IRAK1 deficiency potentiates the efficacy of radiotherapy in repressing cervical cancer development.

IRAK1 has been implicated in promoting development of various types of cancers and mediating radioresistance. However, its role in cervical cancer tumorigenesis and radioresistance, as well as the potential underlying mechanisms, remain poorly defined. In this study, we evaluated IRAK1 expression in radiotherapy-treated cervical cancer tissues and found that IRAK1 expression is negatively associated with the efficacy of radiotherapy. Consistently, ionizing radiation (IR)-treated HeLa and SiHa cervical cancer cells express a lower level of IRAK1 than control cells. Depletion of IRAK1 resulted in reduced activation of the NF-κB pathway, decreased cell viability, downregulated colony formation efficiency, cell cycle arrest, increased apoptosis, and impaired migration and invasion in IR-treated cervical cancer cells. Conversely, overexpressing IRAK1 mitigated the anti-cancer effects of IR in cervical cancer cells. Notably, treatment of IRAK1-overexpressing IR-treated HeLa and SiHa cells with the NF-κB pathway inhibitor pyrrolidine dithiocarbamate (PDTC) partially counteracted the effects of excessive IRAK1. Furthermore, our study demonstrated that IRAK1 deficiency enhanced the anti-proliferative role of IR treatment in a xenograft mouse model. These collective observations highlight IRAK1's role in mitigating the anti-cancer effects of radiotherapy, partly through the activation of the NF-κB pathway. SUMMARY: IRAK1 enhances cervical cancer resistance to radiotherapy, with IR treatment reducing IRAK1 expression and increasing cancer cell vulnerability and apoptosis.

Intranasal esketamine combined with oral midazolam provides adequate sedation for outpatient pediatric dental procedures: a prospective cohort study.

BACKGROUND: Severe dental phobia or failure to cooperate with treatment are very common in outpatient pediatric dentistry. Personalized and appropriate noninvasive anesthesia methods can save medical expenses, improve treatment efficiency, reduce the anxiety of children, and improve the satisfaction of nursing staff. Currently, there is little conclusive evidence for noninvasive moderate sedation strategies in pediatric dental surgery. MATERIALS AND METHODS: The trial was conducted from May 2022 to September 2022. Each child was first given midazolam oral solution 0.5 mg·kg -1 , and when the Modified Observer's Assessment of Alertness and Sedation score reached 4, a biased coin design up-down method was used to adjust the dose of esketamine. The primary outcome was the ED 95 and 95% CI of intranasal esketamine hydrochloride with midazolam 0.5 mg·kg -1 . Secondary outcomes included the onset time of sedation, treatment and awakening times, and the incidence of adverse events. RESULTS: A total of 60 children were enrolled; 53 children were successfully sedated but 7 were not. The ED 95 of intranasal esketamine with 0.5 mg·kg -1 midazolam oral liquid for the treatment of dental caries was 1.99 mg·kg -1 (95% CI 1.95-2.01 mg·kg -1 ). The mean onset time of sedation for all patients was 43.7±6.9 min. 15.0 (10-24.0) min for examination and 89.4±19.5 min for awakening. The incidence of intraoperative nausea and vomiting was 8.3%. Adverse reactions such as transient hypertension and tachycardia occurred during the operations. CONCLUSION: The ED 95 of intranasal esketamine with 0.5 mg·kg -1 midazolam oral liquid for the outpatient pediatric dentistry procedure under moderate sedation was 1.99 mg·kg -1 . For children aged 2-6 years with dental anxiety who require dental surgery, anesthesiologists may consider using midazolam oral solution combined with esketamine nasal drops for noninvasive sedation after a preoperative anxiety scale evaluation.

A simple geometric method for 3D morphology reconstruction of a cell based on two orthogonal phase images.

Fast 3D imaging and measurement of cells are of great importance in many fields associated with the life science. In this paper, only using two phase images in orthogonal directions, a geometric rotation method for 3D fast morphology reconstruction is proposed in view of more spheroid cells in blood cells. In this method, at first, the edges of a cell in two orthogonal projection directions are extracted from the corresponding phase images, and theirs centers and axes are determined. Then, with the geometric rotation method, the 3D surfaces of the cell membrane and its nuclei are reconstructed respectively. After all, the 3D complete morphology of the cell is reconstructed according to their space geometry relation. Simulation and experimental results demonstrate the validity and accuracy of this method for spheroid cells. Compared with other reconstruction methods, the image speed is improved since the multiple measurements or iterative procedures are not required. It provides a new approach to image the 3D morphological structure of spheroid blood cells.