Case report of severe coronary artery tortuosity with coexisting connective tissue disease.

Coronary artery tortuosity (CAT) is frequently detected during coronary angiography or coronary electron-beam computed tomography angiography by cardiovascular interventionalists. In this article, we described the case of a 69-year-old female patient with recurrent chest discomfort for 1 month and recurrence 1 week ago, accompanied by emaciation, gastrointestinal discomfort, and low skin temperature at the extremities. After a series of tests, the patient was finally diagnosed with severe CAT and coexisting connective tissue disease. Accordingly, she was treated with conventional medications, and diet and lifestyle modifications. The symptoms of the patient resolved gradually after 1 year of follow-up. Although there is no unanimous conclusion on the pathogenesis and clinical characteristics of CAT, this disease may provide a clue to the diagnosis of connective tissue disease, and warrants exploration through further research.

The BRD4 Inhibitor dBET57 Exerts Anticancer Effects by Targeting Superenhancer-Related Genes in Neuroblastoma.

Neuroblastoma (NB) is the most common solid tumor of the neural crest cell origin in children and has a poor prognosis in high-risk patients. The oncogene MYCN was found to be amplified at extremely high levels in approximately 20% of neuroblastoma cases. In recent years, research on the targeted hydrolysis of BRD4 to indirectly inhibit the transcription of the MYCN created by proteolysis targeting chimaera (PROTAC) technology has become very popular. dBET57 (S0137, Selleck, TX, USA) is a novel and potent heterobifunctional small molecule degrader based on PROTAC technology. The purpose of this study was to investigate the therapeutic effect of dBET57 in NB and its potential mechanism. In this study, we found that dBET57 can target BRD4 ubiquitination and disrupt the proliferation ability of NB cells. At the same time, dBET57 can also induce apoptosis, cell cycle arrest, and decrease migration. Furthermore, dBET57 also has a strong antiproliferation function in xenograft tumor models in vivo. In terms of mechanism, dBET57 targets the BET protein family and the MYCN protein family by associating with CRBN and destroys the SE landscape of NB cells. Combined with RNA-seq and ChIP-seq public database analysis, we identified the superenhancer-related genes TBX3 and ZMYND8 in NB as potential downstream targets of dBET57 and experimentally verified that they play an important role in the occurrence and development of NB. In conclusion, these results suggest that dBET57 may be an effective new therapeutic drug for the treatment of NB.