Occupational exposure to diesel engine exhaust and serum cytokine levels

The International Agency for Research on Cancer has classified diesel engine exhaust (DEE) as a human lung carcinogen. Given that inflammation is suspected to be an important underlying mechanism of lung carcinogenesis, we evaluated the relationship between DEE exposure and the inflammatory response using data from a cross‐sectional molecular epidemiology study of 41 diesel engine testing workers and 46 unexposed controls. Repeated personal exposure measurements of PM_2.5 and other DEE constituents were taken for the diesel engine testing workers before blood collection. Serum levels of six inflammatory biomarkers including interleukin (IL)‐1, IL‐6, IL‐8, tumor necrosis factor (TNF)‐α, macrophage inflammatory protein (MIP)‐1β, and monocyte chemotactic protein (MCP)‐1 were analyzed in all subjects. Compared to unexposed controls, concentrations of MIP‐1β were significantly reduced by ～37% in DEE exposed workers (P < 0.001) and showed a strong decreasing trend with increasing PM_2.5 concentrations in all subjects (P_trend < 0.001) as well as in exposed subjects only (P_trend = 0.001). Levels of IL‐8 and MIP‐1β were significantly lower in workers in the highest exposure tertile of PM_2.5 (>397 µg/m³) compared to unexposed controls. Further, significant inverse exposure‐response relationships for IL‐8 and MCP‐1 were also found in relation to increasing PM_2.5 levels among the DEE exposed workers. Given that IL‐8, MIP‐1β, and MCP‐1 are chemokines that play important roles in recruitment of immunocompetent cells for immune defense and tumor cell clearance, the observed lower levels of these markers with increasing PM_2.5 exposure may provide insight into the mechanism by which DEE promotes lung cancer. Environ. Mol. Mutagen. 59:144–150, 2018. © 2017 Wiley Periodicals, Inc.     

Comparison of gene expressions in the 2-cell embryos produced in vitro from blocking and non-blocking strain mice

目的:检测阻滞品系昆明小鼠和非阻滞品系B6C3F1小鼠体外发育2-细胞胚内基因表达水平的差异,探讨昆明小鼠植入前胚体外发育阻滞与哪些基因表达调控有关.方法:分别收集昆明小鼠和B6C3F1小鼠体外培养2-细胞胚,运用基因芯片分析和Real-time PCR验证.结果:基因芯片检测共筛出差异表达基因303个,其中昆明小鼠2-细胞胚表达上调基因有168个；下调基因有135个.昆明小鼠2细胞胚表达上调的基因以信号转导、细胞周期、细胞结构和运动、细胞增殖和分化以及发育进程等为主；而下调基因与电子转移、蛋白质代谢和修饰、氨基酸代谢以及蛋白质靶向运输和定位等相关.结论:胚内能量供应不足和蛋白质合成障碍可能是昆明小鼠植入前胚体外发育出现2-细胞阻滞的重要原因.     

观察疏肝健脾法治疗月经不调的临床治疗效果及相应的护理观察

目的:探讨疏肝健脾法治疗月经不调的临床治疗效果,并总结相应护理方法。方法:选取自2017年9月-2018年9月在日照市中医医院接受诊疗的136例肝郁脾虚型月经不调患者随机分为对照组和研究组,对照组行逍遥丸治疗,并给予常规护理;研究组行逍遥散、参苓白术散治疗,并给予针对性护理,比较两组患者的治疗效果与护理满意度。结果:研究组治疗总有效率为91.18%(62/68),明显高于对照组的66.18%(45/68)(P<0.05);研究组患者护理满意率为94.12%(64/68),明显高于对照组的76.47%(52/68)(P<0.05)。结论:针对肝郁脾虚型月经不调患者,采取疏肝健脾法进行治疗具确切临床疗效,辅以针对性护理,还能提高患者护理满意度,值得推广应用。     

1例瑞舒伐他汀联用缬沙坦致梗阻性黄疸的药学监护

目的 探讨临床药师参与的1例冠心病患者联用瑞舒伐他汀和缬沙坦引起肝损害所致的梗阻性黄疸的药学监护。方法 介绍临床药师参与1例冠心病患者的治疗过程,从药理学角度分析他汀类药物引起的肝损害与剂量、代谢及其他药物相互作用的关系,并提供相关建议。结果 医师只考虑由他汀类药物引起,而临床药师利用专业知识,提出瑞舒伐他汀钙与缬沙坦胶囊的相互作用最大,建议同时停用缬沙坦胶囊。结论 通过医师与药师的合作,从而促进合理用药,保证患者用药的安全有效。同时,也为临床药师实施药学监护提供一种新的思维方式。     

Low PRRX1 expression and high ZEB1 expression are significantly correlated with epithelial-mesenchymal transition and tumor angiogenesis in non-small cell lung cancer

Background:Paired related homeobox 1 (PRRX1) and zinc finger E-box binding homeobox 1 (ZEB1) have been observed to play a vital role in the epithelial-mesenchymal transition (EMT) process in different types of cancer. The microvessel density (MVD) is the most common indicator used to quantify angiogenesis. This study aimed to investigate expression of PRRX1 and ZEB1 in non-small cell lung cancer (NSCLC) and to explore associations between these factors and tumor prognosis, EMT markers and angiogenesis.Methods:Data for a total of 111 surgically resected NSCLC cases from January 2013 to December 2014 were collected. We used an immunohistochemical method to detect expression levels of PRRX1, ZEB1, and E-cadherin, and to assess MVD (marked by CD34 staining). SPSS 26.0 was employed to evaluate the connection between these factors and clinical and histopathological features, overall survival (OS) and tumor angiogenesis.Results:PRRX1 expression was obviously lower in tumor samples than in control samples. Low expression of PRRX1, which was more common in the high-MVD group than in the low-MVD group (P = .009), correlated positively with E-cadherin expression (P < .001). Additionally, we showed that ZEB1 was expressed at higher levels in tumor samples than in normal samples. High expression of ZEB1 was associated negatively with E-cadherin expression (P < .001) and positively associated with high MVD (P = .001). Based on Kaplan-Meier and multivariate survival analyses, we found that PRRX1, ZEB1, E-cadherin and the MVD had predictive value for OS in NSCLC patients.Conclusions:These findings suggest that PRRX1 and ZEB1 may serve as novel prognostic biomarkers and potential therapeutic targets.     

左旋精氨酸对大鼠大脑皮质和海马α7 nAChR表达的影响

目的:探讨不同时间应用一氧化氮(nitric oxide,NO)前体左旋精氨酸(L-arginine,L-Arg)对大鼠学习记忆功能及大脑皮质和海马α7烟碱型乙酰胆碱受体(nicotinic acetylcholine receptor,α7 nAChR)表达的影响。方法:Wistar雄性大鼠随机分为6组,分别为连续3、7和14 d侧脑室注射L-Arg(0.5μmol/d,每日1次)的3个实验组,和在相同时间给予同剂量生理盐水的3个对照组。用Y型迷宫刺激器对大鼠进行学习和记忆能力的行为学检测;用NO试剂盒和免疫组化分别检测大鼠大脑前额叶皮质和海马NO含量以及α7 nAChR的表达。结果:大鼠的学习和记忆行为能力、大脑前额叶皮质和海马NO含量以及α7 nAChR阳性细胞数,在三个实验组分别与各自对照组比较均明显增加;在3个实验组之间比较,7 d组较3 d组,14 d组较7 d组比较均明显增加。3个时间点的对照组之间相比较上述指标均没有明显差异。结论:大鼠学习记忆行为改善以及大脑前额叶皮质和海马NO含量和α7 nAChR的表达随着应用L-Arg的延长而增加,NO对学习记忆的影响具有时间依赖性。     

β-Chemokines and neutralizing antibody titers correlate with sterilizing immunity generated in HIV-1 vaccinated macaques

One of the obstacles to AIDS vaccine development is the variability of HIV-1 within individuals and within infected populations, enabling viral escape from highly specific vaccine induced immune responses. An understanding of the different immune mechanisms capable of inhibiting HIV infection may be of benefit in the eventual design of vaccines effective against HIV-1 variants. To study this we first compared the immune responses induced in Rhesus monkeys by using two different immunization strategies based on the same vaccine strain of HIV-1. We then utilized a chimeric simian/HIV that expressed the envelope of a dual tropic HIV-1 escape variant isolated from a later time point from the same patient from which the vaccine strain was isolated. Upon challenge, one vaccine group was completely protected from infection, whereas all of the other vaccinees and controls became infected. Protected macaques developed highest titers of heterologous neutralizing antibodies, and consistently elevated HIV-1-specific T helper responses. Furthermore, only protected animals had markedly increased concentrations of RANTES, macrophage inflammatory proteins 1α and 1β produced by circulating CD8⁺ T cells. These results suggest that vaccine strategies that induce multiple effector mechanisms in concert with β-chemokines may be desired in the generation of protective immune responses by HIV-1 vaccines.