Objective: Exploring potential treatment drugs for pituitary adenoma from marketed drugs based on artificial intelligence technology and drug relocation strategies. Methods: The gene expression profile of pituitary adenoma was analyzed by Gene Expression Omnibus （GEO） database, and the highest scoring Hub gene was screened out. The drug repositioning strategy was used to find therapeutic drugs targeting Hub gene from the global market drug database, and the interaction between drug and target was validated by artificial intelligence technology. In cell experiments, the effect of tamoxifen on the proliferation ability of mouse pituitary adenoma AtT20 cells and rat pituitary adenoma GH3 cells was detected by CCK8 method, the apoptosis rate was detected by flow cytometry, and the expressions of key proteins in the phosphatidylinositol-3-kinase （PI3K）/protein kinase B （AKT） apoptosis pathway was detected by Western blotting. Results: A total of 96 differentially expressed genes were identified from macroadenomas and microadenomas, among which signal transducer and activator of transcription 6 （STAT6） was the gene with the highest score. Tamoxifen was found to be the therapeutic drug targeting STAT6 by relocating from the database. The interaction between tamoxifen and STAT6 was confirmed by artificial intelligence and molecular docking. Finally, in vitro experiments showed that tamoxifen could inhibit the proliferation of pituitary adenoma cells and hormone secretion. Conclusion: Tamoxifen can inhibit the growth of pituitary adenoma, providing strong evidence for the target research and precise treatment of pituitary adenoma.
［Key words］pituitary adenoma; artificial intelligence; drug repositioning; STAT6; Tamoxifen

Objective: To investigate the effects of miR-216a and miR-301a on the proliferation of human pulmonary arterial smooth muscle cells （HPASMC） under hypoxia and to explore the potential mechanisms. Methods: The proliferation activity of HPASMC under normoxia and different hypoxia time was detected by CCK8 assay, and qRT-PCR was used to detect the expression of miR-216a, miR-301a and bone morphogenetic protein receptor type 2 （BMPR2） mRNA in each group. The proliferation ability and proliferating cell nuclear antigen （PCNA） expression levels of HPASMC transfected with anti-miR-216a or anti-miR-301a mimics were detected by CCK8 assay and Western blotting, respectively. The relationship between BMPR2 and miR216a, BMPR2 and miR301a were detected by dual luciferase reporter assay. CCK8 assay and Western blot were used to detect the proliferation ability of HPASMC and the expression levels of BMPR2 and PCNA after simultaneous transfection of miR-216a or miR-301a combined with BMPR2 overexpression plasmid, respectively. Results: With the prolongation of hypoxia time, the proliferation activity of HPASMC and the expression of miR-216a increased, while the expression of BMPR2 mRNA gradually decreased. The expression level of miR-301a was the highest in HPASMC exposed to hypoxia for 24 hours. Down-regulation of miR-216a and miR-301a significantly inhibited the proliferation activity and PCNA expression of HPASMC. Dual luciferase reporter assay confirmed that BMPR2 was a target of miR-216a and miR-301a, respectively. Simultaneously transfected with miR-216a or miR-301a combined with BMPR2 overexpression plasmid, the expression of BMPR2 decreased, and the cell proliferation activity and PCNA expression increased. Conclusion: miR-216a and miR-301a induce pulmonary arterial hypertension by promoting the proliferation of HPASMC under hypoxia via inhibiting the expression of BMPR2.
［Key words］miR-216a; miR-301a; pulmonary arterial hypertension; pulmonary arterial smooth muscle cells; bone morphogenetic protein receptor type 2

肺动脉高压（pulmonary arterial hypertension, PAH）是一种以肺血管重塑为特征的致命性疾病,表现为血管内皮细胞异常增殖、平滑肌肥大和内膜增厚,最终右心功能衰竭而死亡。目前PAH的临床治疗主要采用的是肺血管扩张药物,虽然可以缓解症状,但安全性低、价格昂贵且不能完全治愈疾病。随着遗传学、细胞学、分子生物学、生物信息学等学科的不断发展,以及对PAH发病机制的深入研究,基因技术作为一门新兴的技术,被广泛地应用于生命科学和医学研究的重要领域,为改善甚至治愈PAH提供了新的手段。本文综述近年来基因治疗在PAH中的研究进展。

近年来,再灌注治疗显著增加了急性心肌梗死患者的存活率。尽管如此,心肌缺血再灌注损伤与心肌梗死后的不良重构仍然严重影响了患者的治疗和预后效果。线粒体在心肌缺血再灌注与心肌重构中起着至关重要的作用,是心肌梗死治疗的重要靶标。褪黑素是一种天然的抗氧化剂,对线粒体的保护作用已得到多方验证。本文从褪黑素对线粒体的保护作用入手,介绍了褪黑素治疗心肌梗死的研究进展。