Proteases and their inhibitors as prognostic factors for high-grade serous ovarian cancer

Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance.     

AO跟骨板在Ⅲ、Ⅳ型跟骨骨折的临床应用

目的 评价AO跟骨板治疗Ⅲ、Ⅳ型跟骨骨折的疗效。方法 21例29足严重跟骨骨折按Sanders分型：Ⅲ型18足；Ⅳ型11足，采用AO跟骨板及髂骨(或人工骨)植骨进行有限坚强内固定。对年老、骨质疏松严重的Ⅲ型和Ⅳ型跟骨骨折后距下关节不能达到解剖复位，整复跟骨外形后，AO跟骨板固定，同时一期行距下关节融合术。结果 按Maryland足部评分系统评价术后功能，本组29足Ⅲ、Ⅳ型跟骨骨折行AO跟骨板固定总体优良率为82．8％。结论 AO跟骨板治疗Ⅲ、Ⅳ型跟骨骨折疗效肯定，术后早期功能练习．减少骨折并发症，是一种治疗Ⅲ、Ⅳ型跟骨骨折的理想方法。     

谷氨酰胺和生长激素对短肠综合征患者肠道代偿作用

目的探讨谷氨酰胺和生长激素对短肠综合征(SBS)患者的肠道代偿作用。方法26例短肠综合征患者残余小肠长度为0～100(中位数42.5)cm,手术后接受肠外营养(PN)支持3-52个月,联合应用生长激素(GH)(0.10±0.06)mg·kg-1·d-1和谷氨酰胺(GLN)(0.30±0.17)g·kg-1·d-1进行肠道促代偿治疗。结果26例接受GH加GLN治疗的SBS患者,其中9例(34.6%)治疗后近期内完全摆脱PN;8例(30.8%)经治疗后明显减少了PN用量,从每周需要PN(6.0±1.0)d下降至(4.2±1.0)d,每周PN需要量从(13.6±5.2)L降至(8.2±3.3)L;9例(34.6%)在治疗后仍依赖PN维持。结论经过合适的营养支持和肠道促代偿治疗,大多数短肠综合征患者残留肠道能充分代偿,完全摆脱PN或减少PN用量,长期健康生存。     

残胃癌临床诊治分析

目的分析和总结残胃癌的外科诊断、治疗及预后情况。方法对1990年以来收治的35例残胃癌的发病率、临床表现、治疗情况和预后进行回顾性分析。结果首次胃切除以胃溃疡为主,占65.7%,首次手术BillrothⅡ式占82.9%(29/35)。残胃癌早期缺乏特异的症状,主要为上腹部隐痛不适,首次手术距临床诊断残胃癌的间隔时间平均为16.3年。本组残胃癌手术切除率及根治性切除率分别为77.1%和54.3%,根治性切除患者1、3、5年生存率分为78.9%、52.6%、36.8%,Ⅰ期、Ⅱ期患者的5年生存率为72.7%。结论胃良性病行手术治疗时以BillrothⅠ式为首选,定期胃镜检查是早期诊断残胃癌的关键,根治性切除是治疗残胃癌的有效方法及影响残胃癌预后的重要因素。     

晕可宁颗粒对急、慢性梅尼埃病模型的影响

目的　探讨晕可宁颗粒的主要药效学 ,为临床提供药效学资料及治疗学基础。方法　采用三氯甲烷破坏豚鼠一侧膜迷路感受器模型 ,探讨受试药对眼震颤、摆头及旋转的影响 ;采用内淋巴囊和内淋巴管阻塞手术复制豚鼠膜迷路实验性膜迷路积水模型 ,研究内耳组织平均中阶面积 (SMA)增加率及形态学的变化。结果　抑眩宁阳性对照组、晕可宁颗粒 (8、16g/kg)模型给药组豚鼠眼球震颤次数减少 ,差异有显著意义 (P <0 .0 5 )。成功复制了不同程度膜迷路积水豚鼠模型 ,表现为前庭膜重度膨出 ,前庭阶缩小 ,膜蜗管增大 ,SMA增加率变大 ,差异有显著意义 (P <0 .0 1) ;晕可宁颗粒灌胃后可减轻豚鼠实验性膜迷路积水的程度 ,差异有显著意义 (P <0 .0 1) ;但与空白对照组比较SMA增加率差异无显著意义 (P >0 .0 5 )。结论　晕可宁颗粒可以减轻内淋巴囊积水程度 ,对梅尼埃病症状有对抗治疗作用。     

复方红芪减方对周围神经再生影响的实验研究

目的　研究复方红芪提取液进行减方后对周围神经再生的作用。方法　建立钳夹损伤大鼠双侧坐骨神经的动物模型。按术后每日灌服药物的不同将 40只SD雄性大鼠随机均分为 4组。对照组 :灌服生理盐水 ;复方红芪组 :灌服复方红芪提取液 2ml ;减方组 :灌服复方红芪减方后提取液 2ml;补阳还五汤组 :灌服补阳还五汤 2ml。术后 2周及 4周 ,观察坐骨神经功能指数、运动神经传导速度及单位视野有髓神经纤维计数。结果　坐骨神经功能指数 :红芪组和减方组与对照组、红芪组与减方组的差异均有显著意义 (P >0 .0 5 ) ,且减方组优于红芪组 (P >0 .0 5 )。有髓神经纤维计数 :复方红芪组优于对照组 (P<0 0 1) ,减方组明显优于对照组 (P <0 .0 1) ,而红芪组与减方组间无显著差异。运动神经传导速度 :红芪组、减方组、补阳还五汤组与对照组相比 ,均优于对照组 (P <0 .0 5 ) ,但前 3组间无明显差异。结论　复方红芪减方提取液早期可以促进周围神经再生 ,药效更为专一 ,且优于传统方剂补阳还五汤。     

Erratum: Neurofibromatosis type 1 (NF1): Identification of eight unreported mutations in NF1 gene in Italian patients

In the original version of this article, the title was incorrect. Please find the correct title given here. The publisher deeply regrets this error. The original article to which this Erratum refers was published in Human Mutation 22:179–180 Human Mutation(2003) 22(2) 179–180     

ERK1/2信号转导途径在低切应力上调人脐静脉内皮细胞IL-8基因表达中的作用

血管内皮细胞位于血流和血管壁之间,除受化学因素的调节外还受力学因素的影响。切应力可通过刺激相应的力学感受系统来调节内皮细胞某些基因的表达,其中包括诱导内皮细胞表达IL- 8。为了阐明MAPK信号途径中的ERK1/ 2信号通路是否参与调控低切应力上调人脐静脉内皮细胞IL- 8基因表达,采用Western blot分析了低切应力(4.2 0 dyne/ cm2 )处理不同时间内皮细胞ERK1/ 2的磷酸化水平及TPK抑制剂Genistein,MEK抑制剂PD980 5 9对其磷酸化的影响;采用定量RT- PCR检测内皮细胞经低切应力刺激或给予阻断剂后再行切应力刺激等处理后IL- 8基因的表达。结果显示:(1)低切应力处理可引起内皮细胞ERK1/ 2蛋白磷酸化水平上调,其磷酸化水平与切应力作用时间有关,具有快速、双向性的特点(在刺激10 min时达到高峰,2 h左右降至未刺激水平) ,阻断剂Genistein和PD980 5 9处理后,ERK1/ 2磷酸化水平与低切应力刺激10 min比较明显降低;(2 )阻断剂Genistein,PD980 5 9可显著抑制低切应力所致的内皮细胞IL- 8m RNA上调。结果表明低切应力可通过ERK1/ 2信号途径上调人脐静脉内皮细胞IL- 8基因的表达。     

Parent-reported birth information: birth weight,birth length and gestational age. Validation study in the SENDO project

ObjectiveTo test the validity of parent-reported birth information obtained through an online, self-administered questionnaire.MethodThe SENDO project is a prospective and dynamic paediatric cohort of Spanish children aged 4 to 6 years old at recruitment. Objective data from medical birth records were compared to parent-reported data getting intra-class correlation coefficients (ICC) for quantitative variables and weighted Kappa Index for qualitative ones. Percentage of responders and of total agreement was also evaluated.ResultsParental response rate was over 99% for birth weight and gestational age and 76% for birth length. ICC for birth weight was 0.95 (95% confidence interval [95%CI]: 0.94-0.96) and 0.78 (95%CI: 0.73-0.83) for birth length, both showing very high correlations. The total agreement percentage for gestational age was 97%, and Kappa weighted index was 0.90 (95%CI: 0.89-0.90), showing a very high agreement as well.ConclusionsWe found high correlations and excellent agreement in parent-reported birth data 4 to 6 years after delivery. Our results show parent-reported birth data, especially birth weight, are valid for use in epidemiological research.