Aim Toinvestigatethepro-angiogenic effects of Danshensu derivative ADTM and explore its underlying possible signaling pathway using zebrafish embryosasinvivomodels.Methods Theangiogenesis activities of ADTM were determined in experimental models of normal and VEGFR tyrosine kinase inhibitorⅡ(VRI )-induced vascular defective zebrafish embry-os.Embryos were treated with various concentrations (50,100,200 μmol · L-1 ) of ADTM for indicated time.The diameter and the numbers of endothelial cells of zebrafish SIVs were evaluated,respectively.In VRI model,the number of intact and defective ISVs in each zebrafish embryo was counted.The total RNA of zebrafish embryos was extracted and transcriptional profiling was analyzed by deep sequencing.Quantita-tive real-time PCR(qPCR)was performed to 4 genes selected from transcriptional profiling to validate the data collected from transcriptome analysis.Results ADTMsignificantlyincreasedsubintestinalvessels (SIVs)diameter in a concentration-dependent manner in normal zebrafish as well as restored VRI-induced blood vessels defect in VRI-exposed zebrafish. The transcriptome data analysis demonstrated that 19 signif-icantly changed genes were mapped to insulin signaling pathway.The qPCR data are in good agreement with those obtained by deep sequencing and support the consistency between the two methods for determining relative expression levels in the zebrafish model.Con-clusion Inzebrafishmodel,ADTMexhibitsthe effects of angiogenesis and blood vessel restoration. The underlying mechanism may be involved in the acti-vation of insulin signaling pathway.

Objective:To evaluate the clinical effects of " watching without dealing" aortic root repair technique in acute Stanford type A aortic dissection(ATAAD).Methods:From October 2017 to October 2018, " watching without dealing" technique was performed in ATAAD patients with mild aortic root involvement. The proximal aortic anastomosis was at the level of the sinotubular junction, without " pursuing" complete excision of the intra-sinus dissections. The perioperative clinical data and follow-up imaging results of the patients were collected and analyzed to evaluate early and mid-term efficacy of the technique.Results:A total of 20 patients received " watching without dealing" technique in our hospital, including 15 males and 5 females with a mean age of(48.0±12.1) years old(34-73 years old). The preoperative aortic sinus diameter was(41.3±3.6)mm and the aortic sinotubular junction diameter was(43.9±6.6) mm. All patients underwent ascending aortic replacement and total arch replacement plus frozen elephant trunk surgery. The cardiopulmonary bypass time was(179.5±41.5)min(132~255 min), the cross-clamp time was(120.3±23.7) min(95~180 min), and the circulatory arrest time was(8.8±7.6) min(2~22 min). During perioperative period, no adverse events such as death, secondary opening, renal failure, cerebral infarction, and paraplegia occurred. The CTA examination of the aorta before the patients were discharged showed that all residual false lumen in the sinus disappeared, the diameter of the aortic sinus was(30.8±2.6) mm, and the diameter of the aortic sinotubular junction was(27.2±2.5) mm. The patients were followed up for mean(28.5±7.8) months(3~35 months). No surgical re-intervention of the aortic root occurred. The aortic CTA during follow-up period showed no residual or new dissection in the aortic sinus, the diameters of the aortic sinus and aortic sinotubular junction were(30.9±2.4) mm and(27.5±2.7) mm respectively; the ultrasonic cardiogram showed normal aortic valve structure and function. No statistically significant differences were found when comparing the aortic sinus diameter and aortic sinotubular junction diameter between two time points of at discharge and follow-up.Conclusion:The " watching without dealing" aortic root repair technique for ATAAD is relatively simple to learn and safe in the perioperative period. Early and mid-term follow-up imaging showed normalization of the aortic sinus structure. Further follow-up and observation were necessary to figure out the long-term clinical outcome of this modified aortic root repair.

Currently the main treatment of acute myeloid leukemia (AML) is chemotherapy combining hematopoietic stem cell transplantation. However, the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice. Thus, there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects. Here, we revealed that umbilical cord-derived mesenchymal stem cells (UC-MSC) efficiently induced AML cell differentiation by shuttling the neutrophil elastase (NE)-packaged extracellular vesicles (EVs) into AML cells. Interestingly, the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor (VDR) activation in UC-MSC. Chemical activation of VDR by using its agonist 1α,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model. Based on these discoveries, to evade the risk of hypercalcemia, we synthetized and identified sw-22, a novel non-steroidal VDR agonist, which exerted a synergistic pro-differentiation function with UC-MSC on mitigating the progress of AML. Collectively, our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.

The treatment of acute Stanford type A aortic dissection has always been extremely challenging. Organ malperfusion syndrome is a common severe complication of acute aortic dissection, which can cause organ ischemia and internal environment disorder. Malperfusion increases early mortality, and impacts the long-term prognosis. In recent years, many scholars have done some studies on aortic dissection complicated with malperfusion. They explored the pathogenesis, proposed new classification, and innovated new treatment strategies. However, at present, the treatment strategies of acute Stanford type A aortic dissection complicated with organ malperfusion are different at different centers and consensus on its treatment is still lacking. Therefore, this review summarized the pathogenesis, classification, treatment strategy, and prognosis of acute Stanford type A aortic dissection complicated with malperfusion.