Although opioids are necessary for the treatment of acute pain, cancer pain, and palliative care, opioid abuse is a serious threat to society. Heroin (Diacetylmorphine) is the most commonly abused opioid, and it can have a variety of effects on the body's tissues and organs, including the well-known gastrointestinal depression and respiratory depression; however, there is little known about the effects of diacetylmorphine on cardiac damage. Here, we demonstrate that diacetylmorphine induces abnormal electrocardiographic changes in rats and causes damage to cardiomyocytes in vitro by an underlying mechanism of increased autophosphorylation of CaMKII and concomitant regulation of myocardial contractile protein TPM1 and MYOM2 protein expression. The CaMKII inhibitor KN-93 was first tested to rescue the toxic effects of heroin on cardiomyocytes in vitro and the abnormal ECG changes caused by heroin in SD rats, followed by the TMT relative quantitative protein technique to analyze the proteome changes. Diacetylmorphine causes increased phosphorylation at the CaMKII Thr287 site in myocardium, resulting in increased autophosphorylation of CaMKII and subsequent alterations in myocardial contractile proteins, leading to myocardial rhythm abnormalities. These findings provide a theoretical basis for the treatment and prevention of patients with arrhythmias caused by diacetylmorphine inhalation and injection.

ASAP3 is involved in a variety of biological activities, including cancer progression in humans. In adult glioma, we explore the effects of ASAP3 and NOTCH3 and their relationships on prognosis. The Oncomine, TIMER, and Gene Expression Profiling Interactive Analysis databases were used to investigate ASAP3 expression. Immunohistochemistry was used to assess the levels of ASAP3 and NOTCH3 expressions. The effects of ASAP3 and NOTCH3 on prognosis were assessed using survival analysis. The results revealed that the amount of ASAP3 mRNA in gliomas was much higher than in normal tissue (P < 0.01). Glioma patients with high ASAP3 mRNA expression had a worse overall survival and progression-free survival. ASAP3 overexpression is directly associated with the NOTCH signaling system. Immunohistochemistry revealed that ASAP3 and NOTCH3 were overexpressed in glioblastomas (GBMs). ASAP3 expression was associated with age, recurrence, tumor resection, postoperative chemoradiotherapy, World Health Organization (WHO) grade, and Ki-67 expression. ASAP3 expression was related to the isocitrate dehydrogenase-1 mutation in low-grade glioma. Gender, local recurrence, tumor resection, postoperative radio-chemotherapy, WHO grade, recurrence, and ATRX expression were all associated with NOTCH3 expression. ASAP3 was shown to be positively associated with NOTCH3 (r = 0.337, P = 0.000). Therefore, ASAP3 and NOTCH3 as oncogene factors have the potential to be prognostic biomarkers and therapeutic targets in adult glioma.