ABSTRACT
The typical hallmark of tumor evolution is metabolic dysregulation. In addition to secreting immunoregulatory metabolites, tumor cells and various immune cells display different metabolic pathways and plasticity. Harnessing the metabolic differences to reduce the tumor and immunosuppressive cells while enhancing the activity of positive immunoregulatory cells is a promising strategy. We develop a nanoplatform (CLCeMOF) based on cerium metal-organic framework (CeMOF) by lactate oxidase (LOX) modification and glutaminase inhibitor (CB839) loading. The cascade catalytic reactions induced by CLCeMOF generate reactive oxygen species "storm" to elicit immune responses. Meanwhile, LOX-mediated metabolite lactate exhaustion relieves the immunosuppressive tumor microenvironment, preparing the ground for intracellular regulation. Most noticeably, the immunometabolic checkpoint blockade therapy, as a result of glutamine antagonism, is exploited for overall cell mobilization. It is found that CLCeMOF inhibited glutamine metabolism-dependent cells (tumor cells, immunosuppressive cells, etc.), increased infiltration of dendritic cells, and especially reprogrammed CD8+ T lymphocytes with considerable metabolic flexibility toward a highly activated, long-lived, and memory-like phenotype. Such an idea intervenes both metabolite (lactate) and cellular metabolic pathway, which essentially alters overall cell fates toward the desired situation. Collectively, the metabolic intervention strategy is bound to break the evolutionary adaptability of tumors for reinforced immunotherapy.
ABSTRACT
Objective:To compare the clinical efficacy of minimally invasive anterior column screw placement assisted by orthopedic robot with anterior subcutaneous internal fixation (INFIX) in the treatment of unstable pelvic fracture.Methods:A retrospective cohort study was conducted to analyze 42 patients (25 males and 17 females; aged 16-68 years [(41.8±3.2)years] with unstable pelvic fracture admitted to Guizhou Provincial People′s Hospital from June 2018 to December 2021. Anterior column screw group ( n=22) received orthopedic robot-assisted anterior column screw fixation of anterior pelvic ring fracture, and INFIX group ( n=20) received subcutaneous INFIX of anterior pelvic ring fracture. Posterior pelvic ring injuries were treated with closed reduction and percutaneous sacroiliac screw internal fixation. The operation time of anterior pelvic ring fixation, intraoperative blood loss, intraoperative fluoroscopy times, off-bed activity time when the visual analogue scale (VAS) was<3 points during weight-bearing and fracture healing time were compared between the two groups. The quality of pelvic fracture reduction was assessed according to the Matta scoring criteria at 2 days after surgery. The Majeed functional score was used to assess the functional status at the last follow-up. Intraoperative and postoperative complications were observed in both groups. Results:All patients were followed up for 6-24 months [(11.3±0.5)months].The operation time of anterior pelvic ring fixation was (33.4±2.6)minutes in anterior column screw group and (30.2±2.9)minutes in INFIX group ( P>0.05). The intraoperative blood loss was (15.9±3.1)ml in anterior column screw group and (41.4±6.2)ml in INFIX group ( P<0.01). The intraoperative fluoroscopy times were 12.2±2.4 in anterior column screw group and 14.7±2.5 in INFIX group ( P>0.05). The off-bed activity time was (3.2±0.4) weeks in anterior column screw group and (6.6±1.2)weeks in INFIX group ( P<0.01). The fracture healing time was (12.7±1.4)weeks in anterior column screw group and (16.2±1.9) weeks in INFIX group ( P<0.01). According to Matta scoring criteria, the excellent and good rate of posterior pelvic ring reduction quality was 100% in both groups, while the excellent and good rate of the quality of anterior pelvic ring reduction was 100% (excellent in 16 patients and good in 6) in anterior column screw group compared with 90.0% (excellent in 11 patients, good in 7, and fair in 2) in INFIX group ( P<0.05). During the final follow-up, the excellent and good rate of Majeed functional score was 90.9% (excellent in 16 patients, good in 4 and fair in 2) in anterior column screw group, significantly different from 80.0% (excellent in 10 patients, good in 6 and fair in 4) in INFIX group ( P<0.05). During the operation, no important tissue injuries such as blood vessels, nerves or spermatic cord occurred in either group. In anterior column screw group, no postoperative complications such as infection, spermatic cord injury or implant breakage occurred; in INFIX group, there were 2 patients with incision fat liquefaction, 4 with lateral femoral cutaneous nerve symptoms and 1 with heterotopic ossification, without the occurrence of implant breakage. Conclusion:Compared with anterior subcutaneous INFIX, orthopedic robot-assisted anterior column screw internal fixation for the treatment of unstable pelvic fracture has advantages of less bleeding, earlier tambulation, faster fracture healing, better fracture reduction quality, more satisfied postoperative functional recovery, and fewer complications.