儿童异基因造血干细胞移植术后肺急性移植物抗宿主病与感染CT表现

目的 观察儿童异基因造血干细胞移植（allo-HSCT）术后肺部急性移植物抗宿主病（aGVHD）的CT表现,并与感染性病变鉴别。方法 纳入148例allo-HSCT后出现肺部病变患儿,分为aGVHD组（n=85）和感染组（n=63）。比较组间年龄、术后发病时间及肺部CT征象及分布模式差异。结果 aGVHD组与感染组年龄与发病时间差异均具有统计学意义（P均<0.05）。aGVHD组常见CT征象为磨玻璃影（GGO,35/85,41.18%）、实变影（14/85,16.47%）及胸腔积液（12/85,14.12%）,多呈双侧、弥漫分布,可见胸膜下空逸;感染组常见征象包括实变影（33/63,52.38%）、GGO（32/63,50.79%）及支气管壁增厚（23/63,36.51%）,多呈单侧、局限性分布;2组病变分布模式差异均具有统计学意义（P均<0.05）。支气管壁增厚多见于感染组（P<0.05）。结论 儿童肺aGVHD的CT表现具有特征性,结合发病时间等信息可与感染性病变相鉴别。     

儿童血液病异基因造血干细胞移植后中枢神经系统感染MRI特征

目的 观察儿童血液病异基因造血干细胞移植（allo-HSCT）后中枢神经系统（CNS）感染的MRI特征。方法 回顾2 240例因血液病接受HSCT患儿,分析其中13例经手术、穿刺活检、实验室检查确诊的不同病原CNS感染的MRI表现。结果 血液病allo-HSCT后CNS感染率为0.58%（13/2 240）,死亡率为38.46%（5/13）,发病时间为移植后24~271天,中位数79天;主要临床表现为头痛、抽搐、凝视及颈强直。7例真菌感染（7/13,53.85%）,MRI见幕上、幕下与基底节受累,病灶呈多发或单发结节状、类圆形团块状及脑回样异常信号伴环形强化;细菌感染2例（2/13,15.38%）, MRI显示幕上受累,病灶呈单发或多发脑回样、斑片状异常信号;结核感染2例（2/13,15.38%）,MRI显示幕上受累,病灶呈多发团块状、脑回样及小结节状异常信号,伴簇状环形强化;EB病毒感染2例（2/13,15.38%）,MRI显示幕上、下均受累,病灶呈多发斑片状、类圆形团块状及脑回样异常信号,部分对称分布,伴脑回样、花环样强化。结论 血液病患儿allo-HSCT后CNS感染类型多样,MRI表现各有不同,但具有一定特征性,与临床症状、体征及实验室检查相结合有助于早诊断、早治疗。     

Identification of a novel DRB1 allele through intergenic recombination between HLA-DRB1 and HLA-DRB302 in a Chinese family

In this study, a novel DRB1 allele was revealed by routine HLA-SBT typing noted for its extensive mismatches to any known DRB1 alleles within the exon 2. Sequences containing the exons 2, 3 of HLA-DRB1, their surrounding introns, and the full-length cDNA of DRB1 were analyzed to determine a possible recombination event. Interestingly, the sequences of entire exon 2 were characterized as DRB3^∗02:02:01:01/02; while exon 3 were characterized as DRB1^∗14 like alleles. Further analysis of the sequences using Simplot software suggested that an intergenic recombinant event (i.e. exchange of sequence between non-allelic genes) may have occurred between DRB3^∗02 allele and DRB1^∗14 like allele, and the recombination sites are located at intron 1 and the boundary of exon 2 and intron 2 of DRB1. There are 5 CGGGG sequences flanking each side of exon 2 could serve as potential recombination site. Moreover, the full-length cDNA of the novel allele has been identified. The exon 1 and exon 3 to exon 6 share the same sequence as DRB1^∗14 like alleles. At the mRNA level, the new allele has no significant difference when compared with the other DRB1 allele. This novel recombinant allele is also found to be paternally inherited. In conclusion, this is the first report of a DRB1 and DRB3 intergenic recombination event involving whole exon 2, which generate a new DRB1^∗14:141.     

Low-dose CT urography using deep learning image reconstruction: a prospective study for comparison with conventional CT urography

Objectives:To compare the image quality of low-dose CT urography (LD-CTU) using deep learning image reconstruction (DLIR) with conventional CTU (C-CTU) using adaptive statistical iterative reconstruction (ASIR-V).Methods:This was a prospective, single-institutional study using the excretory phase CTU images for analysis. Patients were assigned to the LD-DLIR group (100kV and automatic mA modulation for noise index (NI) of 23) and C-ASIR-V group (100kV and NI of 10) according to the scan protocols in the excretory phase. Two radiologists independently assessed the overall image quality, artifacts, noise and sharpness of urinary tracts. Additionally, the mean CT attenuation, signal-to-noise ratio (SNR) and contrast-to-noise (CNR) in the urinary tracts were evaluated.Results:26 patients each were included in the LD-DLIR group (10 males and 16 females; mean age: 57.23 years, range: 33–76 years) and C-ASIR-V group (14 males and 12 females; mean age: 60 years, range: 33–77 years). LD-DLIR group used a significantly lower effective radiation dose compared with the C-ASIR-V group (2.01 ± 0.44 mSv vs 6.9 ± 1.46 mSv, p < 0.001). LD-DLIR group showed good overall image quality with average score >4 and was similar to that of the C-ASIR-V group. Both groups had adequate and similar attenuation value, SNR and CNR in most segments of urinary tracts.Conclusion:It is feasibility to provide comparable image quality while reducing 71% radiation dose in low-dose CTU with a deep learning image reconstruction algorithm compared to the conventional CTU with ASIR-V.Advances in knowledge:(1) CT urography with deep learning reconstruction algorithm can reduce the radiation dose by 71% while still maintaining image quality.     

大黄素-8-O-β-D-葡萄糖苷的体内外遗传毒性评价

目的:评价大黄素-8-O-β-D-葡萄糖苷(EG)的体内外遗传毒性,并比较体外细胞试验及大鼠体内实验评价结果的差异。方法:采用体外二维(2D)、三维(3D)细胞培养法分别构建2D、3D HepaRG细胞模型,造模成功后,分别将2D、3D HepaRG细胞分为空白对照组[0.5%二甲基亚砜(DMSO)]、丝裂霉素C组(阳性对照,0.1μg/mL)和EG低、中、高剂量组(10、50、200μg/mL),然后检测各组HepaRG细胞的微核形成率和尾DNA百分含量。将SD大鼠分为空白对照组(0.5%羧甲基纤维素钠)、甲磺酸乙酯组(阳性对照,200 mg/kg)和EG低、中、高剂量组(100、300、1 000 mg/kg),每组6只,连续灌胃给药15 d,每天1次;15 d后检测各组大鼠骨髓嗜多染红细胞、肝细胞的微核形成率及外周血淋巴细胞、肝细胞的尾DNA百分含量、尾距。结果:在体外2D HepaRG细胞模型中,与空白对照组比较,丝裂霉素C组HepaRG细胞的微核形成率和尾DNA百分含量均显著升高(P<0.01),EG各剂量组HepaRG细胞的微核形成率和尾DNA百分含量差异无统计学意义(P>0.05);在3D HepaRG细胞模型中,与空白对照组比较,丝裂霉素C组HepaRG细胞的微核形成率和尾DNA百分含量均显著升高(P<0.01或P<0.001),EG高剂量组HepaRG细胞的尾DNA百分含量显著升高(P<0.01)。在大鼠体内实验中,与空白对照组比较,甲磺酸乙酯组大鼠骨髓嗜多染红细胞、肝细胞的微核形成率和外周血淋巴细胞、肝细胞的尾DNA百分含量、尾距均显著升高(P<0.01),EG高剂量组大鼠外周血淋巴细胞尾DNA百分含量显著升高(P<0.01),EG各剂量组大鼠骨髓嗜多染红细胞、肝细胞的微核形成率和肝细胞尾DNA百分含量、尾距差异无统计学意义(P>0.05),但随剂量增加有升高趋势。结论:本研究结果提示在2D细胞模型中,EG未导致染色体断裂及DNA损伤,但3D细胞模型长期给药和体内重复给药结果均显示EG存在一定DNA损伤风险,故3D HepaRG细胞模型的评价结果更接近大鼠体内实验结果。     

基于嵌合抗原受体的肿瘤免疫治疗的研究进展

近来关于嵌合抗原受体(chimeric antigen receptor,CAR)修饰T细胞在治疗包括淋巴瘤、白血病、脑胶质瘤、黑色素瘤、肺癌、前列腺癌、胰腺癌及卵巢癌等肿瘤所取得成绩令人振奋。CAR是利用基因工程将能够与肿瘤抗原结合的受体与跨细胞膜的部分和细胞内信号转导的部分结合起来形成的一种新型受体,它可脱离主要组织相容性复合体的限制单独执行杀伤细胞的功能。CAR修饰T细胞因其独特的设计和强效的抗肿瘤作用受到人们的追捧。作者就CAR修饰T细胞在临床治疗中的应用、遇到的问题和对应策略作一综述。     

SPECT/CT图像配准测试方法

目的 提出SPECT/CT一体机中SPECT和CT图像配准精度的测试方法。方法 试验模体由立方体构形的8个点源构成,点源由放射性同位素和碘对比剂制备,在SPECT和CT上均可清晰成像,模体构形和尺寸可代表典型的临床应用条件。首先选用具有临床代表性的实验条件和参数,对模体分别行SPECT和CT成像。对图像分别进行分析,得到点源空间坐标,计算配准精度;以点源最大值像素点为中心,得到3个坐标方向的一维分布,分别计算分布重心作为对应方向的坐标值。结果 本文提出的方法在GE和Philips的主流SPECT/CT产品上进行验证,点源都可在SPECT和CT图像中完整成像,测试和分析方法的精度达0.1 mm以上。结论 该实验方法可为SPECT/CT产品性能评估和质量控制提供方法基础。     

2型糖尿病合并冠心病患者对氧磷酶1基因多态性分析

目的探讨对氧磷酶1(PON1)基因多态性与2型糖尿病合并冠心病的相关性。方法使用变性高效液相色谱分析方法检测了202例2型糖尿病合并冠心病患者、177例单纯2型糖尿病患者和206名健康对照者;共检测了PON1基因G-126C、L55M和Q192R 3个多态性的基因型,比较分析3组间各基因型和等位基因频率分布的差异。结果 2型糖尿病合并冠心病组的Q192R位点R等位基因频率明显高于对照组(67.1%比60.2%,P=0.024),其他位点在各组间差异无统计学意义。结论PON1基因Q192R位点R等位基因与2型糖尿病合并冠心病发病相关。     

实验动物冰冻组织切片制备关键要点的探讨

目的 探讨实验动物组织冰冻切片制备的关键要点和注意事项,以提高切片质量。方法 采用美国赛默飞世尔恒温式冷冻切片机,对30例SD大鼠和30例食蟹猴的皮肤、肌肉、乳腺、卵巢、子宫、胃、大肠、甲状腺、肝脏、肾脏、脾脏、淋巴结、脑、脂肪等新鲜组织进行常规冰冻切片取材、包埋、切片、染色后封片。结果 镜下检查组织切面平整,细胞形态完整、清晰,染色良好。结论 不同组织需要区别对待,制作优良的冰冻切片就需要对取材、组织速冻、温度选择、组织包埋、切片、固定等多个环节进行严格谨慎地操作。