Down‐modulation of keratin 8 phosphorylation levels by PRL‐3 contributes to colorectal carcinoma progression

Phosphatase of regenerating liver‐3 (PRL‐3) is a member of the PRL protein tyrosine phosphatase family and has been proposed to promote the invasiveness and metastastic capability of colorectal cancers (CRCs); however, the underlying mechanisms and target molecules of PRL‐3 protein remain unknown. On the basis of the biological significance of PRL‐3 phosphatase activity confirmed by the catalytically inactive PRL‐3 mutant (C104S) and a PRL‐3 inhibitor in CRC‐derived SW480 cells, we performed protein expression profiling to search for PRL‐3‐mediated effector proteins. By a comparative study of phosphorylated proteins that differentially expressed in wild type and C104S mutant PRL‐3‐transfected SW480 cells; the cytoskeletal intermediate filament keratin 8 (KRT8) was identified as a physiological PRL‐3‐interacting protein. Indeed, treatment with the PRL‐3 inhibitor effectively suppressed the phosphorylation of KRT8 at S73 and S431. Moreover, we detected the physiological interaction between PRL‐3 and KRT8 and their colocalization at cellular lamellipodias and ruffles in vivo. In CRC tissue samples, tumor cells with high PRL‐3 expression showed reduction or loss of phosphorylated KRT8 expression, particularly at the invasive front and in the liver metastases. In conclusion, our results indicate that PRL‐3 may play an important role for the promotion of CRC cell migration and metastatic potential through direct KRT8 dephosphorylation. © 2008 Wiley‐Liss, Inc.     

鲁拉西酮联合舒必利治疗精神分裂症的临床研究

目的 探讨盐酸鲁拉西酮片联合舒必利片治疗精神分裂症的临床疗效。方法 选取2020年2月-2022年11月在上海市静安区精神卫生中心就诊的120例精神分裂症患者,按照计算机随机排列法分为对照组和治疗组,每组各60例。对照组患者口服舒必利片,首次剂量1片/次,3次/d,治疗7 d后增加至3片/次,3次/d。治疗组患者在对照组基础上口服盐酸鲁拉西酮片,1片/次,1次/d。两组患者连续治疗2个月。观察两组的临床疗效,比较两组的阳性与阴性症状量表(PANSS)评分、精神分裂症生活质量量表(SQLS)评分以及血清中催乳素(PRL)、白细胞介素-6(IL-6)、白细胞介素-17(IL-17)水平。结果 治疗后,治疗组的总有效率为91.67%,对照组的总有效率为78.33%,组间比较差异有统计学意义(P<0.05)。治疗后,两组的PANSS各项评分均显著降低(P<0.05),且治疗组PANSS各项评分较对照组更低(P<0.05)。治疗后,两组的SQLS各项评分显著降低(P<0.05),治疗组SQLS各项评分降低程度高于对照组(P<0.05)。治疗后,两组的血清PRL水平高于治疗前,血清IL-6、IL-17水平低于治疗前(P<0.05);治疗后,治疗组的血清IL-6、IL-17水平低于对照组(P<0.05)。结论 盐酸鲁拉西酮片联合舒必利片可提高精神分裂症的临床疗效,减轻患者精神症状,提高生活质量,减轻炎症反应,且药物安全性良好。     

Cytokine-like effects of prolactin in human mononuclear and polymorphonuclear leukocytes

Some biochemical events following the binding of prolactin (PRL) to its receptor in normal human leukocytes were investigated. PRL enhanced JAK2 phosphorylation in peripheral blood mononuclear cells (PBMC) but not in granulocytes. PRL also induced phosphorylation of Stat-5 in PBMC and Stat-1 in granulocytes. Subsequent binding of Stat-5- and of Stat-1-like molecules to a GAS responsive element from the β-casein promoter was detected by EMSA. p38 MAPK (but not p42/p44 MAPK) was activated by PRL in both leukocyte populations. PRL induced iNOS and CIS mRNA expression in granulocytes. Increased expression of IRF-1 and SOCS-2 was observed in granulocytes and of SOCS-3 and iNOS in PBMC. Similar effects were obtained with ovine and human PRL. Antiserum to PRL reduced iNOS and IRF-1 expression induced by PRL in granulocytes and reduced iNOS expression in PBMC. Also, pretreatment of granulocytes with a p38 MAPK inhibitor (SB 203580) prevented in part PRL-induced iNOS and IRF-1 expression. In PBMC, the p38 inhibitor decreased PRL-induced iNOS gene expression. These results indicate that PRL-induced gene regulation in leukocytes requires the activation of at least two different pathways: the Stat and the MAP kinase pathways. Moreover, although PRL activates Stat in both leukocyte types, signal transduction is different in granulocytes and in PBMC. Most importantly, PRL modulates the expression of genes crucial to leukocyte function. The present findings reinforce the concept that PRL has “cytokine-like” activity in human leukocytes.     

前列腺癌患者血清IGF-I、PRL及SE-cad测定的临床意义

目的：探讨前列腺癌患者血清IGF-Ⅰ、PRL及SE-cad水平的变化及临床意义。方法：血清IGF-Ⅰ采用放射免疫分析;fPSA及PRL采用化学发光法;血清SE-cad采用酶联免疫分析法。结果：前列腺增生组患者血清IGF-Ⅰ水平较对照组升高显著（P〈0.05）;血清PRL含量也较对照组显著升高（P〈0.05）;SE-cad浓度其测定数值也存在显著性差异（P〈0.05）。而前列腺癌患者组血清IGF-Ⅰ水平较对照组升高更为显著（P〈0.01）;血清PRL含量也较对照组升高极其显著（P〈0.01）;SE-cad浓度其测定数值升高同样非常显著（P〈0.01）。灵敏度分析表明,fPSA＋IGF-Ⅰ和fPSA＋SE-cad两组灵敏度显著高于fPSA单项测定组;fPSA＋PRL组灵敏度略低,但P〉0.05。特异性分析则fPSA＋SE-cad组fPSA单项测定组显著增高（P〈0.05）,fP-SA＋PRL降低明显,fPSA＋IGF-Ⅰ组与单项组差异并不显著（P〉0.05）。结论：血清IGF-Ⅰ、PRL及SE-cad水平的变化与前列腺癌的发生关系密切,与fPSA的联合测定可提高诊断的灵敏度及特异性,有助于前列腺癌的辅助诊断。     

磁分离酶联免疫测定男性生殖激素方法性能评价

目的：对磁分离酶联免疫测定（MAIA）法测定男性生殖激素的方法学性能作临床和实验室评价。方法：将本法与放射免疫测定（RIA）法进行对比研究。结果：MAIA法测定促卵泡生成激素（FSH）、促黄体生成素（LH）、睾酮（T）和催乳素（PRL）的线性分别为0－150IU／L、0－200IU／L、0．5－55ng/L、0－250ng/L；最小检测量分别为0．3mIU/ml、0．25mIU/ml、4μIU/ml、4μIU/ml；批内CV＜4％，批间CV＜8％，平均回收率偏差＜5％，互感率＜3％；与RIA法比较，两法相关系数分别为0．9826、0．8550、0．8512、0．9831。临床质控观察60d，质控稳定；成年健康男性（n=95）血清FSH、LH、T、PRL的参考范围分别为：0．25－10．18IU／L、0．33－8．95IU／L、0．54－11．11ng/L和8．77－33．43ng/L。结论：用MAIA法测定男性生殖激素，方法灵敏，结果可靠，先例临床要求。     

垂宁方治疗泌乳素型垂体瘤的临床疗效观察

【摘要】 目的 探讨垂宁方治疗泌乳素(PRL)型垂体腺瘤的临床疗效,为临床应用提供借鉴依据。方法 将2014年1月至2015年1月收治的60例PRL型垂体瘤随机分为A组、B组和C组。A组患者采用垂宁方进行治疗,B组患者采用溴隐亭进行治疗,C组患者采用溴隐亭联合垂宁方进行治疗;治疗6个月及1年时对患者的瘤体积、血清PRL水平及中医症候积分量表得分进行对比评价。结果 治疗6个月及1年时C组患者肿瘤大小改善情况明显优于A组和B组,差异有统计学意义（P<0.05）;治疗后3组患者血清PRL水平均显著降低（P<0.05）,C组血清中PRL水平改善程度显著高于其余两组（P<0.05）,且开始治疗后C组患者PRL水平均明显低于A组和B组,差异具有统计学意义（P<0.05）;经治疗后C组患者中医证候评价结果明显优于其余两组,差异具有统计学意义（P<0.05）。结论 垂宁方治疗PRL型垂体瘤具有理想的治疗效果,可有效抑制瘤体生长,降低患者血清中泌乳素水平,改善患者预后。     

服棉酚者和其他原因所致的无精症患者血中促性腺激素与甾体激素的变化

本文比较了正常男子(Ⅰ组)、各种无精症患者(包括棉酚服用者。Ⅱ组)、原因不明的无精症者(Ⅲ组)以及Klinefelter 综合征患者(Ⅳ)血浆中FSH、LH、PRL、T、E_2和F 的变化。结果所有无精症患者的平均FSH、LH 水平明显高于Ⅰ组(P<0.001),但PRL、T、E_2及F 的平均值与Ⅰ组无区别(P>0.05)Ⅱ、Ⅲ组患者FSH 水平升高者与正常者各为50%,其余各组明显高于正常。Ⅲ组的LH 及T/LH 比值仍在正常范围内,但T、E_2及F 的平均值升高,PRL 降低;其余各组LH 与FSH 平行升高,T 及T/LH比值明显低于Ⅰ组(P<0.001),但E_2、F 及PRL 则在正常范围内。本实验证实,避孕剂量的棉酚并不损害睾丸合成T 的功能。FSH 过高说明生精上皮损害过度。本文还提出了一些控制棉酚用量的客观指标。     

产后不宜哺乳产妇回乳时机探讨

目的探讨产后回乳的最佳时机。方法将2004年11月-2005年6月自然分娩不宜用母乳喂养的产妇152例,按住院号的单双数分为观察组88例,于产后立即给予维生素B6200 mg口服,3次/d,每日煎服200 g麦芽汁,而对照组64例产妇于产后72 h同法口服维生素B6及麦芽汁。结果观察组产妇回乳效果比对照组产妇好,两者比较有显著性差异(P<0.001)。结论对于产后不宜母乳喂养的产妇应及早采取回乳措施,最好于产后立即进行,以便取得较好的回乳效果。     

子宫内膜分泌不良不孕妇女内膜胞浆女性激素受体和相关血清激素水平关系探讨

本文对内膜分泌不良妇女子宫内膜胞浆雌、孕激素受体含量变化及血清雌二醇、孕酮、促卵泡成热激素及垂体泌乳素水平进行了分析讨沦,了解子宫内膜发育与雌、孕激素受体及血清有关激素之间的关系。结果表明,内膜分泌不良组与对照组比较,雌激素受体含量明显降低(P<0.005),孕激素受体含量同时降低(P<0.05)。提示不孕妇女子宫内膜分泌不良,可能是由于组织胞浆雌、孕激素受休含量降低,使其对相应激素的反应性下降所致。建议对这类患者的治疗方案应从激素水平及受体含量两方面进行考虑。