甲状腺良、恶性病变中增殖细胞核抗原、P_(53)蛋白与AgNOR的检测及相关性研究

本文应用ＬＳＡＢ免疫组织化学方法及ＡｇＮＯＲ技术对７３例甲状腺良、恶性病变ＰＣ－ＮＡ、Ｐ５３蛋白及ＡｇＮＯＲ进行了检测并对其相关性进行了研究。结果显示①ＰＣＮＡ表达在良、恶性病变中有显著差异（Ｐ＜０．０１）;②ＡｇＮＯＲ颗粒均数及其形态在良、恶性病变中有较显著差异;③ＰＣＮＡ表达与ＡｇＮＯＲ计数呈显著正相关性（Ｐ＜０．０１）;④Ｐ５３蛋白在良、恶性病变中的表达均呈阴性,只是在淋巴结转移灶内呈阳性表达。根据研究我们认为检测甲状腺良、恶性病变中ＰＣＮＡ及ＡｇＮＯＲ颗粒对甲状腺良、恶性病变的鉴别、预后及对临床治疗均有意义     

乳腺癌ConA、LCA、PSA免疫组化研究

运用ＡＢＣ法研究５０例乳腺癌三种凝集素受体（Ｌｅｃｔｉｎ－Ｒ）的表达,并以乳腺纤维瘤和乳腺小叶增生症各１０例作为对照。结果表明：该三种凝集素受体在乳腺良、恶性病变中的表达率无显著性差异。ＣＯｎＡ－Ｒ在乳腺癌以胞浆型定位为主,在纤维腺瘤则以胞膜型多见（Ｐ＜０．０５）。ＬＣＡ－Ｒ和ＰＳＡ－Ｒ在乳腺三种病变中均以胞浆型为主。ＣｏｎＡ－Ｒ与乳腺癌分化程度具良好的相关性;ＬＣＡ－Ｒ与乳腺癌瘤体大小有关。该三种凝集素受体与ＥＲ、ＰＲ及ＣＥＡ的表达未显示密切的关联。     

AgNOR染色对甲状腺良、恶性病变诊断价值的研究

本文应用ＡｇＮＯＲ染色技术对７３例甲状腺良恶性病变石蜡切片核仁组成区变化进行观察,其中包括亚急性甲状腺炎５例、腺瘤２５例、结节性甲状腺肿７例、甲状腺癌３６例,结果表明亚急性甲状腺炎、腺瘤、结节性甲状腺肿,细胞核内的ＡｇＮＯＲ颗粒均数及形态与甲状腺癌的均数及形态比较有显著性差异（Ｐ＜０．０１）。我们认为此方法对于区别甲状腺良、恶性病变有一定参考价值。     

胃癌细胞DNA含量、AgNOR计数与其生物学特性关系的研究

本文使用图像分析技术测定了正常胃粘膜、萎缩性胃炎、不典型增生及胃癌共８９例细胞ＤＮＡ相对含量及ＤＮＡ倍体分布;并用银染方法对８９例细胞核仁形成区嗜银蛋白进行定量分析。结果显示：不典型增生往往可观察到与胃癌相似的ＤＮＡ核型即高异倍体的出现,高异倍体的出现可能是重要的癌前标志;在胃粘膜病变中,ＡｇＮＯＲ值随病变异型程度的加重而递增,各组间差异均有非常显著性意义（Ｐ＜０．０１）。早期癌、浸润癌和转移癌间,以及癌转移过程中粘膜层、肌层、淋巴结内癌细胞ＤＮＡ含量无明显差异;ＡｇＮＯＲｓ计数均值差异亦无非常显著性意义（Ｐ＞０．０５）。随癌细胞分化程度升高,ＤＮＡ含量增多及异倍体出现率升高;各期胃癌除粘激腺癌与分化型腺癌差异无显著性意义外,余各型胃癌ＡｇＮＯＲｓ值随分化程度升高而增多,差异有显著性意义（Ｐ＜０．０５或Ｐ＜０．０１）。因此,ＤＮＡ含量及倍体分析,ＡｇＮＯＲｓ计数与胃癌的生物学行为密切相关,可作为胃癌早期诊断,癌前病变预测以及组织分级的一种重要指标。     

眼镜蛇毒心脏毒素对人肺癌A549细胞株的遗传毒性研究

探讨蛇毒心脏毒素（ＣＴＸ）对人肺癌Ａ５４９细胞株的遗传毒性。方法应用眼镜蛇毒（ＣＴＸ）处理体外培养的人肺癌Ａ５４９细胞株,通过细胞生长速率、有丝分裂指数（ＭＩ）、细胞周期动力学指数（ＣＫＩ）、银染核仁组织区计数（ＡｇＮＯＲ）、姐妹染色单体交换（ＳＣＥ）频率、二倍体细胞比率的分析,观察ＣＴＸ所产生的遗传毒性作用。结果ＣＴＸ能明显抑制肺癌Ａ５４９细胞的ＤＮＡ复制过程和ｒＲＮＡ的合成,且随着浓度增大,癌细胞受抑制程度越大。用２ｍｇ／ＬＣＴＸ作用肺癌细胞后,ＳＣＥ频率比对照组明显下降（Ｐ＜０．０１）,但对照组和实验组出现的二倍体细胞比率差异不明显（Ｐ＞０．０５）。结论眼镜蛇毒ＣＴＸ可抑制肺癌细胞的生长恶性程度,但使其恶性表型逆转的作用不明显。     

第二信使介导模拟低氧下丘脑CRF分泌

用模拟高原低氧的方法研究急性低氧条件下促肾上腺皮质激素释放因子（ｃｏｒｔｉｃｏｔｒｏｐｉｎ－ｒｅｌｅａｓｉｎｇｆａｃｔｏｒ,ＣＲＦ）分泌的变化及第二信使参与ＣＲＦ分泌的作用。低氧（海拔７ｋｍ）１ｈ后,正中隆起（ｍｅｄｉａｎｅｍｉｎｅｎｃｅ,ＭＥ）处ＣＲＦ含量明显下降（Ｐ＜０．０５）,下丘脑（ｈｙｐｏｔｈａｌａｍｕｓ,Ｈｙ）ＣＲＦ（不含ＭＥ）含量无明显变化,而Ｈｙ内ｃＡＭＰ含量明显增加（Ｐ＜０．０１）。脑室注射Ｆｏｒｓｋｌｉｎ、ＴＰＡ后低氧暴露（海拔５ｋｍ）１ｈ,ＭＥＣＲＦ含量下降（Ｐ＜０．０５;Ｐ＜０．０５）,ＨｙＣＲＦ无明显变化。脑室注射Ｆｏｒｓｋｌｉｎ后ＨｙｃＡＭＰ含量升高（Ｐ＜０．０５）。脑室注射Ｈ７和ＰＫＡ抑制剂,ＭＥＣＲＦ升高（Ｐ＜０．０５;Ｐ＜０．０１）,ＨｙＣＲＦ和ＨｙｃＡＭＰ均无显著变化。上述结果表明急性低氧应激中ＣＲＦ分泌显著增加,第二信使通路ＰＫＡ和ＰＫＣ通路均参与ＣＲＦ分泌     

AgNORs异型颗粒在乳腺癌细胞核中的观察分析

本文报道了核仁组成区嗜银蛋白（ＡｇＮＯＲｓ）在乳腺癌细胞核中的一组异型颗粒——字母样结构“ＣＥＩＪＲＳＴＵＲＹＸ”等,乳腺良性病变无此结构。研究结果表明,字母样结构在浸润性导管癌中多见,在乳头状癌中未见。结合乳腺癌的临床分期分析,临床分期越高,有字母样结构的乳腺癌所占比分也越高。同时,有字母样结构的乳腺癌组其ＡｇＮＯＲｓ含量和颗粒形态的异型性均明显高于无字母样结构的乳腺癌组。在讨论中认为,ＡｇＮＯＲｓ字母样结构对鉴别诊断乳腺癌可能有一定的形态学参考价值     

金黄色葡萄球菌L型的药敏试验分析

本文从血液和骨髓标本中分离出的金黄色葡萄球菌Ｌ型,分别用Ｌ型平板和ＭＨ平板做药敏试验,结果显示庆大霉素（ＧＥＮ）、氯霉素（ＣＭＰ）、红霉素（ＥＲＹ）、氧哌青霉素（ＰＩＰ）、卡那霉素（ＫＡＮ）、万古霉素（ＶＡＮ）在ＭＨ平板上比在Ｌ型平板上的药物敏感率高,耐药中低（Ｐ＜０．０５）;而氨苄青霉素（ＡＭＰ）、羧苄青霉素（ＣＡＲ）、先锋霉素（ＣＥＦ）、丁胺卡那霉素（ＡＫＮ）、氟哌酸（ＦＰＡ）、先锋必（ＥＦＯＢＩＤ））、螺旋霉素（ＳＰＩ）药物敏感中比Ｌ型平板上低,耐药率高（Ｐ＜０．０５）。苯唑青霉素（ＯＸＡ）、菌必治（ＲＯＣ）、利福平（ＲＩＦＰ）、麦迪霉素（ＭＩＤ）则在两种培养基上的敏感和耐药率基本相同（Ｐ＞０．０５）。     

动情周期中大鼠输卵管上皮凝集素受体的研究

大鼠动情周期包括动情前期（ＰＥ）、动情期（Ｅ）、动脉后期（ＭＥ）和动情间期（ＤＥ）。采用生物素标记的５种凝集素（ＣｏｎＡ、ＰＮＡ、ＲＣＡ、ＵＥＡ－Ｉ以及ＷＧＡ）对大鼠动情周期中输卵管上皮细胞的凝集素受体进行了研究,发现在大鼠动情周期中输卵管粘膜上皮细胞凝集素受体均有不同程度的变化：其中,ＣｏｎＡ的阳性反应以ＰＥ组最强,ＤＥ组最弱（Ｐ＜０．０１）;ＰＮＡ的阳性反应以Ｅ组最强,ＤＥ组为阴性;ＲＣＡ的阳性反应强度以ＰＥ和Ｅ组最强,ＤＥ组最弱（Ｐ＜０．０１）;ＵＥＡ－Ⅰ的阳性反应颗粒可见于动情周期各期,但以ＰＥ组为强（Ｐ＜０．０１）,其它各期间的反应强度差异无显著性（Ｐ＞０．０５）;ＷＧＡ的阳性反应以ＤＥ组最强,与其它各组比较,差异有高度显著性（Ｐ＜０．０１）,其它各组之间阳性反应强度差异无显著性（Ｐ＞０．０５）。说明输卵管上皮细胞的糖组分在动情周期中发生了某些变化。推测这些变化有利于输卵管功能活动的进行     

去甲肾上腺素刺激高原鼠兔CRF的分泌

用脑室注射神经递质去甲肾上腺素（ＮＥ）和ＲＩＡ法测定下丘脑正中隆起处促肾上腺皮质激素释放激素（ＣＲＦ）水平,研究ＮＥ对高原鼠兔下丘脑ＣＲＦ分泌的作用。脑室给予不同剂量ＮＥ３．７５,７．５,１５,３０μｇ／１００ｇＢＷ．正中隆起（ＭＥ）处ＣＲＦ含量分别增加到对照组的１０６．０５％,１３５．２８％（Ｐ＜０．０５）,１３８．９４％（Ｐ＜０．０１）,１０３．６５％,同时,血浆皮质酮浓度也分别增加到对照组的３２３．３５％（Ｐ＜０．０１）,３２３．３５％（Ｐ＜０．００１）,３４６．７１％,３６６．４７％。肾上腺切除后２天和６天时,下丘脑ＮＥ下降到对照的７６．３２％（Ｐ＜０．０５）,７６．２７％（Ｐ＜０．０１）,血浆皮质酮也下降到１６．５７％（Ｐ＜０．０１）,２．０５％（Ｐ＜０．００１）。上述结果表明,ＮＥ刺激高原鼠兔下丘脑ＣＲＦ的分泌并激活下丘脑垂体肾上腺皮质轴。肾上腺皮质激素对维持下丘脑ＮＥ水平和ＣＲＦ神经元活动有一定的紧张作用     

Correlation between AgNOR count and subjective AgNOR pattern assessment score in cytology and histology of breast lumps.

OBJECTIVE: To find the correlation of argyrophilic nucleolar organizer region (AgNOR) count and subjective AgNOR pattern assessment (SAPA) score in cytology and histology of breast lumps. STUDY DESIGN: The study group consisted of 73 patients (46 malignant, 27 benign) with breast lumps. In all cases, fine needle aspiration cytology (FNAC) samples and histologic specimens were studied by conventional and silver staining for AgNORs. RESULTS: AgNOR count and SAPA score were helpful in differentiating benign from malignant tumors in both the cytologic smear and histologic specimen. AgNOR count was 6.94+/-2.74 in FNAC and 6.57+/-2.73 in histology of malignant tumors, while in benign tumors it was 2.75+/-0.74 in FNAC and 2.68+/-0.77 in histology. SAPA score was 9.02+/-4.60 in FNAC and 8.76+/-2.34 in histology in malignant tumors and 5.87+/-0.93 in FNAC and 5.82+/- 0.83 in histology in benign tumors. CONCLUSION: Both AgNOR count and SAPA score gave similar results, but SAPA score is a more convenient, reproducible and rapid method of AgNOR evaluation.     

乳腺良恶性病变剪切波弹性成像的典型表现及其鉴别诊断价值

目的:观察乳腺良恶性病变的剪切波弹性成像(SWE)的典型表现,探讨SWE对乳腺良恶性病变的鉴别诊断价值。方法:选取2017年6月～2019年6月我院收治的162例行SWE检查的乳腺肿块患者,经组织活检或病理证实良性肿块105例(良性组)、恶性肿块57例(恶性组)。对比良、恶性组SWE的典型表现、SWE参数[最大值(Emax)、最小值(Emin)、平均值(Emean)、标准差(SD)、病灶与邻近脂肪弹性比值(SWE-Ratio)]的差异,分析SWE鉴别诊断乳腺良恶性病变的价值。结果:恶性组乳腺肿块"硬边征"检出率、Ⅲ型～Ⅴ型弹性图像检出率、Emax、Emean、SD、SWE-Ratio均高于良性组(P0.05),Emin低于良性组(P0.05)。Logistic多元回归分析结果显示,"硬边征"、Emax、Emean、SWE-Ratio与病理诊断乳腺肿块性质独立相关(P0.05)。受试者工作特征(ROC)曲线分析结果显示,"硬边征"、Emax、Emean、SWE-Ratio鉴别诊断乳腺良恶性病变的曲线下面积(AUC)分别为0.923、0.686、0.873、0.879。结论:SWE是诊断乳腺良恶性病变的有效影像手段,SWE的"硬边征"、SWE-Ratio、Emean对乳腺良恶性病变具有较高的鉴别价值。     

肿瘤标志物联合检测在乳腺癌早期诊断中的应用

目的:探讨肿瘤标志物癌胚抗原(CEA)、糖链抗原19-9(CA19-9)、糖链抗原15-3(CA15-3)联合检测在乳腺癌早期诊断中的应用价值。方法:检测87例乳腺癌患者,55例乳腺良性肿瘤患者和35例健康人血清中CEA、CA19-9、CA153等肿瘤标志物的水平及3种标志物不同组合对乳腺癌的阳性检出率。结果:乳腺癌患者3种肿瘤标志物显著高于正常对照组及乳腺良性肿瘤组(P<0.01)。3项标志物不同组合对不同分期乳腺癌检出的敏感性均高于单项标志物。其中CEA+CA199+CA153组合的检出敏感性较其他组合均高,特别是对早期患者检出率明显提高。结论:CEA+CA199+CA153联合检测能提高乳腺癌的早期诊断率。     

Morphometric analysis of AgNORs in nonkeratinizing carcinoma and adjacent normal epithelia in the nasopharynx

OBJECTIVE: To evaluate the proliferative activity of different types of nonkeratinizing carcinoma and adjacent normal epithelia in the nasopharynx by the quantitative assessment of argyrophilic nucleolar organizer region (AgNOR) proteins. STUDY DESIGN: Silver staining of nucleolar organizer regions (NORs) was applied to 70 paraffin sections of nonkeratinizing carcinoma in nasopharyngeal biopsies. Fifty-four of the 70 cases had differentiated nonkeratinizing carcinoma (DNC), and the remaining 16 had undifferentiated carcinoma (UC). Nineteen of these 70 samples proved to contain, besides carcinoma, normal epithelia (NE), which was used as a control. The epithelial cells and cancer cells were analyzed for their AgNOR features by image cytometric analysis. RESULTS: As compared with normal epithelia, significant differences were found in mean nuclear area, AgNOR count, mean AgNOR area, AgNOR area ratio and AgNOR area/count ratio between NE and DNC (P < .05) and in mean nuclear area, mean AgNOR area and AgNOR area/count ratio between NE and UC (P < .001). Further, the differences in mean nuclear area, mean AgNOR area and AgNOR area/count ratio were statistically significant between DNC and UC. CONCLUSION: The evaluation of AgNORs is a useful histologic assessment of rapidity of cell proliferation in malignant and benign lesions and demonstrated that UC had more rapidly proliferative activity than DNC in this study.     

结合素-4（nectin-4）在乳腺癌中表达及其临床意义研究

目的：观察乳腺癌患者血清及乳腺组织中结合素4的表达并探讨其临床意义。方法：选择2007年6月至2008年12月哈尔滨医科大学附属三院收集的40例乳腺癌患者和20例乳腺良性肿瘤患者为研究对象,分为正常对照组、乳腺癌组、乳腺良性肿瘤组,采用Elisa法和免疫组化法对所选择的血清及组织标本中nectin-4及血清中癌胚抗原（CEA）、CA153的表达进行检测。结果：（1）nectin-4的阳性表达定位于细胞质和细胞膜,其在乳腺癌组织中的阳性表达率显著高于乳腺良性组织（P〈0．05）;nectin-4的表达与患者的年龄、临床分期无关（P〉0．05）,但与乳腺癌的病理类型、腋窝淋巴结转移与否、Her-2、ER和PR的表达均显著相关（P〈0．05）。②乳腺癌组血清nectin-4表达水平最高,为238＋4．95pg／ml;乳腺良性病变组为1205：3．28pg／ml;正常对照组为104±5．86pg／ml,三者之间比较,差别有统计学意义（P〈0．01）。③与正常对照组、乳腺良性病变组比较,乳腺癌组血清CEA、CAl53水平均明显升高,差异有显著统计学意义（P〈0．01）。④nectin-4、CEA和CA153诊断乳腺癌的敏感性分别为31．67％、43-33％、28．33％,特异性分别为92．50％、95％、95％,三者联合检测诊断乳腺癌的敏感性较单独检测显著升高（P〈0．05）,可达81．67％。结论：Nectin-4在乳腺癌中高表达,且与乳腺癌的病理类型、腋窝淋巴结转移与否、Her-2、ER和PR的表达均呈显著相关,通过联合检测血清nectin-4、CEA和CA153水平可显著提高乳腺癌诊断的敏感性,有助于乳腺癌的治疗和预后评估,值得临床进一步深入研究。     

3.0 T磁共振扩散加权成像在乳腺良恶性病变鉴别中的价值及较优b值下ADC值与预后因子相关性研究

摘要 目的：研究3.0 T磁共振扩散加权成像在乳腺良恶性病变鉴别中的价值及较优b值下ADC值与预后因子的相关性。方法：选取2017年11月～2019年11月于我院接受诊治的乳腺病变患者50例进行研究,将其按照良恶性差异分成恶性组40例与良性组10例,另取同期于我院体检的健康志愿者50例作为对照组。对所有人员均进行3.0 T磁共振扩散加权成像,比较不同b值下ADC值在不同乳腺组织中的差异,比较不同b值下诊断乳腺良恶性病变的效能,分析较优b值下ADC值和乳腺癌患者各项预后因子的相关性。结果：对照组、良性组、恶性组在不同b值下的ADC值均呈逐渐降低趋势（P＜0.05）;对照组、良性组、恶性组b值为1000 s/mm²下的ADC值均低于b值为600 s/mm²（P＜0.05）。b值为1000 s/mm²时诊断乳腺恶性病变的敏感度、特异度、准确度分别为92.50%、100.00%、94.00%,高于b值为600 s/mm²的70.00%、60.00%、68.00%（P＜0.05）。b值为1000 s/mm²下雌激素受体、孕激素受阳性患者的ADC值低于阴性患者,而人类表皮生长因子受体2阳性患者的ADC值高于阴性患者（P＜0.05）。经Spearman相关性分析可得,b值为1000 s/mm²下ADC值与雌激素受体、孕激素受体阳性表达均呈负相关关系,而与人类表皮生长因子受体2阳性表达呈正相关关系（P＜0.05）。结论：3.0 T磁共振扩散加权成像在乳腺良恶性病变鉴别中的价值较高,且以b值为1000 s/mm²的诊断能效较优。此外,b值下ADC值和乳腺癌部分预后因子表达状态密切相关。     

胃癌survivin基因mRNA和蛋白的表达与临床病理关系

目的　研究胃癌组织中survivin基因的mRNA和蛋白表达情况及其与临床病理参数的关系。方法　应用原位杂交方法和免疫组化SP法检测 5 4例胃癌 ,34例胃良性病变 ,2 0例胃正常组织标本中survivin基因mRNA及蛋白的表达。并对其与临床病理因素和二者的关系进行分析。结果　Survivin蛋白表达阳性率在胃癌、良性疾病组织和正常组织分别为 87 0 % (47/ 5 4 )、 2 3 5 % (8/ 34)和 15 % (3/ 2 0 ) ;SurvivinmRNA阳性率为 79 6 % (43/ 5 4 )、 2 3 5 % (8/ 34)和2 0 % (4/ 2 0 )。胃癌组远大于正常胃组织和良性疾病组 ,而正常胃组织与胃良性疾病组之间差异无显著性。SurvivinmRNA与蛋白在胃癌中的表达呈正相关 (rs=0 6 79,P <0 0 5 )。且其阳性率高低与性别、年龄、组织学类型无关 ;而与淋巴结转移、TNM分期、组织学分级有关。结论　SurvivinmRNA与蛋白在胃癌中表达较高 ,且与淋巴结转移、TNM分期、组织学分级有关 ,它可作为评估胃癌生物学行为和判断预后的生物学指标。     

Levels of circulating cell-free serum DNA in benign and malignant breast lesions

PURPOSES OF THE STUDY: We analyzed circulating cell-free DNA in the serum of patients with benign and malignant breast disease and in healthy individuals to determine its diagnostic value. BASIC PROCEDURES: Serum samples were obtained from 50 healthy individuals, 33 patients with malignant breast disease and 32 patients with benign breast disease. Circulatory DNA was extracted from serum samples. Cell-free DNA was quantified by real-time quantitative PCR for the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. Tissue samples from patients with malignant and benign breast lesions were histopathologically examined. MAIN FINDINGS: The mean levels of circulating cell-free DNA in serum samples were 41,149 genome equivalents (GE)/mL in patients with malignant disease, 30,826 GE/mL in patients with benign disease, and 13,267 GE/mL in healthy individuals. Healthy individuals had significantly lower levels of cell-free DNA than patients with malignant or benign breast disease (p=0.001, p=0.031). No significant difference was observed between malignant and benign disease. There was a correlation between cell-free DNA levels and tumor size but not with other tumor characteristics. PRINCIPAL CONCLUSION: Our results suggest that levels of circulating cell-free DNA in serum could have diagnostic value to discriminate between healthy individuals and patients with breast lesions but not between patients with malignant and benign breast lesions.     

Significance of AgNOR measurement in thyroid lesions

OBJECTIVE: To evaluate the discriminating potential of AgNOR area measurement and count in thyroid tumors using static cytometry equipment. STUDY DESIGN: Slides were analyzed by a computerized system for image analysis, CAS 200 (Becton & Dickinson, U.S.A.), using the Cell Measurement computer program (CAS 200, Becton & Dickinson). The argyrophilic reaction (NORs) was evaluated with a 400-fold amplification directly from the computer monitor. RESULTS: Thirty-three cases were analyzed for AgNOR staining. The cases studied included 3 goiters, 10 follicular adenomas, 6 Hürthle adenomas, 4 follicular carcinomas, 7 papillary carcinomas, and 3 Hürthle carcinomas. A total of 6,600 nuclei were evaluated. For statistical purposes, lesions were classified as benign and malignant, and both the number and the area of counted NORs showed very similar values. The NORs median among 19 benign tumors was 1.484 (SD +/- 0.265) and of 14 malignant tumors was 1.436 (SD +/- 0.414); the NORs areas were 2.6584 (SD +/- 1.0653) and 2.3643 (SD +/- 0.6320), respectively. CONCLUSION: Our results showed that AgNOR evaluation was not a significant parameter to discriminate between malignant and benign thyroid lesions.