Examination of potential novel biochemical factors in relation to prostate cancer incidence and mortality in UK Biobank

Background Although prostate cancer is a leading cause of cancer death, its aetiology is not well understood. We aimed to identify novel biochemical factors for prostate cancer incidence and mortality in UK Biobank.Methods A range of cardiovascular, bone, joint, diabetes, renal and liver-related biomarkers were measured in baseline blood samples collected from up to 211,754 men at recruitment and in a subsample 5 years later. Participants were followed-up via linkage to health administrative datasets to identify prostate cancer cases. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable-adjusted Cox regression corrected for regression dilution bias. Multiple testing was accounted for by using a false discovery rate controlling procedure.Results After an average follow-up of 6.9 years, 5763 prostate cancer cases and 331 prostate cancer deaths were ascertained. Prostate cancer incidence was positively associated with circulating vitamin D, urea and phosphate concentrations and inversely associated with glucose, total protein and aspartate aminotransferase. Phosphate and cystatin-C were the only biomarkers positively and inversely, respectively, associated with risk in analyses excluding the first 4 years of follow-up. There was little evidence of associations with prostate cancer death.Conclusion We found novel associations of several biomarkers with prostate cancer incidence. Future research will examine associations by tumour characteristics.Subject terms: Predictive markers, Prostate cancer, Risk factors     

Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR_1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR_1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR_1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR_1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR_1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.     

氟苯咪唑CHL培养细胞染色体畸变研究

氟苯咪唑(Fludendazole)由Gelder于1969年合成,直到最近几年才受到各国重视,我国于1983年也合成了该化合物。该药经临床应用疗效显著,抗虫效力高,抗虫谱     

Return of fertility following discontinuation of an injectable contraceptive — Norethisterone oenanthate (NET EN) 200mg dose

The return of fertility following discontinuation of norethisterone oenanthate (NET EN) 200 mg injectable contraceptive after use for a minimum period of six months or more was studied in 69 women who discontinued the method for planning pregnancy. Former users of copper intra-uterine device (CuT 200) were enrolled as a control group. Another 161 women who had discontinued NET EN due to other reasons (e.g. amenorrhoea, excessive bleeding or personal reasons) were also studied for return of fertility after ensuring that they were not using any other method of contraception and were exposed to the risk of pregnancy. The subjects from both groups were followed for a period of one year. The cumulative conception rates at one year were 72.5 and 83.6 per 100 subjects for ex-NET EN and ex-CuT 200 users who had discontinued the method for planning pregnancy and this difference was not statistically significant (P > 0.05). The median time for conception for ex-NET EN users was 7.8 months as compared to 3.7 months in ex-CuT 200 users but the cumulative conception rates at the end of one year show that future return of fertility in NET EN users does not appear to be adversely affected.

In 51 subjects who had discontinued NET EN due to amenorrhoea, the return of fertility was predictably slower and less. The return of fertility in subjects who discontinued NET EN for other reasons (e.g. excessive bleeding and other personal reasons) was similar to ex-NET EN and ex-CuT 200 users.     

Experimentelle Untersuchungen über die Entzündung der Hornhaut

Ohne ZusammenfassungHierzu Taf. XV–XVI.     

近节指骨段屈肌腱鞘不同范围损伤对肌腱功能的影响

目的 探索手指屈肌腱在近节指骨段不同范围损伤时对屈指肌腱功能的影响。方法 采用12只成人尸体手指。实验分为:第一阶段屈指肌腱完整,以后四个阶段依次沿近节指骨掌侧小线闭开小央1/4、1/2、3/4及全长。在掌指关节被动屈80°和掌指关节屈80°同时近侧指关节屈100°时,测量指浅屈肌腱(FDS)和指深屈肌腱(FDP)的滑动距离。根据肌腱力臂和滑动距离的关系,得出屈指肌腱在掌指关节处和近侧指间关节及肌腱在近节指骨段的弓弦畸形程度。结果 腱鞘中央1/4切开时,指屈肌腱的滑动距离、力臂均无显著变化;1/2切开后,单纯屈曲掌指关节时的FDS腱和掌指、近节指间关节屈曲时的FDS、HDP腱的滑动距离和力臂较腱鞘完整时显苫增大(P<0.05);切开3/4长度后,FDS、FDP腱滑动距离均有统计学意义变化,FDS、FDP腱力臂平均增加8～9％;全切开腱鞘,FDS、FDP腱滑动距离变化正统计学上有高度显著性(P<0.01),两腱力臂分别增加16％和15％。随腱鞘切开范围增大,FDS、FDP在近节指骨段的弓弦畸形程度也越来越大。结论 从肌腱的生物力学变化可见,近节指骨段腱鞘的小范围损伤如中间1/4以内损伤时,对肌腱功能影响小,可以不予修复;若损伤超过1/2长度,尤其对腱鞘全长损伤,应予以修复以恢复肌腱功能。     

The glycosaminoglycans of the gubernaculum during testicular descent in the fetus

Tissues were obtained from 387 male pig fetuses ranging from 60 to 120 days of gestation. The relative wet mass and water content of the gubernaculum increased during and decreased after the period of testicular descent. The extracellular glycosaminoglycans (GAG) were assayed to determine whether these polyanionic macromolecules are responsible for the increased water content of the gubernaculum. The total GAG/wet tissue mass in the gubernaculum decreased during and increased after descent, while the total GAG/dry mass decreased during and after descent, indicating an accumulation of water during descent, with a loss of water and an increase in less hydrated tissue components after descent. The major GAG fraction in the gubernaculum was dermatan sulfate, but the percentage hyaluronate in the gubernaculum was two times higher than in striated muscle or umbilical cord, indicating that this GAG fraction may be responsible for the increased water content of the gubernaculum, which probably serves to dilate the inguinal canal and scrotum, thus facilitating descent.     

磷脂酶C与生殖

磷脂酶C(PLC)是磷脂酰肌醇信号转导途径中一个关键酶。目前确认的哺乳类PLC共有PLC β、PLC γ、PLC δ、PLC ε和最近新发现的PLC ζ 5种亚型 ,12种同工酶。不同亚型的结构、调控和组织分布各有差异。PLC在调控信号转导通路中的特性使其在顶体反应、卵子激活中发挥了巨大的作用。本文综述了PLC家族 5种亚型的结构、调控机制及PLC在男性生殖领域的相关内容 ,包括PLC引起卵子发生Ca2 + 振荡、激活卵子、促进胚胎发育等 ,并进一步探讨了PLC在临床上可能的应用前景。     

骨钙素酶免疫检测方法的研究和应用

目的：建立骨钙素酶免疫测定方法，并应用于临床检测血清骨钙素。方法：应用了3种检测模式，根据检测灵敏度、剂量反应曲线的形态进行分析，选择出合适的模式进一步应用于临床血清标本的骨钙素检测。结果：所采用的骨钙素单克隆抗体是钙离子依赖型的。固相抗原竞争法适合于临床定量测定骨钙素。最低可测限为1．4μg/L;20μg/L骨钙素样品批内CV＝3．98％，批间CV＝12．67％。测定正常献血员140名（年龄17－45岁），第5－95百分位点的骨钙素含量，男性为7．5－15．0μg/L女性为7.0-17.5μg/L。70例疑有骨质疏松症患者血清骨钙素含量2．91－30．20μg/L，以第95百分位点的骨钙素含量为cut-off值，升高5例。与进口试剂盒（Novocalcin,USA）相比较，有较好的相关性，r=0.81。结论：固相抗原竞争法酶免疫测定可以灵敏地检测血清中骨钙素含量，有实用价值。