SPA inhibits hBMSC osteogenic differentiation and M1 macrophage polarization by suppressing SETD2 in acute suppurative osteomyelitis.

To clarify the impact of SETD2 on macrophage function in pediatric patients with acute suppurative osteomyelitis and to elucidate the precise underlying mechanism. To gain insights into the potential functions of SETD2, a comprehensive study was conducted utilizing a co-culture model of human bone mesenchymal stem cells (hBMSCs) and bone marrow-derived macrophages (THP-1). A range of techniques were employed, including quantitative polymerase chain reaction, western blotting, ELISA, alkaline phosphatase activity assays, alizarin red S staining, luciferase reporter gene assays, and chromatin immunoprecipitation, to unravel the intricate interactions and molecular mechanisms involving SETD2 in this system. It was observed that SETD2 expression was reduced in THP-1 cells stimulated by staphylococcal protein A (SPA). Furthermore, the downregulation of SETD2 resulted in elevated M1 macrophage polarization and glycolysis, effects that were mitigated by SPA stimulation. Notably, SPA-stimulated THP-1 cells exhibited an increase in HIF-1α expression, which exhibited an inverse correlation with SETD2 levels. Moreover, it was discovered that SETD2 functioned as a catalyst for H3K36me3 and bound to the HIF-1α gene, which, in turn, regulated HIF-1α expression. Furthermore, the suppression of HIF-1α abrogated the consequences of SETD2 downregulation on glycolysis and M1 macrophage polarization. Lastly, the study demonstrated that M1 macrophage polarization serves as a mediator for BMP4's inhibitory effect on osteogenic differentiation of hBMSCs. This research has uncovered a previously unknown role of SETD2 in macrophages during osteomyelitis, revealing its significance in the pathogenesis of this condition. These findings suggest SETD2 as a novel target for the treatment of osteomyelitis.

Analysis on Influencing Factors of Recurrence after Indirect Inguinal Hernia Laparoscopic Surgery.

This paper aims to analyze the recurrence of indirect inguinal hernia in children after laparoscopic surgery and investigate the influencing factors that may lead to recurrence so as to guide the prevention and treatment of postoperative recurrence of this kind of disease in the future. The data of 260 children with indirect inguinal hernia treated by laparoscopic surgery and followed up in our hospital from July 2019 to July 2021 were selected. A self-designed questionnaire was used to collect the basic data. The recurrence was analyzed, and the influencing factors of recurrence were analyzed by univariate analysis and multivariate analysis. Among 400 children after indirect inguinal hernia laparoscopic surgery, an occurrence was observed in 15 children, and the recurrence rate was 5.77%. Univariate analysis showed that the age and course of disease were not correlated with recurrence after indirect inguinal hernia laparoscopic surgery (P > 0.05). Being male, bilateral lesions, exact high ligation, loose hernia back wall peritoneum, deciduous ligature, incorrect ligation of the fascia of musculus obliquus externus abdominis, large inguinal hernia, circumferential wiring, and too early off-bed activity were the influencing factors of recurrence after indirect inguinal hernia laparoscopic surgery (P < 0.05). Logistic multivariate regression analysis showed that being male, bilateral lesions, loose hernia back wall peritoneum, deciduous ligature, incorrect ligation of the fascia of musculus obliquus externus abdominis, large inguinal hernia, and too early off-bed activity were the influencing factors of recurrence after indirect inguinal hernia laparoscopic surgery (OR>1, P < 0.05). Exact high ligation and circumferential wiring were protective factors of recurrence after indirect inguinal hernia laparoscopic surgery (OR>1, P < 0.05). After indirect inguinal hernia laparoscopic surgery, recurrences were affected by many factors, such as gender, site of pathological changes, and loose hernia back wall peritoneum. For these children with risk factors, reasonable intervention should be taken to reduce recurrence; exact high ligation and circumferential wiring are the protective factors. If permitted, the children meeting related indications can be treated by high ligation or circumferential wiring to reduce the risk of recurrence after indirect inguinal hernia laparoscopic surgery.