控制性促排卵下凝血相关因素变化研究

控制性超促排卵(COH)是体外受精-胚胎移植(IVF-ET)的关键步骤,但与自然周期相比较,其胚胎着床率和妊娠率仍低于自然周期,这可能和该过程中激素水平的波动有关,该过程中产生超生理剂量的雌、孕激素,可引起多种凝血相关因素的改变,与血栓的形成密切相关,由此继发的子宫内膜微循环障碍可能是影响子宫内膜容受性进而影响着床率和妊娠率的重要原因之一。COH过程中凝血和纤溶系统均有不同程度的激活,凝血因子、抗凝因子、纤溶因子、血液流变学及血管内皮功能等均有不同程度的改变,这些改变与COH中高雌、孕激素状态密切相关。     

Neck Circumference Measurements in Second Trimester Fetuses with Down's Syndrome

Ultrasound examinations were performed on 132 normal fetuses between 12 and 25 weeks of gestation to measure the fetal neck circumference (NC), biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). The relationships between the fetal neck circumference and gestational age, as well as between the fetal neck circumference and fetal biometric parameters (BPD, HC, AC, FL) were linear. Nomograms between the fetal neck circumference and all other parameters were established including the 5th, 50th, and 95th percentile lines. Only one of nine fetuses with Down's syndrome was found to have abnormally increased fetal neck circumference (above the 95th percentile), whereas the remaining eight cases were equally distributed above and below the 50th percentile of these nomograms. The positive predictive value of an abnormally increased fetal neck circumference was 1.6% in our tested population, where the prevalence of Down's syndrome was 1 in 132. Our observations suggest that the use of fetal neck circumference in second trimester fetuses does not add in the prenatal diagnosis of Down's syndrome.     

Does sodium lauryl sulfate concentration vary with time?

When performing skin irritation tests with sodium lauryl sulfate (SLS), the quality of the test solution is of major importance for the reproducibility and comparability of the results. The influence of 4 different storage parameters (concentration, duration, temperature, material of the storage vials) on the stability of aqueous SLS solutions was investigated under non-sterile conditions. SLS solutions at 5 different concentrations (0.001%, 0.01%, 0.1%, 0.5%, 1%) were analysed by mobile phase ion chromatography. Analyses were performed after a storage time of 3 h, 1 week, and 4 weeks. Storage was carried out at different temperatures: -18 degrees C, 6 degrees C, and 23 degrees C. The storage containers were of 2 different materials (glass and polypropylene). After a storage of 1 week, no decrease in SLS concentration was observed, regardless of the chosen conditions. After 4 weeks at 6 degrees C and 23 degrees C, the SLS concentration was found to be significantly decreased for the 2 lowest concentrations (0.001% and 0.01%). At higher concentrations and lower temperatures, no decrease in SLS concentration had occurred. In parallel to the loss of SLS, contamination with bacteria was found in the solutions, especially at the 2 lowest concentrations. Bacterial growth was not observed at higher concentrations. The possibility of biodegradation of SLS has to be taken into account, especially when dealing with low concentrations of SLS.     

应用植入遥测技术对恒河猴部分生理指标的观测

目的应用植入遥测技术观测清醒恒河猴呼吸、血压、心电、体温等生理指标的昼夜变化规律和应激时的变化。方法取3~5岁雌雄各半的8只恒河猴行遥测植入子植入手术,恢复3周后用DSI遥测系统获取清醒无束缚恒河猴连续24 h的呼吸、血压、心电、体温数据,用Ponemah软件分析上述指标并统计实验结果。结果恒河猴的部分心电指标存在明显的昼夜差异(P0.05或P0.01),其中心率(HR)的昼夜均值在每分钟155.0~122.4次之间波动;呼吸频率间期(RR-I)为410.8~535.7 ms;T波幅度(T-A)为0.181~0.157 m V;PR间期(PRI)为80.4~87.4;QT间期(QT-I)为224.8~263.9 ms;校正QT间期(QTcb)为352.3~366.7 ms。猴的血压与呼吸指标白昼均值显著高于夜晚(P0.01),其中收缩压(SYS)昼夜波动范围为144.6~131.6 mm Hg;舒张压(DIA)为99.8~89.9 mm Hg;平均动脉压(MAP)为121.5~110.2 mm Hg;潮气量(TV)为64.5~36.6 m L;分钟通气量(MV)为1931.9~920.1 m L/min;呼吸频率(RR)为每分钟32.3~25.4次。实验室工作人员清扫、喂食活动对猴有一定的应激影响。结论应用植入遥测技术观察到的恒河猴呼吸、血压、心电、体温等生理指标基本均有明显的昼夜节律变化,呼吸、血压、心电、体温等指标白昼均高于夜晚,符合正常恒河猴的生理周期特性。经过驯养的恒河猴在饥饿状态下受工作人员的喂食、清扫活动的应激影响比较强烈。应用植入遥测技术可以对清醒无束缚状态下恒河猴心电、血压、呼吸、体温等进行连续监测,能真实地反映恒河猴24 h内上述生理指标的变化规律,为恒河猴在药理毒理学研究中的应用提供参考。同时应用植入遥测技术,有助于提高药物安全药理学研究的效率,减少动物的使用数量,符合3R原则。     

垂盆草提取物流化床制粒过程参数的响应曲面模型及偏最小二乘模型研究

目的研究响应曲面回归模型及偏最小二乘回归模型对流化床制粒的颗粒粒径分布拟合结果。方法采用流化床制粒制备垂盆草颗粒,利用Box-Behnken试验设计考察粘合剂加入速度(X_1),液固比(X_2),进风温度(X_3)对颗粒粒径的影响,并分别用响应曲面回归模型及偏最小二乘回归模型研究过程参数对粒径分布的拟合情况。结果回归分析结果表明响应曲面回归模型及偏最小二乘回归模型均能较好的模拟流化床制粒结果,且响应曲面回归模型具有较好的模型拟合精度和预测能力。结论结合实验设计与不同的统计模型可深入研究流化床制粒过程,提升对流化床制粒过程的理解,为今后该产品产业化发展提供了参考和技术支持。     

干燥综合征患者全血中羟氯喹及其代谢物浓度与临床指标相关性研究

目的：建立一种高效液相色谱法检测全血中羟氯喹及其代谢物去乙基羟氯喹、去乙基氯喹的新方法,并分析干燥综合征患者血药浓度与免疫相关临床指标的相关性。方法：取100 μL全血样本,加入内标,以两倍量的乙腈沉淀蛋白,离心取上清进样。用Zorbax SB-C₁₈色谱柱分离,流动相为0.2 mol·L^-1磷酸二氢钾-乙腈=15：85（磷酸调至pH3.0）,流速1 mL·min^-1,检测波长254 nm,柱温35℃。考察该方法的专属性、标准曲线和定量限、精密度和准确度、提取回收率、稳定性;测定53例患者羟氯喹及其代谢物血药浓度,并收集患者白细胞水平、血小板计数、谷丙转氨酶、谷草转氨酶、血细胞沉降率等临床检验指标,用SPSS软件分析血药浓度与临床指标的关系。结果：羟氯喹、去乙基羟氯喹、去乙基氯喹、内标氯喹的保留时间分别在8.6,4.1,5.2 min和12.8 min左右,羟氯喹及其代谢物在3~3 000 ng·mL^-1范围内线性良好,最低定量限为3 ng·mL^-1,批内、批间精密度、方法回收率符合要求;患者用药后白细胞水平有明显降低,其他临床指标无明显变化,血药浓度高组患者白细胞水平较高,其他指标在高低浓度组间没有明显差异。结论：该方法灵敏度高、结果准确、样品处理简单、分析快速,可用于临床检测。干燥综合征患者服用羟氯喹后白细胞计数有统计学差异,服药后高浓度组患者白细胞计数显著高于低浓度组患者。     

Combined pre-treatment MRI and 18F-FDG PET/CT parameters as prognostic biomarkers in patients with cervical cancer

Objective

To determine the associations of quantitative parameters derived from multiphase contrast-enhanced magnetic resonance imaging (CE-MRI), diffusion-weighted (DW) MRI and 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/computed tomography (PET/CT) with clinico-histopathological prognostic factors, disease-free survival (DFS) and overall survival (OS) in patients with cervical cancer.

Methods and materials

Our institutional review board approved this retrospective study of 49 patients (median age, 45 years) with histopathologically proven IB-IVB International Federation of Gynecology and Obstetrics (FIGO) cervical cancer who underwent pre-treatment pelvic MRI and whole-body 18F-FDG PET/CT between February 2009 and May 2012. Maximum diameter (_maxTD), percentage enhancement (PE) and mean apparent diffusion coefficient (ADC_mean) of the primary tumor were measured on MRI. Maximum standardized uptake value (SUV_max), metabolic tumor volume (MTV), total lesion glycolysis (TLG) were measured on 18F-FDG PET/CT. Correlations between imaging metrics and clinico-histopathological parameters including revised 2009 FIGO stage, tumor histology, grade and lymph node (LN) metastasis at diagnosis were evaluated using the Wilcoxon rank sum test. Cox modeling was used to determine associations with DFS and OS.

Results

Median follow-up was 17 months. 41 patients (83.6%) were alive. 8 patients (16.3%) died of disease. Progression/recurrence occurred in 17 patients (34.6%). Significant differences were observed in ADC_mean, SUV_max, MTV and TLG according to FIGO stage (p < 0.001–0.025). There were significant correlations between ADC_mean, MTV, TLG and LN metastasis (p = 0.017–0.032). SUV_max was not associated with LN metastasis. FIGO stage (p = 0.017/0.033), LN metastases (p = 0.001/0.020), ADC_mean (p = 0.007/0.020) and MTV (p = 0.014/0.026) were adverse predictors of both DFS/OS. _maxTD (p = 0.005) and TLG (p = 0.024) were adverse predictors of DFS. PE and SUV_max did not correlate with DFS or OS (p = 0.18–0.72).

Conclusions

Quantitative parameters derived from pre-treatment DW-MRI (ADC_mean) and from 18F-FDG PET/CT (MTV and TLG) were associated with high-risk features and may serve as prognostic biomarkers of survival in patients with cervical cancer.     

Dosimetry for 131Cs and 125I seeds in solid water phantom using radiochromic EBT film

PurposeTo measure the 2D dose distributions with submillimeter resolution for ¹³¹Cs (model CS-1 Rev2) and ¹²⁵I (model 6711) seeds in a Solid Water phantom using radiochromic EBT film for radial distances from 0.06 cm to 5 cm. To determine the TG-43 dosimetry parameters in water by applying Solid Water to liquid water correction factors generated from Monte Carlo simulations.MethodsEach film piece was positioned horizontally above and in close contact with a ¹³¹Cs or ¹²⁵I seed oriented horizontally in a machined groove at the center of a Solid Water phantom, one film at a time. A total of 74 and 50 films were exposed to the ¹³¹Cs and ¹²⁵I seeds, respectively. Different film sizes were utilized to gather data in different distance ranges. The exposure time varied according to the seed air-kerma strength and film size in order to deliver doses in the range covered by the film calibration curve. Small films were exposed for shorter times to assess the near field, while larger films were exposed for longer times in order to assess the far field. For calibration, films were exposed to either 40 kV (M40) or 50 kV (M50) x-rays in air at 100.0 cm SSD with doses ranging from 0.2 Gy to 40 Gy. All experimental, calibration and background films were scanned at a 0.02 cm pixel resolution using a CCD camera-based microdensitometer with a green light source. Data acquisition and scanner uniformity correction were achieved with Microd3 software. Data analysis was performed using ImageJ, FV, IDL and Excel software packages. 2D dose distributions were based on the calibration curve established for 50 kV x-rays. The Solid Water to liquid water medium correction was calculated using the MCNP5 Monte Carlo code. Subsequently, the TG-43 dosimetry parameters in liquid water medium were determined.ResultsValues for the dose-rate constants using EBT film were 1.069±0.036 and 0.923±0.031 cGy U⁻¹ h⁻¹ for ¹³¹Cs and ¹²⁵I seed, respectively. The corresponding values determined using the Monte Carlo method were 1.053±0.014 and 0.924±0.016 cGy U⁻¹ h⁻¹ for ¹³¹Cs and ¹²⁵I seed, respectively. The radial dose functions obtained with EBT film measurements and Monte Carlo simulations were plotted for radial distances up to 5 cm, and agreed within the uncertainty of the two methods. The 2D anisotropy functions obtained with both methods also agreed within their uncertainties.ConclusionEBT film dosimetry in a Solid Water phantom is a viable method for measuring ¹³¹Cs (model CS-1 Rev2) and ¹²⁵I (model 6711) brachytherapy seed dose distributions with submillimeter resolution. With the Solid Water to liquid water correction factors generated from Monte Carlo simulations, the measured TG-43 dosimetry parameters in liquid water for these two seed models were found to be in good agreement with those in the literature.     

A predictive model for blastocyst formation based on morphokinetic parameters in time-lapse monitoring of embryo development

Purpose

The aim of the study was to create a predictive model of blastocyst development based on morphokinetic parameters of time-lapse embryoscope monitoring.

Methods

Time-lapse recordings of 432 embryos (obtained from 77 patients), monitored in Embryoscope, were involved in the study. Patients underwent in vitro fertilization according to standard procedure between June 2012 and April 2013. A retrospective analysis of morphokinetic features, focused on duration of time from the Intracytoplasmic Sperm Injection (ICSI) procedure to consecutive embryo division for 2, 3, 4 and 5 blastomeres, as well as time intervals between each division, was conducted. All embryos were observed for 5 days.

Results

Based on the distribution of analyzed morphokinetic parameters and number of embryos developed to blastocyst, a range denoting the possibility of an embryo reaching blastocyst stage was determined. According to the obtained results, univariate and multivariate logistic regression analyses were performed. Based on the times of division for two and five blastomeres and intervals between the second and third division, a multivariate predictive model was created. The predictive equation was constructed based on the parameters of logistic regression analysis (odds ratios). Statistically significant differences (p < 0.001) in the size of the prediction parameter between the group of embryos developed to blastocyst (the median value: Me = 9.95, and quartiles: Q₁ = 7.59, Q₃ = 12.30) and embryos that did not develop to the blastocyst stage (Me = 4.66, Q₁ = 2.33, Q₃ = 8.19) were found. A Receiver Operating Characteristic (ROC) curve was created for the constructed predictive model. The Area Under the Curve was AUC = 0.806 with a 95 % confidence interval (0.747, 0.864). The predictive model constructed in this study has been validated using an independent data set, which indicates that the model is reliable and repeatable.

Conclusions

Time-lapse imaging presents a new diagnostic tool for parametric evaluation of embryo development, from the oocyte stage, through fertilization, up to the blastocyst stage. The assessment of morphokinetic parameters can help us to provide more accurate information about the reproductive potential of embryos. It allows for early selection of embryos with high reproductive potential and shortens embryo incubation.     

编辑多叶光栅缩小剂量热点方法在乳腺癌根治术后放疗中的应用

目的:探究编辑多叶光栅（multi-leaf collimator,MLC）缩小剂量热点方法在乳腺癌根治术后放疗中应用的可行性。方法:选取10例接受放疗的乳腺癌根治术后患者的CT图像,勾画胸壁、腋窝与锁骨上下相关预防照射区域和危及器官,基于医科达Precise医用直线加速器和CMS XiO 4.80计划系统,以5 000 cGy/25 f处方剂量分别对每例患者设计采用编辑MLC缩小剂量热点方法前、后2种放疗计划（plan1和plan2）,采用SPSS 20.0统计学软件评估2种计划靶区和危及器官剂量学参数及治疗参数的差异。结果:2种计划靶区剂量分布和危及器官受照剂量均满足临床要求,plan2相对于plan1,PTV的D1 cc降低1.87%（t=37.467,P=0.000）、D98%降低0.38%（t=2.664,P=0.000）、V107%降低7.30%（t=2.595,P=0.029）、V110%降低23.58%（t=6.684,P=0.000）,PTV的其它剂量学参数差异无统计学意义（P＞0.05）;危及器官剂量学参数和治疗参数差异无统计学意义（P＞0.05）。结论:编辑MLC缩小剂量热点方法有利于缩小PTV的剂量热点,对其它参数的影响甚微,建议设计乳腺癌根治术后放疗计划时采用该方法。