晚期NSCLC患者血液EGFR基因检测研究进展

目的:随着表皮生长因子受体酪氨酸酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI)在非小细胞肺癌(Non-Small Cell Lung Cancer,NSCLC)治疗中的应用,患者的生活质量及生存期均有很大程度的提高,但是,组织表皮生长因子受体(epidermal growth factor receptor,EGFR)检测结果为能否接受EGFR-TKI治疗的先决条件,而晚期肺癌患者却因组织量少、质量不佳、组织异质性无法进行检测,血液EGFR检测便应运而生,本研究将综述晚期非小细胞肺癌(Non-Small Cell Lung Cancer,NSCLC)患者血液EGFR基因检测研究。方法:检索Pub-med、SCI、Medline及中国生物文献数据库中晚期非小细胞肺癌患者血液EGFR基因检测的相关研究。结果:对于晚期NSCLC患者,血液EGFR基因检测有较高的敏感度与特异度,并且能够较好的预测患者对EGFR-TKI的疗效以及进行耐药监测。结论:当组织获取困难及质量不佳时,血液可替代组织行EGFR基因检测。     

稳心颗粒与瑞舒伐他汀治疗老年冠心病的临床疗效及安全性

目的:探究稳心颗粒联合瑞舒伐他汀治疗老年冠心病患者临床疗效及安全性。方法:选取42例本院收治的老年冠心病患者,按照随机数字表法分为实验组和对照组。对照组21例,予美托洛尔片25 mg,起始量12.5 mg/日口服,日2次,如无首剂反应将剂量加至25 mg/日,日2次,瑞舒伐他汀片10 mg口服,日1次;实验组21例予稳心颗粒9g温开水冲服,日3次,瑞舒伐他汀10 mg口服,日1次。治疗28天后,观察和比较两组患者治疗前后CK-MB、肝功能及临床疗效。结果:治疗后,实验组有效率(95.2%)显著高于对照组(81.0%),差异有统计学意义(P0.05)。与治疗前相比,两组患者治疗后谷草转氨酶(AST)、谷丙转氨酶(ALT)、总胆红素(TBil)、胱抑素C水平、左室射血分数(LVEF)均升高(P0.05),总胆固醇(TC)、低密度脂蛋白(LDL-C)水平及磷酸肌酸激酶同工酶(CK-MB)水平均降低(P0.05)。与对照组相比,实验组LVEF及胱抑素C水平较高(P0.05)。结论:稳心颗粒联合瑞舒伐他汀治疗老年冠心病患者可有效降低血脂,缓解患者胸闷、心悸等症状,对肝脏及肾脏功能损伤小,且安全性高。     

阻塞性黄疸患者总胆汁酸的表达及与血脂水平的关系研究

目的:探讨阻塞性黄疸(OJ)患者血清总胆汁酸(TBA)水平与血脂水平的关系。方法:选择2015年5月到2015年12月我院收治的70例OJ患者作为观察组,同期选择70例健康人员作为对照组。检测并比较两组血清TBA、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白AI(Apo AI)、载脂蛋白B(Apo B)、脂蛋白α[Lp(α)]、总胆红素(T-Bil)及直接胆红素(D-Bil)水平,并分析血清TBA与血脂水平的关系。结果:观察组患者的血清TBA、TG、TC、Apo B、T-Bil及D-Bil水平均明显低于对照组,血清LDL-C、HDL-C、Apo AI及Lp(α)水平均明显高于对照组,差异均具有统计学意义(P0.05)。Pearson直线相关性分析结果表明,血清TBA水平与血清TG、TC、Apo B、T-Bil及D-Bil呈正相关性,与血清LDL-C、HDL-C、Apo AI及Lp(α)水平呈负相关性。结论:OJ患者体内存在血脂水平紊乱,血清TBA可能是导致OJ患者血脂代谢紊乱的重要因素。     

美沙拉嗪对溃疡性结肠炎患者血清炎症因子与凝血指标的影响

目的:分析美沙拉嗪对溃疡性结肠炎患者血清炎症因子与凝血指标的影响。方法:按抽签法将102例溃疡性结肠炎患者分作对照组和研究组,各51例,对照组治疗采用柳氮磺胺吡啶,研究组治疗采用美沙拉嗪,观察两组治疗前后血清白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子α(TNF-α),血小板(PLT)、纤维蛋白原(Fg)、凝血酶原时间(PT)、D-二聚体(D-D)水平,氧化应激指标,免疫功能,临床疗效及安全性。结果:治疗后,研究组患者血清IL-1β、IL-6、IL-8、TNF-α、Fg、D-D水平及PLT均显著低于对照组,PT高于对照组,差异有统计学意义(P0.05)。研究组氧化应激过氧化脂质(LPO)、丙二醛(MDA)、超氧化物歧化酶(SOD)、免疫功能(CD3~+、CD4~+、CD8~+、CD4~+/CD8~+)改善均优于对照组(P0.05)。研究组总有效率高于对照组,不良反应率低于对照组,均有统计学差异(P0.05)。结论:美沙拉嗪治疗溃疡性结肠炎患者可显著抑制炎症,改善氧化应激状态,纠正凝血功能障碍并改善免疫功能,且临床疗效和安全性均较好。     

“Show me which parasites you carry and I will tell you what you eat”, or how to infer the trophic behavior of hematophagous arthropods feeding on wildlife

Most emerging infectious diseases are zoonoses originating from wildlife among which vector‐borne diseases constitute a major risk for global human health. Understanding the transmission routes of mosquito‐borne pathogens in wildlife crucially depends on recording mosquito blood‐feeding patterns. During an extensive longitudinal survey to study sylvatic anophelines in two wildlife reserves in Gabon, we collected 2,415 mosquitoes of which only 0.3% were blood‐fed. The molecular analysis of the blood meals contained in guts indicated that all the engorged mosquitoes fed on wild ungulates. This direct approach gave only limited insights into the trophic behavior of the captured mosquitoes. Therefore, we developed a complementary indirect approach that exploits the occurrence of natural infections by host‐specific haemosporidian parasites to infer Anopheles trophic behavior. This method showed that 74 infected individuals carried parasites of great apes (58%), ungulates (30%), rodents (11%) and bats (1%). Accordingly, on the basis of haemosporidian host specificity, we could infer different feeding patterns. Some mosquito species had a restricted host range (An. nili only fed on rodents, whereas An. carnevalei, An. coustani, An. obscurus, and An. paludis only fed on wild ungulates). Other species had a wider host range (An. gabonensis could feed on rodents and wild ungulates, whereas An. moucheti and An. vinckei bit rodents, wild ungulates and great apes). An. marshallii was the species with the largest host range (rodents, wild ungulates, great apes, and bats). The indirect method substantially increased the information that could be extracted from the sample by providing details about host‐feeding patterns of all the mosquito species collected (both fed and unfed). Molecular sequences of hematophagous arthropods and their parasites will be increasingly available in the future; exploitation of such data with the approach we propose here should provide key insights into the feeding patterns of vectors and the ecology of vector‐borne diseases.     

Sleep duration,nightshift work,and the timing of meals and urinary levels of 8-isoprostane and 6-sulfatoxymelatonin in Japanese women

It has been hypothesized that disruption of circadian rhythms affects human health. Shift work and sleep deprivation are thought to disrupt the normal light–dark cycle, although the disruption due to shiftwork may be dependent on sleep deprivation. Both conditions have been suggested to be associated with an increased risk of cardiometabolic disorders. Non-photic environmental factors, such as the timing of eating, are also thought to regulate circadian rhythm and thus, may have effects on health, but the evidence from human studies is scarce. Oxidative stress is a risk factor of cardiometabolic disorders. Some laboratory studies suggest an involvement of circadian clock genes in the regulation of the redox system. The present study aimed to examine the association of sleeping habits, nightshift work, and the timing of meals with urinary levels of 8-isoprostane, a marker of oxidative stress, and 6-sulfatoxymelatonin, the principal metabolite of melatonin. Study subjects were 542 women who had previously attended a breast cancer mass screening in a community in Japan. Information on bedtimes and wake-up times, history of nightshift work, and the timing of meals was obtained by a self-administered questionnaire. The 8-isoprostane and 6-sulfatoxymelatonin were measured using the first morning void of urine and expressed per mg of creatinine. The geometric mean of 8-isoprostane levels was 12.1% higher in women with ≤6 hours of sleep than that in those with >8 hours of sleep on weekdays, and longer sleep duration on weekdays was significantly associated with lower urinary levels of 8-isoprostane after controlling for covariates (p for trend = 0.04). Women who were currently working the nightshift had a 33.3% higher geometric mean of 8-isoprostane levels than those who were not working nightshift (p = 0.03). Urinary 6-sulfatoxymelatonin levels were unrelated to sleep habits or nightshift work. Women who ate breakfast at irregular times had a 19.8% higher geometric mean of 8-isoprostane levels than those who ate breakfast at a regular time or who did not eat (p = 0.02). Women who ate nighttime snacks at irregular times had a 16.2% higher geometric mean of 8-isoprostane levels than those who did not eat nighttime snacks or who ate nighttime snacks at a regular time (p = 0.003). Among women who ate dinner at a regular time, earlier times for dinner were associated with higher 8-isoprostane and 6-sulfatoxymelatonin levels (p values for trends were 0.01 and 0.02, respectively). However, the times of dinner and nighttime snack are overlapping, and the time of last meal of the day was not associated with 8-isoprostane and 6-sulfatoxymelatonin levels. The time of breakfast or lunch was not associated with these biomarkers among women who ate the meal at regular times. Disturbing the rhythmicity of daily life may be associated with oxidative stress.     

Effects of novel triple-stage antimalarial ionic liquids on lipid membrane models

Primaquine-based ionic liquids, obtained by acid-base reaction between parent primaquine and cinnamic acids, were recently found as triple-stage antimalarial hits. These ionic compounds displayed significant activity against both liver- and blood-stage Plasmodium parasites, as well as against stage V P. falciparum parasites. Remarkably, blood-stage activity of the ionic liquids against both chloroquine-sensitive (3D7) and resistant (Dd2) P. falciparum strains was clearly superior to those of the respective covalent (amide) analogues and of parent primaquine. Having hypothesized that such behaviour might be ascribed to an enhanced ability of the ionic compounds to permeate into Plasmodium-infected erythrocytes, we have carried out a differential scanning calorimetry-based study of the interactions between the ionic liquids and membrane models. Results provide evidence, at the molecular level, that the primaquine-derived ionic liquids may contribute to an increased permeation of the parent drug into malaria-infected erythrocytes, which has relevant implications towards novel antimalarial approaches based on ionic liquids.     

液态发酵豆粕制备纳豆激酶方法的优化

纳豆激酶是一种丝氨酸蛋白酶,具有很强的纤溶活性,由于具有安全性好、作用迅速持久、成本低等优点,适合用于开发新一代的溶栓剂或保健食品,具有广阔的市场前景。本研究探讨了以豆粕为原料液态发酵豆粕生产纳豆激酶的发酵方法。首先通过单因素实验发现影响产酶的主要因素有接菌量、发酵时间、培养基pH及豆粕含量,再由正交实验得到最优组合为接菌量1%,豆粕含量2%,pH为7.0,发酵时间48h,该条件下发酵酶活力最高达到4 429.6U/mL。本研究确定了以豆粕为原料制备纳豆激酶的最佳条件,为豆粕的合理使用和纳豆激酶的工业化生产提供了实验依据。     

In-Situ Bioremediation of DDTs and PAH Contaminated Aging Farmland Soil Using Blood Meal

The use of blood meal was studied for in-site bioremediation of contaminated farmland soil. The combination of blood meal and indigenous microorganisms helped to in-site remediate the combined contaminated aging farmland soil of DDTs and PAH in Shenyang, China. The concentration of DDTs and PAHs was 47.94 ± 0.63 μg/kg and 690.10 ± 5.16 μg/kg, respectively. Biostimulation using blood meal or glucose promoted the bioremediation rate of DDTs and PAHs. Compared to glucose, blood meal was a longer term repair additive of DDTs and PAHs, and the remediation result was more efficient and durable. In the blood meal treatment, plowing the soil once every 7 days could increase the soil enzyme activities and bacterial populations, and it could significantly promote the remediation rates of DDTs (P < 0.05) and more evidently promote the remediation rates of PAHs. The DDTs and PAHs remediation rates increased from 32.18% and 20.17% to 43.41% and 26.09%, respectively, in soil treated with blood meal and plowed weekly after the five month remediation. This study provides an highly efficient in-site farmland soil bioremediation technology that could have practical utility.     

Effects of electromagnetic pulse exposure on gelatinase of blood–brain barrier in vitro

The biological effects of electromagnetic pulse (EMP) on the brain have been focused on for years. It was reported that gelatinase played an important role in maintaining brain function through regulating permeability in the blood–brain barrier (BBB). To investigate the effects of EMP on gelatinase of BBB, an in vitro BBB model was established using primary cultured rat brain microvascular endothelial cells (BMVEC), astrocytes and half-contact culture of these cells in a transwell chamber. Cultured supernatant and cells were collected at different time points after exposure to EMP (peak intensity 400 kV/m, rise time 10 ns, pulse width 350 ns, 0.5 pps and 200 pulses). Protein levels of cellular gelatinase MMP-2 and MMP-9, and endogenous inhibitor TIMP-1 and TIMP-2 were detected by Western blot. The activity of gelatinase in culture supernatant was detected by gelatin zymography. It was found that compared with the sham-exposed group, the protein level of MMP-2 was significantly increased at 6 h (p < 0.05), and the protein level of its endogenous inhibitor TIMP-2 did not change after EMP exposure. In addition, the protein levels of MMP-9 and its endogenous inhibitor TIMP-1 did not change after EMP exposure. Gelatin zymography results showed that the activity of MMP-2 in the inner pool and the outer pool of the transwell chamber was significantly increased at 6 h after EMP exposure compared with that of the sham group. These results suggested that EMP exposure could affect the expression and activity of MMP-2 in the BBB model.