Modifiable lifestyle factors and cognitive reserve: A systematic review of current evidence

This systematic review aims to summarize cognitive reserve (CR) evaluation approaches and to examine the role of seven selected modifiable lifestyle factors (diet, smoking, alcohol consumption, physical activity, cognitive leisure activity, sleep, and meditation) in mitigating the impacts of age- or disease-related brain changes on cognition. Eighteen population-based English empirical studies were included. We summarize the study designs and identify three CR models that were broadly used in these studies, including a residual model assessing lifestyle factors in relation to unexplained variance in cognition after accounting for brain markers, a moderation model testing whether lifestyle factors moderate the relationship between brain status and cognition, and a controlling model examining the associations between lifestyle factors and cognition when controlling for brain measures. We also present the findings for the impact of each lifestyle factor. No studies examined diet, sleep, or meditation, and only two studies focused on smoking and alcohol consumption each. Overall, the studies suggest lifestyle activity factors (physical and cognitive leisure activities) may contribute to CR and attenuate the damaging impact of brain changes on cognition. Standardized measurements of lifestyle factors and CR are needed, and mechanisms underlying CR need to be further addressed as well.     

TRIM59 通过结合 BCLAF1 调控人皮肤黑色素瘤 SK-MEL-2 细胞的恶 性生物学行为

目的：探究三结构域蛋白59（TRIM59）调控人皮肤黑色素瘤细胞SK-MEL-2增殖、细胞周期、凋亡及迁移侵袭的作用机制，及其与Bcl2相关转录因子1（BCLAF1)之间的关系。方法：qPCR和WB法检测人表皮黑色素细胞HEMn-LP、人皮肤黑色素瘤细胞SK-MEL-2、UACC903、A375及36例邢台市人民医院2019年2月至2021年7月收集的皮肤黑色素瘤组织中TRIM59的mRNA和蛋白表达，使用脂质体将si-con、si-TRIM59转染至SK-MEL-2细胞中，WB法检测干扰TRIM59表达对细胞中周期蛋白D1（CCND1）、细胞周期素依赖性激酶2（CDK2）、肿瘤抑制蛋白基因（TP53）和 BCLAF1 蛋白表达的影响，CCK-8法、流式细胞术、划痕愈合实验、Transwell实验检测对细胞的活性、凋亡、迁移和侵袭的影响，免疫共沉淀（Co-IP）实验检测对细胞中TRIM59蛋白与BCLAF1结合能力的影响。结果：与HEMn-LP细胞相比，SK-MEL-2、UACC903、A375细胞中TRIM59 mRNA和TRIM59、BCLAF1蛋白均呈高表达（均P<0.05），SK-MEL-2细胞中TRIM59表达水平最高。相较于si-con组和Normal组，沉默TRIM59后，SK-MEL-2细胞的活性显著降低，细胞周期阻滞于G2期，CCND1、CDK2的蛋白表达显著降低，TP53蛋白和细胞凋亡率均显著升高，划痕抑制率明显升高，迁移侵袭细胞数明显降低（均P<0.05）。免疫共沉淀实验结果显示，TRIM59与BCLAF1之间存在蛋白结合关系。TRIM59与 BCLAF1 在肿瘤组织中的表达呈显著的正相关（r=0.878，P<0.001）。结论：干扰TRIM59表达能够抑制人皮肤黑色素瘤SK-MEL-2细胞的增殖、迁移和侵袭而促进凋亡，抑制SK-MEL-2细胞的恶性生物学行为，其机制可能与TRIM59结合BCLAF1有关。     

基于iTRAQ技术探讨人胃癌细胞乙酰肝素酶调控的信号通路北大核心

目的:探讨人胃癌细胞中乙酰肝素酶(HPSE)调控的差异蛋白和信号通路,为以HPSE为靶点防治胃癌提供依据。方法:利用siRNA干扰技术,在乙酰肝素酶(HPSE)基因高表达的SGC7901细胞中转入干扰HPSE的慢病毒载体(LV-HPSE-RNAi),通过嘌呤霉素筛选出稳定株,利用qPCR和Western blot分别检测HPSE mRNA和蛋白表达;利用细胞划痕实验和Transwell侵袭实验测定细胞的迁移和侵袭能力;利用同位素标记的相对和绝对定量(iTRAQ)联合二维液相色谱串联质谱(2DLC-MS/MS)技术筛查差异蛋白,并进行生物信息学分析,对差异蛋白PKCa应用Western blot进一步验证。结果:人胃癌SGC7901细胞和沉默HPSE表达的ZSGC7901细胞对比检测出98个差异蛋白,并且富集在157条信号通路上。与肿瘤发生发展关系密切的有6条:细胞外基质和受体相互作用、局灶性黏附、PI3K-Akt信号通路、癌途径、癌中microRNAs、Wnt信号通路。且上调的FAK、ITGA、PKCa等蛋白和下调的PKA、CDK6等蛋白在通路中处于重要的位置。Western blot结果证明PKCa在沉默HPSE的ZSGC7901细胞中表现为上调,差异具有统计学意义(P<0.05),与蛋白质组学筛选结果一致。结论:HPSE在人胃癌细胞中调控的蛋白,参与细胞重要生物学过程、参与重要分子功能及重要信号途径,有望可以成为防治胃癌的新靶点。     

Prosthetic choice in mitral valve replacement for severe chronic ischemic mitral regurgitation: Long-term follow-up

BackgroundProsthetic choice for mitral valve replacement is generally driven by patient age and patient and surgeon preference, and current guidelines do not discriminate between different etiologies of mitral valve disease. Our objective was to assess and compare short- and long-term outcomes after mitral valve replacement among patients with biological or mechanical prostheses in the setting of severe ischemic mitral regurgitation.MethodsBetween 2000 and 2016, 424 patients underwent mitral valve replacement for severe ischemic mitral regurgitation at our institution, using biological prosthesis in 188 (44%) and mechanical prosthesis in 236 (56%). A 1:1 propensity score match (n = 126 per group) and inverse probability of treatment weighting were used to compare groups. Short-term outcomes included in-hospital mortality and other cardiovascular adverse events. Long-term outcomes included survival and hospital readmission for cardiovascular causes, stroke, and major bleeding.ResultsIn-hospital mortality and early postoperative adverse events were similar between groups in the propensity score match and inverse probability of treatment weighting cohorts. Overall long-term survival was similar at 5 and 9 years, but mechanical prosthesis recipients were more frequently readmitted to hospital for cardiovascular causes, including stroke and non-neurological bleeding in propensity score matching and inverse probability of treatment weighting analyses (all P values < .004). Type of prosthesis did not independently influence all-cause mortality (hazard ratio, 1.01; 95% confidence interval, 0.71-1.43; P = .959), but placement of a mechanical prosthesis was associated with increased risk of readmission for cardiovascular events (hazard ratio, 1.65; 95% confidence interval, 1.17-2.32; P = .004) among matched patients.ConclusionsThe type of prosthesis has no influence on long-term survival among patients with severe ischemic mitral regurgitation undergoing mitral valve replacement. There may be an increased risk of neurologic events and serious bleeding associated with mechanical prostheses.     

补肾壮督方联合阿仑膦酸钠及骨水泥分期灌注椎体后凸成形术对kummell病远期临床疗效和血清标志物的影响＊

目的 探讨补肾壮督方联合阿仑膦酸钠及骨水泥分期灌注椎体后凸成形术对kummell病远期临床疗效和血清标志物的影响。方法 选取90例2019年1月-2020年3月因kummell病住院手术治疗的患者，随机分为试验组45例和对照组45例。对照组给予骨水泥分期灌注椎体后凸成形术，术后口服阿仑膦酸钠治疗，试验组术后加用补肾壮督方口服治疗。记录两组术中骨水泥注入量。采用VAS疼痛评分标准评估术后疼痛改善情况，采用ODI评分评估功能障碍改善情况。采用伤椎前缘高度比值和伤椎椎体楔形角评估脊柱稳定性。采用碱性磷酸酶（ALP），骨钙素（OC），骨保护素（OPG）评估治疗前后血清骨形成情况。结果 与对照组比较，试验组术后第3天VAS疼痛评分明显低于对照组，差异有统计学意义（P<0.05）；试验组术后第3天、术后6个月和术后12个月ODI评分明显低于对照组，差异有统计学意义（P<0.05）；试验组术后6个月和术后12个月伤椎前缘高度比值明显高于对照组，差异有统计学意义（P<0.05）；试验组术后6个月和术后12个月伤椎椎体楔形角明显低于对照组，差异有统计学意义（P<0.05）。试验组术后6个月和术后12个月碱性磷酸酶（ALP），骨钙素（OC），骨保护素（OPG）明显高于对照组，差异有统计学意义（P<0.05）。结论 补肾壮督方联合阿仑膦酸钠及骨水泥分期灌注椎体后凸成形术治疗kummell病可加快术后患者疼痛改善和功能恢复，促进骨形成，有效抑制患者中远期椎体压缩塌陷，维持脊柱稳定性。     

健脾消癌方通过PI3K/Akt信号通路抑制结肠癌血管生成的研究＊

目的 观察结肠癌HCT116细胞健脾消癌方的条件培养液对HUVEC细胞管腔形成的影响，从PI3K/Akt生物轴调控角度探讨其作用机制。方法 培养HCT116细胞，细胞设3组：对照组，健脾消癌方组（加入15%健脾消癌方含药血清）及人参皂苷Rg3组；制备HCT116细胞健脾消癌方条件培养液（分组及制备方法见实验方法），用条件培养液干预HUVEC（脐静脉内皮细胞，Human Umbilical Vein Endothelial Cells），Matrigel基质胶法检测HCT116细胞健脾消癌方条件培养液对HUVEC小管形成的影响。随后采用蛋白免疫印迹法（Western blot）检测各组HCT116细胞磷脂酰肌醇3-激酶（PI3K）、蛋白激酶B（Akt）、p-Akt、VEGF（血管内皮生长因子，Vascular endothelial growth factor）蛋白表达。最后在结肠癌HCT116荷瘤小鼠中验证健脾消癌方对肿瘤生长速度的影响，并经瘤组织VEGF蛋白表达、CD31免疫组化染色检测肿瘤内血管生成情况。结果 模型组HUVEC细胞管腔形成较空白血清组显著增加（P<0.05）；健脾消癌方组及人参皂苷Rg3组较模型组HUVEC细胞管腔形成显著减少（P<0.01）。p-Akt和VEGF蛋白表达水平模型组高于空白血清组（P<0.05），健脾消癌方组及人参皂苷Rg3组显著低于模型组（P<0.01）；PI3K、Akt蛋白表达量组间差异无统计学意义。与对照组比较，模型组荷瘤小鼠肿瘤体积显著性增大，瘤组织内VEGF表达、CD31阳性面积显著性增加，差异有统计学意义（P<0.05）；与模型组比较，健脾消癌方组及人参皂苷Rg3组荷瘤小鼠肿瘤体积显著减小，瘤组织内VEGF表达、CD31阳性面积降低，差异有统计学意义（P<0.05）。结论 健脾消癌方可抑制肿瘤的血管生成和生长，其作用机制可能与PI3K/Akt生物轴调控VEGF表达有关。     

泽泻化学成分及药理作用研究进展

泽泻为我国传统中药,广泛应用于中医临床复方及多种中成药中。目前从泽泻中分离到了220余个化合物,包括三萜、倍半萜、二萜、糖类、含氮化合物、苯丙素、黄酮、甾体等。药理学研究表明泽泻醇提物、水提物及一些单体类成分具有利尿、抗结石及肾脏保护、降血脂及保肝、降血糖、抗癌、抗氧化损伤、抗炎、抗补体等作用。该文对近五十年来泽泻的化学成分和药理作用进行了全面系统的整理,以期为泽泻的深入研究和开发利用提供理论依据。     

肿瘤标志物检验在胃癌诊断中的临床价值分析

目的分析探讨肿瘤标志物检验在胃癌诊断中的临床价值。方法选择在本院进行治疗的胃癌患者40例,将其列为观察组,选取体检健康者40例,将其列为普通组,具体的选择时间为2018年2月-2019年2月,对两组患者的CEA、CA72-4、CA19-9水平及阳性表达率进行比较分析。结果观察组患者CEA、CA72-4、CA19-9明显高于普通组,差异具有统计学意义(P<0.05)。观察组患者的肿瘤标志物阳性表达率明显高于普通组,差异具有统计学意义(P<0.05)。结论肿瘤标志物在胃癌的诊断中具有非常重要的意义,肿瘤标志物对胃癌患者的诊断较为确切,利于患者的确诊及后期治疗,从而提高患者的生命及生活质量。     

清肠解毒方对大肠癌术后复发化疗患者肿瘤标记物水平及生活质量的影响

摘 要 目的: 探讨清肠解毒方对大肠癌术后复发化疗患者的生活质量及肿瘤标记物水平的影响。方法:选取出现复发的大肠癌患者60例，随机分为观察组与对照组各30例。两组化疗方案均为奥沙利铂联合卡培他滨或者盐酸伊立替康联合卡培他滨，观察组加用清肠解毒方治疗。比较两组患者治疗前后血清CEA、AFP、CA 125、CA 199水平与ECOG评分变化。结果: 两组患者治疗后血清CEA、AFP、CA 125、CA 199水平显著低于治疗前（P＜0.05）。此外，治疗后观察组患者的血清CEA和CA 199水平显著低于对照组（P＜0.05）。生活质量方面，治疗后两组患者ECOG评分均显著低于治疗前，差异有统计学意义（P＜0.05）；且观察组患者治疗后ECOG评分显著低于对照组，差异有统计学意义（P＜0.05）。结论: 清肠解毒方能够明显改善大肠癌术后化疗患者的生活质量，降低血清肿瘤标记物浓度，值得临床应用。     

The effect of nettle (Urtica dioica) supplementation on the glycemic control of patients with type 2 diabetes mellitus: A systematic review and meta‐analysis

Type 2 diabetes mellitus (T2DM) is a major health problem, worldwide, that is associated with increased morbidity and mortality. Several randomized controlled clinical trials (RCTs) have investigated the effect of nettle (Urtica dioica) supplementation on markers of glycemic status in patients with T2DM, with conflicting results. Therefore, the present study assessed the effect of nettle on some glycemic parameters in patients with T2DM. A comprehensive search was conducted in PubMed, Scopus, Cochrane Library, and Web of Science, from database inception up to June 2019, to identify RCTs investigating the effect of nettle supplementation on glycemic markers, including fasting blood sugar (FBS) concentrations, insulin levels, homeostasis model assessment‐estimated insulin resistance index, and glycosylated hemoglobin percentage in adults with T2DM. The Cochrane Collaboration tool was used to assess the methodological quality of the included studies. Results of this meta‐analysis were reported based on the random effects model. Eight RCTs, comprising 401 participants, were included in the present systematic review and meta‐analysis. Based on the Cochrane Collaboration risk of bias tool, five studies were considered as good quality, one was fair, and two studies were poor, respectively. The results of the meta‐analysis revealed a significant reduction in FBS concentrations (weighted mean difference [WMD]: ?18.01 mg/dl, 95% confidence interval [CI]: ?30.04 to ?5.97, p < .001, I² = 94.6%) following nettle supplementation. However, no significant reduction was observed in insulin levels (WMD: 0.83 Hedges' g, 95% CI: ?0.26 to 1.92, p = .13, I² = 89.4%), homeostasis model assessment‐estimated insulin resistance index (WMD: ?0.22, 95% CI: ?0.83 to 0.40, p = .49, I² = 69.2%), or glycosylated hemoglobin percentage (WMD: ?0.77%, 95% CI: ?1.77 to 0.22, p = .12, I² = 83.0%). The findings of the present study suggest that nettle supplementation may be effective in controlling FBS for T2DM patients. However, further studies are needed to confirm the veracity of these results.