中期18F-FDG PET-CT两种图像判读法在弥漫性大B细胞淋巴瘤预后评估中的应用

目的:探讨中期正电子发射型计算机断层显像(positron emission tomography-computed tomography,PET-CT)Deauville五分法(Deauville five-point scale,5-PS)与最大标准摄取值缩减率(maximum standard uptake value variation,△SUVmax)两种图像判读法在弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)患者预后评估中的应用价值。方法:回顾性分析2012年10月至2018年6月重庆医科大学附属第一医院收治的94例DLBCL患者资料。采用Kaplan-Meier法及Cox比例风险回归模型进行生存资料分析,计算并采用χ2检验比较5-PS和△SUVmax对DLBCL患者预后预测的能力。结果:5-PS和△SUVmax分别以4分、86%进行分组。5-PS<4分组、△SUVmax≥86%组的患者无进展生存期(progression free survival,PFS)和总生存期(overall survival,OS)均优于5-PS≥4分组、△SUVmax<86%组的患者(P<0.05)。△SUVmax与5-PS对患者PFS和OS均有影响,较高的阴性预测值(89.4%,93.6%;76.1%,85.9%),较低的阳性预测值(48.9%,31.9%;47.8%,34.8%),并且△SUVmax对于患者的敏感性优于5-PS(82.1%,83.3%vs.39.3%,44.4%)。单因素分析中国际预后指数(international prognostic index,IPI)(P=0.007)、△SUVmax(P<0.001)、5-PS(P=0.014)及基线全身肿瘤代谢体积(total metabolic tumor volume,TMTV)(P=0.001)与PFS相关,△SUVmax(P=0.014)、5-PS(P=0.033)、TMTV(P=0.004)与OS相关;多因素分析显示TMTV是OS的独立预测因子(P=0.005),△SUVmax和TMTV是PFS的独立预测因子(P=0.002,P=0.020),并且△SUVmax<86%且高水平TMTV患者较低TMTV患者的PFS明显缩短(P=0.001)。结论:5-PS和△SUVmax均能初步评估DLBCL患者预后,但△SUVmax具有更高的预测价值,并且联合基线TMTV可以对DLBCL患者进行再次危险度分层。     

超高CD34+采集的动员方案序贯二次自体造血干细胞移植治疗难治性 霍奇金淋巴瘤

目的:探讨超高CD34+采集的动员方案后序贯二次自体造血干细胞移植治疗难治性霍奇金淋巴瘤的疗效和安全性。方法:对1例经过多疗程一线、二线、新药、免疫等均难治的霍奇金淋巴瘤患者，予以IA+C方案化疗+G-CSF动员干细胞后采集出超高水平CD34+细胞，之后行自体造血干细胞移植，移植后获得完全缓解，再予序贯第二次自体造血干细胞移植进行巩固治疗。结果:总计输注单个核细胞数13.67×108/kg，CD34+细胞48.68×106/kg，第一次自体造血干细胞移植术后第7天造血功能恢复，复查全身PET-CT提示获得完全缓解，第二次自体造血干细胞移植术后第8天造血功能恢复，两次自体造血干细胞移植相关并发症均在可控范围内。结论:超高CD34+细胞采集的IA+C方案化疗+G-CSF动员可以让患者有机会进行多次自体造血干细胞移植，是临床动员的创新方案。对于难治性霍奇金淋巴瘤，序贯二次自体造血干细胞移植可达到更深层次缓解，且安全性较高，延长患者无疾病生存期及总生存期，为难治性霍奇金淋巴瘤治疗提供更多临床依据。     

Research progress on the biomimetic remineralization of hard tooth tissues based on polyamide-amine dendrimer

聚酰胺—胺树枝状聚合物（PAMAM）作为一种新型超支化大分子聚合物,因其出色的化学和生物学特性,一直被众学者称之为“人工蛋白”。 PAMAM的特点是存在内部空腔,并含有大量的反应性末端基团,这些结构使得PAMAM可以被用作仿生大分子,模拟天然有机基质在牙体组织表面进行仿生矿化,即PAMAM作为有机模板调控矿物质成核以及晶体的生长,以此来建造比传统的异体材料更加理想的牙体修复材料。本文就 PAMAM 诱导牙体硬组织仿生矿化的研究进展作一综述。     

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.     

凉血通瘀方干预高血压大鼠急性脑出血模型对脑组织中差异miRNA表达的影响＊

目的 研究凉血通瘀方对高血压大鼠急性脑出血模型脑组织miRNA表达的影响，对差异表达的miRNA靶基因进行分析，探索凉血通瘀方可能的药效机制。方法 将自发性高血压大鼠随机分成对照组（B）和实验组（C）。适应性饲养一周后，C组灌胃凉血通瘀方，B组灌胃等体积生理盐水，连续5天，每天1次。构建脑出血模型后收集脑组织，借助全转录组测序技术获得miRNA表达量，与miRBase数据库比对获取已知miRNA，使用miRDeep2预测新miRNA。差异分析软件为DESeq2，筛选阈值为|log₂FC| ≥1 并且P <0.05。对显著差异表达的miRNA进行靶基因预测，对靶基因进行GO功能、KEGG通路富集和PPI网络分析。结果 实验组和对照组对比，共发现21个显著差异表达的miRNA，上调有9个，下调有12个，共预测得到1243个有统计学意义的靶基因。GO富集分析发现，生物过程中突触囊泡分泌的调节、神经递质分泌的调节和神经递质运输的调节占前三位，神经元投射终点、全膜、质膜区域和细胞投射则是主要的细胞成分。分子功能分别为小GTPase绑定、底物特异性跨膜转运蛋白活性和离子跨膜转运体活性。通路分析结果显示，靶基因在癌证通路、pI3K-Akt信号通路、人类乳头瘤病毒感染、神经活性配体-受体相互作用和MAPK通路等分布广泛。采用STRING网站和Cytoscape软件，根据MCC算法筛选出ADRA2C、CASR、CCL28、CCR1、DRD2、GNAT3、GRM2、DYNC1LI1、GABBR1、GNAI1等核心靶基因。结论 凉血通瘀方对脑出血急性期鼠脑组织内miRNA的表达有重要影响；显著差异表达miRNAs可能通过靶向核心基因调控凉血通瘀方干预急性脑出血的病理过程及预后。