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.     

枸橼酸咖啡因与氨茶碱对早产儿神经行为发育影响分析

目的 比较枸橼酸咖啡因和氨茶碱对早产儿神经行为发育的影响,为早产儿早期合理干预提供临床依据。方法 选择2014年6月-2018年6月在中国西电集团医院新生儿科住院接受枸橼酸咖啡因治疗的原发性呼吸暂停(AOP)早产儿62例作为研究组;2011 年 12 月-2014年5月同在中国西电集团医院新生儿科住院采用氨茶碱治疗的AOP患儿69例作为对照组。出生3~8 d及矫正胎龄40周时分别行头颅MRI检查,评估脑白质损伤(WMD)并进行两组比较;6个月及12个月时应用Gesell婴幼儿发育量表测试比较两组神经行为发育水平。结果 两组患儿在性别、出生胎龄及体重、产前孕母糖皮质激素应用及分娩方式、5 min Apgar评分、辅助通气和表面活性物质的应用等方面差异均无统计学意义(P>0.05)。首次头颅MRI显示两组患儿WMD差异无统计学意义(P>0.05)。矫正胎龄40周时头颅MRI显示,咖啡因组WMD较氨茶碱组明显改善,差异有统计学意义(P<0.05);且6个月及12个月时Gessell婴幼儿发育量表测试,随访至校正6月龄时,咖啡因组患儿的大运动、精细运动及个人-社交评分均高于氨茶碱组(P<0.05);随访至校正12月龄时,咖啡因组患儿的大运动、精细运动、语言、适应性评分均高于氨茶碱组(P<0.05)。结论 枸橼酸咖啡可明显改善AOP患儿6个月及12个月时的神经行为发育。     

透析液钙离子浓度对肾功能衰竭血液透析患者血清钙离子水平及血压的影响

目的 观察不同钙离子浓度的透析液对血液透析患者透析后血清钙离子水平及血压变化的影响，为肾功能衰竭血液透析患者的高钙血症及高血压的防治提供依据。方法 选择不同钙离子浓度的透析液，将维持性血液透析患者分为高钙组（1．75mmol／L）和低钙组（1．25mmol／L），比较患者每次透析前后脉搏、血压，同时抽查患者透析前后血钙及血肌酐浓度的变化。结果透析后两组患者血肌酐浓度均显著下降，透析前后差异均具有统计学意义（P〈0．01）；高钙组患者透析后血钙较透析前升高，差异具有统计学意义（P〈0．01），而低钙组患者血钙比透析前略降低，差异无统计学意义（P〉0．05）。高钙组患者透析后较透析前收缩压、舒张压及平均动脉压都升高，差异均具有统计学意义（P〈0．05），而低钙组患者透析后较透析前收缩压、舒张压及平均动脉压都降低，差异均具有统计学意义（P〈0．05）。透析后两组血钙比较差异具有统计学意义（P〈0．01）；透析后低钙组较高钙组患者的收缩压、舒张压及平均动脉压都降低，三者差异均具有统计学意义（P〈0．01）。结论透析液钙离子浓度与血液透析患者血清钙离子水平及血压呈正相关，低钙透析液透析有助于维持性血液透析患者高血压的控制。     

Changes of Unit Discharge of the Medullary Respiratory Neurons during Apnea

Changes of the neuronal discharge of 128 medullary respiratory unitswere recorded and studied during the period of expiratory apnea induced reflexlyby intracarotid sinus injection of sodium citrate in rabbits.Generally,theneuronal discharge of inspiratory units began,stopped and recovered at the sametime with those of the phrenic nerve.But,about 5% the phase-spanninginspiratory units near the obex showed a different time course with the dischargeof the phrenic nerve.They fired continuously in a low frequency while thephrenic nerve was quiet.When increasing progressively and approaching to acertain level,the firing rate increased abruptly and at the same time phrenic nervebegan to fire.So it seemed that they acted as the pacemaker of inspiration.Comparison of the cycle-triggered histograms(CTH)of these inspiratory unitswith those of phrenic nerve showed clearly the above mentioned phasicrelationship.They started firing before the phrenic nerve,but they reached theirmaximal rate and then declined and stopped quite in accordance with the phrenicnerve.It is,therefore,reasonable to assume that the central mechanism of theswitch from expiratory apnea to inspiration may originate from this kind ofneurons.Most of the expiratory units show tonic discharges during the period of apneawith a higher discharge rate than normal and then the rate decreases just beforerecovery of phrenic firing.In addition,small portion of the expiratory units weredepressed as the phrenic discharge ceased.The function of these two differentkinds of neurons in the mechanism of development of respiratory rhythm is,apparently,different.     

Effect of buffering on pharmacokinetics of ketoprofen enantiomers in man

Aims Concomitant administration of magnesium hydroxide may affect the rate or extent of absorption of non-steroidal anti-inflammatory drugs. In order to find out whether or not buffering modifies the pharmacokinetics of ketoprofen, plasma concentration-time courses resulting from oral administration of unbuffered formulations were compared with those of buffered formulations.
Methods Two groups of 12 healthy and young male subjects were included in two randomized cross-over studies and received single oral doses of ketoprofen 12.5 or 25  mg, respectively, given as tablets which were either unbuffered or buffered with magnesium hydroxide/citrate. Ketoprofen enantiomers in plasma were determined by h.p.l.c. up to 24  h post-dose.
Results Maximum plasma concentrations ( C _max ) of both the (R)- and (S)-enantiomer, observed after administration of the buffered formulations (12.5 and 25  mg), were higher compared with the unbuffered tablets by about 50–80%. The area under concentration-time data (AUC) was unaffected, and, hence, C _max/AUC was increased by buffering. Time to C _max ( t _max ) and mean residence time (MRT) tended to be or was shortened by buffering.
Conclusions It is concluded that buffering of two ketoprofen formulations with magnesium hydroxide/citrate enhanced the concentration maximum by increasing the rate of absorption and leaving AUC unaffected.     

Oxidative stress induced by iron released from transferrin in low pH peritoneal dialysis solution

Background. Transferrin binds extracellular iron and protectstissues from iron-induced oxidative stress. The binding of ironand transferrin is pH dependent and conventional peritonealdialysis (PD) solutions have unphysiologically low pH values.Herein, we investigated whether conventional PD solution releasesiron from transferrin and if the released iron causes oxidativestress. Methods. Effects of PD solutions on iron binding to transferrinwere examined with purified human transferrin and transferrinin dialysates drained from PD patients. Oxidative stress inducedby iron released from transferrin was evaluated in terms ofthe formation of thiobarbituric acid reactive substance (TBARS)and protein carbonylation in the human red blood cell (RBC)membrane. The iron deposition in peritoneal tissue from PD patientswas evaluated by Perls' staining with diaminobenzidine intensification. Results. Low pH PD solution released iron from transferrin.This iron release occurred within 1 min. Iron release was notobserved in neutralized PD solution. Iron released from transferrinin low pH PD solution increased TBARS formation and proteincarbonylation in the human RBC membrane. Iron deposition, whichis prominent in the fibrotic area facing the peritoneal cavity,was observed in the peritoneum of PD patients. Conclusions. Iron released from transferrin in low pH PD solutioncan produce oxidative stress in the peritoneum of a PD patient.Neutralizing PD solution can avoid this problem. Iron depositionin the peritoneum may participate in the pathogenesis of peritonealfibrosis in PD patients.     

Role of citric acid in primary hyperparathyroidism with renal lithiasis

Summary Nephrolithiasis is presented in 18–40% of patients with primary hyperparathyroidism. Our work suggests that citrate, an inhibitor of calcium salts, could be involved in the presence of renal lithiasis because hyperparathyroid stone formers show less citrate elimination than nonstone formers.     

小剂量阿斯匹林辅助促排卵过程中对子宫血流及内膜厚度的影响

目的　探讨小剂量阿斯匹林在促排卵过程中对子宫血流及内膜厚度的影响及其作用机理。方法　采用前瞻性随机双盲的方法 ,对不明原因的不孕妇女在克罗米酚 (CC)促排卵治疗同时 ,自月经第 1～ 2 0d连续服用小剂量阿斯匹林 ,75mg/d。 结果　试验组子宫动脉血流阻力指数 (RI)明显低于对照组 (P <0 0 1) ,子宫内膜厚度明显较对照组厚 (P <0 0 5 )。结论　小剂量阿斯匹林可增加子宫血流供应 ,从而改善促排卵治疗时CC所致的子宫内膜发育不良     

克罗米芬兴奋试验预测卵巢储备功能的价值

目的探讨克罗米芬兴奋试验（CCT）在不孕妇女中预测卵巢储备功能的作用。方法对2001年1月至2005年2月就诊于广东省妇幼保健院的666例不孕症患者作为研究对象，分为A组（≥35岁）461例为高龄组，B组（〈35岁）205例为低龄组，另取156例年龄〈35岁、非女方不孕原因者作为对照组，对三组受试者进行CCT。结果CCT异常发生率A组、B组及对照组分别为27．76％、34．14％、2．56％，A组及B组与对照组比较差异均有非常显著性意义（P〈0．01）。基础卵泡刺激素（FSH）〈10IU／L、雌二醇（E2）〈180pmot／L的不孕患者CCT异常发生率分剐为17．46％、24．19％，均明显低于FSH≥10IU／L、E2≥180pmol／L患者的64．19％及39．4％（P〈0．01）。结论CCT预测卵巢储备功能较基础FSH更敏感，CCT可作为常规了解卵巢储备功能的一项检测方法。