ObjectiveTo elucidate the mechanism whereby advanced glycation end products (AGEs) accelerate atherosclerosis (AS) and to explore novel therapeutic strategies for atherosclerotic cardiovascular disease.Methods and resultsThe effect of AGEs on low-density lipoprotein (LDL) transcytosis across endothelial cells (ECs) was assessed using an in vitro model of LDL transcytosis. We observed that AGEs activated the receptor for advanced glycation end products (RAGE) on the surface of ECs and consequently upregulated Caveolin-1, which in turn increased caveolae-mediated LDL transcytosis and accelerated AS progression. Our molecular assessment revealed that AGEs activate the RAGE-NF-κB signaling, which then recruits the NF-κB subunit p65 to the RAGE promoter and consequently enhances RAGE transcription, thereby forming a positive feedback loop between the NF-κB signaling and RAGE expression. Increased NF-κB signaling ultimately upregulated Caveolin-1, promoting LDL transcytosis, and inhibition of RAGE suppressed AGE-induced LDL transcytosis. In ApoE−/− mice on a high-fat diet, atherosclerotic plaque formation was accelerated by AGEs but suppressed by EC-specific knockdown of RAGE.ConclusionAGEs accelerate the development of diabetes-related AS by increasing the LDL transcytosis in ECs through the activation of the RAGE/NF-κB/Caveolin-1 axis, which may be targeted to prevent or treat diabetic macrovascular complications.

PurposeThe purpose of this study was to introduce the surgical method of K-wire combined with screw in the treatment of Arbeitsgemeinschaftfür Osteosynthesefragen (AO) type B3.1 phalangeal fractures and to compare its clinical, radiological and functional outcomes with K-wire fixation.MethodsThis was a retrospective comparative study. From January 2015 to February 2022, we treated 86 patients with AO type B3.1 phalangeal fractures. A total of 71 patients were finally included in the statistical analysis. Thirty-nine patients received K-wires combined with screw, and 32 patients received simple K-wires. The follow-up time was at least 6 months. Outcome measures included general information, operative time, total active motion (TAM), pinch strength, radiological union time, pain assessed by visual analog scale (VAS), Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score, cost, and complications.ResultsThe follow-up time was 6–12 months, with an average of 7.9 months. All patients achieved clinical and radiological union. Compared with the K-wire fixation group, the TAM, radiological union time and VAS score of the K-wire combined with screw group had obvious advantages. Compared with the opposite healthy hand, the grip strength of the two groups was similar, and there was no significant difference in the QuickDASH score. The incidence rate of complications in the K-wire combined with screw group (2/39) was lower than that in the K-wire fixation group (7/32).ConclusionsCompared with simple K-wire fixation, K-wire combined with screw in the treatment of AO type B3.1 phalangeal fractures is a safer and reliable surgical method. K-wire controls the rotation and plays a role similar to a “lock”. The screw can exert pressure and fix it more firmly. It shortens the time of fracture healing and has a higher TAM and fewer postoperative complications.