Relationship between intervertebral disc height and post operative dysphagia secondary to single-level anterior cervical discectomy and fusion- a retrospective study.

BACKGROUND: One goal of Anterior Cervical Discectomy and Fusion (ACDF) is to restore the loss of intervertebral disc height (IDH) results from the degenerative process. However, the effects of IDH on postoperative dysphagia after ACDF remain unclear. METHODS: Based on the results of a one-year telephone follow-up, A total of 217 consecutive patients after single-level ACDF were enrolled. They were divided into dysphagia and non-dysphagia groups. The age, BMI, operation time and blood loss of all patients were collected from the medical record system and compared between patients with and without dysphagia. Radiologically, IDH, spinous process distance (SP) of the operated segment, and C2-7 angle (C2-7 A) were measured preoperatively and postoperatively. The relationship between changes in these radiological parameters and the development of dysphagia was analyzed. RESULTS: Sixty-three (29%) cases exhibited postoperative dysphagia. The mean changes in IDH, SP, and C2-7 A were 2.84 mm, -1.54 mm, and 4.82 degrees, respectively. Changes in IDH (P = 0.001) and changes in C2-7 A (P = 0.000) showed significant differences between dysphagia and non-dysphagia patients. Increased IDH and increased C2-7 A (P = 0.037 and 0.003, respectively) significantly and independently influenced the incidence of postoperative dysphagia. When the change in IDH was ≥ 3 mm, the chance of developing postoperative dysphagia for this patient was significantly greater. No significant relationship was observed between the change in spinous process distance (SP) and the incidence of dysphagia. The age, BMI, operation time and blood loss did not significantly influence the incidence of postoperative dysphagia. CONCLUSION: The change in IDH could be regarded as a predictive factor for postoperative dysphagia after single-level ACDF.

Intramedullary spinal cord metastasis from esophageal squamous cell carcinoma: case report and literature review.

BACKGROUND: Intramedullary spinal cord metastasis (ISCM) of malignant tumors rarely happens. To the best of our knowledge, only five cases of ISCM from esophageal cancer have been reported in literature. We here report the sixth descripted case of ISCM from esophageal cancer. CASE PRESENTATION: A 68-year-old male presented with weakness of right limbs and localized neck pain two years after diagnosed esophageal squamous cell carcinoma. The gadolinium enhanced Magnetic resonance imaging (MRI) of cervical spine showed a mixed-intense intramedullary tumor with typical more intense thin rim of peripheral enhancement in C4-C5. The patient died fifteen days after diagnosis of irreversible respiratory and circulatory failures. An autopsy was refused by his family. CONCLUSIONS: This case highlights the importance of gadolinium enhanced MRI for diagnosis in ISCM. We believe that early diagnosis and surgery for selected patients shows helpfulness to save their neurologic function and improve quality of life.

Is intervertebral disc degeneration associated with reduction in serum ferritin?

OBJECTIVE: Ferritin autophagy is characterized by intracellular ferroptosis and selective ferritin degradation. However, the role of ferritin in the development of intervertebral disc degeneration (IDD) has not been elucidated. The study aimed to investigate the role of serum iron metabolism markers, especially serum ferritin (SF), in IDD. METHODS: 217 patients who came to the spine surgery department of our hospital for low back pain were recruited, and blood samples were collected for routine examination after admission. The cumulative grade was also calculated by summing up the Pfirrmann grade of all lumbar discs. RESULTS: Correlation analysis showed that cumulative grade was correlated with SF (r = - 0.185, p = 0.006), not with serum iron (SI), transferrin saturation (TS), unsaturated iron-binding capacity (UIBC) and total iron-binding capacity (TIBC) (all p > 0.05). In addition, SF levels in the low severity IDD were significantly higher than high severity IDD in cumulative grade (p = 0.003) and single disc grade. No statistically significant difference was found in the other four indicators. A statistically significant difference was observed between the high (cumulative grade > 17) and low score (cumulative grade ≤ 17) groups in terms of age. According to the ROC curve, the cut-off value of SF levels was 170.5. Patients with SF < 170.5 ng/mL had severe disc degeneration. The sensitivity and specificity were 0.635 and 0.602, respectively. CONCLUSION: This study preliminarily showed that SF was negatively correlated with the degree of IDD and can be used to predict IDD severity.

Construction of a circular RNA-based competing endogenous RNA network to screen biomarkers related to intervertebral disc degeneration.

BACKGROUND: Intervertebral disc degeneration (IDD) is a leading cause of disability with limited treatment strategies. A better understanding of the mechanism of IDD might enable less invasive and more targeted treatments. This study aimed to identify the circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) competing endogenous RNA (ceRNA) regulatory mechanisms in IDD. METHODS : The GSE67567 microarray dataset was downloaded from the Gene Expression Omnibus database. After data preprocessing, differentially expressed circRNAs, miRNAs and mRNAs between IDD and controls were identified. A ceRNA network was constructed on the basis of the interaction between circRNAs and miRNAs, and miRNAs and mRNAs. Pathway enrichment analysis was performed on the mRNAs in the ceRNA network. Then, with 'intervertebral disc degeneration' as keywords, IDD-related Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were searched for in the Comparative Toxicogenomics Database. RESULTS: A total of 105 differentially expressed circRNAs, 84 miRNAs and 967 mRNAs were identified. After analysis, 86 circRNA-miRNA, and 126 miRNA-mRNA regulatory relationship pairs were obtained to construct a ceRNA network. The mRNAs were enriched in six KEGG signalling pathways, and four were associated with IDD: the hsa04350: TGF-beta signalling pathway, hsa04068: FoxO signalling pathway, hsa05142: Chagas disease (American trypanosomiasis) and hsa04380: Osteoclast differentiation. An IDD-related ceRNA network was constructed involving four circRNAs, three miRNAs and 11 mRNAs. Auxiliary validation showed that the expression levels of miR-185-5p, miR-486-5p, ACVR1B, FOXO1, SMAD2 and TGFB1 were consistent in different databases. CONCLUSIONS: Our study identified some circRNA-miRNA-mRNA interaction axes potentially associated with the progression of IDD, viz.: circRNA_100086-miR-509-3p-MAPK1, circRNA_000200-miR-185-5p-TGFB1, circRNA_104308-miR-185-5p-TGFB1, circRNA_400090-miR-486-5p-FOXO1 and circRNA_400090-miR-486-5p-SMAD2.

MicroRNA-137 inhibits the inflammatory response and extracellular matrix degradation in lipopolysaccharide-stimulated human nucleus pulposus cells by targeting activin a receptor type I.

This study aimed to investigate the role played by microRNA (miR)-137 in intervertebral disc degeneration via targeting activin A receptor type I (ACVR1) and the underlying mechanism. Human nucleus pulposus cells were exposed to 10 ng/mL lipopolysaccharide (LPS) to establish an in vitro intervertebral disc degeneration model. ACVR1, extracellular matrix degradation-associated genes (aggrecan and collagen type II) and miR-137 levels were assessed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting assays. The MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay and flow cytometry were used to evaluate nucleus pulposus cell viability and apoptosis. Additionally, the association between miR-137 and ACVR1 was predicted and verified using bioinformatic software and dual-luciferase reporter assays. Furthermore, the secretion of inflammatory factors was analyzed via enzyme linked immunosorbent assay (ELISA). Our results confirmed that ACVR1 was upregulated in lipopolysaccharide-treated nucleus pulposus cells. Lipopolysaccharide suppressed cell viability, promoted apoptosis, enhanced the secretion of inflammatory factors, and reduced aggrecan and collagen type II expression. However, these results were reversed upon ACVR1 silencing. Our data revealed that ACVR1 directly targets miR-137 and is negatively regulated by miR-137 in nucleus pulposus cells. Additionally, the miR-137 mimic promoted cell growth, reduced cell apoptosis, reduced the secretion of inflammatory cytokines, and accelerated extracellular matrix accumulation in lipopolysaccharide-exposed nucleus pulposus cells. However, ACVR1 plasmid abolished the functions of the miR-137 mimic in lipopolysaccharide-exposed nucleus pulposus cells. Together, these findings indicate that miR-137 suppresses the inflammatory response and extracellular matrix degradation in lipopolysaccharide-treated nucleus pulposus cells by targeting ACVR1.

Roles of the Neuron-Restrictive Silencer Factor in the Pathophysiological Process of the Central Nervous System.

The neuron-restrictive silencer factor (NRSF), also known as repressor element 1 (RE-1) silencing transcription factor (REST) or X2 box repressor (XBR), is a zinc finger transcription factor that is widely expressed in neuronal and non-neuronal cells. It is a master regulator of the nervous system, and the function of NRSF is the basis of neuronal differentiation, diversity, plasticity, and survival. NRSF can bind to the neuron-restrictive silencer element (NRSE), recruit some co-repressors, and then inhibit transcription of NRSE downstream genes through epigenetic mechanisms. In neurogenesis, NRSF functions not only as a transcriptional silencer that can mediate the transcriptional inhibition of neuron-specific genes in non-neuronal cells and thus give neuron cells specificity, but also as a transcriptional activator to induce neuronal differentiation. Many studies have confirmed the association between NRSF and brain disorders, such as brain injury and neurodegenerative diseases. Overexpression, underexpression, or mutation may lead to neurological disorders. In tumorigenesis, NRSF functions as an oncogene in neuronal tumors, such as neuroblastomas, medulloblastomas, and pheochromocytomas, stimulating their proliferation, which results in poor prognosis. Additionally, NRSF-mediated selective targets gene repression plays an important role in the development and maintenance of neuropathic pain caused by nerve injury, cancer, and diabetes. At present, several compounds that target NRSF or its co-repressors, such as REST-VP16 and X5050, have been shown to be clinically effective against many brain diseases, such as seizures, implying that NRSF and its co-repressors may be potential and promising therapeutic targets for neural disorders. In the present review, we introduced the biological characteristics of NRSF; reviewed the progress to date in understanding the roles of NRSF in the pathophysiological processes of the nervous system, such as neurogenesis, brain disorders, neural tumorigenesis, and neuropathic pain; and suggested new therapeutic approaches to such brain diseases.

Is There Any Relationship between Plasma IL-6 and TNF-α Levels and Lumbar Disc Degeneration? A Retrospective Single-Center Study.

Intervertebral disc degeneration (IDD) is one of the most common degenerative diseases all over the world. A growing number of studies have proved that large amounts of cytokines are produced during the development of IDD, and the inflammatory responses induced by these cytokines aggravate the occurrence and development of the disc degeneration. In this retrospective single-center study, a total of 182 lumbar spine cases were retrospectively reviewed between July 2020 and October 2021. An appropriate cutoff value was found for discriminating severity of IDD by William rank-sum test and locally weighted scatterplot smoothing algorithm. The cumulative grade was also calculated by summing Pfirrmann grades for all lumbar spine intervertebral discs. It was found that high-score group (total score > 18) plasma interleukin-6 (IL-6) concentration was significantly higher than that of the low-score group (total score ≤ 18) (9.6 ± 1.75 vs. 5.40 ± 0.61 pg/ml, p = 0.002), tumor necrosis factor-α (TNF-α) following the same trend (5.27 ± 1.48 vs. 2.97 ± 0.23, p = 0.006), which was most pronounced in the upper lumbar intervertebral discs (L1-3). In the entire sample, preoperative IL-6 concentration was significantly higher than that of the postoperation (p < 0.001), while the TNF-α was the opposite (p = 0.039). It was also found that there were significant differences in the two groups with respect to age and hypertension (p < 0.001 and p = 0.037). In conclusion, this study preliminarily indicated the relationship between IL-6 and TNF-α and the severity of lumbar disc degeneration.

Krüppel like factor 10 prevents intervertebral disc degeneration via TGF-ß signaling pathway both in vitro and in vivo.

BACKGROUND: Krüppel like factor 10 (KLF10), which is also known as TGF-ß Inducible Early Gene-1 (TIEG1), plays a crucial role in regulating cell proliferation, cell apoptosis and inflammatory reaction in human carcinoma cells. Moreover, KLF10 knockout in mice leads to severe defects associated with muscle, skeleton and heart etc. However, the function of KLF10 in intervertebral disc degeneration (IVDD) has not been reported yet. METHODS: The relationship between KLF10 and IVDD were investigated in nucleus pulposus (NP) tissues from human and rats. The role of KLF10 in NP cells was explored via loss or gain of function experiments. IVDD rat models were constructed through needle puncture and the effects of KLF10 in IVDD model of rats were investigated via intradiscal injection of KLF10. RESULTS: We first found that KLF10 was lowly expressed in degenerative NP tissues and the level of KLF10 showed negative correlation with the disc grades of IVDD patients. Loss or gain of function experiments demonstrated that KLF10 could inhibit apoptosis and enhance migration and proliferation of IL-1ß induced NP cells. And KLF10 overexpression reduced extracellular matrix (ECM) degeneration and enhanced ECM synthesis, whereas knockdown of KLF10 resulted in adverse effects. These positive effects of KLF10 could be reversed by the inhibition of TGF-ß signaling pathway. In vivo, KLF10 overexpression alleviated IVDD. CONCLUSIONS: This is the first study to reveal that KLF10 was dysregulated in IVDD and overexpressed KLF10 could alleviate IVDD by regulating TGF-ß signaling pathway both in vitro and in vivo, which were involved in prohibiting apoptosis, promoting proliferation and migration of NP cells.The translational potential of this article: Overexpression of KLF10 might be an effective therapeutic strategy in the treatment of IVDD.

Clinical Application of a New Assessment Tool for Myelopathy Hand Using Virtual Reality.

STUDY DESIGN: A cross-sectional study. OBJECTIVE: To assess the effectiveness of a new assessment tool, myelopathy-hand functional evaluation system (MFES), in evaluating the hand dysfunction of patients with cervical myelopathy in the 10-second grip-and-release test (10 second G-R test). SUMMARY OF BACKGROUND DATA: Clumsy fingers movement is a common symptom of myelopathy patients. Evaluating the impaired hand function can provide a strong basis in assessing the severity of myelopathy. Currently, no objective and effective evaluation method is widely accepted in clinical practice. METHODS: MFES mainly consists of a pair of wise-gloves and a computer with software. One hundred and ninety-eight consecutive participants were asked to wear the wise-gloves and then perform 10 seconds G-R test. The movements of each finger were recorded by MFES and converted into waveforms. Relevant waveform parameters were measured and analyzed. The Japanese Orthopedics Association (JOA) scores of each patient were marked and the maximum spinal cord compression (MSCC) was measured on midsagittal T2-weighted magnetic resonance imaging (MRI). RESULTS: Myelopathy patients had a lower number of G-R cycles and a longer time per cycle than healthy subjects. There were significant differences in adduction and abduction time in patients with JOA scores greater than 6, but not in healthy subjects and patients with JOA scores less than 6. The waveforms of ulnar three fingers in myelopathy patients were lower and wider than those in healthy individuals. The average ratio value of wave height to wave width (a/b) could quantitatively reflect such differences of waveforms. According to receiver operating characteristic (ROC) curve analysis, the optimal threshold value of the normal average ratio was more than 1.92. The average a/b value was correlated with the JOA scores of the motor function in the upper extremities (r = 0.842). CONCLUSION: MFES appears to be an objective and quantitative assessment tool for patients with cervical myelopathy. LEVEL OF EVIDENCE: 3.