利用CNV-seq技术产前诊断Pallister-Killian综合征胎儿一例

应用拷贝数变异测序(copy number variation sequencing,CNV-seq)技术鉴别来源不明的胎儿标记染色体,明确其遗传物质的来源,并探讨此技术在产前诊断中的应用价值。讨论Pallister-Killian综合征(Pallister-Killian syndrome,PKS)的临床特征及遗传学特点,提高对此类罕见染色体疾病的认识。该病例因在妊娠中期超声发现胎儿异常而行羊水穿刺进行CNV-Seq检测,同时分析胎儿和父母的核型。羊水CNV-Seq结果示该样本12号染色体p13.33-p11.1处检测到拷贝数为3.5、片段大小为34.70 Mb的嵌合重复区域;羊水染色体核型结果为47,XY,+i(12)(p10)[58]/46,XX[42],综合上述结果考虑为PKS。通过结合超声结果,综合应用染色体G显带核型分析和CNV-seq技术能准确确认染色体异常片段来源,在产前有效诊断PKS患者。     

二补助育汤对胚胎着床障碍小鼠子宫血管生成相关因子表达的影响

目的：探讨二补助育汤对胚胎着床障碍模型小鼠子宫内膜形态及血管生成素-1（Ang-1）mRNA、血管内皮生长因子（VEGF）mRNA的表达和定位的影响。方法：24只ICR雌性小鼠随机分为空白组、模型组、戊酸雌二醇组、二补助育汤组，每组6只，用米非司酮建立胚胎着床障碍动物模型，各组给予相应药物灌胃，妊娠第5天处死小鼠后，检测各组妊娠率、平均着床位点数、子宫内膜Ang-1和VEGF mRNA表达量及其蛋白定位。结果：模型组小鼠平均胚胎着床位点数、Ang-1 mRNA、VEGF mRNA表达量明显低于空白组（均P<0.05）；与模型组比较，二补助育汤组平均胚胎着床位点数、Ang-1 mRNA、VEGF mRNA表达量显著提高（均P<0.05）。结论：二补助育汤可提高子宫内膜Ang-1和VEGF蛋白表达量，促进子宫内膜血管生成，从而提高子宫内膜容受性。     

Reflection of neuroblastoma intratumor heterogeneity in the new OHC-NB1 disease model

Accurate modeling of intratumor heterogeneity presents a bottleneck against drug testing. Flexibility in a preclinical platform is also desirable to support assessment of different endpoints. We established the model system, OHC-NB1, from a bone marrow metastasis from a patient diagnosed with MYCN-amplified neuroblastoma and performed whole-exome sequencing on the source metastasis and the different models and passages during model development (monolayer cell line, 3D spheroid culture and subcutaneous xenograft tumors propagated in mice). OHC-NB1 harbors a MYCN amplification in double minutes, 1p deletion, 17q gain and diploid karyotype, which persisted in all models. A total of 80–540 single-nucleotide variants (SNVs) was detected in each sample, and comparisons between the source metastasis and models identified 34 of 80 somatic SNVs to be propagated in the models. Clonal reconstruction using the combined copy number and SNV data revealed marked clonal heterogeneity in the originating metastasis, with four clones being reflected in the model systems. The set of OHC-NB1 models represents 43% of somatic SNVs and 23% of the cellularity in the originating metastasis with varying clonal compositions, indicating that heterogeneity is partially preserved in our model system.     

Association Between Clinical Tumor Burden and Efficacy of Immune Checkpoint Inhibitor Monotherapy for Advanced Non–Small-Cell Lung Cancer

BackgroundProgrammed cell death 1 (PD-1) inhibitors have become a standard treatment, albeit not completely effective, for patients with advanced non–small-cell lung cancer (NSCLC). Previous studies of advanced melanoma have revealed that the tumor burden predicted the response to PD-1 inhibitors, although this relationship has remained unclear for NSCLC.Patients and MethodsThe present single-center retrospective study evaluated 163 patients with advanced NSCLC who had received PD-1/programmed cell death ligand 1 (PD-L1) inhibitor monotherapy from December 2015 to December 2018. The clinical tumor burden was estimated using the baseline sum of the target lesions’ longest diameters (BSLDs), measured according to the Response Evaluation Criteria for Solid Tumors, and the baseline number of metastatic lesions (BNMLs).ResultsThe optimal cutoff values for predicting progression-free survival (PFS) were 5 for the BNMLs and 76 mm for the BSLDs, using the minimum P value method. The low-BNML group included 73 patients (44.8%). The median PFS was 12.2 months in the low-BNML group and 2.8 months in the high-BNML group (hazard ratio, 0.51; P = .0005). The low-BSLD group included 92 patients (56.4%). The median PFS was 9.6 months in the low-BSLD group and 3.4 months in the high-BSLD group (hazard ratio, 0.52; P = .0006). Multivariable analysis revealed that low-BSLD, low-BNML, nonsquamous histologic type and a PD-L1 tumor proportion score of ≥ 50% were independently associated with prolonged PFS.ConclusionsPD-L1 expression and the clinical tumor burden can predict the efficacy of PD-1/PD-L1 inhibitor monotherapy for NSCLC.     

精子冷冻环无保护剂玻璃化冷冻方法的初步研究

目的探讨精子冷冻环无保护剂玻璃化冷冻方法的可行性。方法正常精液标本上游处理后,进行常规冷冻和冷冻环无保护剂的玻璃化冷冻,复苏后分别从活力参数及电镜下超微结构等指标比较两种冷冻方法的效果。结果两种方法冷冻后精子存活率、活动率之间差异无显著性(48%∶48%;44.5%∶43.5%,P>0.05),但均较未冷冻的89%和88.5%明显下降(P<0.001)。超微结构亦较未冷冻时发生了一定的改变,但核结构基本保持完整。结论精子冷冻环无保护剂的玻璃化冷冻是一种简单、方便而行之有效的冷冻方法。     

Kindergarten children's representation and understanding of written number symbols

Two samples of kindergarten children's representation and understanding of written number symbols were examined in two time points in one academic year. About 85% of Chinese five year olds (mean = 5 years 10 months) were able to use conventional number symbols to represent the quantity of 30 or larger. At the end of the kindergarten year, 94% of Chinese six year olds (mean = 6 years 4 months) were able to use conventional number symbols to represent the quantity of 100 or larger. Some Chinese six year olds had problems in representing written addition and subtraction tasks. Children's ability to represent written number symbols, ability to represent written addition and subtraction formula and their performance on written addition and subtraction were closely related. The performance of children in a university-affiliated childcare center was better than that of the center serving working-class families in Time 1, but the performance reversed at the end of the kindergarten year.     

某铜矿山巷道内气溶胶浓度与粒径分布的测量和分析

目的 定性了解矿山巷道内气溶胶的浓度和粒径分布特性。方法 在巷道内的不同区间,分别用凝结核颗粒计数器和个人气溶胶测量仪巡测气溶胶的粒子数和质量浓度,并通过质量浓度的分级测量定性评价微米级气溶胶的粒径分布;在调度室内外,用金属丝网筛扩散法测量亚微米级气溶胶的粒径分布。结果 巷道内可吸入颗粒物(PM10)的平均质量浓度为0.42 mg/m³,其量值大小因工作断面而异,且受人工活动影响变化较大;巷道内粒径大于1.0 μm的颗粒物广泛存在,而粒子直径小于5 nm的气溶胶基本上未被检出。结论 矿山巷道内气溶胶特性因工作断面、人工活动和通风条件的不同而变化明显,在开展内照射剂量评价时应考虑粒径大于1.0 μm放射性气溶胶粒子的剂量贡献。     

Measurement in clinical trials: A neglected issue for statisticians?

Biostatisticians have frequently uncritically accepted the measurements provided by their medical colleagues engaged in clinical research. Such measures often involve considerable loss of information. Particularly, unfortunate is the widespread use of the so‐called ‘responder analysis’, which may involve not only a loss of information through dichotomization, but also extravagant and unjustified causal inference regarding individual treatment effects at the patient level, and, increasingly, the use of the so‐called number needed to treat scale of measurement. Other problems involve inefficient use of baseline measurements, the use of covariates measured after the start of treatment, the interpretation of titrations and composite response measures. Many of these bad practices are becoming enshrined in the regulatory guidance to the pharmaceutical industry. We consider the losses involved in inappropriate measures and suggest that statisticians should pay more attention to this aspect of their work. Copyright © 2009 John Wiley & Sons, Ltd.     

Image processing in digital radiography

Image processing is a critical part of obtaining high-quality digital radiographs. Fortunately, the user of these systems does not need to understand image processing in detail, because the manufacturers provide good starting values. Because radiologists may have different preferences in image appearance, it is helpful to know that many aspects of image appearance can be changed by image processing, and a new preferred setting can be loaded into the computer and saved so that it can become the new standard processing method.Image processing allows one to change the overall optical density of an image and to change its contrast. Spatial frequency processing allows an image to be sharpened, improving its appearance. It also allows noise to be blurred so that it is less visible. Care is necessary to avoid the introduction of artifacts or the hiding of mediastinal tubes.