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Aims

In this investigation, we administered oxidative stress to nucleus pulposus cells (NPCs), recognized DNA-damage-inducible transcript 4 (DDIT4) as a component in intervertebral disc degeneration (IVDD), and devised a hydrogel capable of conveying small interfering RNA (siRNA) to IVDD.

Methods

An in vitro model for oxidative stress-induced injury in NPCs was developed to elucidate the mechanisms underlying the upregulation of DDIT4 expression, activation of the reactive oxygen species (ROS)-thioredoxin-interacting protein (TXNIP)-NLRP3 signalling pathway, and nucleus pulposus pyroptosis. Furthermore, the mechanism of action of small interfering DDIT4 (siDDIT4) on NPCs in vitro was validated. A triplex hydrogel named siDDIT4@G5-P-HA was created by adsorbing siDDIT4 onto fifth-generation polyamidoamine (PAMAM) dendrimer using van der Waals interactions, and then coating it with hyaluronic acid (HA). In addition, we established a rat puncture IVDD model to decipher the hydrogel’s mechanism in IVDD.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 80 - 90
20 Jan 2023
Xu J Si H Zeng Y Wu Y Zhang S Liu Y Li M Shen B

Aims. Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive. Methods. Predicted whole-blood and skeletal muscle gene expression and genome-wide association study (GWAS) data from a DCS database were integrated, and functional summary-based imputation (FUSION) software was used on the integrated data. A transcriptome-wide association study (TWAS) was conducted using FUSION software to assess the association between predicted gene expression and DCS risk. The TWAS-identified genes were verified via comparison with differentially expressed genes (DEGs) in DCS RNA expression profiles in the Gene Expression Omnibus (GEO) (Accession Number: GSE153761). The Functional Mapping and Annotation (FUMA) tool for genome-wide association studies and Meta tools were used for gene functional enrichment and annotation analysis. Results. The TWAS detected 420 DCS genes with p < 0.05 in skeletal muscle, such as ribosomal protein S15A (RPS15A) (PTWAS = 0.001), and 110 genes in whole blood, such as selectin L (SELL) (PTWAS = 0.001). Comparison with the DCS RNA expression profile identified 12 common genes, including Apelin Receptor (APLNR) (PTWAS = 0.001, PDEG = 0.025). In total, 148 DCS-enriched Gene Ontology (GO) terms were identified, such as mast cell degranulation (GO:0043303); 15 DCS-enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified, such as the sphingolipid signalling pathway (ko04071). Nine terms, such as degradation of the extracellular matrix (R-HSA-1474228), were common to the TWAS enrichment results and the RNA expression profile. Conclusion. Our results identify putative susceptibility genes; these findings provide new ideas for exploration of the genetic mechanism of DCS development and new targets for preclinical intervention and clinical treatment. Cite this article: Bone Joint Res 2023;12(1):80–90


The Bone & Joint Journal
Vol. 98-B, Issue 2 | Pages 238 - 243
1 Feb 2016
Qian L Li P Wu W Fang Y Zhang J Ouyang J

Aims

This study aimed to determine the relationship between pedicle-lengthening distance and bulge-canal volume ratio in cases of lumbar spinal stenosis, to provide a theoretical basis for the extent of lengthening in pedicle-lengthening osteotomies.

Methods

Three-dimensional reconstructions of CT images were performed for 69 patients (33 men and 36 women) (mean age 49.96 years; 24 to 81). Simulated pedicle-lengthening osteotomies and disc bulge and spinal canal volume calculations were performed using Mimics software.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 5 | Pages 684 - 689
1 May 2012
Tsirikos AI Smith G

We reviewed 31 consecutive patients with Friedreich’s ataxia and scoliosis. There were 24 males and seven females with a mean age at presentation of 15.5 years (8.6 to 30.8) and a mean curve of 51° (13° to 140°). A total of 12 patients had thoracic curvatures, 11 had thoracolumbar and eight had double thoracic/lumbar. Two patients had long thoracolumbar collapsing scoliosis with pelvic obliquity and four had hyperkyphosis. Left-sided thoracic curves in nine patients (45%) and increased thoracic kyphosis differentiated these deformities from adolescent idiopathic scoliosis. There were 17 patients who underwent a posterior instrumented spinal fusion at mean age of 13.35 years, which achieved and maintained good correction of the deformity. Post-operative complications included one death due to cardiorespiratory failure, one revision to address nonunion and four patients with proximal junctional kyphosis who did not need extension of the fusion. There were no neurological complications and no wound infections. The rate of progression of the scoliosis in children kept under simple observation and those treated with bracing was less for lumbar curves during bracing and similar for thoracic curves. The scoliosis progressed in seven of nine children initially treated with a brace who later required surgery. Two patients presented after skeletal maturity with balanced curves not requiring correction. Three patients with severe deformities who would benefit from corrective surgery had significant cardiac co-morbidities.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 3 | Pages 365 - 372
1 Mar 2012
Cheng B Li FT Lin L

Diastematomyelia is a rare congenital abnormality of the spinal cord. This paper summarises more than 30 years’ experience of treating this condition. Data were collected retrospectively on 138 patients with diastematomyelia (34 males, 104 females) who were treated at our hospital from May 1978 to April 2010. A total of 106 patients had double dural tubes (type 1 diastematomyelia), and 32 patients had single dural tubes (type 2 diastematomyelia). Radiographs, CT myelography, and MRI showed characteristic kyphoscoliosis, widening of the interpedicle distance, and bony, cartilaginous, and fibrous septum. The incidences of symptoms including characteristic changes of the dorsal skin, neurological disorders, and congenital spinal or foot deformity were significantly higher in type 1 than in type 2. Surgery is more effective for patients with type 1 diastematomyelia; patients without surgery showed no improvement.


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 1 | Pages 88 - 90
1 Jan 2009
Nordin L Sinisi M

We describe three patients with pre-ganglionic (avulsion) injuries of the brachial plexus which caused a partial Brown-Séquard syndrome.


The Journal of Bone & Joint Surgery British Volume
Vol. 78-B, Issue 5 | Pages 754 - 758
1 Sep 1996
Ochiai N Nagano A Sugioka H Hara T

We have assessed the efficacy of free nerve grafts in 90 cases of brachial plexus injury. Relatively good recovery of the elbow flexor and extensor muscles and of those of the shoulder girdle was found but recovery of the flexors and extensors of the forearm and of the intrinsic muscles of the hand was extremely poor. Poor results were found when spinal nerve roots seemed normal to the touch and appeared intact but had abnormal somatosensory evoked potentials or myelography. Recovery of the deltoid and infraspinatus muscles was better when injury had occurred to the circumflex and suprascapular nerves rather than to the plexus itself, perhaps because these nerves were explored in their entirety to determine the presence of multiple lesions. It is important to visualise the entire nerve thoroughly to assess the overall condition. Thorough exploration of the plexus and the use of intraoperative recording of somatosensory evoked potentials are essential