BMP-driven NRF2 activation in esophageal basal cell differentiation and eosinophilic esophagitis

Tissue homeostasis requires balanced self-renewal and differentiation of stem/progenitor cells, especially in tissues that are constantly replenished like the esophagus. Disruption of this balance is associated with pathological conditions, including eosinophilic esophagitis (EoE), in which basal progenitor cells become hyperplastic upon proinflammatory stimulation. However, how basal cells respond to the inflammatory environment at the molecular level remains undetermined. We previously reported that the bone morphogenetic protein (BMP) signaling pathway is critical for epithelial morphogenesis in the embryonic esophagus. Here, we address how this pathway regulates tissue homeostasis and EoE development in the adult esophagus. BMP signaling was specifically activated in differentiated squamous epithelium, but not in basal progenitor cells, which express the BMP antagonist follistatin. Previous reports indicate that increased BMP activity promotes Barrett’s intestinal differentiation; however, in mice, basal progenitor cell–specific expression of constitutively active BMP promoted squamous differentiation. Moreover, BMP activation increased intracellular ROS levels, initiating an NRF2-mediated oxidative response during basal progenitor cell differentiation. In both a mouse EoE model and human biopsies, reduced squamous differentiation was associated with high levels of follistatin and disrupted BMP/NRF2 pathways. We therefore propose a model in which normal squamous differentiation of basal progenitor cells is mediated by BMP-driven NRF2 activation and basal cell hyperplasia is promoted by disruption of BMP signaling in EoE.     

产后盆底肌训练对盆底功能的恢复效果观察

目的观察产后盆底肌训练对提高盆底肌力、改善尿失禁及盆腔脏器脱垂的效果。方法选取94例产后盆底功能障碍性疾病患者,随机分为两组,各47人。观察组采用标准的盆底肌训练,每周进行2次,5周为1个疗程;对照组完成相关健康教育和练习产后操。两组患者治疗前后均进行盆底肌力测定以及评价压力性尿失禁和盆腔脏器脱垂的发生情况。结果观察组与对照组盆底肌力治疗有效率分别为66.0%和89.4%,压力性尿失禁治疗有效率分别为59.6%和78.7%,盆腔脏器脱垂治疗有效率分别为57.4%和74.5%,差异均有统计学意义(P<0.05)。结论产后盆底肌训练对提高盆底肌力、改善尿失禁及盆腔脏器脱垂效果较好,值得推广应用。     

Acute coronary syndrome during dissection of left main as a complication of radiofrequency ablation

We present a case of 44 year-old female who was admitted to the hospital due to performed radio frequency ablation because of VF during WPW syndrome, which was complicated by dissection of left main. The dissection was treated with success by primary percutaneous coronary intervention with two metal stents.