β-榄香烯治疗结直肠癌作用机制研究进展

结直肠癌具有较高的发病率和病死率,药物治疗可延长生存期,但会出现不同程度的耐药。β-榄香烯是从温郁金中提取的活性成分,具有广谱的抗肿瘤活性,可抑制肿瘤细胞生长和增殖、诱导肿瘤细胞凋亡、抑制肿瘤细胞侵袭和转移、逆转肿瘤药物耐药、联合化疗增效减毒、同步放疗增敏、改善免疫功能。综述了β-榄香烯治疗结直肠癌的作用机制研究进展,以期为β-榄香烯临床治疗结直肠癌提供参考。     

基于中性粒细胞胞外诱捕网探讨白及修复溃疡性结肠炎大鼠肠 黏膜屏障的作用及机制

目的 基于中性粒细胞胞外诱捕网(NETs)探讨白及对溃疡性结肠炎(UC)大鼠肠黏膜屏障的修复作用及机制。方法 将48只SD大鼠随机分为正常组、模型组、柳氮磺胺吡啶组(0.3 g·kg^-1)及白及低、中、高剂量组(0.3、0.6、1.2 g·kg^-1),每组8只。采用2,4,6-三硝基苯磺酸(TNBS)-乙醇灌肠法复制UC大鼠模型,造模成功后按照设定剂量灌胃给药,每日1次,连续灌胃给药21 d。在给药干预的第1、11、21天进行疾病活动指数(DAI)评分;采用HE染色法观察大鼠结肠组织病理变化;ELISA法检测大鼠血清中肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)含量;Western Blot法及免疫组化法检测大鼠结肠组织中NETs相关蛋白髓过氧化物酶(MPO)、中性粒细胞弹性蛋白酶(NE)、血管内皮生长因子(VEGF)以及紧密连接(TJs)相关蛋白封闭蛋白2(CLDN2)、闭锁小带蛋白1(ZO-1)的表达水平。结果 与正常组比较,模型组大鼠DAI明显升高(P<0.05);结肠组织黏膜层出现大面积变性坏死且肠腺结构消失...     

Relationship of body fat and left ventricular hypertrophy with the risk of all-cause death in patients with coronary artery disease

BACKGROUNDLeft ventricular hypertrophy (LVH) is prevalent in obese individuals. Besides, both of LVH and obesity is associated with subclinical LV dysfunction. The study aims to investigate the interplay between body fat and LVH in relation to all-cause death in patients with coronary artery disease (CAD).METHODSIn this retrospective cohort study, a total of 2243 patients with angiographically proven CAD were included. Body fat and LV mass were calculated using established formulas. Patients were grouped according to body fat percentage and presence or absence of LVH. Cox-proportional hazard models were used to observe the interaction effect of body fat and LVH on all-cause death.RESULTSOf 2243 patients enrolled, 560 (25%) had a higher body fat percentage, and 1045 (46.6%) had LVH. After a median follow-up of 2.2 years, the cumulative mortality rate was 8.2% in the group with higher body fat and LVH, 2.5% in those with lower body fat and no LVH, 5.4% in those with higher body fat and no LVH, and 7.8% in those with lower body fat and LVH (log-rank P < 0.001). There was a statistically significant interaction between body fat percentage and LVH ( P interaction was 0.003). After correcting for confounding factors, patients with higher body fat and LVH had the highest risk of all-cause death (HR = 3.49, 95% CI: 1.40–8.69, P = 0.007) compared with those with lower body fat and no LVH; in contrast, patients with higher body fat and no LVH had no statistically significant difference in risk of death compared with those with lower body fat and no LVH (HR = 2.03, 95% CI: 0.70–5.92, P = 0.195). CONCLUSIONA higher body fat percentage was associated with a different risk of all-cause death in patients with CAD, stratified by coexistence of LVH or not. Higher body fat was significantly associated with a greater risk of mortality among patients with LVH but not among those without LVH.

Last 40 years have witnessed sharply rise of obesity prevalence at any age and gender around the world. In the concept of obesity transition, China has been classified into stage 2, which is characterized by a significant increase of obesity prevalence in adults surpassing that among children, and a narrowing distinction between sexes.^[1] In 2012, obesity prevalence in Chinese residents aged over 18 years old is 11.9%. About 13.5% of cardiovascular deaths were attributable to high body mass index in 2017; furthermore, the direct economic burden of overweight and obesity rose to 90.768 billion yuan (RMB), which is accounted for 4.5% of total health expenditure of China in 2010.^[2] Obesity, itself or concomitant with other comorbidities, contribute to a higher risk of incident coronary artery disease (CAD).^[3] Cardiac remodeling and functional changes are also prevailing phenomena in obese individuals. A meta-analysis showed that the prevalence of left ventricular hypertrophy (LVH) in obese individuals was 56%, ranging from 20% to 85% according to different criteria of LVH.^[4] In patients with coronary artery stenosis, LVH was associated with the presence of myocardial ischemia and the extent of involvement independent of traditional cardiovascular risk factors.^[5]With in-depth research on the pathogenesis heart failure with preserved ejection fraction, increasing weight has been given to the impact of obesity and LVH on cardiovascular system.^[6] Although we are well aware of the adverse effects of body fat on cardiovascular metabolism, for patients who have been diagnosed with CAD, the role of body fat may be heterogeneous.^[7,8] In other words, for those patients, some studies have reported the phenomenon of the obesity paradox, while other studies have observed the U-shaped curve between obesity and prognosis, and some studies have not observed the relationship between obesity and better clinical endpoints.^[8,9] It is very important to clarify the association between body fat and the prognosis among patients with CAD because it will determine how to guide them on weight management. Actually, physical activity can improve the cardiopulmonary function status of patients with cardiovascular disease. Therefore, identifying which patients with obesity have a worse prognosis and need to be focused on as target population to improve management and reduce the burden of disease is worthy of further observation. Since LVH is very closely related to adipose tissue and adverse cardiovascular events, it may play an important role in the risk stratification of patients with obesity concomitant with CAD.^[10] Previous studies demonstrated that the reaction of ventricular sarcomere contractility to increased calcium stimulation was substantially depressed in severely obese patients; furthermore, LVH and obesity had a superposition effect on regional LV dysfunction.^[11,12] In this study, we investigated the interplay relationship of body fat and LVH with the risk of all-cause death in patients with CAD.     

男性对配偶围产期丧失体验的Meta整合

目的 系统整合男性对配偶围产期丧失体验的质性研究,为制订相关心理干预措施提供依据.方法 检索中国生物医学文献数据库、中国知网、PubMed、Web of Science、CINAHL、PsychINFO、Embase、Cochrane Library数据库及数据平台中有关男性对配偶围产期丧失体验的质性研究,检索时限为建...     

靶向AKT1和COX-2的RNAi抑制U251胶质瘤细胞侵袭的体外实验

目的应用RNA干扰(RNA interference,RNAi)技术敲低恶性胶质瘤细胞系U251中AKT1和COX-2表达后,在体外对细胞侵袭转移的抑制作用,初步探讨其可能的作用机制。方法构建重组腺病毒载体rAd5-A-C同时搭载靶向AKT1和COX-2的shRNA干扰序列,将其转染至恶性胶质瘤细胞系U251细胞。Realtime PCR检测RNAi后目的基因mRNA的表达水平,Western Blot检测目的基因及MMP-2、MMP-9、TIMP-2的表达情况。酶联免疫吸附试验检测转染前后分泌到细胞外的MMP-2和MMP-9的浓度变化。划痕实验和Transwell实验评价肿瘤细胞转染前后的细胞侵袭能力的变化。结果rAd5-A-C转染组AKT1和COX-2的mRNA和蛋白表达均明显抑制;MMP-2、MMP-9表达下调,TIMP-2表达则上调。ELISA检测胞外MMP-2、MMP-9浓度明显减低;划痕实验显示细胞转移运动能力明显减弱,Transwell体外侵袭实验结果显示穿过细胞数明显减低(P0.001)。结论重组腺病毒介导的RNAi技术可以序列特异性地抑制U251细胞AKT1和COX-2的表达,在体外对U251细胞侵袭转移产生明显抑制作用,可能成为恶性胶质瘤治疗的新策略。     

脑胶质瘤信号转导通路研究进展

脑胶质瘤是临床最为常见的原发性颅内肿瘤,约占颅内肿瘤的46%,占成年人全身肿瘤的2%;恶性胶质瘤的发病率为(5～8)/100万,在1998年     

RNA干扰抑制Nogo-A基因表达对PC12细胞多巴胺释放的影响

目的 研究Nogo-A基因沉默对PC12细胞多巴胺释放的影响.方法 构建靶向Nogo-A的短发夹样RNA(shRNA)真核表达载体,并经脂质体转染PC12细胞,以逆转录聚合酶链反应(RT-PCR)和免疫印迹法检测对Nogo-A mRNA及蛋白的抑制效应.采用高效液相色谱仪(HPLC)检测转染前后多巴胺释放的变化.结果 将重组质粒转染到PC12细胞48h后,Nogo-A基因表达明显受抑、多巴胺释放量减少.结论 Nogo-A可能参与PC12细胞多巴胺的释放.     

Study on Tat Mediated Having Composite Magnetic Nanoparticles Targeting Function

This paper describes a new formulation of magnetic nanoparticles coated by a novel polymer matrix-O-Carboxylmethylated Chitosan （O-CMC） as a drug/gene carrier. The O-CMC magnetic nanoparticles were derivatized with a peptide sequence from the HIV-tat protein and transferrin to improve the translocational property and cellar uptake of the nanoparticles. To evaluate the O-MNPs-Tat-Tf as a drug carrier, Methotrexate （MTX） was incorporated as a model drug and MTX-loaded O-MNPs-Tat-Tf with an average diameter of 75 nm were prepared and characterized by TEM, AFM and VSM. The cytotoxicity of MTX-loaded O- MNPs-Tat-Tf was investigated with C6 cells. The results showed that the MTX-loaded O-MNPs-Tat-Tf retained significant antitumor toxicity.     

核转染对成体骨髓源性干细胞的影响

背景:成体骨髓源性干细胞是实施细胞治疗的重要细胞来源。对成体骨髓源性干细胞的示踪,是研究其移行、分化的规律与机制并进一步阐明再生潜能、疗效的关键。目的:探讨经转染后的成体骨髓呈克隆样干细胞,在细胞表型、增殖能力、心肌分化潜能是否存在的影响。方法:应用核转染技术利用U-23程序将编码maxGFP报告基因的载体对成体骨髓呈克隆样干细胞进行转染,应用MTT法对核转染前后的生长曲线进行测定,使用3μmol/L5-氮胞苷对核转染前后成体骨髓呈克隆样干细胞进行向心肌分化诱导,并利用RT-PCR对向心肌分化的特异性标记物GATA4与MLC-2v的表达进行测定。使用成年SD大鼠心肌梗死左前降支结扎模型,对使用经maxGFP转染的成体骨髓呈克隆样干细胞施心内注射并于注射后的第2天和第7天对经注射心脏行冰冻切片并观察maxGFP在体内的表达情况。结果与结论:经核转染24h后,第47代及第119代成体骨髓呈克隆样干细胞的转染率为49.4%和43.1%,转染后5h,开始出现呈绿色荧光阳性的细胞,经核转染后仍能保持小圆球形、可贴壁、呈克隆样生长。MTT检测结果显示:核转染前后第47代及第119代均具有相似的生长曲线。核转染前第47代及119代细胞平均群体倍增时间分别为8.57,10.28h;核转染后分别为9.42,10.42h,各代前后比较差异无显著性意义(P=0.551,P=0.774)。RT-PCR检测结果显示:核转染前5-氮胞苷处理前后均表达GATA4,处理后MLC-2v条带更强;核转染后5-氮胞苷处理前后均表达GATA4,处理后MLC-2v条带更强,上述2个向心肌分化指标于转染前后变化并不明显。体内实验结果:心内注射经核转染后的成体骨髓呈克隆样干细胞,第2天及第7天可在经注射心肌中发现有少量绿色荧光阳性的细胞。提示,核转染可快速地将外源基因导入细胞,经核转染后的成体骨髓呈克隆样干细胞仍能保持其细胞形态、增殖能力及向心肌分化潜能,然而,经maxGFP基因核转染的成体骨髓呈克隆样干细胞,移植入心肌后只有少数细胞能表达经转染基因。     

静脉药物配置中心24h运行模式下批量配置顺铂方法探讨

目的探讨静脉用药调配中心（PIVAS）批量配置顺铂的操作方法,以保证患者及时、准确用药。方法实验组和对照各200支顺铂。实验组将顺铂充人溶媒后放振荡器振荡1min后放人恒温水浴中,根据水温将实验组分为5个亚组,每亚组40支顺铂,即A组（水温46oC）、B组（水温48oC）、C组（水温50oC）、D组（水温52℃）、E组（水温54℃）。放入温水中3’min后每隔1min观察顺铂溶解情