced a significant increase of the inflammatory cytokines including interleukin (IL)‐6, IL‐8, IL‐1β and tumor necrosis factor α. Meanwhile, PM_2.5 triggered autophagy formation and alteration of the nuclear factor erythroid‐2‐related factor 2 pathway. Furthermore, human bronchial epithelial cells were co‐treated with PM_2.5 and resveratrol in the presence or absence of 3‐methylamphetamine, an inhibitor of autophagic formation. It was revealed that resveratrol intervention abolished PM_2.5‐induced oxidative injury partially through the suppression of autophagy deregulation. Findings from this study could provide new insights into the molecular mechanisms of pulmonary intervention during PM_2.5 exposure.     

Higher rate of hyperglycemia than hypoglycemia during Ramadan fasting in patients with uncontrolled type 1 diabetes: Insight from continuous glucose monitoring system

Background

Patients with uncontrolled type 1 diabetes mellitus (T1DM) are at a high risk for Ramadan fasting and are exempt from fasting; however, most still insist on fasting. The aim of this study was to examine glucose level fluctuations in those patients during Ramadan fasting using a real-time continuous glucose monitoring system (RT-CGMS).

Ultrafine particulate matter exposure impairs vasorelaxant response in superoxide dismutase 2-deficient murine aortic rings

Studies have linked exposure to ultrafine particulate matter (PM) and adverse cardiovascular events. PM-induced oxidative stress is believed to be a key mechanism underlying observed adverse vascular effects. Advanced age is one factor known to decrease antioxidant defenses and confer susceptibility to the detrimental vascular effects seen following PM exposure. The present study was designed to investigate the vasomotor responses following ultrafine PM exposure in wild type (WT) and superoxide dismutase 2-deficient (SOD2^+/–) mice that possess decreased antioxidant defense. Thoracic aortic rings isolated from young and aged WT and SOD2^+/– mice were exposed to ultrafine PM in a tissue bath system. Aortic rings were then constricted with increasing concentrations of phenylephrine, followed by relaxation with rising amounts of nitroglycerin (NTG). Data demonstrated that ultrafine PM decreased the relaxation response in both young WT and young SOD2^+/– mouse aortas, and relaxation was significantly reduced in young SOD2^+/– compared to WT mice. Ultrafine PM significantly diminished the NTG-induced relaxation response in aged compared to young mouse aortas. After ultrafine PM exposure, the relaxation response did not differ markedly between aged WT and aged SOD2^+/– mice. Data demonstrated that the greater vascular effect in aortic rings in aged mice ex vivo after ultrafine PM exposure may be attributed to ultrafine PM-induced oxidative stress and loss of antioxidant defenses in aged vascular tissue. Consistent with this conclusion is the attenuation of NTG-induced relaxation response in young SOD2^+/– mice.

Abbreviations: H₂O₂: hydrogen peroxide; NTG: nitroglycerin; PAH: polycyclic aromatic hydrocarbons; PE: l-phenylephrine; PM: particulate matter; ROS: reactive oxygen species; SOD2: superoxide dismutase 2 deficient; WT: wild type     

冠状动脉旁路移植手术与经皮冠状动脉介入治疗多支血管病变合并糖尿病患者的预后比较

目的比较冠状动脉旁路移植手术(CABG)与经皮冠状动脉介入(PCI)治疗多支血管病变(MVD)合并糖尿病(DM)患者的预后结果。方法连续收集2010年1月至2012年12月于咸阳市中心医院住院接受CABG和PCI的MVD合并DM患者入组。收集并获取患者基线资料,包括性别、年龄、既往病史、左心室射血分数、血生化指标、住院天数、住院费用、出院诊断等信息,并进行术后定期随访。结果本研究共收集MVD合并DM患者625例,其中接受CABG的共205例,接受PCI的共420例。与PCI组相比,CABG患者冠状动脉狭窄程度及左主干狭窄程度更严重(P<0.001),患者遭受的并发症更多(P<0.001);CABG组的主动脉内球囊反搏使用率高,住院总花费也显著偏高(P<0.001);CABG组患者的住院死亡率(1.5%)略高于PCI组患者(0.5%),但差异不显著(P>0.05);CABG组的五年生存率(98.0%)显著高于PCI组(74.5%);CABG组患者的预后显著优于PCI组,五年内发生心梗和心脑血管不良事件的概率也更低(P<0.05)。结论对于MVD合并DM患者,CABG手术的长期预后结局优于PCI手术。     

基于AMPK信号通路探讨花旗泽仁对2型糖尿病糖、脂代谢作用的实验研究

目的:基于AMPK信号通路探讨花旗泽仁对2型糖尿病糖、脂代谢的作用机制。方法:db/m小鼠10只,为空白组;db/db小鼠40只,随机分为4组,每组10只,为模型组、阳性药组(0.2 g/kg)、花旗泽仁高剂量组(32 g/kg)、花旗泽仁低剂量组(16 g/kg)。给药6周后,检测各组小鼠空腹血糖(FPG)及血清中胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C),Western blot法检测各组小鼠肝脏中单磷酸腺苷酸活化蛋白激酶(AMPK)、促进葡萄糖转运体4(GLUT4)、瘦素(Leptin)、过氧化物酶体增殖活化受体-1a(PGC-1a)蛋白质相对表达量。结果:花旗泽仁可显著降低FPG及血清中TC、TG和HDL-C的含量,上调小鼠肝脏中AMPK、GLUT4、Leptin、PGC-1a蛋白质相对表达量。结论:花旗泽仁可显著改善db/db小鼠糖、脂代谢紊乱,其作用可能与调节肝脏中AMPK相关信号通路有关。     

精蛋白生物合成人胰岛素注射液（预混30R）和门冬胰岛素30注射液的疗效、安全性比较

目的评价精蛋白生物合成人胰岛素注射液（预混30R）和门冬胰岛素30注射液治疗两种或两种以上口服降糖药失效的2型糖尿病患者的有效性与安全性。方法选择2012年2月－2012年7月在南京医科大学附属常州二院内分泌科住院治疗的使用两种或两种以上口服降糖药失效的2型糖尿病患者80例,随机分为两组。一组使用预混30R治疗,另一组使用门冬胰岛素30注射液治疗,疗程4个月。结果治疗口服降糖药失效的2型糖尿病患者4个月后,和治疗前相比,两组糖化血红蛋白、空腹血糖、三餐后两小时血糖明显降低（P〈0.05）,每日胰岛素用量较初始治疗时明显降低（P〈0.05）,总低血糖发生率、糖尿病治疗月平均费用明显增加（P〈0.05）,BMI、空腹C肽、OGTT2h C肽无明显变化。预混30R组治疗后患者低血糖发生率较治疗前增加（P〈0.05）,而门冬胰岛素30组无明显变化。治疗后两组比较,患者HbA1c、空腹血糖、BMI、空腹C肽、OGTT2h C肽无明显差异。门冬胰岛素30组三餐后血糖、低血糖发生率、每日胰岛素用量较预混30R组低（P〈0.05）,而治疗月平均费用较高（P〈0.05）。结论预混30R胰岛素注射或门冬胰岛素30注射是治疗两种或两种以上口服降糖药失效的2型糖尿病患者的安全有效的方法,能有效降低血糖,提高糖化血红蛋白达标率,但费用较单用口服降糖药高。门冬胰岛素30注射液在降低餐后血糖方面优于预混30R,且患者低血糖发生率低,胰岛素用量更少,但费用也更高。     

亚胺培南／西司他丁临床使用药物利用评价分析

目的：利用DUE模式,评价亚胺培南临床使用规范性、合理性,为临床规范合理使用提供参考。方法依据卫生部《2012年全国抗菌药物临床应用专项整治活动方案》、卫生部2012年《抗菌药物临床应用管理办法》、2011年《抗菌药物临床应用指导原则》、亚胺培南使用说明、有关文献等,制定“亚胺培南临床使用DUE标准”。并依据该标准对某医院2013年住院患者使用亚胺培南196例次病历进行抗菌药物管理、用药指征、用药过程、治疗结果4个方面进行回顾性分析、统计、总结。结果①管理项：微生物送检率70.4%（80%）;处方权限符合率91.3%（100%）;②用药指征：适合率85.2%（90%）;③用药过程：给药途径、溶媒选择、配伍禁忌正确率100%（100%）;滴注时间医嘱未注明无法评价;疗效监测项符合率52.0%（85%）;老人及肾功能损伤4例未进行剂量调整。④用药结果有效率73%（80%）。结论某医院亚胺培南临床使用与多项预期目标值存在一定差距。医院应针对存在问题进行干预和整改,确保抗菌药物的规范合理使用。认为“亚胺培南临床使用DUE标准”对临床规范、合理使用亚胺培南有一定促进作用。     

Time course of systemic oxidative stress and inflammatory response induced by an acute exposure to Residual Oil Fly Ash

It is suggested that systemic oxidative stress and inflammation play a central role in the onset and progression of cardiovascular diseases associated with the exposure to particulate matter (PM). The aim of this work was to evaluate the time changes of systemic markers of oxidative stress and inflammation, after an acute exposure to Residual Oil Fly Ash (ROFA). Female Swiss mice were intranasally instilled with a ROFA suspension (1.0 mg/kg body weight) or saline solution, and plasma levels of oxidative damage markers [thiobarbituric acid reactive substances (TBARSs) and protein carbonyls], antioxidant status [reduced (GSH) and oxidized (GSSG) glutathione, ascorbic acid levels, and superoxide dismutase (SOD) activity], cytokines levels, and intravascular leukocyte activation were evaluated after 1, 3 or 5 h of exposure. Oxidative damage to lipids and decreased GSH/GSSG ratio were observed in ROFA-exposed mice as early as 1 h. Afterwards, increased protein oxidation, decreased ascorbic acid content and SOD activity were found in this group at 3 h. The onset of an adaptive response was observed at 5 h after the ROFA exposure, as indicated by decreased TBARS plasma content and increased SOD activity. The observed increase in oxidative damage to plasma macromolecules, together with systemic antioxidants depletion, may be a consequence of a systemic inflammatory response triggered by the ROFA exposure, since increased TNF-α and IL-6 plasma levels and polymorphonuclear leukocytes activation was found at every evaluated time point. These findings contribute to the understanding of the increase in cardiovascular morbidity and mortality, in association with environmental PM inhalation.