A novel repair strategy using knotless squeeze anchors for lumbar disc herniation with endplate junction lesions under biportal endoscopic spinal surgery.

BACKGROUND: Annulus fibrosus-endplate (AF-EP) junction lesions are important determinants for lumbar disc herniation (LDH). Utilizing biportal endoscopic spinal surgery (BESS), we introduce a novel repair method using bioabsorbable PushLock anchors with suture fibers to stretch disconnected AF tissues to the vertebral cortex. METHODS: The viewing and working portals are established to excise herniated disc materials causing radiculopathy. Through the working portal, a suture strand is passed through the intact AF tissue near the lesion and retrieved using the Suture Crossing Device. Then, the knotless suture limbs are secured into the cortical bone socket of the vertebral body with a PushLock anchor. CONCLUSION: The procedure is a simple, safe, and feasible knotless suturing technique for the treatment of LDH with AF-EP junction lesions.

A novel missense COL9A3 variant in a pedigree with multiple lumbar disc herniation.

Trp3 allele in COL9A3 gene has been widely studied in populations with intervertebral disc disease. We identified a novel pathogenic variant in COL9A3 gene in a pedigree with multiple lumbar disc herniation (LDH). The proband was a 14-year-old boy who developed LDH at the L4/5 and L5/S1 spinal segments. His father, paternal aunt and grandfather were diagnosed with LDH at an age of 35, 30 and 23, respectively. By applying whole exome sequencing, a heterozygous missense variant (c.1150C > T, p.Arg384Trp) in COL9A3 was identified. According to the ACMG guidelines, this variant is predicted to be pathogenic. In addition, prediction tools found COL9A3 protein of this variant a reduced stability, some changed charge properties, and an altered spatial conformation. Findings expanded the mutational spectrum of LDH and contributed to the understanding of COL9A3 in the pathogenesis of LDH.

CXCR4-mediated signaling regulates autophagy and influences acute myeloid leukemia cell survival and drug resistance.

CXCR4 surface expression is considered an independent prognostic factor for disease relapse and survival in acute myeloid leukemia (AML) patients. Herein, we investigated targetable autophagy-related mechanisms of CXCR4 for AML therapy. Our experiments show that activation of CXCR4 signaling in AML cells increases autophagic activity and decreases cytarabine-induced apoptosis. Accordingly, combined use of autophagy inhibitors significantly increased the sensitivity of AML cells to cytarabine in vitro and in vivo. Moreover, expression of autophagy-related protein SIRT1 was correlated with SDF-1α-CXCR4 signaling, which interacts with autophagy proteins, such as ATG5 and LC3. Furthermore, in primary human AML samples, high CXCR4 expression was associated with elevated expression levels of SIRT1 and other autophagy-related proteins. Collectively, our data suggest new roles of SDF-1α-CXCR4 signaling on autophagy induction in AML cells, which further promoted their survival under stress. Targeting the SDF-1α-CXCR4-autophagy signaling may contribute to an enhanced efficacy of active treatments.