The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Despite the deepening of research on breast cancer,improving of treatment techniques,there are still many patients will appear local-regional recurrence after surgery.For patients with local recurrence after radical mastectomy,according to whether the postoperative radiotherapy performed,prognosis and treatment protocols are absolutely different.As for patients with local recurrence after breast-conserving surgery,more and more studies have shown that lumpectomy (secondary breast conserving surgery) combined with brachytherapy can achieve a similar effect with radical surgery in recent years,so it is a worth considering treatment protocol.

Objective To explore the efficacy of multilevel anterior cervical discectomy and fusion for aged patients with cervical spondylotic myelopathy. Methods 25 aged patients with cervical spondylotic myelopathy were treated by multilevel anterior cervical discectomy and fusion. Japanese Orthopedic Association (JOA) scores were evaluated,clinical results were graded from excellent to poor using Odoms criteria,and the sagittal alignment of fusion segements were measured using Cobb method. Bone fusion and complications was evaluated. Results The final follow up score according to Odoms criteria was excellent in 8 patients ,good in 14 patients,and fair in 3 patients ,with excellent and good rate of 88%. The JOA score at final follow up(7.8) was significantly higher than preoperative(12. 8),with average improvement rate of 54%. At final follow up,bone fusion rate was 100%. Conclusion Multilevel anterior discectomy and fusion for aged patients with cervical spondylotic myelopathy was effective.