PELP1 signaling contributes to medulloblastoma progression by regulating the NF-κB pathway

Medulloblastoma (MB) is the most common and deadliest brain tumor in children. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a scaffolding protein and its oncogenic signaling is implicated in the progression of several cancers. However, the role of PELP1 in the progression of MB remains unknown. The objective of this study is to examine the role of PELP1 in the progression of MB. Immunohistochemical analysis of MB tissue microarrays revealed that PELP1 is overexpressed in the MB specimens compared to normal brain. Knockdown of PELP1 reduced cell proliferation, cell survival, and cell invasion of MB cell lines. The RNA-sequencing analysis revealed that PELP1 knockdown significantly downregulated the pathways related to inflammation and extracellular matrix. Gene set enrichment analysis confirmed that the PELP1-regulated genes were negatively correlated with nuclear factor-κB (NF-κB), extracellular matrix, and angiogenesis gene sets. Interestingly, PELP1 knockdown reduced the expression of NF-κB target genes, NF-κB reporter activity, and inhibited the nuclear translocation of p65. Importantly, the knockdown of PELP1 significantly reduced in vivo MB progression in orthotopic models and improved the overall mice survival. Collectively, these results suggest that PELP1 could be a novel target for therapeutic intervention in MB.     

中药对肺炎克雷伯菌的抗菌作用的研究进展

肺炎克雷伯菌,因其耐药谱广,耐药率高,其治疗问题已成为世界性难题。中药具有低耐药性、多作用靶位的广谱抗菌效果,因此进行中药治疗或与西药联合治疗是一种对抗多重耐药菌的新型手段。检索近年来中国知网、万方全文和Pubmed等数据库的文献,从肺炎克雷伯的耐药机制和中药抗肺炎克雷伯菌耐药性作用等研究成果,阐述中药复合制剂以及其有效成分在临床上用于治疗肺炎克雷伯菌引起的感染的疗效及作用机制。中药可以通过抑制β-内酰胺酶、对抗生物膜的形成、对抗内毒素的作用以及抑制外排泵等起到抗肺炎克雷伯菌作用。通过对中药的抗菌作用机制进行深入研究,有助于准确全面地评价药效,为今后抗生素的合理选择提供依据。     

基于物联网的医院消防安全管理

医院消防物联网将原本与网络无关的消防设施和网络结合起来,将消防监督管理、防火灭火所需的相关信息进行汇总,可以让医院更加轻松地发现和处理医院的警情信息,降低火灾发生频率。医院火灾的特点医院是人员密集场所,发生火灾时,极容易出现踩踏等问题,进而严重威胁群众的生命财产安全。医院拥有大量贵重的医疗设备,一旦这些医疗设备发生火灾,将带来巨大损失。医院内部老弱病残者居多,发生火灾时,人员转移困难,很多患者由于自身问题难以快速逃生,增加了救护的难度。     

姜黄素对类风湿关节炎破骨细胞分化中NF-κB p65和NFATc1表达的影响

目的研究姜黄素(curcumin,Cur)对类风湿关节炎(rheumatoid arthritis,RA)破骨细胞(osteoclast,OC)分化中核因子-κB(nuclear factor kappa B,NF-κB)p65、活化T细胞核因子c1(nuclear factor of activated T cells cytoplasmic 1,NFATc1)表达的影响。方法密度梯度离心法分离RA患者外周血单个核细胞(peripheral blood mononuclear cell,PBMC),经核因子κB受体活化因子配体(receptor activator of nuclear factor-κB ligand,RANKL)和巨噬细胞集落刺激因子(macrophage colony-stimulating factor,M-CSF)诱导培养为OC,通过抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)染色及骨吸收功能检测鉴定OC,分别用不同浓度(0、2.5、5及10μmol/L)的Cur进行干预。采用CCK-8法进行Cur细胞毒性检测;计数TRAP染色阳性细胞数;Western-blotting检测NF-κB p65、NFATc1蛋白的表达;免疫荧光染色检测NF-κB p65核易位。结果 CCK-8结果示,Cur2.5、5和10μmol/L的浓度对PBMC未产生细胞毒性;TRAP染色结果示,Cur抑制RANKL诱导的RA-OC分化;Westernblotting结果示,经不同浓度Cur干预后,NF-κB p65在细胞浆中的表达明显升高,在细胞核中的表达明显降低,NFATc1的蛋白表达明显降低;免疫荧光染色结果示Cur抑制NF-κB p65核易位。结论 Cur能明显抑制NF-κB的入核表达,降低NFATc1的表达,从而抑制RA-OC的分化。     

Influence of epileptogenic region on brain structural changes in Rolandic epilepsy

Brain Imaging and Behavior - To investigate the influence of epileptogenic cortex (Rolandic areas) with executive functions in Rolandic epilepsy using structural covariance analysis of structural...     

CpG-ODN2216刺激健康人外周血淋巴细胞TH1/TH2细胞因子的表达

目的 观察CpG-ODN2216对健康人外周血单个核细胞（PBMC）中TH1/TH2淋巴细胞的极化作用,以及培养上清液中TH1/TH2型细胞因子的水平.方法 取健康献血员外周血用淋巴细胞分离液分离PBMC,与CpG-ODN2216共培养24 h,流式细胞仪检测PBMC中TH1/TH2淋巴细胞的改变,ELISA法测定培养上清液中IFN-γ、IL-2、IL-4和IL-10的释放水平.结果 CpG-ODN2216能刺激淋巴细胞向TH1、Tc1转化,对TH2无明显的刺激作用.培养上清液中IFN-γ的表达水平显著增高（P＜0.01）,IL-2、IL-4和IL-10无明显改变（P＞0.05）.结论 CpG-ODN2216可以促进外周血淋巴细胞向TH1、Tc1极化,并诱导PBMC产生高水平的TH1型细胞因子IFN-γ,介导TH1型免疫应答.     

组合式输尿管软镜钬激光碎石术治疗肾结石47例

目的评价组合式输尿管软镜钬激光碎石术治疗肾结石的临床效果。方法回顾分析我院2012年11月—2013年5月采用组合式输尿管软镜钬激光碎石术治疗肾结石患者47例。结石位于肾中、上盏8例,肾下盏16例,肾盂20例,多肾盏结石3例。结石直径5.0~30.0(16.0±4.0)mm。硬膜外麻醉下,探及结石后使用200μm光纤,0.8~1.0 J/15~20Hz(12~20 W)功率钬激光将结石击碎。术后常规留置5~6 F双J管。术后3 d内尿路平片(KUB)评价碎石效果;术后4周B超或KUB评价结石排净率。结果本组47例中,结石探及率91.5%(43/47);单次碎石成功率93.2%(41/44);手术时间65~155(125±16)min。结论组合式输尿管软镜钬激光碎石术治疗肾结石疗效确切、并发症少,是一种安全、有效的方法。     

Milrinone for the Treatment of Acute Heart Failure After Acute Myocardial Infarction: A Systematic Review and Meta‐Analysis

Despite advancements in modern medicine, the treatment of acute heart failure (AHF) after acute myocardial infarction (AMI) remains challenging. Milrinone is effective in the treatment of chronic congestive heart failure, but its safety and efficacy in patients with AHF after AMI have not been systematically evaluated. This meta‐analysis was performed to assess the safety and efficacy of milrinone in patients with AHF after AMI. We used a pre‐designed protocol to search electronic databases for randomized trials assessing milrinone for the treatment of AHF after AMI. Data were abstracted from relevant studies. Heterogeneity was assessed qualitatively using a Q test and quantified using the I² statistic. Pooled risk estimates with 95% confidence intervals (CIs) were obtained using fixed‐effects models unless substantial heterogeneity was observed (I² ≥ 50% and heterogeneity p ≤ 0.1). Four randomized trials met the inclusion criteria. However, there were no significant differences in deaths, blood pressure, premature ventricular contractions, gastrointestinal reactions, or ventricular tachycardia or fibrillation (all p > 0.05) between control group and milrinone treatment group. Pooled estimates showed that milrinone significantly increased the left ventricular ejection fraction (MD 5.69; 95% CI 4.27 to 7.10; p < 0.00001) and cardiac output (MD 0.35, 95% CI: 0.13 to 0.56; p = 0.002, I² = 24%). While studies to date are few and limited by small sample sizes and poor quality, they suggest that treatment with milrinone may be safe and effective for patients with AHF after AMI. However, this meta‐analysis did not show that milrinone could improve prognosis or the survival rate.     

多西他赛联合基质金属蛋白酶抑制剂SB-3CT对前列腺癌移植瘤生长的影响

目的 探讨多西他赛联合基质金属蛋白酶抑制剂（SB-3CT）对前列腺癌移植瘤生长的影响及其可能的作用机制。方法 用前列腺癌PC-3细胞建立裸鼠皮下移植瘤模型，随机分为SB-3CT组（注射SB-3CT溶液25 mg/kg），联合用药组（SB-3CT 25 mg/kg+静脉注射多西他赛溶液 10 mg/kg）和空白对照组（注射等量生理盐水），每组5只。测量肿瘤体积和质量并绘制生长曲线。免疫组化检测移植瘤组织中PDK1和PFKFB4的表达。结果 联合用药组、空白对照组和SB-3CT组平均瘤体质量比较差异有统计学意义（F=29.556，P=0.001），且联合用药组的肿瘤生长速度明显较空白对照组和SB-3CT组慢。免疫组化结果显示，PDK1在联合用药组、空白对照组和SB-3CT组的染色评分分别为（2.33±0.47） 分、（6.00±0.81） 分和（4.33±0.48） 分，组间比较差异有统计学意义（F=18.200，P=0.003），且联合用药组评分低于SB-3CT组（P=0.017）；PFKFB4在3组的染色评分分别为（5.33±0.49） 分、（11.33±0.47） 分和（9.00±1.41） 分，组间比较差异有统计学意义（F=17.643，P=0.003），且联合用药组评分低于SB-3CT组（P=0.011）。结论 多西他赛联合基质金属蛋白酶抑制剂SB-3CT对前列腺癌移植瘤生长具有抑制作用，糖代谢相关酶PDK1和PFKFB4表达下调可能是潜在的分子机制。