Dexlansoprazole prevents pulmonary artery hypertension by inhibiting pulmonary artery smooth muscle cell to fibroblast transition.

OBJECTIVES: To validate that dexlansoprazole, an anti-acid drug, can prevent pulmonary artery hypertension (PAH) in preclinical animal models and find the possible mechanism of action of dexlansoprazole for this new indication. METHODS: The efficacy of dexlansoprazole to attenuate PAH in vivo was evaluated in PAH animal models. Plasma guanosine 3', 5'-cyclic phosphate (cGMP) in PAH rats was measured by enzyme linked immunosorbent assay (ELISA). To investigate the anti-PAH effect of dexlansoprazole in vitro, proliferation and migration assays of primary cultured pulmonary artery smooth muscle cells (PASMCs) were performed. Furthermore, dexlansoprazole's function on fibroblast transition of vascular smooth muscle cells (VSMC) was explored by single cell ribonucleic acid (RNA) sequencing and RNAscope. RESULTS: Dexlansoprazole could attenuate the pathologic process in monocrotaline (MCT)-, hypoxia-induced PAH rats and SU5416/hypoxia (SuHy)-induced PAH mice. The intervention with dexlansoprazole significantly inhibited elevated right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and pulmonary vascular wall thickness. Furthermore, plasma cGMP in MCT-induced PAH rats was restored after receiving dexlansoprazole. In vitro, dexlansoprazole could inhibit PASMCs' proliferation and migration stimulated by platelet derived growth factor-BB (PDGF-BB). Moreover, dexlansoprazole significantly ameliorated pulmonary vascular remodeling by inhibiting VSMC phenotypic transition to fibroblast-like cells in a VSMC-specific multispectral lineage-tracing mouse. CONCLUSIONS: Dexlansoprazole can prevent PAH through promoting cGMP generation and inhibiting pulmonary vascular remodeling through restraining PASMCs' proliferation, migration, and phenotypic transition to fibroblast-like cells. Consequently, PAH might be a new indication for dexlansoprazole.

[Cerebrospinal rhinorrhen of 5 cases].

OBJECTIVE: To investigate the approaches of diagnosis and therapy to cerebrospinal rhinorrhea and to improve the effects of diagnosis and therapy. METHOD: Five cases of cerebrospinal rhinorrhea were analyzed retrospectively. Four were performed repair assisted by operation navigation instrument and endoscopy, 1 was performed forehead craniotomy with coronal incision and reconstruction with pedicled galeal flaps. RESULT: Followed up half a year, all the patients were healed. CONCLUSION: The patient of cerebrospinal rhinorrhea can be repaired by endoscopy if the opening is small. The navigation instrument is evidently helpful to find the opening more quickly and exactly. The patients with wider opening had better to accept reconstruction with appropriate materials after undergoing craniotomy to ensure the effects of the therapy.