Ethnopharmacological relevance Wenshen Xiaozheng Tang (WXT), a traditional Chinese medicine (TCM) decoction, is effective for treating endometriosis. However, the effect of WXT on endometrium-derived mesenchymal stem cells (eMSCs) which play a key role in the fibrogenesis of endometriosis requires further elucidation. Aims of the study The aim of this study was to clarify the potential mechanism of WXT in improving fibrosis in endometriosis by investigating the regulation of WXT on differentiation and paracrine of eMSCs. Materials and methods The nude mice with endometriosis were randomly divided into model group, WXT group and mifepristone group. After 21 days of treatment, the lesion volume was calculated. Fibrosis in the lesions was evaluated by Masson staining and expression of fibrotic proteins. The differentiation of eMSCs in vivo was explored using a fate-tracking experiment. To further clarify the regulation of WXT on eMSCs, primary eMSCs from the ectopic lesions of endometriosis patients were isolated and characterized. The effect of WXT on the proliferation and differentiation of ectopic eMSCs was examined. To evaluate the role of WXT on the paracrine activity of ectopic eMSCs, the conditioned medium (CM) from ectopic eMSCs pretreated with WXT was collected and applied to treat ectopic endometrial stromal cells (ESCs), after which the expression of fibrotic proteins in ectopic ESCs was assessed. In addition, transcriptome sequencing was used to investigate the regulatory mechanism of WXT on ectopic eMSCs, and western blot and ELISA were employed to determine the key mediator. Results WXT impeded the growth of ectopic lesions in nude mice with endometriosis and reduced collagen deposition and the expression of fibrotic proteins fibronectin, collagen I, α-SMA and CTGF in the endometriotic lesions. The fate-tracking experiment showed that WXT prevented human eMSCs from differentiating into myofibroblasts in the nude mice. We successfully isolated eMSCs from the lesions of patients with endometriosis and demonstrated that WXT suppressed proliferation and myofibroblast differentiation of ectopic eMSCs. Moreover, the expression of α-SMA, collagen I, fibronectin and CTGF in ectopic ESCs was significantly down-regulated by the CM of ectopic MSCs pretreated with WXT. Combining the results of RNA sequencing, western blot and ELISA, we found that WXT not only reduced thrombospondin 4 expression in ectopic eMSCs, but also decreased thrombospondin 4 secretion from ectopic eMSCs. Thrombospondin 4 concentration-dependently upregulated the expression of collagen I, fibronectin, α-SMA and CTGF in ectopic ESCs, indicating that thrombospondin 4 was a key mediator of WXT in inhibiting the fibrotic process in endometriosis. Conclusion WXT improved fibrosis in endometriosis by regulating differentiation and paracrine signaling of eMSCs. Thrombospondin 4, whose release from ectopic eMSCs is inhibited by WXT, may be a potential target for the treatment of endometriosis.

子宫内膜异位症(EMs)是育龄期妇女的常见病、多发病,目前其发病机制尚不明确.因具有激素依赖性、侵袭强和复发率高等特点,在临床诊疗过程中有一定的难度和挑战.近年来旁分泌成为EMs的研究热点.旁分泌效应产生的各种生物活性分子和外泌体参与EMs的形成,具体可能通过介导炎症与免疫反应,促细胞增殖与抑制凋亡,促血管新生,分化或转化,细胞外基质的合成等途径参与EMs的发生发展.本文综述了近年来常见的旁分泌因子及外泌体在EMs发病机制中的作用及研究进展,为EMs的防治提供新的切入点.

多囊卵巢综合征(PCOS)好发于育龄期妇女,以月经失调、不孕等为主要临床表现,发病率逐年升高.目前西医治疗以降低雄激素、改善胰岛素抵抗、促排卵为主,但有一定的局限性,包括疗效欠佳、并发症多等.多项研究发现,PCOS发生发展与肠道菌群相关.肠道菌群被称为"人类第二大基因组""被遗忘的器官",近年来成为感染性、免疫性以及代谢性疾病的研究热点.本文主要从肠道菌群失调所致的高雄激素血症、胰岛素抵抗、慢性炎症及代谢综合征探讨与PCOS发生和发展的相关性.中医运用中药复方、针灸等方式调和胃肠肝脾、平衡肠道菌群、维持肠道内环境稳态,为PCOS病因病机的认识及治疗提供新的切入点.

肠道微生物菌落在出生时已开始建立,婴幼儿期是微生物菌落和宿主建立关系的重要时期,也是婴幼儿大脑发育的关键阶段.在生命的前2～3年,婴儿的肠道菌群迅速繁殖,逐渐变得多样化和丰富,随着对肠道微生态研究的不断深入发现生命早期肠道微生态的异常建立与婴幼儿罹患孤独症谱系障碍(ASD)的关系密切,而目前对ASD的诊断一般在3岁以后,诊断后治疗困难,故对ASD相关的危险因素进行早期筛查与预防就显得尤为重要.笔者主要回顾生命早期肠道微生物的生理、病理状态下的主导菌群及ASD相关微生物-肠-脑轴方面的研究进展,提出对可能患有ASD的高危人群在肠道菌群稳定之前进行早期干预,使其肠道菌群恢复至正常生理状态,达到降低ASD发生率的可能,希望能够为临床早期筛查及预防ASD提供参考.