脂蛋白相关磷脂酶A2与脑梗死患者颈部动脉粥样硬化斑块的关系

目的 探讨脑梗死患者血清脂蛋白相关磷脂酶A2（lipoprotein-related phospholipase A2，Lp-PLA2）及 超敏C反应蛋白（hi gh-sensitivity C-reactive protein，hs-CRP）水平与颈部动脉粥样硬化性斑块的关系。 方法 选择2017年1月-2018年3月郑州市第三人民医院诊断为脑梗死的患者243例，另外选择同期 体检的无脑梗死患者120例作为对照组。2组研究对象均检测血清Lp-PLA2、hs-CRP水平。依据颈部动 脉超声检查结果将脑梗死患者进一步分为无斑块组、稳定斑块组和易损斑块组。 结果 ①脑梗死患者的血清Lp-PLA2（[ 180.04±35.02）ng/mL vs（152.13±39.67）ng/mL，P=0.014]、 hs-CRP[（10.02±0.47）mg/L vs（2.64±0.33）mg/L，P =0.017]水平高于对照组。②稳定斑块组 （[ 162.96±11.34）ng/mL，P=0.013]和易损斑块组（[ 197.79±32.56）ng/mL，P=0.004]Lp-PLA2水平高 于无斑块组（[ 143.67±12.35）ng/mL]；易损斑块组Lp-PLA2水平高于稳定斑块组（P=0.007），差异均 有统计学意义。③易损斑块组血清hs-CRP水平[（12.86±1.67）mg/L]高于稳定斑块组[（10.82±0.53） mg/L，P=0.029]及无斑块组（[ 9.54±0.47）mg/L，P=0.037]，差异有统计学意义。 结论 在脑梗死患者中，血清Lp-PLA2与hs-CRP可能与颈部动脉粥样硬化斑块的发生及其不稳定性 有关。     

Heparin-binding EGF-like growth factor (HB-EGF) antisense oligonucleotide protected against hyperlipidemia-associated atherosclerosis

Background and aims

Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model.

Effects of folic acid supplementation on C-reactive protein: A systematic review and meta-analysis of randomized controlled trials

Background and aim

Given the contradictory results of previous randomized controlled trials (RCTs), we performed a systematic review and meta-analysis to quantify and summarize the effects of folic acid supplementation on C-reactive protein (CRP).

槲皮素对脑出血大鼠神经细胞凋亡与Bcl-2、Bax蛋白表达的作用研究

目的通过观察大鼠脑出血后神经细胞凋亡与Bcl-2、Bax蛋白表达的动态变化及槲皮素的干预作用,探讨槲皮素可能的神经保护作用及机制。方法以雄性健康SD大鼠通过自体血注入法制备大鼠脑出血模型,并随机分为假手术组、脑出血模型组、槲皮素低剂量组、槲皮素高剂量组,共4组,每组30只;槲皮素低剂量组和槲皮素高剂量组分别给予槲皮素10、50 mg/(kg·d)腹腔内注射,假手术组和脑出血模型组给予同等体积生理盐水腹腔内注射,每日1次,连续7 d;各组大鼠分别在术后第6小时、1天、2天、3天、7天通过前肢放置试验评分法评估神经功能缺损,采用TUNEL法检测血肿周围神经细胞凋亡,采用Western blot法检测血肿周围Bcl-2和Bax蛋白的表达情况。结果与模型组比较,槲皮素低剂量组在脑出血后第3天、7天及槲皮素高剂量组在第2天、3天、7天的前肢放置试验评分和Bcl-2蛋白表达均明显增加(P<0.01);与模型组比较,槲皮素低剂量组在第3天、7天及槲皮素高剂量组在第1天、2天、3天、7天的神经细胞凋亡率和Bax蛋白表达均明显降低(P<0.01)。结论槲皮素能减轻脑出血后神经功能损伤,其机制可能与上调Bcl-2蛋白表达,下调Bax蛋白表达,从而减少神经细胞凋亡有关。     

The investigation of the effects of topiramate on the hypothalamic levels of fat mass/obesity-associated protein and neuropeptide Y in obese female rats

Objective: The aim of the present study is to investigate the effects of topiramate on the fat mass/obesity-associated protein (FTO) and on the neuropeptide Y (NPY) level in the hypothalamus depending on the recently increased prevalence of obesity.

Method: In this study, twenty-four female rats were divided into four equal groups: Non-obese control, obese control, non-obese topiramate, and obese topiramate. Obese groups were fed with a 40% high-fat diet. At the end of the 9th week, the drug treatment started and the subjects were treated with topiramate once a day for 6 weeks. All animals underwent cardiac perfusion under high-dose anesthesia on the 15th week. Tissues were analyzed using biochemical, histological, and stereological methods.

Results: In terms of neuron number in the arcuate nucleus area, a significant difference was observed among all groups (P?<?0.01). The neuron number of the non-obese topiramate group was found to be significantly higher than that of the non-obese control group (P?<?0.01). In the examination of the ventromedial nucleus of the entire group, it was observed that the neuron number of the non-obese control group was significantly lower than those of the other groups (P?<?0.01). A significant increase in the NPY levels of the obese groups compared to the groups treated with topiramate was observed. Furthermore, the amount of the FTO protein increased in obese rats, while FTO and NPY levels decreased in the groups treated with topiramate.

Discussion: In conclusion, the mechanism of the effect of topiramate to create a state of obesity is thought to involve the decrease in the levels of NPY and FTO.     

Therapeutic potential of trametinib to inhibit the mutagenesis by inactivating the protein kinase pathway in non-small cell lung cancer

Introduction:Mitogen-activated protein kinase (MAPK) pathway is known to be involved in the tumorigenesis of cancer cells including non-small cell lung cancer (NSCLC) and kinases involved in this pathway are frequently mutated. The development of new targeted therapies in cancer has led to the evaluation of MEK-inhibitors.

Areas covered: This article reviews different studies using trametinib alone, in combination with other targeted therapies or associated with other non-targeted therapies in NSCLC, with a focus on KRAS mutant and BRAF mutant NSCLC.

Expert commentary: Trametinib demonstrated activity in association with a BRAF inhibitor when BRAF was mutated. The combination of trametinib and dabrafenib has been approved for this population of BRAF mutant NSCLC patients. For KRAS mutant NSCLC, the combination of trametinib with chemotherapy has showed promising results and should be further assessed. Several clinical trials are ongoing, assessing trametinib in combination with other targeted therapies. In addition, preclinical studies suggest a synergistic effect of trametinib in combination with immune checkpoint inhibitors and such combinations should be studied in clinical trials.     

养阴利咽饮与玉液散吹喉对阴虚肺燥型慢性咽炎患者血清因子的影响

目的:探讨养阴利咽饮与玉液散吹喉对阴虚肺燥型慢性咽炎患者血清炎性因子的影响。方法:将2015年8月至2017年3月山东省淄博市第四人民医院收治的慢性咽炎患者118例作为研究对象,按治疗方法不同分为对照组和观察组,每组59例。对照组用常规西药治疗,观察组用养阴利咽饮与玉液散吹喉治疗,均连续治疗30 d。比较2组临床疗效,观察并比较治疗前后2组患者主要临床症状改善情况,唾液中分泌型免疫球蛋白A(SIgA)、血清炎性因子水平及生命质量变化。结果:治疗后观察组总有效率为91.53%,高于对照组的76.27%(P<0.05)。治疗后2组咽痛、干咳、咽黏膜充血水肿临床症状积分低于治疗前,且观察组低于对照组(P<0.01)。与治疗前比较,治疗后2组患者唾液中SIgA水平均明显升高,血清肿瘤坏死因子-α(TNF-α)及C-反应蛋白(CRP)水平均明显降低,且2组比较差异均有统计学意义(均P<0.01)。治疗后2组患者SF-36各项评分均明显高于治疗前,且观察组高于对照组(P<0.05或P<0.01)。结论:养阴利咽饮与玉液散吹喉联用可降低阴虚肺燥型慢性咽炎患者血清TNF-α、CRP水平,升高唾液中SIgA含量,改善患者临床症状,提高患者生命质量。     

支气管扩张症合并感染患者血清人分泌型磷脂酶A2-X表达情况及其与炎性指标的相关性研究

背景　支气管扩张症是呼吸系统常见病、多发病，感染是引起支气管扩张症的最常见原因。人分泌型磷脂酶A2-X（sPLA2-X）在炎性反应中发挥重要作用，并可促进炎性反应的发生、发展，而支气管扩张症合并感染患者血清sPLA2-X表达情况及其与重要炎性指标如降钙素原（PCT）、C反应蛋白（CRP）、诱导型一氧化氮合酶（iNOS）、白介素（IL）-6、IL-17、IL-33是否存在相关性尚未见相关报道。目的　研究支气管扩张症合并感染患者血清sPLA2-X表达情况及其与炎性指标--PCT、CRP、iNOS、IL-6、IL-17、IL-33的相关性，并进一步研究血清sPLA2-X对支气管扩张症合并感染的影响。方法　选取2017年2月-2019年1月在贵州省人民医院呼吸与危重症医学科住院治疗的支气管扩张症合并感染患者47例为病例组，选取同期在贵州省人民医院健康体检中心体检的健康志愿者21例为健康对照组。收集研究对象一般资料，分别检测健康对照组体检当天、观察组治疗前（入院当天）与治疗后（出院前1天）血清sPLA2-X、白细胞计数、PCT、CRP、iNOS、IL-6、IL-17、IL-33。比较两组治疗前后观察指标，分析病例组治疗前血清sPLA2-X与PCT、CRP、iNOS、IL-6、IL-17、IL-33的相关性。结果　病例组治疗前血清sPLA2-X、白细胞计数、PCT、CRP、iNOS、IL-6、IL-17、IL-33均高于健康对照组（P<0.05）；病例组治疗后血清sPLA2-X、PCT、CRP、iNOS、IL-17均高于健康对照组（P<0.05）；两组治疗后白细胞计数、IL-6、IL-33比较，差异无统计学意义（P>0.05）。病例组治疗后血清sPLA2-X、白细胞计数、PCT、CRP、iNOS、IL-6、IL-17、IL-33均低于本组治疗前（P<0.05）。病例组治疗前血清sPLA2-X与PCT、CRP、iNOS、IL-6、IL-17、IL-33均呈正相关（r=0.526 2、 0.640 1、0.550 7、0.516 8、0.609 9、0.357 4，P值均<0.01）。结论　支气管扩张症合并感染患者血清sPLA2-X升高，且其与PCT、CRP、iNOS、IL-6、IL-7、IL-33呈正相关，表明血清sPLA2-X与支气管扩张症合并感染有重要的关联，血清sPLA2-X可作为评估支气管扩张症合并感染的参考指标。     

基于PKC/P2X3通路探讨正天丸对偏头痛大鼠的保护作用

目的探讨正天丸对偏头痛大鼠的保护作用,并初步探究其可能的作用机制。方法将大鼠分为对照组(0.9%NaCl溶液)、模型组(0.9%NaCl溶液)、正天丸组(1.62 g/kg)、蛋白激酶C(PKC)激动剂组(2 mg/kg TPPB)、正天丸+TPPB组(1.62 g/kg正天丸+2 mg/kg TPPB),每组12只,采用硝酸甘油注射法制备偏头痛大鼠模型,造模后观察大鼠耳红出现、消失的时间以及不同时间段内爬笼、抓头次数;HE染色观察脑组织神经细胞形态学变化;ELISA法检测血清中TNF-ɑ、IL-6、嗜中性粒细胞趋化因子(CINC-1)水平;放射免疫法检测脑组织匀浆中降钙素基因相关肽(CGRP)、5-羟色胺(5-HT)水平;Western blot法检测脑组织PKC、P2X3蛋白表达。结果①与对照组比较,模型组0～45 min、45～75 min、75～120 min内挠头及爬笼次数增加,血清TNF-α、IL-6、CINC-1水平升高,脑组织CGRP水平升高,5-HT水平降低,PKC、P2X3蛋白表达升高(P0.05)。②与模型组比较,正天丸组挠头及爬笼次数均显著减少,耳红出现时间显著延长,耳红消失时间显著缩短,TNF-α、IL-6、CINC-1水平降低,CGRP水平降低,5-HT水平升高,PKC、P2X3蛋白表达降低(P0.05);TPPB组挠头及爬笼次数增加,耳红出现时间显著缩短,耳红消失时间显著延长,血清TNF-α、IL-6、CINC-1水平升高,脑组织CGRP水平升高,5-HT水平降低,PKC、P2X3蛋白表达升高(P0.05);正天丸+TPPB组挠头及爬笼次数、耳红消失时间、血清TNF-α、IL-6、CINC-1水平、脑组织CGRP水平、PKC、P2X3蛋白低于TPPB组,5-HT水平、耳红出现时间高于TPPB组(P0.05)。结论正天丸可缓解偏头痛大鼠神经细胞损伤,缓解头痛,其可能是通过抑制PKC/P2X3通路实现的。     

小柴胡汤对非酒精性脂肪性肝炎模型小鼠的保护作用研究

目的通过构建蛋氨酸-胆碱缺乏(MCD)饮食诱导的小鼠非酒精性脂肪性肝炎(NASH)模型,研究小柴胡汤对NASH模型小鼠的保护作用。方法选择C57BL/6小鼠为研究对象,将其随机分为对照组、模型组、小柴胡汤(高、中、低剂量)组、易善复组和强肝胶囊组。通过饲喂MCD饲料建立NASH模型,造模同时按分组给予不同药物进行干预;实验过程中记录小鼠体质量、日摄食量、日饮水量变化,实验结束对肝组织进行HE染色观察病理变化,检测血清生化指标丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、白细胞介素6(IL-6)和肿瘤坏死因子-α(TNF-α)的水平变化,检测肝组织中TC、TG的水平变化,利用q RT-PCR技术检测肝组织脂肪酸合成酶(FAS)和固醇调节元件结合蛋白1c(SREBP-1c)的表达水平。结果小鼠体质量、日摄食量、日饮水量及肝脏系数等数据显示MCD饮食诱导的模型组小鼠会出现体质量降低、摄入量减少及肝脏湿质量下降的特点,而小柴胡汤给药组小鼠体质量、摄入量及肝脏系数较模型组小鼠显著升高;HE染色结果显示小柴胡汤可明显减轻肝组织脂肪变性和炎症程度,改善肝细胞的形态和结构;生化指标检测结果显示小柴胡汤能显著降低NASH模型小鼠血清及肝组织TG、TC水平,升高血清中HDL-C水平,降低血清中AST、ALT、IL-6、TNF-α水平;q RT-PCR结果显示模型组小鼠肝组织FAS和SREBP-1c的基因表达水平明显升高,小柴胡汤可显著降低FAS和SREBP-1c的基因表达水平。结论小柴胡汤对MCD饮食诱导的NASH模型小鼠有明显保护作用,其机制可能通过调控抑制脂肪酸合成基因(FAS、SREBP-1c)的表达,减少脂肪堆积,实现调脂作用,并通过抑制炎症因子的表达改善肝组织的损伤。