Hypomethylation of <Emphasis Type="Italic">hepatocyte nuclear factor-1beta (HNF-1beta)</Emphasis> CpG island in clear cell carcinoma of the ovary

Expression of hepatocyte nuclear factor-1beta (HNF-1beta) is significantly up-regulated in ovarian clear cell carcinoma (CCC). The mechanism of up-regulation, however, remains unclear. It has been recognized that hypomethylation of specific gene promoters is involved in aberrant gene expression in carcinogenesis. In the present study, ovarian CCCs were examined whether there was a correlation between the methylation and expression status of HNF-1beta, using combined bisulfite restriction analysis (COBRA), bisulfite-sequencing and immunocyto/histochemistry. In 2 CCC cell lines, hypomethylation of HNF-1beta CpG island strongly correlated with HNF-1beta expression, at both the mRNA and protein levels. In archival surgical specimens, 20 of 20 CCCs were immunohistochemically positive for HNF-1beta, whereas none of 20 serous adenocarcinomas (SAs) or 12 normal ovaries were positive for it. By COBRA, methylation of HNF-1beta CpG island was less frequently detected in CCCs (8 of 20, 40%) than SAs (18 of 20, 90%) or normal ovaries (12 of 12, 100%) (p < 0.01), which was confirmed by bisulfite-sequencing. In addition, HNF-1beta hypomethylation correlated with a high HNF-1beta immunostaining score in CCCs. These results strongly suggest that hypomethylation of the HNF-1beta CpG island participates in the HNF-1beta up-regulation in ovarian CCC.     

Design optimization for bioMEMS studies of enzyme-controlled metabolic pathways

Biological microelectromechanical systems (bioMEMS) provide an attractive approach to understanding and modifying enzymatic pathways by separating and interrogating individual reaction steps at localized sites in a microfluidic network. We have previously shown that electrodeposited chitosan enables immobilization of an enzyme at a specific site while maintaining its catalytic activity. While promising as a methodology to replicate metabolic pathways and search for inhibitors as drug candidates, these investigations also revealed unintended (or parasitic) effects, including products generated by the enzyme either (1) in the homogeneous phase (in the liquid), or (2) nonspecifically bound to microchannel surfaces. Here we report on bioMEMS designs which significantly suppress these parasitic effects. To reduce homogeneous reactions we have developed a new packaging and assembly strategy which eliminates fluid reservoirs that are commonly used for fluidic interconnects with external tubing. To suppress reactions by nonspecifically bound enzyme on microchannel walls we have implemented a cross-flow microfluidic network design so that enzyme flow for assembly and substrate/product for reaction share only the region where the enzyme is immobilized at the intended reaction site. Our results show that the signal-to-background ratio of sequential enzymatic reactions increases from 0.72 to 1.28 by eliminating the packaging reservoirs, and increases to 2.43 by separating the flow direction of enzymatic reaction from that of enzyme assembly step. These techniques can be easily applied to versatile microfluidic devices to minimize parasitic reactions in sequential biochemical reactions.     

Adjuvant therapy in patients with clear cell endometrial carcinoma: An analysis of the National Cancer Database

Objective

To assess the impact of adjuvant treatment, sociodemographic and tumor factors on the survival of patients with non-metastatic clear cell endometrial carcinoma (CCC).

清热养肝丸对慢性乙型病毒性肝炎患者免疫功能的影响

目的探讨清热养肝丸对慢性乙型病毒性肝炎患者细胞与体液免疫功能的影响。方法应用随机数字表将96例慢性乙型病毒性肝炎患者随机分为观察组和对照组（每组各48例）,观察组在常规西医治疗基础上加用清热养肝丸治疗,对照组采用常规西医治疗加安慰剂,疗程均为6个月。检测并比较患者治疗前后的血清免疫球蛋白IgA、IgG、IgM含量及T淋巴细胞亚群CD3＋、CD4＋、CD8＋、CD4＋/CD8＋比值。结果治疗后两组血清IgA、IgG、IgM水平均降低,但观察组降低幅度更大,两组之间比较,差异均有统计学意义（P〈0.05）;治疗后两组T淋巴细胞亚群CD3＋、CD4＋、CD4＋/CD8＋比值均升高,CD8＋均降低,但观察组变化幅度更大,两组之间比较,差异均有统计学意义（P〈0.05）。结论清热养肝丸具有双向免疫调节作用,可明显改善慢性乙型病毒性肝炎患者的细胞与体液免疫功能。     

滋阴泻火、清热燥湿中药对雌性大鼠肥胖和性发育相关指标的影响

目的观察滋阴泻火、清热燥湿中药对营养性肥胖大鼠的减重效果及性发育相关指标的影响。方法建立营养性肥胖动物模型，灌喂中药，观察其体重、耐疲劳能力、血清性激素水平及卵巢发育情况。结果灌喂中药后，可以使大鼠体重明显减轻，但不影响其身长和负重游泳时间，并可以使其血脂、肝脏脂肪变发生率降低；中药还可以使血中雌二醇水平、同期黄体出现率降低，下丘脑促性腺激素释放激素表达下降。结论滋阴泻火、清热燥湿中药对雌性大鼠有明显的减重作用，使肝脂肪变的发生率降低，来日J副作用，可能与该类中药调整其性腺轴、抑制肥胖时性成熟提前倾向有关。     

从中医体质学与临床证型探究肛周湿疹的病因及辨证论治

肛周湿疹属于肛肠科难治性常见病,主要症状为肛周剧烈瘙痒难忍,具有反复发作、经久不愈及易复发等特点,对患者造成很大的痛苦; 西医上认为此病是一种非传染性过敏性炎性皮肤病。中医理论认为肛周湿疹为多种病邪所致,主要包括风、湿、热三种病邪,邪客肌肤、湿热下注为其发病机制,主要与人脾气亏虚有关; 其中,湿邪为其核心病邪,脾虚为本。结合患者中医体质、临床证型分析肛周湿疹中医证型,提出以清热除湿、健脾化湿和养血润燥为药物治疗原则,方可取得良好的临床疗效。     

应用生物信息学方法分析肾透明细胞癌中FKBP11的表达

目的 探讨FK506结合蛋白11(FKBP11)在肾透明细胞癌(ccRCC)中的表达,并分析FKBP11表达水平与患者临床病理特征之间的相关性。 方法 利用Ualcan、GEPIA 数据库和HPA数据库分析FKBP11在ccRCC 组织中mRNA和蛋白表达水平的变化、FKBP11表达与ccRCC 临床及病理特征的相关性及其对患者预后的影响,通过这几个维度分析FKBP11在ccRCC中的作用。 结果 FKBP11在ccRCC中mRNA的表达较正常肾组织升高,通过Ualcan数据库检测发现FKBP11在ccRCC病理分级中正常肾组织与Grade1、Grade2、Grade3、Grade4中表达差异分别为P=5.78E-05、P=1.62E-12、P=1.11E-16、P=1.63E-12,在ccRCC亚型(ccA和ccB)中正常与ccA及ccB中表达差异均为P=1.62E-12, TNM分期中正常与N0及N1分期各亚组之间的表达有差异(P<1E-12、P=8.26E-05),以上差异均具有统计学意义(P<0.05),且随着ccRCC病理分级的升高,FKBP11的表达存在上调趋势,其表达水平与ccRCC的进展相关,而FKBP11的表达水平与年龄、性别、人种各亚组之间相互比较差异均无统计学意义(P>0.05)。FKBP11高表达患者的总生存率较低表达组患者差异有统计学意义(P<0.01)。 结论 通过检索分析数据库信息发现FKBP11在ccRCC中呈高表达,其在ccRCC的不同分期、病理分级及亚型各亚组之间存在表达差异,较差的病理分级及分期FKBP11的表达较高,且高表达的FKBP11的ccRCC患者预后较差。     

无托槽隐形矫治技术推磨牙向远中的研究进展

无托槽隐形矫治器在实现所有类型牙齿移动上,推磨牙向远中的效率最高.但临床中容易出现磨牙远中倾斜,支抗丧失等问题.该文就隐形矫治推磨牙向远中的适应证、临床疗效、远移效率、支抗设计等4个方面进行综述,为临床提供参考.     

肾透明细胞癌联合免疫治疗新策略——有氧糖酵解的研究进展及展望

肾恶性肿瘤的发病率逐年上升,其中肾透明细胞癌约占所有肾恶性肿瘤的80%,肾透明细胞癌独特的遗传背景和突变特征往往涉及以乏氧信号、糖酵解代谢、氨基酸代谢、线粒体氧化磷酸化等通路为代表的肿瘤微环境（tumor microenvironment,TME）内稳态失调。免疫检查点抑制剂（immune checkpoint inhibitor,ICI）联合酪氨酸激酶抑制剂（tyrosine kinase inhibitor,TKI）已经成为晚期肾透明细胞癌患者的一线治疗方案,但是,联合治疗方案的疗效仍有待提高,且缺乏明确诊断、指导用药、评估预后的生物标志物。近年来,多组学研究从不同层次探索肾透明细胞癌分子通路的异常改变。肾透明细胞癌发生代谢重编程,在氧气充足的情况下也以低效能的糖酵解为能量供应来源,促进自身无限生长,并且有氧糖酵解通路展现的显著异常与不良预后相关。肾透明细胞癌异常的糖酵解信号能促进肿瘤生长,并与TME中的免疫细胞相互作用,使促肿瘤免疫和抗肿瘤免疫平衡失调,造成抑制性免疫微环境,介导肿瘤免疫逃逸,从而对免疫治疗产生不利影响。因此,通过阻断异常糖代谢来抑制肿瘤生长,以有氧糖酵解通路和免疫微环境为切入点,可为肾透明细胞癌以及泛肿瘤治疗提供新的研究方向。然而,如何在复杂的肿瘤免疫微环境中最大程度地将肿瘤细胞代谢重编程转化为用药靶点并运用于临床实践仍待探讨。在肾透明细胞癌中,糖酵解抑制剂联合ICI或TKI作为新方案或能协同发挥抗肿瘤效应,逆转治疗抵抗。本文通过对糖酵解代谢途径中的关键限速酶、转运体及其抑制剂与肿瘤免疫微环境之间的关系进行综述,探讨糖酵解抑制剂在肾透明细胞癌中的作用机制和肿瘤免疫微环境的变化,及其与靶向治疗或免疫治疗联合应用的巨大临床转化价值,未来将为肾透明细胞癌的临床诊疗提供新思路,为患者带来临床获益。     

双膜透明矫治器移动兔下颌中切牙的效果评价

目的:应用双膜透明矫治器对兔下颌中切牙进行正畸移动,评价双膜透明矫治器移动牙的效果。方法:选用6只新西兰大白兔,实验组为双膜透明矫治器加力组（3只）,设计戴用3步矫治器,每一步牙移动0.33 mm,先戴用薄膜透明矫治器2 d,再戴用厚膜透明矫治器2 d;对照组为常规厚度膜片透明矫治器加力组（3只）,设计戴用3步矫治器,每一步牙移动0.20 mm,每步矫治器戴4 d。在每组兔分别戴用第1、2和3步矫治器后制取模型,测量牙移动数据。采用SPSS 19.0软件包对数据进行统计学分析。结果:2组牙移动表达的精确度从牙冠切端向龈端逐渐降低,实验组的精确度随矫治时间增加呈下降趋势,而对照组的精确度随矫治时间增加无明显变化。实验组牙冠切端、中端和龈端牙移动速率均显著大于对照组（P<0.001）。结论:兔下颌中切牙在透明矫治器的作用下产生倾斜移动。采用双膜透明矫治器矫治,牙移动速率加快,但牙移动表达的精确度降低。