Osimertinib is an effective epidermal growth factor receptor-tyrosine kinase inhibitor choice for lung cancer with epidermal growth factor receptor exon 18-25 kinase domain duplication: report of two cases.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are an effective treatment for common EGFR mutations in non-small-cell lung cancer (NSCLC). Rarer EGFR mutations such as kinase domain duplications (KDDs) have been identified, but the optimal therapy following treatment resistance remains unknown. We report two patients who were diagnosed with NSCLC including KDD. For case 1, afatinib (40 mg once daily) was at first effective but then became ineffective. Consequently, osimertinib therapy (80 mg once daily) was administered. As of 26 May 2021, the osimertinib therapy achieved a stable disease state according to the chest computed tomography scan. As for case 2, the patient received second-line chemotherapy and anlotinib (12 mg once daily) for 6 months and died in May 2020. Here, we describe osimertinib as an effective therapy for EGFR-KDD positive lung adenocarcinoma and thereby provide a new alternative for further treatment following resistance to first- and second-generation EGFR-TKIs.

Effects of Mitochondrial ATP-Sensitive Potassium Channel in Rats with Acute Myocardial Infarction and Its Association with the AKT/mTOR Pathway.

BACKGROUND: Myocardial infarction is associated with the autophagy and apoptosis of cardiomyocytes, and the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway plays a crucial role in this mechanism. METHODS: Acute myocardial infarction rat models were assessed 0.5, 2, 4, and 6 hours after the induction of the myocardial infarction using hematoxylin and eosin staining, triphenyl tetrazolium chloride staining, myocardial enzyme measurements, and levels of autophagic activity. Additionally, diazoxide, 5-hydroxydecanoate, and LY294002 were intraperitoneally administered to rat models at peak myocardial injury to assess their effects on cardiac injury. The expression levels of autophagy-related and apoptosis-related proteins, as well as p-AKT and p-mTOR, were measured. Electron microscopy was used to assess the ultrastructure and the number of autophagosomes in the cardiac tissue. RESULTS: We demonstrated that the degree of myocardial injury and the level of autophagy were significantly elevated in the experimental cohort compared with the control cohort. In addition, the myocardial infarct size was significantly smaller in diazoxide-treated acute myocardial infarction rats compared with untreated rats. Diazoxide also decreased the levels of myocardial injury markers, autophagy, and apoptosis, while it also induced the levels of AKT and mTOR phosphorylation, decreased the number of autophagosomes, and improved the myocardial ultrastructure of the acute myocardial infarction rats. 5-Hydroxydecanoate treatment resulted in an opposite effect to those observed upon diazoxide treatment. LY294002 was also able to reverse diazoxide treatment effects. CONCLUSION: Peak levels of myocardial tissue injury and autophagy were observed 2 hours post-acute myocardial infarction induction in rats. Diazoxide treatment inhibited myocardial autophagy and apoptosis while protecting cardiac tissue from ischemic injury, which is likely to have proceeded through activation of the AKT/mTOR pathway.

Occlusal force characteristics of masseteric muscles after intramuscular injection of botulinum toxin A(BTX - A)for treatment of temporomandibular disorder.

Our aim was to evaluate the occlusal force and therapeutic efficacy of the masseteric muscles after intramuscular injection of botulinum toxin A (BTX-A) for the treatment of patients with concurrent temporomandibular disorders (TMD) and bruxism. Thirty patients with TMD associated with bruxism were randomised into three groups (n=10 in each group), and treated by bilateral intramuscular injection of BTX-A into the masseter, placebo, or control. We used an occlusal force analysis system to collect several measures of occlusal force such as duration of biting and closing, the maximum occlusal force, and the distribution of occlusal force. The occlusal force in the intercuspid position was reduced in all three groups. There was a significant difference between the BTX-A and placebo groups (F(df=1)=8.08, p=0.01) but not between the control group and the other two(F(df=1)=4.34, p=0.047). The duration of occlusion was significantly increased in the BTX-A group after 3 months' treatment (t=4.07, p=0.003). The asymmetrical distribution of occlusal force was reduced in all three groups, but not significantly so (Levene's test F(df=2)=0.25, p=0.78,ANOVA F(df=2)=0.50, p=0.61). Treatment of TMD with BTX-A is effective in reducing the occlusal force, but psychological intervention plays an important part in treatment.