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关键词： FLT3-ITD   CEBPA   Minimal residual disease   HSCT   Prognosis   AML  

摘要： Purpose Genetic changes have prognostic significance in cytogenetically normal acute myeloid leukemia (CN-AML). We set out to evaluate the prognostic of 6 gene mutations in CN-AML. Methods We performed a mutational analysis and evaluated prognostic findings of six genes (NPM1, CEBPA, DNMT3A, FLT3-ITD, FLT3-TKD, and C-KIT) in 428 CN-AML patients at our center over 10 years. Results A total of 282 patients (65.9%) had at least one gene mutation, and the mutation frequencies were as follows: 29.7% (NPM1), 24.1% (CEBPA), 20.1% (FLT3-ITD), 4.0% (FLT3-TKD), 11.9% (DNMT3A), and 4.7% (C-KIT). Multivariate analysis indicated that FLT3-ITDmut and CEBPA(wt) were independent risk factors correlated with poor overall survival (OS) and disease-free survival (DFS) of CN-AML. Compared with patients who received chemotherapy as consolidation, hematopoietic stem cell transplantation (HSCT) significantly improved OS of CN-AML patients. For standard/high risk patients, HSCT improved both OS and DFS. Combined analysis showed that patients with CEBPA(mut)/FLT3-ITDwt had the best prognosis, and patients with CEBPA(wt)/FLT3-ITDmut had the worst OS, with 3-year OS of only 44%. In 212 patients who received HSCT, FLT3-ITD/CEBPA mutations and minimal residual disease (MRD) were correlated with OS and DFS in univariate analysis. Conclusions We found that HSCT significantly improves the prognosis of standard/high risk CN-AML patients with superior OS and DFS. Molecular marker analyses, especially combined analysis of the FLT3-ITD and CEBPA status revealed a correlation with the prognosis of CN-AML. For patients who have received HSCT, MRD before transplantation was a strong prognostic marker predicting patient outcome.

关键词： Genomic imprinting   Imprinted genes   Cytogenetically abnormal-acute myeloid leu-kemia   Five-year survival   ZNF215  

摘要： Genomic imprinting is a form of epigenetic regulation and imprinted genes are silenced in a parental-specific manner. Imprinting is associated with various human diseases and cancers, but its roles in leukemogenesis remains elusive. In this study, the expression of a panel of 16 human imprinted genes was investigated using realtime quantitative polymerase chain reaction and 8 of them were further validated in 114 patients newly diagnosed with cytogenetically abnormal-acute myeloid leukemia (CA-AML) and 85 healthy subjects. Our results demonstrated upregulated expression of 8 imprinted genes (C15orf2, COPG2, H19, IGF2, PEG3-AS1, PRIM2, SLC22A3 and ZNF215) was observed in patients with CA-AML (p < 0.001). Patients' survival days were negatively correlated with the expression levels of H19 (p = 0.024), PGE3-AS1 (p = 0.038), and ZNF215 (p = 0.012). Multivariate logistic regression analysis further revealed the expression level ZNF215 can be used as a predictor for five-year survival for patients with CA-AML (p = 0.009) with a hazard ratio of 0.870 (95.0% confident interval: 0.784-0.965). Our results demonstrated that loss of imprinting of imprinted genes is critical for the leukemogenesis of AML under CA condition, and loss of ZNF215 imprinting is associated with poor five-year survival of patients with CA-AML.

摘要： The current thesis focused on imaging genetics of specific reading disability (SRD), to better understand the biological risk factors that contribute to SRD. Part 1 of the thesis was a systematic review focusing on summarizing the current imaging genetics literature and characterizing effect sizes of these results, revealing significant associations between reading disability risk genes and brain phenotypes. A Fisher's test revealed promising results for risk genes that had been replicated, including as DCDC2, KIAA0319, FOXP2, SLC2A3, and ROBO1. Part 2 of the thesis specifically examined associations of the novel candidate gene Semaphorin 6d (SEMA6D) on reading-related regions of interest and reading, revealing associations with white matter volume in the left transverse temporal gyrus, which was significantly associated with reading performance measures. Other phenotypes related to SEMA6D SNPs included cortical thickness in the fusiform gyrus and gyrification in the supramarginal gyrus, but these regions were not related to reading in the current sample. It is possible that the transverse temporal gyrus was more related to reading in this sample due to young participants who are still developing reading skills, with greater reliance on auditory processing for reading. Part 3 applied the imaging genetics literature to a clinical case to determine whether risk factors were related to SRD in a family consisting of twins discordant for SRD and an older sibling with reading difficulty. Results indicated that SNPs in the genes ZNF385D, LPHN3, CNTNAP2, FGF18, NOP9, CMIP, MYO18B, and RBFOX2 corresponded with SRD. Furthermore, cortical thickness in reading-related regions of interest was more similar among the siblings with SRD compared to the twins, with specific asymmetry differences in the transverse temporal and superior temporal gyri. The siblings with SRD also demonstrated reduced leftward asymmetry of grey matter volume and cortical surface area in the fusiform gyrus

关键词： 生物学联赛   遗传学   试题分析  

摘要： 本文从试题赋分占比、试题命题变化情况两个方面分析了2003年-2020年全国中学生生物学联赛遗传学部分试题,针对性地总结了遗传学部分的常见考点,并对生物学教学、学生生物学核心素养的提升以及遗传这一模块的学习提出了建议,希望能为加强学科教学育人,提升青少年的生命科学素质和人才选拔措施提供参考.

关键词： 医学遗传学   范式改革   课程教学   创新能力   非标准答案  

摘要： 为进一步提升研究生创新能力,提高课程教学质量,引导学生科学探究的兴趣,真正实现全员、全程、全方位育人,在范式改革的倡导下,总结分析对研究生“医学遗传学”课程的教学方法、教学手段及考核评价机制进行改革探索。该项改革的实施激发了研究生主动思考和解决问题的能力,提高了创新能力的培养质量,培养了学生综合运用相关学科知识的能力,为临床工作实践打下良好基础,并实现了从胜任型人才向创新型人才的转变。

关键词： 微生物遗传学   高效课堂   毕业论文   知识框架   生物学科   合成生物学   授课对象   细胞生物学  

摘要： 教学背景微生物遗传学是以病毒、细菌和真菌等微生物为研究对象进行遗传学研究的学科,与微生物学、遗传学、生物化学、细胞生物学、分子生物学及合成生物学等学科有紧密联系。许多分子生物学和基因编辑技术,如接合转移、噬菌体转染、转化、克隆、蛋白质表达、TALEN及CRISPR-Cas9等在不同程度上都来源于微生物遗传学研究。选修本课程的授课对象主要为本科三年级学生,他们已经学习了生物学科的基本知识,具备一定的解决问题能力,并已经开始进入实验室进行科研训练或项目研究,且即将正式开始毕业论文的课题研究。这一阶段的学生需要进一步整合知识框架,提升科学研究的能力。

关键词： 淋巴瘤,B细胞,边缘区   NF-κB   受体,Notch   易位,遗传   突变  

摘要： 边缘区淋巴瘤(MZL)是起源于边缘区的B细胞淋巴瘤,属于惰性淋巴瘤。MZL按照起源部位不同,分为3种亚型:黏膜相关淋巴组织(MALT)淋巴瘤、淋巴结MZL和脾MZL。起源于脾或者淋巴结外的淋巴瘤被称为结外MZL(EMZL),即MALT淋巴瘤,最常见的原发部位是胃肠道,患者预后相对较好。研究发现,EMZL患者具有部分共同且独特的遗传学改变,与其预后不良和向侵袭性淋巴瘤转化相关。这些遗传学改变调控核因子-κB和NOTCH信号通路,包括染色体易位和体细胞突变。笔者通过对EMZL患者核因子-κB和NOTCH信号通路相关常见遗传学改变及其与患者预后的关系进行综述,为遗传学改变在临床实践中的广泛应用和寻找EMZL潜在治疗靶点提供新的思路。

关键词： 表观遗传学   慢性疼痛   针刺   综述  

摘要： 慢性疼痛是困扰全人类的难题之一,由于其发病机制尚不完全清楚,导致其并未得到完全有效的控制。针刺治疗在世界范围内已成为治疗慢性疼痛的主要疗法之一,但其作用机制仍不清晰。表观遗传学主要研究在基因核苷酸序列不发生改变的情况下,表型或基因表达发生变化,其与慢性疼痛的发生、发展密切相关。本文以表观遗传学为主要研究方向,在分子层面对其在慢性疼痛的发生、发展中的机制进行综述,并探讨表观遗传学视角下针刺的镇痛机制,以期为针刺镇痛的机制研究提供一个新的视角。