以宫腔积液为首发症状的胃型宫颈腺癌1例报道并文献复习

宫腔积液指宫腔内液体积存(积水、积血或积脓),是绝经后女性常见体征之一,常于超声检查时发现。持续宫腔积液患者,需宫腔镜检查寻找病因。本文报道1例以宫腔积液为首发症状,经宫腔镜检查确诊为胃型宫颈腺癌的患者。通过病例回顾并文献复习,以期为更多绝经后宫腔积液及宫颈病变的诊断提供参考,避免漏诊及误诊。1病例资料患者67岁,女,主因"绝经18年,不规则阴道出血2月"于2020年5月就诊于首都医科大学附属北京妇产医院妇科微创中心。     

Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.     

地鳖纤溶蛋白口服时间/pH依赖结肠靶向微囊的开发及评价＊

地鳖中的纤溶活性蛋白是从地鳖中提取的具有抗栓及抗肿瘤作用的有效成分，其口服易被上消化道酶分解从而限制了应用。采用恒流泵滴制法开发地鳖纤溶活性蛋白时间/pH依赖口服结肠靶向微囊（EnpolypHaga fibrinolytic protein oral colon targeting microcapsules， CTM-EFP）。采用单因素实验和正交实验相结合的方法寻找到包封率为60.17 % ± 2.72 %、载药量为15.50 % ± 0.44 % 的最佳配方。扫描电子显微镜（SEM）显示微囊呈球形、表面光滑，在人工肠液中24 h的累积释放度为99.53 % ± 0.69 %，在人工胃液中24 h累积释放度为7.43 ± 1.04 %，通过时间/pH依赖达到结肠靶向作用。CTM-EFP在人工肠液中的体外释放曲线符合Korsmeyer方程，提示地鳖纤溶活性蛋白（EnpolypHaga fibrinolytic protein， EFP）是通过扩散和侵蚀机制结合释放的。CTM-EFP为EFP的口服给药提供了一种新的剂型，为EFP应用于临床提供参考。     

Proteomic Profiling of Small Extracellular Vesicles Isolated from the Plasma of Vietnamese Patients with Non-Small Cell Lung Cancer Reveals Some Potential Biomarkers

Background: Considering the poor prognosis of non-small cell lung cancer (NSCLC), the objective of this study was to examine the potential of plasma-derived vesicles as a source of lung cancer-specific proteins. Extracellular vesicle (EV) cargos are specific to the source cells, hence they have the potential of being a source of cancer-specific proteins.  Methods: The proteins differently expressed in cancer were determined and derived from EVs isolated from the plasma of NSCLC patients at the National Lung Hospital. To this end, purification was done using gel filtration chromatography and ultracentrifugation. In addition, nano liquid chromatography mass spectrometry (LC–MS/MS) was used for analyzing. Results: Fifty-seven EV-derived proteins related to NSCLC were highlighted in this research. Some of them have not been addressed before, such as EEF1A1 (elongation factor 1-α1), KPNB1 (Importin subunit beta 1), SRC (proto-oncogene tyrosine-protein kinase) and ACTC1 (actin, alpha cardiac muscle 1). This list was further confirmed through a comparison with ExoCarta and Vesiclepedia. Conclusion: This study is the first work to show the involvement of several novel proteins of small EV (EEF1A1, KPNB1, SRC, and ACTC1) in the progression of NSCLC. The results suggested that they could serve as novel biomarkers for non-small cell lung cancer in the future.     

人脑胶质母细胞瘤miR-4516表达与病人预后的关系

目的 探讨人胶质母细胞瘤（GBM）组织微小核糖核酸-4516（miR-4516）的表达情况及其与病人预后的关系。方法选取 2015年 1月~2019年 5月手术切除的 GBM组织 89例和颅脑损伤内减压术切除的非肿瘤脑组织 35例为对照组，采用 qRT-PCR检测 miR-4516的表达水平，根据 miR-4516表达水平的中位数分为高表达和低表达。GBM病人术后随访 2年，记录生存情况。结果 GBM组织 miR-4516表达水平（[ 5.32±1.75）]明显高于对照组（[ 1.13±0.45）；P<0.01]。术后 2年随访，42例（47.19%）生存，47例 47（52.81%）死亡。多因素 Cox回归分析显示，miR-4516高表达是 GBM生存预后病例的独立危险因素（P<0.05）。生存曲线分析显示 miR-4516高表达组 2年累积生存率（27.45%）明显低于低表达组（73.68%；P<0.001）。结论 GBM组织 miR-4516表达增高，其高表达是病人预后不良的危险因素。     

基于网络药理学和分子对接技术分析筒鞘蛇菰多糖治疗肝损伤的作用机制及体内实验研究＊

目的 基于网络药理学探讨并分析筒鞘蛇菰（Balanophora involucrata Hook. f.，BIH）治疗肝损伤的作用及分子机制，并通过大鼠体内实验验证相关预测靶点及筒鞘蛇菰提取物-蛇菰多糖（Polysaccharides of Balanophora involucrata Hook. f.，BPS）对实验性肝损伤的保护作用。方法 化学专业数据库、TCMID和TCMSP平台检索筒鞘蛇菰组成的化合物及可能靶点，以肝损伤为关键词检索GeneCards和网站，获得相关靶点，绘制Venn图，选交集靶点，将“化合物-靶点和疾病-靶点”关系导入Cytoscape V3.7.2软件，获得化合物-靶点-疾病的三重网络，对化合物及相关靶点蛋白行分子对接，并用交集靶点绘制蛋白互作网络图及进行GO生物功能和KEGG信号途径富集分析。结果 筒鞘蛇菰主要成分有11个化合物，其中与肝损伤有37个交集靶点，高度关联靶点包括NOS3、ESR1、TNF、MAOA、PTGS2、IL10等，GO和KEGG富集分析发现筒鞘蛇菰治疗肝损伤的分子机制，可能与调节肾上腺素能信号通路、cGMP-PKG信号及神经活性配体-受体交互通路等有关，而且ADRA1B、ADRA2A、ADRA2C、ADRB1/2等基因高度富集于这些通路中。动物体内实验发现BPS灌胃处理可减轻肝组织损伤、调控血清炎症因子肿瘤坏死因子α（Tumor necrosis factor， TNF-α）和白细胞介素10（IL-10）水平、提高抗氧化酶超氧化物歧化酶（superoxide dismutase，SOD）活性，并增强肝组织内氧化应激相关蛋白核因子E2相关因子2（NF-E2-related factor 2，NRF2）和醌NADH脱氢酶1（NQO1）的表达，从而抑制大鼠体内氧化应激损伤、减轻炎症反应和细胞凋亡，达到保护实验性肝损伤的作用。结论 本研究初步确定筒鞘蛇菰治疗肝损伤的有效成分、“化合物-蛋白-靶点”关联网络及发挥作用的分子机制，并通过动物体内实验证实蛇菰多糖保护肝损伤的机制与上调NRF2/NQO1通路来减轻氧化应激反应性损伤、减轻肝细胞凋亡有关。