外阴癌中HPV感染与p53、MDM2表达的关系

目的 :探讨HPV6/ 11、16/ 18在外阴癌组织中的感染情况及与p5 3、MDM2蛋白表达的关系。方法 :用原位杂交法 (ISH)检测HPV6/ 11、16/ 18在 30例外阴癌、2 1例外阴上皮内瘤变 (VIN)及 10例外阴正常皮肤组织中的表达。同时用免疫组化SP法检测p5 3、MDM2蛋白的表达。结果 :HPV6/ 11、16/ 18在外阴癌、VIN中的阳性表达率分别为 60 % (18/30 )、33.33% (10 / 30 ) ,4 2 .86% (9/ 2 1)、2 8.5 7% (6/ 2 1) ,正常对照组没有表达。p5 3、MDM2蛋白在外阴癌、VIN、正常对照组中的阳性表达率分别为 63.33% (19/ 30 )、4 0 .0 0 % (12 / 30 ) ,4 7.62 %(10 / 2 1)、5 2 .38% (11/ 2 1) ,0 % (0 / 10 )、0 % (0 / 10 )。HPV6/ 11的表达在外阴癌组、VIN组与正常组差异有显著性 (P <0 .0 5 ) ,外阴癌组HPV16/ 18表达与正常组差异有显著性 (P <0 .0 5 )。外阴病变各组p5 3、MDM2与正常组差异有显著性 (P <0 .0 5 )。结论 :HPV6/ 11、HPV16/ 18、p5 3、MDM2蛋白在外阴组织的不同病变中表达均差异有显著性 ,在外阴癌的发生发展中HPV感染、p5 3突变和MDM2表达可能起一定的作用     

Synthesis and evaluation of 5,7‐dichloro‐4‐(3‐{4‐[4‐(2‐[18F]fluoroethyl)‐piperazin‐1‐yl]‐phenyl}‐ureido)‐1,2,3,4‐tetrahydroquinoline‐2‐carboxylic acid as a potential NMDA ligand to study glutamatergic neurotransmission in vivo

The neurotransmitter glutamate is thought to be crucially involved in a huge number of neurological and psychiatric disorders, such as Morbus Parkinson, Alzheimer's disease and schizophrenia. Aiming at an improved diagnostic tool for PET a new [¹⁸F]fluorine labelled NMDA receptor ligand was developed that may potentially allow the in vivo visualization of glutama‐tergic neurotransmission. The ¹⁹F‐analogue trans‐5,7‐dichloro‐4‐(3‐{4‐[4‐(2‐fluoroethyl)‐piperazin‐1‐yl]‐phenyl}‐ureido)‐1,2,3,4‐tetrahydro quinoline‐2‐carboxylic acid was synthesised to determine the binding affinity, lipophilicity and biodistribution of the ligand. This substance exhibits a K_i of 12 nM for the glycine binding site using [³H]MDL‐105,519 assays on pig cortical membranes. A logD of 1.3 was determined for this compound according to the OECD guidelines employing the HPLC method. Radiosynthesis of this ligand was achieved by labelling the precursor trans‐5,7‐dichloro‐4‐[3‐(4‐piperazin‐1‐yl‐phenyl)‐ureido]‐1,2,3,4‐tetrahydroquinoline‐2‐carboxylic acid methyl ester with 2‐[¹⁸F]fluoroethyltosylate and subsequent cleaving of the methyl ester moiety, resulting in an overall decay corrected yield of 35% of the final product trans‐5,7‐dichloro‐4‐(3‐{4‐[4‐(2‐[¹⁸F]fluoroethyl)‐piperazin‐1‐yl]‐phenyl}‐ureido)‐1,2,3,4‐tetrahydroquinoline‐2‐carboxylic acid. The biodistribution kinetics of this compound were determined with Sprague Dawley rats ex vivo for brain, liver, kidney, and bone. The ligand showed a maximum brain uptake 30 min.p.i. of about 0.1% ID/g. Copyright © 2003 John Wiley & Sons, Ltd.     

Biological activity of silylated amino acid containing substance P analogues

Abstract: The need to replace natural amino acids in peptides with nonproteinogenic counterparts to obtain new medicinal agents has stimulated a great deal of innovation on synthetic methods. Here, we report the incorporation of non‐natural silylated amino acids in substance P (SP), the binding affinity for the two hNK‐1 binding sites and, the potency to stimulate phospholipase C (PLC) and adenylate cyclase of the resulting peptide. We also assess the improvement of their stability towards enzyme degradation. Altogether, we found that replacing glycine with silaproline (Sip) in position 9 of SP leads to a potent analogue exhibiting an increased resistance to angiotensin‐converting enzyme hydrolysis.     

天津市双口生活垃圾卫生填埋场渗沥液处理

介绍了天津市双口生活垃圾卫生填埋场渗沥液处理情况，对渗沥液处理场运行中出现的一些现象做了初步分析。     

建筑工地外来务工人员心理卫生状况调查

目的 :了解建筑工地外来务工人员的心理卫生状况 ,为预防心理疾病 ,增进身心健康提供依据。方法 :采用症状自评量表 (SCL - 90 )对建筑工地外来务工人员 5 18人的心理卫生状况进行评价。结果 :9个因子分与中国常模比较差异均有显著性 (P<0 .0 1) ,且各年龄组与中国常模比较差异也有显著性 ,均低于常模 ;各因子分在不同年岭 ,不同文化的建筑工地外来务工人员间比较差异无显著性。研究还发现做事“必须反复检查”、“必须反复洗手、点数目或触摸某些东西”、“做事必须做得很慢以保证做得正确”等强迫症状是建筑工地外来务工人员中较常见的阳性项目。结论 :建筑工地外来务工人员强迫症状发生频率较其它症状高 ,应加强其心理卫生教育     

Placental site trophoblastic tumor in a patient with brain and lung metastases

Placental site trophoblastic tumor is a rare neoplasm that arises from intermediate trophoblasts and shows diversity of biological behaviors, resulting in the absence of consistency in treatment modalities. A case of placental site trophoblastic tumor that extended to the cervix, with primary manifestation of amenorrhea and yellow foul-smelling vaginal discharge, is presented. Total abdominal hysterectomy was performed initially, and serial measurements of human chorionic gonadotropin levels were obtained. She was admitted with metastases to brain and lung 1.5 years after surgery. Combination chemotherapy (etoposide-methotrexate-dactinomycin/cyclophosphamide-vincristine) and radiotherapy were administered. There was no significant response to chemoradiotherapy. Despite changing chemotherapy regimen, she is still alive with progressive disease.     

抑制JAK/STAT通路对培养乳鼠心肌细胞模拟缺血/再灌注损伤的作用

目的研究抑制Janus激酶/信号转导和转录激活子(JAK/STAT)通路对乳鼠心肌细胞缺血再灌注损伤的保护作用。方法采用体外培养的新生大鼠心肌细胞造成缺血再灌注(I/R)模型,随机分为正常对照组,缺血再灌注组,JAK抑制剂-AG490治疗组,STAT抑制剂-RMP治疗组。采用MTT法检测心肌细胞活性,检测以上不同条件下细胞上清液中的乳酸脱氢酶(LDH)、丙二醛(MDA)、超氧化物歧化酶(SOD)含量,并检测各组细胞的凋亡率。结果与正常对照组相比,缺血再灌组心肌细胞成活率明显降低(P<0.01),细胞上清液中LDH、MDA含量明显升高(P<0.01),SOD活力则显著降低(P<0.01),缺血再灌组凋亡率升高明显(P<0.01)。AG490及RMP处理后,心肌细胞成活率明显升高(P<0.01),LDH、MDA显著低于缺血再灌组(P<0.01),SOD则高于缺血再灌组(P<0.01)。结论抑制JAK/STAT通路有助于减轻缺血再灌注所致心肌损伤。     

子宫颈癌HPV16/18感染与微血管密度和血管内皮生长因子表达的关系

目的 探讨人乳头状瘤病毒16／18（HPV16／18）在子宫颈癌组织中的感染情况及与微血管密度（MVD）和血管内皮生长因子（VEGF）表达的关系。方法 用原位杂交法检测HPV16／18在60例子宫颈癌（鳞癌40例、腺癌20例）、29例宫颈上皮内肿瘤（CIN）和16例正常子宫颈组织中的HPV16／18感染情况；采用免疫组织化学方法（SP）检测VEGF蛋白的表达，并以CD34抗原作为血管内皮细胞标记，测定其微血管密度。结果 HPV16／18在子宫颈鳞癌、腺癌、CIN和正常子宫颈组织中感染率分别为67．50％（27／40）、35．00％（7／20）、68．97％（20／29）、6．25％（1／16）。HPV16／18感染率鳞癌组与腺癌组和正常组比较差异均有显著性意义（均P〈0．01），而鳞癌组与CIN组相比差异无显著性意义（P〉0．05）。随着宫颈病变的进展，MVD逐渐增大，VEGF的阳性表达率渐增高。MVD在以上5种组织间相比差异均有极显著性意义（均P〈0．01）。VEGF在子宫颈鳞癌、腺癌、CIN、正常宫颈组织细胞质中的阳性表达率分别为95．00％（38／40）、100．00％（20／20）、82．80％（24／29）、18．80％（3／16）。病变患者与正常者相比差异有极显著性意义（P〈0．01）。HPV16／18感染与VEGF表达呈正相关（r=0．245，P〈0．05），而与MVD无相关性（r=．04，P〉0．05）；VEGF的表达与MVD无相关性（r=0．01，P〉0．05）。淋巴转移阳性者MVD的表达量较阴性者高（P〈0．05）。结论 在子宫颈癌的发生发展中HPV16／18的感染起一定的作用，MVD与VEGF在子宫颈组织的不同病变中的表达均有差异性，推测VEGF有促进子宫颈癌组织血管形成作用，MVD与子宫颈癌的恶性程度密切相关。HPV16／18感染可能通过促进VEGF的表达而有利于子宫颈癌组织的生长。     

An Exploration of Site Effects in a Multisite Trial of OROS-Methylphenidate for Smokers with Attention Deficit/Hyperactivity Disorder

Background: Multisite trials, the gold standard for conducting studies in community-based settings, can mask variability across sites resulting in misrepresentation of effects in specific sites. In a placebo-controlled trial of osmotic-release oral system methylphenidate (OROS-MPH) as augmentation treatment for smokers with attention deficit hyperactivity/impulsivity disorder (ADHD), three types of sites were selected according to their clinical research specialty (ADHD, smoking cessation, and general mental health). Objective: Analysis was conducted to determine if clinical outcomes, that is, reduction in ADHD symptoms and smoking cessation rates, and the effect of treatment on these outcomes would differ by type of site. Method: A total of 255 adult smokers diagnosed with ADHD were enrolled in three clinic types: 72 in ADHD, 79 in tobacco dependence, and 104 in the mental health clinics. Results: The three site-types were similar in demographic characteristics, smoking history, baseline level of ADHD symptoms, and history of psychiatric illness. Site-type but not a site-type by treatment interaction predicted prolonged smoking abstinence. A significant three-way interaction of site-type, treatment, and time-predicted improvement in ADHD symptoms. Moderate to strong effects of OROS-MPH relative to placebo were observed in the mental health and the ADHD clinics; a weak effect was observed in the tobacco dependence clinics. Conclusion: OROS-MPH benefit varied by site for reducing ADHD symptoms but not for improving smoking abstinence. Scientific Significance: Assessment of site-type effects can indicate the generalizability of findings from multisite trials and should be routinely incorporated in the design of multisite trials.