Towards a new WHO classification of renal cell tumor: what the clinician needs to know—a narrative review

In 1952, renal cell carcinomas had been divided into 2 categories—clear cell or granular cell—depending upon their cytoplasmic staining characteristics. In the following years, the inventory of renal epithelial tumors has expanded by the addition of tumors named by their architectural pattern (i.e., papillary RCC, tubulocystic RCC), anatomic location (i.e., collecting duct carcinoma, renal medullary carcinoma), associated diseases (i.e., acquired cystic disease-associated RCCs). With the extensive application of molecular diagnostic techniques, it becomes possible to detect genetic distinctions between various types of renal neoplasm and discover new entities, otherwise misdiagnosed or diagnosed as unclassified RCC. Some tumors such as ALK rearrangement-associated RCC, MiT family translocation renal carcinomas, SDH-deficient renal cancer or FH-deficient RCC, are defined by their molecular characteristics. The most recent World Health Organization (WHO) classification of renal neoplasms account for more than 50 entities and provisional entities. New entities might be included in the upcoming WHO classification. The aim of this review is to summarise and discuss the newly acquired data and evidence on the clinical, pathological, molecular features and on the prognosis of new RCC entities, which will hopefully increase the awareness and the acceptance of these entities among clinicians and improve prognostication for individual patients.     

Species differences in activating and inactivating enzymes related to the control of mutagenic metabolites

Microsomal monooxygenases catalyze the biosynthesis of epoxides from olefinic and aromatic compounds whilst microsomal epoxide hydratase and cytoplasmic glutathione S-transferases are responsible for their further biotransformation. Although catalytically very efficient the cytoplasmic glutathione S-transferases play, due to their subcellular localization, a minor role in the inactivation of epoxides derived from large lipophilic compounds and were, therefore, not included in this study. It was shown with such a lipophilic compound, benzo(a)pyrene, as a model substance and with liver enzyme mediated bacterial mutagenesis as biological endpoint that species and strain differences in epoxide hydratase and monooxygenases are reflected in very dramatic differences in mutagenicity of benzo(a)pyrene which varied from extremely potent to a degree which could easily be overlooked. In order to investigate whether the differences in enzyme activities were causally linked to the observed differences in mutagenicity, the enzyme activities were modulated by inhibition and induction. These manipulations were always accompanied by the corresponding changes in mutagenicity.It is concluded that species such as mice which possess high monooxygenase activity but very low epoxide hydratase activity are much more susceptible than man to those toxic effects which are mediated by metabolically formed epoxides which are substrates of epoxide hydratase. In this regard, it is especially noteworthy that mice possess a much lower hepatic epoxide hydratase activity than man.Presented at the Symposium Influence of Metabolic Activations and Inactivations on Toxic Effects held at the 18th Spring Meeting of the Deutsche Pharmakologische Gesellschaft, Section Toxicology, D-6500 Mainz, March 15, 1977     

癫痫病儿血清神经元特异性烯醇化酶水平的检测

①目的　探讨癫痫病儿发作后不同时间血清神经元特异性烯醇化酶 (NSE)的动态变化。②方法采用放射免疫分析法测定 11例癫痫病儿发作后 4 8h内、2～ 4d、5～ 7d血清中NSE水平 ,并与 2 2例正常儿童进行对照。③结果　癫痫病儿发作 4 8h内及 2～ 4d血清NSE水平与对照组比较 ,差异有显著性 (t =4 .32、2 .5 8,P<0 .0 1、0 .0 5 )。④结论　癫痫发作后血清NSE水平升高可能与脑神经元损害有关。     

99Tcm-HL91显像、CT和血清肿瘤标志物测定联合应用诊断肺癌

目的探讨Tc^m-4，9-二氮．3，3，10，10-四甲基十二烷-2，11-二酮肟(HL91)显像、CT、血清肿瘤标志物[癌胚抗原(CEA)、细胞角蛋白19片断(CYFRA21-1)、神经元特异性烯醇酶(NSE)]测定联合应用对肺癌的诊断价值。方法46例疑为肺癌患者在1周内进行^99Tc^m-HL91 SPECT显像、CT检查和血清肿瘤标志物测定。计算每种方法及三法联合应用诊断肺癌的灵敏度、特异性及准确性。结果最终经病理检查或细胞学诊断证实肺癌26例，经病理检查或治疗后影像学随访确诊肺部良性病变20例。^99Tc^m-HL91 SPECT显像、CT及血清肿瘤标志物测定诊断肺癌的灵敏度、特异性及准确性分别为77％、80％、78％，96％、60％、80％及50％、60％、54％。三法联合应用诊断肺癌的灵敏度、特异性及准确性分别为100％、90％、96％，其综合诊断效能明显优于其中任何一种检查方法。结论^99Tc^m-HL91显像、CT、血清肿瘤标志物测定联合应用在肺部肿瘤良恶性鉴别诊断中有较大价值。     

异丙酚预处理对全脑缺血再灌注大鼠脑组织S100β和神经元特异性烯醇化酶的影响

目的探讨异丙酚预处理对全脑缺血再灌注大鼠脑组织S100β及神经元特异性烯醇化酶（NSE）含量的影响，评价异丙酚对脑组织的保护作用。方法30只雄性SD大鼠，随机分为假手术组（A组）、单纯脑缺血再灌注组（B组）和缺血前2h异丙酚预处理组（C组），每组10只，C组动物在缺血前腹腔注射异丙酚100mg／kg，采用线栓法制作全脑缺血再灌注模型，于脑缺血再灌注后24h评估并记录动物的神经行为学评分，测定大鼠脑组织S100β和NSE含量。结果异丙酚预处理组神经行为学评分较单纯脑缺血再灌注组高（P〈0．05），假手术组评分也明显高于单纯脑缺血再灌注组（P〈0．05），异丙酚预处理组脑组织中S100β和NSE含量明显低于单纯脑缺血再灌注组（P〈0．05）。结论异丙酚可以降低脑缺血再灌注损伤大鼠脑组织S100β和NSE的含量，减轻神经损害，缺血前2h异丙酚预处理可以改善大鼠脑缺血再灌注损伤后的神经行为学评分，有明显的脑保护作用。     

神经元特异性烯醇化酶和U266细胞株对破骨样细胞作用的研究

目的：探讨神经元特异性烯醇化酶（NSE）和人多发性骨髓瘤细胞U266对人破骨样细胞（OLC）功能的影响。方法采用正常人外周血单个核细胞加用细胞核因子κB受体激治蛋白配体（RANKL）＋巨噬细胞集落刺激因子（M‐CSF）的方法诱导培养OLC ;实验分3组,NSE组：将6孔培养板中培养14 d的OLC ,分别加入100 ng／mL重组人NSE培养24、48、72 h;共培养组：将6孔Transwell小室下室中培养14 d的OLC ,各上室分别加入1×105／孔U266细胞进行共培养24、48、72 h;对照组：单独培养的OLC。通过实时荧光定量PCR比较NSE和U266细胞株对OLC的RANKL、扩胃蛋白（OPG）、IL‐6和抗酒石酸酸性磷酸酶（TRAP） mRNA转录水平的影响。结果共培养组、NSE组和对照组RANKL、OPG、IL‐6 mRNA在OLC均不表达;与对照组相比,共培养组、NSE组的TRAP mRNA表达水平升高,差异有统计学意义（P＜0．01）;TRAP mRNA表达水平的升高尤其以48 h和72 h明显。结论本试验中OLC表达TRAP ,NSE是促进骨髓瘤骨病中OLC分化和成熟的因素,提示NSE能增强OLC的活性。     

血清神经元特异性烯醇化酶与急性脊髓损伤程度的相关性研究

目的 通过监测急性脊髓损伤患者血清神经元特异性烯醇化酶(NSE)含量的变化,探讨血清NSE与脊髓损伤程度间的关系. 方法 自2007年4月至2008年1月,用酶联免疫吸附法动态监测41例急性脊髓损伤患者血清NSE含量,其中男24例,女17例;年龄21～67岁,平均43.8岁.脊髓损伤部位:颈髓损伤7例,胸髓损伤13例,采髓损伤21例.对急性脊髓损伤患者伤后血清NSE水平与正常血清标本NSE进行比较,并与脊髓损伤程度进行相火性分析;对血清NSE与评价脊髓损伤程度的影像学指标(MRI和CT)进行比较. 结果正常血清标本NSE为(7.16±1.77)μg/L.急性脊髓损伤患者伤后第1、2、3、5、7天血清NSE分别为(7.77±1.77)、(15.04±10.37)、(22.77±8.58)、(20.55±8.39)、(7.48±2.11)μg/L,第2、3、5天血清NSE值与正常对照标本比较差异均有统计学意义(P<0.05).急性脊髓损伤患者伤后第1、2、3、5、7天血清NSE与急性脊髓损伤程度均呈相关(P<0.05).伤后第2、3天血清NSE与脊髓损伤程度的相关性高于MRI评分,伤后第2、3、5天血清NSE与脊髓损伤程度的相关性高于CT评分. 结论血清NSE水平与脊髓损伤程度呈正相关,对血清NSE的检测可反映脊髓损伤程度.     

出血性脑卒中临床预后因素的分析

目的探讨转化生长因子β1(TGF-β1)、神经元特异性烯醇化酶(NSE)等对出血性脑卒中后脑损伤和临床预后的影响。方法检测103例急性出血性脑卒中患者(出血性脑卒中组)血清TGF-β1、NSE水平并与68例健康体检者(健康对照组)比较,以3个月Barthel指数评分为临床预后指标,各因素进行单因素与多元回归分析。结果出血性脑卒中组患者急性期血清TGF-β1低于健康对照组(P<0.01)。NSE高于健康对照组(P<0.01)。单因素分析,TGF-β1、住院天数为出血性脑卒中患者神经功能恢复好的因素。NSE高、意识障碍程度重、出血量大、入院神经功能缺损评分高、空腹血糖高、外周血白细胞计数高、发热、最高体温高、患者年龄大、合并感染者神经功能恢复差。多元回归分析,血清TGF-β1、NSE、出血量、意识障碍程度、入院神经功能缺损评分影响出血性脑卒中患者临床预后。结论出血性脑卒中患者急性期血清TGF-β1明显下降;重症患者NSE显著增高。     

脑外伤患者血清NSE、Tau、S100、MMP-9水平与脑水肿相关性的研究

[目的] 探讨脑外伤患者血清神经烯醇化酶(NSE)、Tau蛋白、S100蛋白、基质金属蛋白酶9(MMP-9)与脑水肿的相关性.[方法] 选择2013年1月至2016年11月本院收治的96例颅脑外伤患者的临床资料,将其分为观察组,选择同期招募的60名健康者作为对照组,脑外伤患者于入院时、入院后d3和d7分别行头部CT检查评估脑水肿体积.采用ELISA法检测脑外伤患者入院当日的血清NSE、Tau、S100、MMP-9蛋白水平,所有健康对照在入选后亦检测相同指标.比较两组患者的血清NSE、Tau、S100、MMP-9蛋白水平,分析观察组脑水肿体积与各血清蛋白Pearson相关性.[结果] 观察组患者入院当日血清NSE、S100、MMP-9水平均高于对照组,差异均具有统计学意义(均P<0.05).对照组血清Tau蛋白水平高于观察组,但差异无统计学意义(P>0.05).入院时观察组患者的血清NSE、Tau、S100、MMP-9水平均与入院当天CT检测的脑水肿体积呈显著正相关性(均P<0.05);入院时血清S100、MMP-9水平与入院d3的脑水肿体积亦呈显著正性相关性(均P<0.05).入院时血清S100、MMP-9水平与脑水肿进展值呈显著正相关性.[结论] 血清NSE、Tau、S100和MMP-9水平可在一定程度上反映脑外伤后脑水肿的程度,并且MMP-9、S100还可提示脑水肿的进展可能,对评估患者受伤后脑水肿的情况具有参考价值.