Integrating Multi-Omics for Uncovering the Architecture of Cross-Talking Pathways in Breast Cancer

Cross-talk among abnormal pathways widely occurs in human cancer and generally leads to insensitivity to cancer treatment. Moreover, alterations in the abnormal pathways are not limited to single molecular level. Therefore, we proposed a strategy that integrates a large number of biological sources at multiple levels for systematic identification of cross-talk among risk pathways in cancer by random walk on protein interaction network. We applied the method to multi-Omics breast cancer data from The Cancer Genome Atlas (TCGA), including somatic mutation, DNA copy number, DNA methylation and gene expression profiles. We identified close cross-talk among many known cancer-related pathways with complex change patterns. Furthermore, we identified key genes (linkers) bridging these cross-talks and showed that these genes carried out consistent biological functions with the linked cross-talking pathways. Through identification of leader genes in each pathway, the architecture of cross-talking pathways was built. Notably, we observed that linkers cooperated with leaders to form the fundamentation of cross-talk of pathways which play core roles in deterioration of breast cancer. As an example, we observed that KRAS showed a direct connection to numerous cancer-related pathways, such as MAPK signaling pathway, suggesting that it may be a central communication hub. In summary, we offer an effective way to characterize complex cross-talk among disease pathways, which can be applied to other diseases and provide useful information for the treatment of cancer.     

腹腔镜术后联合GnRH-a治疗卵巢型内异症并不孕的疗效观察

目的:研究腹腔镜保守术后联合短期促性腺激素释放激素激动剂(GnRH-a)对卵巢型子宫内膜异位症合并不孕患者的治疗效果。方法:回顾性分析2008年5月-2011年5月在我院治疗内异症合并不孕的126例患者的临床资料,比较腹腔镜手术后联合GnRH-a治疗(用药组)和术后期待处理(对照组)的症状缓解率和妊娠情况。结果:用药组患者症状缓解率比对照组高,且差异有统计学意义(P0.05);用药组总妊娠率较对照组高,差异无统计学意义(P0.05),流产率比较无统计学差异(P0.05);治疗后患者1年内妊娠率最高,两组比较无统计学差异(P0.05),随访期间累积妊娠率比较,用药组高于对照组,无统计学意义(P0.05);用药组及对照组中Ⅰ-Ⅱ期及Ⅲ-Ⅳ期患者妊娠率均在50%以上,两组比较均无统计学差异(P0.05)。结论:此研究进一步明确腹腔镜术联合GnRH-a治疗卵巢子宫内膜异位症合并不孕患者能较好提高其症状缓解率和妊娠率,但妊娠率提高与期待治疗无差别。经手术或联合GnRH-a治疗后患者首次妊娠多发生在治疗后1年内,如果1年以上仍未妊娠,可根据实际情况选择其他助孕方法如辅助生育技术,以增加受孕机会。     

Agrotis segetum雄蛾触角叶性信息素反应神经元对电刺激触角神经的反应

为探讨电刺激Agrotis segetum雄蛾触角神经是否可以作为MGC中神经元的识别手段,采用细胞内电生理记录方法,共记录34个对性信息素有反应的MGC神经元,并测试了其中12个神经元对性信息素刺激的反应,22个神经元对性信息素刺激和电刺激的反应。结果表明,MGC神经元对性信息素及电刺激的反应模式基本一致,为一种双相反应模式。两种刺激方式均能诱导出兴奋反应,电刺激得到的兴奋反应比由信息素刺激引起的要短;MGC神经元对两种刺激的超极化反应（抑制反应）幅度影响没有显著性差别,在电刺激实验的22个神经元上,超极化反应幅度和抑制时间都与神经元本身放电频率有一定的相关性。超极化反应是在LN参与下一定的神经回路对刺激所产生的反应而形成的。这提示两种刺激所作用的神经回路应是一致的,但从整个实验过程记录到的神经元情况来看,还须进一步结合形态学实验来验证电刺激触角神经作为MGC神经元的识别手段。     

重组人干扰素—β的中试研究

从大肠杆菌中大规模纯化新型干扰素β(IFN-βser17).首先建立IFN-βser17发酵和纯化工艺,连续大量纯化三批,并对纯化终产品进行全面鉴定.建立了稳定的发酵和纯化工艺流程,中试三批菌产量平均为4.33g/L,IFNβser17的表达量平均为20%,经破碎、粗提、精制后IFN-βser17的比活达2×107IU/mg以上,纯度超过96%,其他检定项目也均符合规程要求.     

Regulation of c-Myc Expression by Ahnak Promotes Induced Pluripotent Stem Cell Generation

We have previously reported that Ahnak-mediated TGFβ signaling leads to down-regulation of c-Myc expression. Here, we show that inhibition of Ahnak can promote generation of induced pluripotent stem cells (iPSC) via up-regulation of endogenous c-Myc. Consistent with the c-Myc inhibitory role of Ahnak, mouse embryonic fibroblasts from Ahnak-deficient mouse (Ahnak^−/− MEF) show an increased level of c-Myc expression compared with wild type MEF. Generation of iPSC with just three of the four Yamanaka factors, Oct4, Sox2, and Klf4 (hereafter 3F), was significantly enhanced in Ahnak^−/− MEF. Similar results were obtained when Ahnak-specific shRNA was applied to wild type MEF. Of note, expressionof Ahnak was significantly induced during the formation of embryoid bodies from embryonic stem cells, suggesting that Ahnak-mediated c-Myc inhibition is involved in embryoid body formation and the initial differentiation of pluripotent stem cells. The iPSC from 3F-infected Ahnak^−/− MEF cells (Ahnak^−/−-iPSC-3F) showed expression of all stem cell markers examined and the capability to form three primary germ layers. Moreover, injection of Ahnak^−/−-iPSC-3F into athymic nude mice led to development of teratoma containing tissues from all three primary germ layers, indicating that iPSC from Ahnak^−/− MEF are bona fide pluripotent stem cells. Taken together, these data provide evidence for a new role for Ahnak in cell fate determination during development and suggest that manipulation of Ahnak and the associated signaling pathway may provide a means to regulate iPSC generation.     

大豆倒伏性相关QTL的整合及Overview分析

倒伏性是影响大豆产量的重要因素,发掘与大豆倒伏相关的基因对于培育抗倒伏优良高产大豆品种具有重要意义。目前利用不同群体所构建的遗传图谱已经定位了大量与大豆倒伏性相关的QTLs。本研究在对已报道的QTLs进行物理整合的基础上,选择元分析方法将这些倒伏性相关的QTLs进一步整合,鉴定出位于C2(6号染色体)、F(13号染色体)、L(19号染色体)这3个连锁群上重复次数较多的QTL区间6个。选用基于统计学原理的Overview方法进行优化,获得了这些QTL在各个连锁群上的有效遗传位置,这些QTL的置信区间长度最小可缩至0.2 cM。通过在这些区间内进一步筛选,获得一个稳定性较好的标记Satt277。本研究可为大豆抗倒伏基因发掘及分子标记辅助选择育种提供理论依据。     

Structural modulation of gut microbiota during alleviation of type 2 diabetes with a Chinese herbal formula

The gut microbiota is hypothesized to have a critical role in metabolic diseases, including type 2 diabetes (T2D). A traditional Chinese herbal formula, Gegen Qinlian Decoction (GQD), can alleviate T2D. To find out whether GQD modulates the composition of the gut microbiota during T2D treatment, 187 T2D patients were randomly allocated to receive high (HD, n=44), moderate (MD, n=52), low dose GQD (LD, n=50) or the placebo (n=41) for 12 weeks in a double-blinded trial. Patients who received the HD or MD demonstrated significant reductions in adjusted mean changes from baseline of fasting blood glucose (FBG) and glycated hemoglobin (HbA1c) compared with the placebo and LD groups. Pyrosequencing of the V3 regions of 16S rRNA genes revealed a dose-dependent deviation of gut microbiota in response to GQD treatment. This deviation occurred before significant improvement of T2D symptoms was observed. Redundancy analysis identified 47 GQD-enriched species level phylotypes, 17 of which were negatively correlated with FBG and 9 with HbA1c. Real-time quantitative PCR confirmed that GQD significantly enriched Faecalibacterium prausnitzii, which was negatively correlated with FBG, HbA1c and 2-h postprandial blood glucose levels and positively correlated with homeostasis model assessment of β-cell function. Therefore, these data indicate that structural changes of gut microbiota are induced by Chinese herbal formula GQD. Specifically, GQD treatment may enrich the amounts of beneficial bacteria, such as Faecalibacterium spp. In conclusion, changes in the gut microbiota are associated with the anti-diabetic effects of GQD.     

根管治疗失败病例根管内细菌对根尖周组织致病力的实验研究

目的观察根管治疗失败病例根管内分离的主要微生物对狗牙根尖周组织的影响。方法选择成年健康杂种狗5只,共有40个实验牙,80个实验牙根。实验一组于狗牙根管内接种溶血链球菌、微小消化链球菌、产黑色素类杆菌及具核梭杆菌;实验二组于狗牙根管内接种粪肠球菌及上述4种细菌;对照组不接种细菌。对狗牙完成根管治疗。分别于治疗后3、6、12个月拍摄根尖X线片,并记录牙齿和根尖周组织的临床表现;根管治疗后12个月处死动物,制备根尖周组织病理标本,观察根尖周骨组织破坏情况;动物处死前,根管内进行微生物的取样、培养和鉴定。结果实验组可见狗牙槽骨尖周骨质吸收,牙周膜纤维排列受到破坏,实验二组对根尖周破坏重于实验一组,对照组根尖周骨组织无破坏。结论从根管治疗失败病例根管内分离的主要微生物粪肠球菌、溶血链球菌、微小消化链球菌、产黑色素类杆菌及具核梭杆菌对狗牙根尖周组织有明显的破坏作用。     

8个禾本科草坪草品种遗传多样性的RAPD分析

利用RAPD技术,对禾本科4属4种8个品种的草坪草进行遗传多样性分析。15个有效引物用于PCR扩增,共获得RAPD谱带144条带,多态性带占63.2%。8个草坪草品种间的遗传距离在0.0857~0.2928之间,脱壳狗牙根与普通狗牙根间的遗传距离最小,交战2号与爱神特之间的遗传距离最大。用UPGMA和邻接法进行聚类分析,得到2个拓扑结构基本一致的树系图。同一种不同品种间的亲缘关系最近;不同属种间的遗传距离加大,同族不同属的草坪草基本构成一支;4个暖季型草坪草品种构成一个单系类群,但属于冷季型草种的黑麦草(爱神特)单独构成一支,并未与同族的其它3个冷季型草坪草品种(高羊茅)聚在一起。本研究不支持将黑麦草属与羊茅属放在同一族内的分类处理,并建议将高羊茅划分为过渡类型的草坪草。