M6A methylation-regulated autophagy may be a new therapeutic target for intervertebral disc degeneration.

Degeneration of intervertebral discs is considered one of the most important causes of low back pain and disability. The intervertebral disc (IVD) is characterized by its susceptibility to various stressors that accelerate the senescence and apoptosis of nucleus pulposus cells, resulting in the loss of these cells and dysfunction of the intervertebral disc. Therefore, how to reduce the loss of nucleus pulposus cells under stress environment is the main problem in treating intervertebral disc degeneration. Autophagy is a kind of programmed cell death, which can provide energy by recycling substances in cells. It is considered to be an effective method to reduce the senescence and apoptosis of nucleus pulposus cells under stress. However, further research is needed on the mechanisms by which autophagy of nucleus pulposus cells is regulated under stress environments. M6A methylation, as the most extensive RNA modification in eukaryotic cells, participates in various cellular biological functions and is believed to be related to the regulation of autophagy under stress environments, may play a significant role in nucleus pulposus responding to stress. This article first summarizes the effects of various stressors on the death and autophagy of nucleus pulposus cells. Then, it summarizes the regulatory mechanism of m6A methylation on autophagy-related genes under stress and the role of these autophagy genes in nucleus pulposus cells. Finally, it proposes that the methylation modification of autophagy-related genes regulated by m6A may become a new treatment approach for intervertebral disc degeneration, providing new insights and ideas for the clinical treatment of intervertebral disc degeneration.

Randomized controlled trial of all-inside and standard single-bundle anterior cruciate ligament reconstruction with functional, MRI-based graft maturity and patient-reported outcome measures.

BACKGROUND: All-inside anterior cruciate ligament reconstruction (ACLR) is a novel technique that has gained attention due to its minimally invasive and graft-saving properties. However, studies comparing MRI-based graft maturity between all-inside and standard ACLR are lacking. PURPOSE: This study focused on the functional, knee laxity, and MRI-based graft maturity characteristics of all-inside and standard single-bundle ACLR. STUDY DESIGN: Randomized controlled trial (RCT). METHODS: Fifty-four patients were randomly assigned to an all-inside reconstruction group (n = 27) or standard reconstruction group (n = 27). Using the same rehabilitation strategy. The Tegner, International Knee Documentation Committee, and Lysholm scores were recorded at postoperative months 3, 6, and 12 to assess functional recovery. MRI was conducted to measure the signal/noise quotient (SNQ) of the intra-articular graft to assess the maturity. A higher SNQ indicates lower graft maturity. Knee laxity was assessed using GNRB arthrometer at the postoperative month 12. RESULTS: The graft SNQ of the all-inside group was significantly higher than that of the standard group at postoperative month 6 (p < 0.05). There was no statistical difference in graft SNQ between the two groups at postoperative months 3 and 12 (p > 0.05). Both groups exhibited the highest SNQ in the middle region of the graft, followed by the proximal region, and the distal region. Functional scores improved significantly for both groups and had no statistical difference (p > 0.05). The knee laxity was higher in the all-inside group (p < 0.05) at postoperative month 12. There was no correlation between the functional scores and graft maturity in both groups (p > 0.05). CONCLUSIONS: All-inside and standard single-bundle ACLR show good functional outcomes; however, knee laxity was relatively higher in the all-inside ACLR group than in the standard ACLR group. Moreover, both techniques exhibited poor maturity in the middle graft region and the best in the distal region. Graft maturity with all-inside ACLR is inferior to that with standard ACLR in the early postoperative stages. There is no correlation between knee function and graft maturity. TRIAL REGISTRATION: Clinical trial registration numbers: ChiCTR1800018543 . Date of registration: 09/23/2018.