Background and Purpose: CX-5461 is a novel selective RNA polymerase I (Pol I) inhibitor. Previously, we found that CX-5461 could inhibit pathological arterial remodelling caused by angioplasty and transplantation. In the present study, we explored the pharmacological effects of CX-5461 on experimental pulmonary arterial hypertension (PAH) and PAH-associated vascular remodelling.

Background: Low-grade endometrial stromal sarcoma (LGESS) is the second most common malignant mesenchymal tumor of the uterus which usually affects young women. However, the researches on the safety and feasibility of the fertility-sparing management of it are limited.Methods: A retrospective analysis was performed including 5 women diagnosed with LGESS treated with fertility-sparing management at Qilu Hospital of Shandong University from 2010 to 2019. Besides that, 1,070 patients diagnosed with LGESS in SEER database from 1973 to 2016 were examined. By using the Kaplan-Meier method, survival curves were estimated, and comparisons of statistical significance were performed with the stratified log-rank test within each group.Results: Five patients with LGESS were enrolled in this study. All patients were submitted to fertilitysparing surgeries, after surgery, they all continued hormonal therapy for one year. Four out of the 5 patients recurred, to be more exact, 3 of them recurred in uterus and the other one in the uterus and iliac vascular region. They all suffered further surgery and all 5 patients were alive at the time of last contact. Besides, among these patients, two conceived naturally and delivered a healthy baby by cesarean section. Among 1,070 patients in SEER database, only 28 (2.6%) patients underwent local tumor excision, including excisional biopsy (39%), myomectomy (25%), laser ablation or excision (4%) and polypectomy (4%). There was no statistical significance was observed among TH±BSO, radical hysterectomy, subtotal hysterectomy and local tumor excision (P=0.29).Conclusions: Our analysis indicated that for those young LGESS patients who wish to preserve their fertility, the feasibility and safety of fertility-sparing management should be considered after gynecological oncologist and gynecological pathologist making professional decisions.

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In this study, we tested the possibility that macrophages might contribute to neointima formation by stimulating microRNA expressions in mural cells. Thoracic aortas from F344 rats were transplanted into recipient Lewis rats. Clodronate liposome was used for in vivo macrophage depletion. Using miR-21 as a prototypic example of vascular enriched microRNA, we showed that macrophage depletion reduced the expression level of miR-21, which was upregulated in the allograft. This effect of macrophage depletion was accompanied by attenuations in neointimal hyperplasia and transplantation-induced vascular inflammation. Using in vitro assays, we identified that macrophages might stimulate miR-21 expression in smooth muscle cells and adventitial fibroblasts via the release of tumor necrosis factor-α. We also showed that silencing of miR-21 suppressed tumor necrosis factor-induced proliferation, migration, and inflammatory responses in mural cells. Our results suggest that macrophage may promote transplantation-induced neointima formation by stimulating miR-21 expression in vascular mural cells, which promotes mural cell proliferation, migration and/or inflammation. Moreover, we have established that tumor necrosis factor-α has a major role in mediating this paracrine process.

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