Hypoxemia is a common pathological state characterized by low oxygen saturation in the blood. This condition compromises mucosal barrier integrity particularly in the gut and oral cavity. However, the mechanisms underlying this association remain unclear. This study used periodontitis as a model to investigate the role of platelet activation in oral mucosal immunopathology under hypoxic conditions. Hypoxia upregulated methyltransferase-like protein 4 (METTL4) expression in platelets, resulting in N⁶-methyladenine modification of mitochondrial DNA (mtDNA). This modification impaired mitochondrial transcriptional factor A-dependent cytosolic mtDNA degradation, leading to cytosolic mtDNA accumulation. Excess cytosolic mt-DNA aberrantly activated the cGAS-STING pathway in platelets. This resulted in excessive platelet activation and neutrophil extracellular trap formation that ultimately exacerbated periodontitis. Targeting platelet METTL4 and its downstream pathways offers a potential strategy for managing oral mucosa immunopathology. Further research is needed to examine its broader implications for mucosal inflammation under hypoxic conditions.
DNA, Mitochondrial/metabolism* ; Mouth Mucosa/pathology* ; Hypoxia/immunology* ; Methyltransferases/metabolism* ; Blood Platelets/metabolism* ; Animals ; Periodontitis/immunology* ; Humans ; Platelet Activation ; Mice

In educating postgraduate students in aerospace medicine in our country, there are some deficiencies such as the course content lacking forward looking and systematicness, and students' mastery of technology or skills lacking professional characteristics, innovation and divergent thinking. Based on the original foundations, the School of Aerospace Medicine, Fourth Military Medical University, has been con-structing and improving the course system by modifying the course contents, reforming the practical teach-ings, expanding the academic communications, and managing the processes. Finally, they have achieved certain results.

Objective To investigate the currents impact on delayed rectifier potassium (HERG)regulated by cyclooxygenase (COX)-2 in gastric cancer cells and its mechnism. Methods ① The HERG mRNA, protein and current in gastric cancer cells transfected with or without COX-2 antisense vector were measured by RT-PCR, Western blot and patch-clamp, respectively. ② cAMP concentration in gastric cancer cells transfected with or without COX-2 antisense vector was measured by ELISA. ③ The mutant HERG, which was absence of cAMP-binding domain, was constructed by PCR and transfected into gastric cancer cells. ④ The impact of COX-2 inhibitor and proglandin (PG) E2 on HERG current in gastric cancer cells transfected with or without mutant HERG was investigated by patch clamp. ⑤ The effects of agonist and antagonist of cAMP and inhibitor of protein kinase (PK) A on HERG current in gastric cancer cells transfected with or without HERG mutant were observed by patch clamp. Results ① The expression of HERG mRNA and protein in gastric cancer cells transfected with COX-2 antisense vector were not altered, but the amplitude of HERG current was diminished (P<0.05). ② The cAMP concentration in gastric cancer cells transfected with COX-2 antisense vector was lower than that in parental gastric cancer cells (P<0.05). ③ COX-2 inhibitor and PGE2 had influence on the HERG currents in gastric cancer cells. COX-2 inhibitor reduced and PGE2 enhanced the amplitude of HERG current in gastric cancer cells. However, neither COX-2 inhibitor nor PGE2 showed any negative or positive effects on currents of mutant HERG. ④ cAMP agonist enhanced the amplitude of HERG current and cAMP antagonist reduced the amplitude in gastric cancer cells. Neither agonist nor antagonist had effect on currents of mutant HERG. ⑤ PKA inhibitor did not influence the HERG current of parental gastric cancer cells and gastric cancer cells transfected with mutant. Conclusions COX-2 regulates HERG current through its catalytic product of PGE2, which binds with its receptor on the gastric cancer cells and alters cAMP level in gastric cancer cells, cAMP interacts with HERG protein by binding with cAMP-binding domain of HERG protein and exerts impact on HERG current. PKA does not participate in this process.