血清磷酸丙酮酸水合酶在脑损伤中的临床诊断价值

 目的 研究血清神经烯醇化酶（Nse）在早期诊断放射性脑损伤中的作用。方法 采用酶联免疫吸附试验检测56例颅内恶性肿瘤患者（脑转移瘤26例,脑瘤30例）在接受放射性治疗前、后的血清Nse水平,利用成组设计的方差分析比较其差异。同时比较颅内恶性肿瘤患者不同放疗方案（普通放疗组32例;适形放疗组24例）、瘤周水肿程度(轻度18例,中度的20例,重度的18例)对血清Nse水平的影响,比较其差异。 结果 放疗前对照组与脑瘤组血清Nse水平分别为4.12μg/L、4.66μg/L,差异无统计学意义（t= 1.48 P= 0.186 ）; 脑瘤组放疗前、后血清Nse水平分别为4.66μg/L、7.84μg/L,差异有统计学意义（t=3.89 P= 0.001）;普通放疗与适形放疗组血清Nse水平分别为13.59μg/L、6.14μg/L,差异有统计学意义（t= 3.73 P=0.002 ）;放疗后水肿程度（轻、中、重）血清Nse水平分别为4.47μg/L、6.87μg/L、15.21μg/L,差异有统计学意义（F=15.61 P=0.0001）。而放疗前三种水肿程度的患者血清NSE水平无显著性差异 （P>0.05） . 结论 脑瘤组在放疗前不存在或存在轻微的脑损伤,放疗后其血清Nse水平明显增高,其与放疗造成不同程度脑损伤有关;适形放疗组较普通放疗组血清Nse水平低,说明适形放疗能减少脑损伤的发生;重度脑水肿组血清Nse的水平要明显高于其他两组,可能与重度水肿损伤脑神经细胞较多所致。因此Nse可作为脑损伤的临床标志物,为脑损伤的预防和治疗提供依据。     

联合检测肿瘤标志物在肺癌诊断中的临床价值

目的 探讨肿瘤标志物CEA、CA125、神经元特异性烯醇化酶(NSE)、细胞角蛋白19片段抗原(CYFRA21-1)联合检测在肺癌中的诊断价值.方法 研究对象为2010年10月至2012年3月的确诊肺癌住院患者138例(男82例,女56例,平均年龄58.6岁),肺良性病变住院患者96例(男56例,女40例,平均年龄51.3岁);健康体格检查者45名(对照组,男30名,女15名,平均年龄43.9岁).用电化学发光法检测血清CEA、CA125、NSE和CYFRA21-1水平,各指标的组间比较采用单因素方差分析及q检验.按病理类型分组,对鳞状细胞癌[简称鳞癌(66例)]、腺癌(52例)和小细胞肺癌(20例)的肿瘤标志物水平进行比较,计算单项及联合检测对各类型肺癌的诊断效能.结果 肺癌组血清CEA、CA125、NSE、CYFRA21-1水平均高于肺部良性病变组和健康对照组[CEA:(19.99±30.99)、(10.78± 19.77)、(3.25±3.42) μg/L,CA125:(79.70±95.98)、(44.96±44.97)、(20.66±7.13) μg/L,NSE:(35.23±40.22)、(15.31±8.42)、(13.30± 5.65) μg/L,CYFRA21-1:(18.07±43.71)、(8.30±8.83)、(3.13±1.60) μg/L;F=4.481、5.436、4.776和6.002,均P＜0.05].CEA在腺癌中水平较鳞癌和小细胞肺癌高(F=4.932,P＜0.05),NSE在小细胞肺癌中水平较高(F=5.119,P＜0.05),CYFRA21-1在鳞癌中水平较高(F=5.378,P＜0.05).单项肿瘤标志物在肺癌诊断中灵敏度:鳞癌中CYFRA21-1灵敏度最高(78.8％,52/66),腺癌中CEA灵敏度最高(57.7％,30/52),而在小细胞肺癌中NSE灵敏度最高(75.0％,15/20).在联合检测中CEA+CYFRA21-1+ NSE组合对鳞癌诊断灵敏度最高(89.4％,59/66),腺癌诊断中CEA+CA125+NSE组合灵敏度最高(78.8％,41/52),小细胞肺癌中CEA+CYFRA21-1+NSE组合灵敏度最高(80.0％,16/20).结论 CEA、CA125、NSE、CYFRA21-1联合检测对肺癌的诊断有一定的临床价值,不同病理类型肺癌4种肿瘤标志物表达有所不同.     

ECHS1 acts as a novel HBsAg-binding protein enhancing apoptosis through the mitochondrial pathway in HepG2 cells

We aimed to confirm the role of ECHS1 as a binding protein of HBsAg (HBs) and investigate its function during the development of hepatocellular carcinoma (HCC). Our results show that both exogenous and endogenous ECHS1 proteins bind to HBs and co-localize in the cytoplasm in vitro. The coexistence of HBs and ECHS1 enhances HepG2 cell apoptosis, affects ECHS1 localization in the mitochondria and induces apoptosis by decreasing the mitochondrial membrane potential (MMP). These findings suggest that ECHS1 may be applied as a potential therapeutic target during the treatment of HBV-related hepatitis or HCC.     

肿瘤标志物的联合检测在肺癌诊断中的临床价值

目的探讨血清中CEA、CA125、NSE和CYFRA21-1四种肿瘤标志物联合检测在不同组织类型肺癌中的临床诊断价值。方法采用电化学发光免疫分析技术测定116例肺癌患者及65例健康人血清中的CEA、CA125、NSE利CYFRA21-1水平。结果CYFRA21-1、NSE、CEA、CA125四项肿瘤标志物肺癌组检测水平均显著高于对照组（P〈0．01）,肿瘤标志物测定水平与病理组织类型有关。其中CYFRA21-1在鳞癌及腺癌的阳性率分别为73．21％、63．64％;NSE在小细胞肺癌的阳性率为62．50％;CEA和CA125检测的阳性率及血清水平以腺癌最高;四项联合检测的阳性率为82．76％。结论血清CEA、CA125、NSE和CYFRA21-1的联合检测有助于提高肺癌的诊断效率,并对组织分型有较高的参考价值。     

A cancer-predisposing "hot spot" mutation of the fumarase gene creates a dominant negative protein

The Fumarase (Fumarate Hydratase, FH) is a tumor suppressor gene whose germline heterozygous mutations predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC). The FH gene encodes an enzyme of the Krebs cycle, functioning as a homotetramer and catalyzing the hydration of fumarate to malate. Among the numerous FH mutations reported so far, the R190H missense mutation is the most frequent in HLRCC patients. Here we show the functional analyses of the R190H, in comparison to the better characterized E319Q mutation. We first expressed wild-type and mutated proteins in FH deficient human skin fibroblasts, using lentiviral vectors. The wild-type transgene was able to restore the FH enzymatic activity in cells, while the R190H- and E319Q-FH were not. More interestingly, when the same transgenes were expressed in normal, FH-proficient cells, only the R190H-FH reduced the endogenous FH enzymatic activity. By enforcing the expression of equal amount of wild-type and R190H-FH in the same cell, we showed that the mutated FH protein directly inhibited enzymatic activity by nearly abrogating the FH homotetramer formation. These data demonstrate the dominant negative effect of the R190H missense mutation in the FH gene and suggest that the FH tumor-suppressing activity might be impaired in cells carrying a heterozygous mutation.     

肺癌患者胸水和血清中细胞角蛋白19片段、神经元特异性烯醇化酶和肿瘤相关抗原72-4测定的临床价值

目的探讨胸水和血清中细胞角蛋白19片段(CYFRA21-1)、神经元特异性烯醇化酶(NSE)和肿瘤相关抗原(CA)72-4测定对肺癌的诊断和鉴别诊断价值。方法采用电化学发光法测定61例肺癌、33例良性疾病患者胸水和血清中CYFRA21-1、NSE和CA72-4水平。结果癌性胸水中CYFRA21-1、NSE和CA72-4水平分别为(73.1±42.9)μg/L、(34.3±25.7)μg/L和(21.6±13.2)μg/L,显著高于癌性血清组(P<0.01)和良性胸水组(P<0.01),良性胸水中CYFRA21-1、NSE和CA72-4水平与良性血清组差异无统计学意义(P>0.05);癌性胸水中CYFRA21-1对肺鳞癌敏感,NSE对小细胞肺癌敏感,CA72-4对肺腺癌敏感。结论联合检测CYFRA21-1、NSE和CA72-4三种肿瘤标志物对诊断和鉴别诊断良、恶性胸水有重要临床价值。     

Effects of commonly consumed vegetables on hepatic xenobiotic-metabolizing enzymes in the mouse

To investigate the effects of consuming a variety of common vegetables on the activities of xenobiotic-metabolizing enzymes in the mouse liver, male C57BL/6 mice were fed purified diets supplemented isocalorically with 20% freeze-dried powdered kidney bean, soya bean, alfalfa, cauliflower, mustard greens, carrot, kale, Brussels sprouts, beet, egg plant or onion or with 40% sweet potato. Hepatic ethoxycoumarin O-deethylase (ECD) activity was increased significantly (P less than or equal to 0.05) over the controls in the mice fed diets containing kidney bean (1.5-fold), alfalfa (1.6-fold), cauliflower (2.2-fold), mustard greens (1.2-fold), carrots (1.2-fold) and kale (1.3-fold). No significant increases in ECD activity were seen in the other groups. Aryl hydrocarbon hydroxylase (AHH) activity was assayed in the cauliflower and Brussels sprouts groups and was found to be unaffected by these diets. Glutathione S-transferase (GST) and epoxide hydratase (EH) activities were increased (P less than or equal to 0.05) by soya bean (1.2- and 1.6-fold respectively), Brussels sprouts (2.0- and 1.6-fold), cauliflower (1.2- and 1.6-fold), alfalfa (1.3- and 2.0-fold) and onion (1.8- and 2.3-fold). No significant increases in GST or EH activities were seen in the other groups. Of the twelve vegetables investigated, only three (sweet potato, beet and egg plant) had no statistically significant effects on any of the xenobiotic-metabolizing parameters tested. However, the beet diet caused an apparent inhibition of ECD activity (74% of control) and the sweet potato diet caused an apparent increase (1.3-fold) in GST activity, although statistical significance could not be established at P less than or equal to 0.05.     

改良振幅整合脑电图评分联合血清神经元特异性烯醇化酶水平对新生儿胆红素脑损伤的早期预测价值

目的探讨改良振幅整合脑电图(aEEG)评分联合血清神经元特异性烯醇化酶(NSE)水平,对新生儿胆红素脑损伤的早期预测价值。 方法选择2017年3月至2018年2月,于苏北人民医院新生儿病房住院治疗的80例高胆红素血症新生儿为研究对象。根据头颅MRI检查结果是否有苍白球高信号改变,将其分为脑损伤组(n＝37)及无脑损伤组(n＝43);并选择本院产科同期出生的40例健康足月新生儿为对照组。对3组受试儿进行aEEG监测,并进行改良aEEG评分,检测血清总胆红素(TBiL)浓度及NSE水平,以及脑干听觉诱发电位(BAEP)。对3组受试儿一般临床资料、改良aEEG评分、血清TBiL浓度及NSE水平,采用单因素方差分析及最小显著性差异法(LSD)-t检验,进行总体比较及两两比较;对改良aEEG评分、血清NSE水平及aEEG分度分别与BAEP分度的相关性,采用Spearman秩相关分析法;绘制受试者工作特征曲线(ROC),比较改良aEEG评分、血清NSE水平及二者联合,对高胆红素血症新生儿发生胆红素脑损伤的预测价值。本研究遵循本院伦理委员会所制定的伦理学标准,并得到批准(审批文号：2016KY-064),所有纳入对象监护人知情同意。 结果①3组新生儿性别构成,入院时日龄及胎龄,出生时体重、身长、头围及胸围,以及其母亲孕次、产次比较,差异均无统计学意义(P>0.05)。②脑损伤组新生儿的改良aEEG评分为(7.7±1.6)分,分别低于无脑损伤组及对照组的(10.4±1.5)分和(10.9±1.3)分;而血清TBiL浓度及NSE水平分别为(349.7±74.0) μmol/L、(47.6±13.2) μg/L,均分别高于无脑损伤组的(295.7±31.4) μmol/L、(32.3±7.7) μg/L及对照组的(185.1±35.9) μmol/L、(28.6±7.3) μg/L,并且差异均有统计学意义(均为P<0.001)。③本研究受试儿的改良aEEG评分与BAEP分度呈负相关关系(r_s＝-0.718,P<0.001),血清NSE水平及aEEG分度,均与BAEP分度呈正相关关系(r_s＝0.685,P<0.001;r_s＝0.647,P<0.001)。④改良aEEG评分、血清NSE水平及二者联合,预测高胆红素血症新生儿发生胆红素脑损伤的ROC曲线下面积(ROC-AUC)分别为0.875(95%CI：0.795～0.954,P<0.001),0.853(95%CI：0.769～0.937,P<0.001)及0.938(95%CI：0.861～0.980,P<0.001);3种方法预测脑损伤的敏感度分别为86.5%、62.2%、83.8%,特异度分别为74.4%、93.0%、90.7%。 结论改良aEEG评分联合血清NSE水平,对新生儿胆红素脑损伤的早期预测价值,较单一采用改良aEEG评分或血清NSE水平更高。     

豚鼠噪声暴露后畸变产物耳声发射及神经元特异性烯醇化酶表达的观察

为观察豚鼠暴露于强噪声后畸变产物耳声发射(DPOAE)及神经元特异性烯醇化酶(NSE)的变化,选用13只Preyer's反射正常的健康豚鼠,分为二组,8只噪声暴露组,5只为NSE表达对照组。噪声强度115dB(A),连续暴露4小时,DPOAE幅值于噪声暴露前后进行测试,结果DPOAE幅值噪声暴露前后差异明显(P<0.001),豚鼠内耳内、外毛细胞及螺旋神经细胞胞浆、隧道贯穿纤维NSE免疫组化反应均呈阳性表达,暴震前后无明显变化。结果提示豚鼠接受短时间强噪声刺激后,DPOAE幅值的下降为暂时阈移,而内耳神经元及其末梢未受损伤。