Background: Biological pacemakers derived from pluripotent stem cell (PSC) have been considered as a potential therapeutic surrogate for sick sinus syndrome. So it is essential to develop highly efficient strategies for enrichment of sinoatrial node-like cells (SANLCs) as seed cells for biological pacemakers. It has been reported that BMP, FGF, and RA signaling pathways are involved in specification of different cardiomyocyte subtypes, pacemaker, ventricular, and atrial cells. We aimed to investigate whether combined modulation of BMP, FGF, and RA signaling pathways could enrich the differentiation of SANLC from human pluripotent stem cell (hiPSC). Methods: During the differentiation process from human induced pluripotent stem cell to cardiomyocyte through small molecule-based temporal modulation of the Wnt signaling pathway, signaling of BMP, FGF, and RA was manipulated at cardiac mesoderm stage. qRT-PCR, immunofluorescence, flow cytometry, and whole cell patch clamp were used to identify the SANLC.

Shear stress regulates endothelial cell function through SR-B1-eNOS signaling pathway. SR-B1 may play a pivotal role in the process of anti-atherosclerosis.

Background : Biological pacemakers derived from pluripotent stem cell (PSC) have been considered as a potential therapeutic surrogate for sick sinus syndrome. So it’s essential to develop high efficient strategies for enrichment of sinoatrial node-like cells (SANLC) as seed cells for biological pacemakers. It has reported that BMP, FGF and RA signaling pathways were involved specification of different cardiomyocyte subtypes, pacemaker, ventricle, and atria cells. Methods : During the differentiation process from human induced pluripotent stem cell (hiPSC) to cardiomyocyte through small molecule based temporal modulation of the Wnt signaling pathway, signaling of BMP, FGF and RA was manipulated at cardiac mesoderm stage. The methods of qRT-PCR, immunofluorescence, flow cytometry and whole cell patch clamp were used to identify the SANLC.Results : qRT-PCR results showed that manipulating each one of BMP, FGF and RA signaling was effective for the upregulation of SANLC markers. Moreover, combined modulation of such three pathways displayed the best efficiency for the expression of SANLC markers, which was further confirmed at protein level using immunofluorescence, flow cytometry. Finally, the electrophysiological characteristics of induced SANLC were verified by patch clamp method. Conclusion : An efficient transgene-independent differentiation protocol for generating SANLC from hPSC was developed, in which combined modulating BMP, FGF and RA signaling at cardiac mesoderm stage generates SANLC at high efficiency. It may serve as a potential approach for biological pacemaker construction.

Background: Reconstruction of the aortic arch and its three supra-aortic vessels remains a great surgical challenge with postoperative complications. We present a simplified total arch reconstruction with a modified stent graft (s-TAR) and compared its operative outcomes with conventional total arch replacement (c-TAR).Methods: This retrospective analysis of prospectively collected data from all consecutive patients who had ascending aortic aneurysm with extended aortic arch dilation and underwent simultaneous ascending aorta replacement and aortic arch reconstruction with the s-TAR or c-TAR between 2018 and 2021. The indication for intervention was maximum diameter of ascending aorta >55 mm and aortic arch in zone II >35 mm.Results: A total of 84 patients were analyzed: 43 in the s-TAR group and 41 in the c-TAR group. No inter-group differences were found for sex, age, comorbidities, or EuroSCORE II results. All patients were successfully treated with s-TAR or c-TAR, and none died intraoperatively. Cardiopulmonary bypass, selective cerebral perfusion, and lower-body circulatory arrest time were significantly shorter in the s-TAR group, which also had a lower incidence of prolonged ventilation and transient neurologic dysfunction. No patient in either group experienced permanent neurologic dysfunction. The incidence of recurrent laryngeal nerve injury and paraplegia was markedly increased in the c-TAR group; however, no such events were observed in the s-TAR group. Both perioperative blood loss and the incidence of reoperation for bleeding were significantly lower in the s-TAR group. The in-hospital mortality rate was 0% in the s-TAR group and 4.9% in the c-TAR group. The s-TAR group had significantly shorter ICU stay and lower total hospitalization costs. Conclusions:The s-TAR technique is a safe and effective alternative for total arch reconstruction with shorter operation time, lower rate of postoperative complications and lower total hospitalization costs compared with c-TAR.