子宫体、乳腺双原发癌的临床病理特征

目的 探讨子宫体、乳腺双原发癌的临床病理特征。方法 回顾性分析首都医科大学附属北京朝阳医院2004年1月至2015年1月收治子宫体、乳腺双原发癌患者（双癌组）29例和子宫体恶性肿瘤患者（单癌组）319例的临床病理资料。结果 双癌组合并糖尿病（χ²=8.02,P=0.007）、肿瘤家族史（χ²=31.76,P<0.001）及其他部位恶性肿瘤（χ²=31.76,P<0.001）的比例显著高于单癌组,双癌组Ⅱ型子宫体恶性肿瘤（χ²=5.52,P=0.030）及低分化癌（χ²=8.39,P=0.020）的构成比明显高于单癌组。单癌组的总生存率（overall survival,OS）明显优于双癌组（Log-rank=6.75,P=0.011）。分层分析显示,在双癌组中,首发子宫体癌的双癌患者Ⅱ型子宫内膜癌的构成比明显高于首发乳腺癌组（58.33%vs 11.76%,χ²=6.882,P=0.014）。首发子宫体癌与首发乳腺癌的两癌发病间隔时间显著不同,前者的间隔时间明显缩短（t=2.23,P=0.028）。两组双原发癌间隔时间的分布差异有统计学意义（χ²=9.60,P=0.010）。结论 合并乳腺癌的子宫体恶性肿瘤与子宫体恶性肿瘤的临床、病理特征不同。乳腺癌后子宫体恶性肿瘤与子宫体恶性肿瘤术后发生乳腺癌的临床、病理特征不同。     

肝力注射液逆转人肝癌细胞获得性多药耐药的体外研究

目的研究肝力注射液体外逆转人肝癌细胞5-Fu获得性多药耐药的作用。方法MTT法检测肝力注射液对人肝癌BEL-7402/5-Fu耐药细胞株的增殖抑制率及对5-Fu获得性多药耐药的逆转指数,倒置显微镜及Wright-Giemsa染色观察细胞形态学改变,流式细胞术检测细胞内阿霉素荧光强度。结果人肝癌BEL-7402/5-Fu细胞株对临床常用化疗药物显示出不同程度的交叉抗药性,肝力注射液(以苦参碱计)在0.230、0.115、0.058mg/mL3个质量浓度对人肝癌BEL-7402耐药细胞株72h的增殖抑制率分别为(9.25±2.38)%、(8.46±1.90)%、(4.23±2.05)%,对5-Fu的逆转指数分别为5.50、3.83、2.25,肝力注射液在0.230mg/mL质量浓度预处理细胞2h能提高细胞内阿霉素的量约38.61%。结论肝力注射液在体外具有逆转人肝癌细胞5-Fu获得性多药耐药的作用。     

Genetic damage induced by organic extract of coke oven emissions on human bronchial epithelial cells

Coke oven emissions are known as human carcinogen, which is a complex mixture of polycyclic aromatic hydrocarbon. In this study, we aimed to clarify the mechanism of action of coke oven emissions induced carcinogenesis and to identify biomarkers of early biological effects in a human bronchial epithelial cell line with CYP1A1 activity (HBE-CYP1A1). Particulate matter was collected in the oven area on glass filter, extracted and analyzed by GC/MS. DNA breaks and oxidative damage were evaluated by alkaline and endonucleases (FPG, hOGG1 and ENDO III)-modified comet assays. Cytotoxicity and chromosomal damage were assessed by the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The cells were treated with organic extract of coke oven emissions (OE-COE) representing 5, 10, 20, 40 μg/mL extract for 24 h. We found that there was a dose–effect relationship between the OE-COE and the direct DNA damage presented by tail length, tail intensity and Olive tail moment in the comet assay. The presence of lesion-specific endonucleases in the assays increased DNA migration after OE-COE treatment when compared to those without enzymes, which indicated that OE-COE produced oxidative damage at the level of pyrimidine and purine bases. The dose-dependent increase of micronuclei, nucleoplasmic bridges and nuclear buds in exposed cells was significant, indicating chromosomal and genomic damage induced by OE-COE. Based on the cytotoxic biomarkers in CBMN-Cyt assay, OE-COE may inhibit nuclear division, interfere with apoptosis, or induce cell necrosis. This study indicates that OE-COE exposure can induce DNA breaks/oxidative damage and genomic instability in HBE-CYP1A1 cells. The FPG-comet assay appears more specific for detecting oxidative DNA damage induced by complex mixtures of genotoxic substances.     

高频焊接仪闭合动脉血管的安全性与可靠性研究

目的:探讨高频焊接仪(HFWD)闭合动脉血管的安全性与可靠性。方法:将6头西藏小型猪均随机分为HFWD组与超声刀组(HS组),全麻后分离裸化颈、股动脉,分别采用HFWD与HS闭合离断血管。比较两组血管闭合后的爆破压、闭合时间、闭合过程中的最高温度及闭合处病理热损伤。结果:不区分血管管径大小时,HFWD组平均爆破压高于HS组(489.64 mm Hg vs.439.88 mm Hg,P0.05),当血管直径≤3 mm时,HFWD组与HS组爆破压无明显差异(593.40 mm Hg vs.572.48 mm Hg,P0.05),对于直径3~5 mm、5~7 mm的血管,HFWD组爆破压均大于HS组(457.02 mm Hg vs.404.32 mm Hg;418.51 mm Hg vs.342.84 mm Hg,均P0.05);无论血管直径大小,HFWD组闭合血管所需时间均少于超声刀(均P0.05)。HFWD组闭合处的平均最高温度低于HS组(65.91℃vs.105.25℃,P0.05);HFWD组闭合处血管壁胶原变性及血管平滑肌损伤程度轻于HS组。结论:HFWD闭合动脉血管是安全可靠的。     

基于U-Net模型从低能锥形束CT图像实现高能成像的研究

目的基于U-Net网络深度学习的方法, 实现在放疗临床中低能锥形束CT(CBCT)图像转换成高能CBCT图像, 以期提供双能CBCT成像图像基础且降低辐射剂量。方法利用放疗机载CBCT设备采集CIRS电子密度模体和CIRS头部体模在80和140 kV能量下的CBCT图像数据, 数据集按10∶1分为训练集和测试集。利用U-Net网络从低能量(80 kV)CBCT图像预测高能量(140 kV)下CBCT图像。采用平均绝对误差(MAE)、结构相似度指数(SSIM)、信噪比(SNR)和峰值信号噪声比(PSNR)4种度量指标, 定量评价预测高能CBCT图像。结果预测高能图像与真实高能图像之间总体结构差异较小(SSIM:0.993 ±0.003)。预测高能图像噪声较低(SNR:15.33±4.06), 但组织间分辨力有损失。预测高能图像比真实高能图像平均CT值偏低, 在低密度组织中差异较小(<10 HU, P > 0.05), 而在高密度组织中差异大(< 21 HU, t = -7.92, P < 0.05)。结论利用深度学习方法可以从低能CBCT图像获得结构相似度高的高能...     

凝血酶原G20210基因多态性与中国汉族人群肺血栓栓塞症的相关性

目的探讨凝血酶原基因3’端非翻译区20210 G/A多态性与中国汉族人群肺血栓栓塞症(PTE)发生的相关性。方法采用病例-对照研究,病例组为经放射性核素肺通气/灌注显像和(或)螺旋CT肺动脉造影(CTPA)检查,并结合临床资料确诊的PTE患者101例;对照组为与PTE患者来自相同地区,性别、年龄相匹配的健康对照101例。应用碘化钾-氯仿-异丙醇法提取基因组。应用聚合酶链反应(PCR)、HindⅢ限制性内切酶片段长度多态性分析(RFLP)及聚丙烯酰胺凝胶电泳(PAGE)等方法检测凝血酶原G20210多态性。结果健康对照人群GⅡ20210A位点的基因频率符合Hardy-Weinberg平衡定律,PTE病例组及对照组GⅡ20210A位点均为野生型(GG)纯合子,GA、AA基因型频率为0,A等位基因频率为0。结论凝血酶原G20210A基因多态性与中国汉族人群PTE发生可能无关。     

HPLC紫外检测法测定血浆甲磺酸瑞波西汀浓度

目的建立测定血浆甲磺酸瑞波西汀浓度的高效液相色谱检测法。方法以麦普替林为内标,取血浆样本1mL,用饱和Na2HPO4碱化后以重蒸乙醚5mL提取,再用0.2mol.L-1盐酸0.2mL反提取,80℃～100℃热水浴下氮气吹干盐酸层,用50μL流动相重组后进样。采用InertsilODS-3柱(GLSciense,5μm,4.6mm×150mm)进行分离。流动相为乙腈-50mmol/L磷酸钠缓冲液(pH=6)(40:60,v/v),流速为0.6mL.min-1,紫外检测波长210nm。结果瑞波西汀对内标的峰高比与血浆甲磺酸瑞波西汀浓度直线相关,相关系数r=0.9997,线性范围3.12～200ng.mL-1。甲磺酸瑞波西汀的最低检测限0.5ng,最低检测浓度2ng.mL-1,提取回收率在82.50%～86.08%之间,批内和批间RSD分别为2.02%～5.33%和3.83%～8.50%。结论本法具有较高的灵敏度、精密度和特异性,适用于甲磺酸瑞波西汀的药代动力学和治疗药物监测的研究。     

流行性感冒病毒裂解疫苗和23价肺炎球菌多糖疫苗改善老年人慢性阻塞性肺疾病的社区干预试验

目的 探索流行性感冒病毒裂解疫苗（流感疫苗）和23价肺炎球菌多糖疫苗（肺炎疫苗）接种对老年COPD患者症状改善效果。方法 2013年11月至2014年10月,分别在重庆市和宁波市的各3个国家级慢性病综合防控示范区各选择4个社区组,整群抽样分为流感疫苗接种组、肺炎疫苗接种组、流感疫苗与肺炎疫苗联合接种组和对照组,以COPD患者自我评估测试（COPD assessment test,CAT）结果为主要评估指标,观察并比较社区内60~75岁COPD患者疫苗接种1年后症状改善程度。采用SAS 9.4软件分析,比较COPD患者疫苗接种前后的CAT评分及其症状改善的情况。结果 对4个社区组COPD患者使用倾向评分方法进行匹配后,共纳入研究对象1 244人。基线CAT评分M=21（IQR：17~26）分。接种疫苗1年后,CAT评分M=18（IQR：14~24）分,3个疫苗接种组的CAT评分均有明显降低,差异有统计学意义（流感疫苗接种组,配对t=-6.531,P=0.403;肺炎疫苗接种组,Wilcoxon配对检验H=-9 623,P<0.001;流感及肺炎疫苗联合接种组,配对t=-10.803,P<0.001）,而对照组患者CAT评分无明显改善,差异无统计学意义（Wilcoxon配对检验M=1 167,P=0.403）。CAT分级为"严重影响"及"非常严重影响"者比例在3个疫苗接种组明显降低,对照组变化不明显。析因分析发现流感疫苗对COPD患者整体症状、以及咳嗽、胸闷、气喘、活动、外出、精力6项指标均有改善作用;肺炎疫苗对整体症状及全部8项单独指标均有改善作用。结论 对COPD患者给予流感疫苗和肺炎疫苗接种可有效改善其疾病症状。     

Multimodal investigation of dopamine D2/D3 receptors,default mode network suppression,and cognitive control in cocaine-use disorder

Stimulant-use disorders have been associated with lower availability of dopamine type-2 receptors (D2R) and greater availability of type-3 receptors (D3R). Links between D2R levels, cognitive performance, and suppression of the default mode network (DMN) during executive functioning have been observed in healthy and addicted populations; however, there is limited evidence regarding a potential role of elevated D3R in influencing cognitive control processes in groups with and without addictions. Sixteen individuals with cocaine-use disorder (CUD) and 16 healthy comparison (HC) participants completed [¹¹C]-(+)-PHNO PET imaging of D2R and D3R availability and fMRI during a Stroop task of cognitive control. Independent component analysis was performed on fMRI data to assess DMN suppression during Stroop performance. In HC individuals, lower D2R-related binding in the dorsal putamen was associated with improved task performance and greater DMN suppression. By comparison, in individuals with CUD, greater D3R-related binding in the substantia nigra was associated with improved performance and greater DMN suppression. Exploratory moderated-mediation analyses indicated that DMN suppression was associated with Stroop performance indirectly through D2R in HC and D3R in CUD participants, and these indirect effects were different between groups. To our knowledge, this is the first evidence of a dissociative and potentially beneficial role of elevated D3R availability in executive functioning in cocaine-use disorder.Subject terms: Addiction, Cognitive control     

HIV-1-specific cytotoxic T lymphocyte (CTL) responses against immunodominant optimal epitopes slow the progression of AIDS in China

To assess the immunodominance patterns of HIV-1-specific cytotoxic T lymphocyte (CTL) responses and the contribution of these responses against the peptides scanning optimal epitopes in chronic infection, we test the HIV-1-specific CTL responses against a panel of 413 overlapping peptides spanning HIV-1 Asian B sequence, including 147 peptides corresponding to optimal clade B epitopes in 49 chronically HIV-1 infected individuals by interferon-gamma Elispot assay. A large variation in the recognition of peptides restricted by the same HLA class I allele is presented. Some epitopes are targeted frequently by individuals while other epitopes restricted by the same allele are rarely recognized in our research. HLA-B35 and HLA-A03 rather than other HLA alleles contribute greatly to total virus-specific CTL responses. Furthermore, there is a significant inverse correlation between the total contribution of HIV-1-specific CTL responses restricted by different HLA alleles to virus-specific immune responses and viral load in the individuals during advanced infection (P=0.002, r=-0.549). The peptides targeted by individuals have significantly lower entropy compared with those not targeted but restricted by the same HLA class I alleles (P<0.05) in 49 individuals infected by HIV-1, especially the advanced infection subgroup (P=0.044). These data demonstrate that the consistent immunodominance patterns of HIV-1-specific CTL responses of Chinese HIV-1 infected individuals and an inverse correlation between the relative contribution of responses restricted by HLA alleles and viral load, which indicates the important protective effect of optimal epitopes against slow disease progression even in advanced infection.