转录因子和miRNA在复杂疾病中的共调控网络研究
Transcription factors (TFs) are key regulators controlling the transcription of target genes by binding to specific DNA sequences on the promoter of target genes. Both the TFs and miRNAs are regulators of gene expression and they may mutual regulate each other to form feedback loops (FBL), or they regulate the same target gene to form a feed-forward loop (FFL). It has been reported that hundreds of potential miRNA-mediated feedback and feed-forward loops are available at the genome level. To predict the TF-miRNA co-regulatory FFL and FBL loops, we integrated multiple data of TF targets and miRNA targets including both experimentally validated and predicted. Thus, we developed a strategy to predict the TF-miRNA co-regulatory FFL and FBL loops. We used these methods to study the TF-miRNA co-regulation in specific diseases including schizophrenia and T-cell acute lymphoblastic leukemia (T-ALL). We identified and verified some key miRNA and genes in these diseases. In the T-ALL, we obtained 120 FFLs among T-ALL related genes, miRNAs and TFs. Afterwards, a T-ALL miRNA and TF co-regulatory network was constructed and its significance was tested by statistical methods. Four miRNAs in the miR-17~92 cluster and 4 important genes (CYLD, HOXA9, BCL2L11, and RUNX1) were found as hubs in the network. Particularly, we found that miR-19 was highly expressed in T-ALL patients and cell lines. Ectopic expression of miR-19 repress CYLD expression, while miR-19 inhibitor treatment induce CYLD protein expression and decreases NF-κB expression in the downstream signaling pathway. Thus, miR-19, CYLD and NF-κB form a regulatory feed-forward loop, which provides new clues for sustained activation of NF-κB in T-ALL. Some single nucleotide polymorphisms (SNPs) in miRNA genes or target sites (miRNA-related SNPs) have been proved to be associated with human diseases by affecting the miRNA mediated regulatory function. To systematically analyze miRNA-related SNPs and their effects, we performed a genome-wide scan for SNPs in human pre-miRNAs, miRNA flanking regions, target sites and designed a pipeline to predict the effects of them on miRNA-target interaction. As a result, we identified 48 SNPs in human miRNA seed regions and thousands of SNPs in 3'- untranslated regions with the potential to either disturb or create miRNA-target interactions. Furthermore, we experimentally confirmed 7 loss-of-function SNPs and 1 gain-of-function SNP by luciferase assay. All useful data were complied into miRNASNP, a user-friendly free online database (http://www.bioguo.org/miRNASNP/). These data will be a useful resource for studying miRNA function, identifying disease-associated miRNAs, and further personalized medicine.
sRNA Induces the Large-scale Transdetermination of Mesenchymal Stem Cells into Hematopoietic Stem Cells in Human.
Mesenchymal stem cells (MSCs) can differentiate into cells of bone, endothelium, adipose tissue, cartilage, muscle, and brain. However, whether they can transdeterminate into hematopoietic stem cells (HSCs) remains unsolved. We report here that a subpopulation of human MSCs that are CD44+,CD29+, CD105+, CD166+,CD133-,CD34- could differentiate into hematopoietic stem cells (CD150+/CD133+/CD34+) and their descending blood cells in vitro, when transfected with new endogenous shRNAs The sRNA was high-effectively delivered into MSCs by a novel peptide means. These induced MSC-HSCs could form different types of hematopoietic colonies as nature-occurring HSCs did. Upon transplantation into sublethally irradiated NOD/SCID mice, these MSC-HSCs engrafted and differentiated into all hematopoietic lineages such as erythrocytes, lymphocytes, myelocytes and thrombocyte. More importantly, these induced HSCs could successfully engraft and effectively function in patients with severe aplastic anemia. Furthermore, we demonstrated the first evidence that the transdetermination of MSCs was induced by acetylation of histone proteins and activation of many transcriptional factors. Together, our findings identify the sRNAs that dictates a directed differentiation of MSCs toward HSCs and open up a new source for HSCs used for the treatment of blood diseases and artificial stem cell-made blood.
钟厉勇：糖尿病认知功能障碍与1β-羟类固醇脱氢酶1型
1、认知功能障碍是糖尿病的一种“新型”慢性并发症。 2、葡萄糖毒性可诱导海马神经元11β-HSD1的过表达与细胞凋亡，可能与高血糖相关的认知功能障碍有关。 3、PPAR-γ激动剂具有11β-HSD1抑制剂作用。 4、吡格列酮可通过PPAR-γ受体下调11β-HSD1酶活性，进而降低海马局部糖皮质激素浓度，保护高糖环境诱导的海马神经元凋亡。 5、11β-HSD1抑制剂可能是预防和质量糖尿病认知功能障碍的潜在药物。
口腔颌面-头颈部黑色素瘤的个体化诊治与思考
近十年上海第九人民医院由原来的单纯手术切除发展为采用多学科的个体化序列治疗的方法:原发灶冷冻治疗→术前辅助化疗→选择性颈清术±原发灶切除→生物治疗→康复治疗，口腔黏膜恶性黑色素瘤5年生存率由单纯手术治疗的0提高到30.3%。
肝癌的转化医学研究
在肝癌中，分子诊断标记物的筛选、分子分型及个体化靶向药物的发展是转化医学中非常重要的领域。转化医学的发展将沟通基础研究及临床实践，不但可以提高对肝癌发生、发展相关分子机制的理解，而且将促进肝癌临床治疗的发展及进步。
林旭：中国人群营养和遗传因素与代谢性疾病的队列研究
林旭研究员介绍了其团队针对中国人群营养和遗传因素与代谢性疾病相关的研究成果： 1 亚洲人比白种人更易罹患糖尿病，中国人更具有“代谢性肥胖”特征。2 中国人群代谢性肥胖表型和疾病的高易感性，不仅仅与遗传因素相关，环境因素也起了非常重要的作用。上世纪90年代以来我国居民膳食能量来源的巨大改变，随之而来的是，近年来我国糖尿病患者数量激增。 3 北京上海两地原住民饮食习惯的不同，更为合理膳食搭配使得上海居民糖尿病患病率低于北京。4 维生素D、乳制品的摄取可降低糖尿病的发病率。体内视黄醇结合蛋白4、C反应蛋白、铁蛋白、内毒素结合蛋白含量的升高预示罹患糖尿病的风险增加。
The Inner Life of the Cell
由哈佛大学制作的专业视频，描述了从细胞连接、细胞的运动到细胞膜的结构与功能，从细胞骨架到胞内物质的运输，从蛋白质合成到运输与分泌等等，揭示了生命的强大和奇妙。
刘帆：移动医疗与未来发展趋势
移动医疗与移动健康区分；一线医院工作人员对移动医疗未来发展的期望 （1）移动医疗是解决临床信息化的最后20米的工具 a 初步完成临床信息化的建设：门诊医生站、住院医生站、电子病历 b 信息系统的局限性：终止于医生办公室、护士站；床旁、病人旁仍手工（纸笔）、不可追溯、不可追踪，不可统计 c 移动护理系统应运而生 d 案例：摆（包）药机散装口服药识别的问题 住院药房-药师审核， 工人配送-取药核对， 病区交接-接收核对， 输液配药 摆药， 发药 口服UDD床旁执行-扫药袋 系统警告 目标：用药“零”错误 药品全流程闭环管理 用药安全+物流管理 耗材管理 被服、刷手衣管理
刘帆：移动医疗与未来发展趋势（2）
课程介绍了HIMSS Analytics of PKUPH，包括移动信息化促进多学科，部门管理整合胸痛中心,移动信息化促进医院精细化管理物流与资产管理,移动信息化提供便捷服务
刘帆：移动医疗与未来发展趋势（3）
远程移动查房，远程视频移动终端，应用场景 医院信息化发展历程 趋势1：专用医用终端与BYOD 基于互联网开放平台 跨平台终端应用 趋势2：多网融合”“简约网络” 趋势3：无边际网络的安全 趋势4：技术服务于需求 医院面临的挑战