Prognostic validity of the American joint committee on cancer eighth edition staging system for well-differentiated pancreatic neuroendocrine tumors

BackgroundThe American Joint Committee on Cancer (AJCC) made improvements for staging pancreatic neuroendocrine tumors (pNETs) in its 8th Edition; however, multicenter studies were not included.MethodsWe collected multicenter datasets (n = 1,086, between 2004 and 2018) to validate the value of AJCC 8 and other coexisting staging systems through univariate and multivariate analysis for well-differentiated (G1/G2) pNETs.ResultsCompared to other coexisting staging systems, AJCC 7 only included 12 (1.1%) patients with stage III tumors. Patients with European Neuroendocrine Tumor Society (ENETS) stage IIB disease had a higher risk of death than patients with stage IIIA (hazard ratio [HR]: 4.376 vs. 4.322). For the modified ENETS staging system, patients with stage IIB disease had a higher risk of death than patients with stage III (HR: 6.078 vs. 5.341). According to AJCC 8, the proportions of patients with stage I, II, III, and IV were 25.7%, 40.3%, 23.6%, and 10.4%, respectively. As the stage advanced, the median survival time decreased (NA, 144.7, 100.8, 72.0 months, respectively), and the risk of death increased (HR: II = 3.145, III = 5.925, and IV = 8.762).ConclusionThese findings suggest that AJCC 8 had a more reasonable proportional distribution and the risk of death was better correlated with disease stage.     

1H nuclear magnetic resonance-based metabolic profiling of cerebrospinal fluid to identify metabolic features and markers for tuberculosis meningitis

BackgroundTuberculosis meningitis (TBM) is the most severe form of tuberculosis, and currently lacks efficient diagnostic approaches. Metabolomics has the potential to differentiate patients with TBM from those with other forms of meningitis and meningitis-negative individuals. However, no systemic metabolomics research has compared the cerebrospinal fluid (CSF) of these patients.Methods¹H nuclear magnetic resonance (NMR) was used for CSF metabolic profiling. Principal component analysis and orthogonal signal correction-partial least squares-discriminant analysis (OPLS-DA) were used to screen for important variables. The Human Metabolome Database was used to identify metabolites, and MetaboAnalyst 4.0 was used for pathway analysis and over-representation analysis.ResultsOPLS-DA modeling could distinguish TBM from other forms of meningitis, and several significantly changed metabolites were identified. Additionally, 23, 6, and 21 metabolites were able to differentiate TBM from viral meningitis, bacterial meningitis, and meningitis-negative groups, respectively. Pathway analysis indicated that these metabolites were mainly involved in carbohydrate and amino acid metabolism, and over-representation analysis indicated that some of these pathways were over-represented.ConclusionsThe metabolites identified have the potential to serve as biomarkers for TBM diagnosis, and carbohydrate and amino acid metabolism are perturbed in the CSF of patents with TBM. Metabolomics is a valuable approach for screening TBM biomarkers. With further investigation, the metabolites identified in this study could aid in TBM diagnosis.     

奥沙利铂通过调控miRNA-7-5p/RAF-1促进胃癌SGC-7901细胞凋亡的研究

目的探讨奥沙利铂如何调控MAPK通路,抑制胃癌细胞的增殖。方法NCBI检索文献,利用TargetScan、StarBase和miRBase数据库,进行GO分析与KEGG通路富集,找到相关miRNAs,预测靶基因。应用Real-time PCR、MTT、Hoechst33258、流式细胞术、细胞划痕实验、Western blot等方法分析人胃癌SGC-7901细胞的增殖、细胞周期、侵袭及蛋白表达情况。结果胃癌细胞中miR-7-5p显著低表达,RAF1与miR-7-5p存在互靶关系。miR-7-5p mimics与奥沙利铂均可促进SGC-7901细胞的凋亡,提高G1期细胞百分率(P<0.05),降低侵袭、迁移速度。caspase3、caspase9蛋白表达升高,Bcl-2/Bax比值降低(P<0.05)。结论过表达miR-7-5p与奥沙利铂均可促进胃癌SGC-7901细胞的凋亡,提示奥沙利铂可能通过上调miRNA-7-5p促进SGC-7901细胞的凋亡,降低侵袭、迁移速度。     

CTLA4-Ⅰg对老年支气管哮喘病人CD4^＋CD45RO^＋T细胞功能的影响

目的 研究老年支气管哮喘病人周围血CD4^＋CD45RO^＋T细胞表达IL4及IL-13的情况及CTLA4-Ⅰg对其影响。方法 用ELISA方法测定老年支气管哮喘病人CD4^＋CD45RO^＋T细胞产生IL-4和IL-13的水平及CTLA4-Ⅰg对其影响。结果 老年支气管哮喘病人CD4^＋CD45RO^＋T细胞分泌IL4、IL-13增多，IL-13增多较IL-4更为明显（P〈0．01），CTLA4-Ⅰg可有效抑制老年哮喘病人CD4^＋CD45RO^＋T细胞分泌IL-4和IL-13（P〈0．01）。结论 CD4^＋CD45RO^＋T细胞产生的IL-4和IL-13在老年哮喘发病中起重要作用，CTLA4-Ⅰg可有效抑制IL-4和IL-13的分泌。     

低能体外冲击波和低剂量间歇人重组甲状旁腺激素1-34刺激对体外培养大鼠成骨细胞增殖分化的影响

目的探讨低能体外冲击波（ESW）和低剂量间歇人重组甲状旁腺素1-34（rhPTH1-34）对体外培养大鼠成骨细胞（ROBs）增殖和成骨分化的影响。方法分别用不同次数的低能ESW刺激、不同浓度及作用方式的rhPTH1-34刺激，以及ESW和低剂量间歇性rhPTH1-34刺激共同作用于ROBs后，用细胞计数、MTY和流式细胞术细胞周期分析检测ROBs的增殖，用酶标仪检测ALP活性，用免疫组化检测I型胶原表达来观察ROBs成骨分化。结果60～150次0．18mJ／mm^2 ESW刺激、间歇性rhPTH1-34（1×10^-11和1×10^-10 mol／L）刺激以及ESW＋间歇性rhPTH1-34（1×10^-11mol／L）刺激均可显著促进体外培养ROBs细胞增殖和成骨分化（与对照组比较，P〈0．05）；其中60～150次ESW刺激＋间歇性rhPTH1-34（1×10^-11 mol／L）刺激各组作用最强。结论适当的ESW应力刺激和低剂量间歇性rhPTH1-34刺激可显著促进体外培养ROBs细胞增殖和成骨分化，两者联合应用作用最强。     

低剂量辐射增强小鼠肿瘤基因-放射治疗效应的免疫学机制研究

目的 探讨低剂量辐射全身照射对小鼠Lewis肺癌移植肿瘤基因-放疗方案中的免疫增强作用机制。方法 小鼠右后肢皮下接种Lewis肺癌细胞建立荷瘤模型,基因-放疗组中小鼠肿瘤局部注射由多聚乙烯亚胺包裹的pEgr-IL18-B7.1重组质粒,分别接受由2 Gy 局部照射和0.075 Gy 全身照射组合的不同治疗方案,通过³H-TdR标记方法检测小鼠CTL和NK细胞毒活性,ELISA方法检测TNF-α和IFN-γ分泌活性,观察各治疗组对荷瘤小鼠抗肿瘤免疫的作用。结果 在pEgr-IL18-B7.1基因治疗方案中,单次大剂量辐射局部照射后加多次低剂量全身照射与常规多次大剂量辐射局部照射相比,小鼠CTL和NK细胞毒活性显著增强,TNF-α和IFN-γ分泌活性有不同程度的增高。 结论 低剂量辐射可以通过促进CTL和NK细胞毒效应,上调TNF-α和IFN-γ细胞因子表达,从而增强机体抗肿瘤免疫功能,提高肿瘤基因-放疗的抑瘤效果。     

β-catenin和核因子-κB表达与胃癌的相关性研究

目的研究核因子-κB(NF-κB)和β-catenin在胃癌及癌前病变中的表达及与胃癌临床病理特征的关系。方法应用免疫组化检测72例胃癌组织及12例正常胃组织中NF-κBp65与β-catenin表达。结果β-catenin和NF-κBp65在胃癌组织中的阳性表达率明显高于正常胃组织(P<0.05),二者在胃癌组织中的阳性表达率为65.3%和61.1%。β-catenin的表达与肿瘤病理分化程度、有无淋巴结转移、病理分型、浸润深度密切相关(P<0.05)。NF-κBp65的表达与肿瘤大小、有无淋巴结转移、病理分型、肿瘤浸润深度密切相关(P<0.05)。结论β-catenin和核因子-κB在胃癌组织表达有相关性,提示其与胃癌的发生、发展和转移有关,二者可作为判断胃癌预后的指标和化疗的靶向。     

过量氟对大鼠肾组织骨桥蛋白表达的影响

目的检测骨桥蛋白(OPN)mRNA和蛋白在氟处理大鼠肾组织中的表达差异和蛋白定位,并探讨OPN与氟中毒肾损害的关系。方法经饮水投氟喂养Wistar大鼠48只,用免疫组织化学法进行骨桥蛋白的组织学检测。提取各组大鼠肾组织mRNA,采用RT-PCR法检测骨桥蛋白mRNA的表达变化。结果免疫组织化学结果表明,骨桥蛋白主要定位于肾组织的肾小管上皮细胞质中,常食和偏食对照组大鼠肾组织OPN蛋白只是散在表达,而常食和偏食加氟组的OPN蛋白表达较相应对照组明显增强(与常食对照组比较,q=18．4,P< 0．05;与偏食对照组比较,q=12．0,P<0．01)。2个投氟组的OPN mRNA表达水平均较相对应的对照组增加,但差异无统计学意义。结论过量氟可促进大鼠。肾组织OPN表达,且随着投氟量的增加,OPN伴随着肾损伤加重而表达增强,提示OPN与氟中毒肾损伤程度密切相关,很可能作为一种氟中毒肾损害的预测标志。     

β—半乳糖苷酶核酸免疫初探

将带有编码β－半乳糖苷酶基因片段的质粒ｐＳＶ－β－Ｇａｌａｃｔｏｓｉｄａｓｅ通过股四头肌接种小鼠，利用ＥＬＩＳＡ方法检测鼠体内β－半乳糖苷酶获得得表达后刺激机体产生抗β－半乳糖苷酶抗体的情况。