SIAH1 promotes senescence and apoptosis of nucleus pulposus cells to exacerbate disc degeneration through ubiquitinating XIAP.

BACKGROUND: Using clinical samples and database analysis, this study aimed to investigate the signaling pathways that mediated degeneration of nucleus pulposus cells (NPCs) in patients with intervertebral disc degeneration (IDD). METHODS: NPCs were extracted from enucleated intervertebral discs of IDD patients, and the senescence, apoptosis, and extracellular matrix (ECM) synthesis levels of cells were confirmed by ß-galactosidase (SA-ß-gal), Western blot, and measurement of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH). The microarray expression profile of GSE56081 was downloaded to screen differentially expressed mRNAs. CO-IP and ubiquitination assays were used to determine the targeted regulation of XIAP by SIAH1. Methylation of mRNA was verified by m6A RIP and actinomycin D assays. RESULTS: NPCs extracted from the enucleated intervertebral discs of IDD patients exhibited marked senescence, apoptosis, elevated levels of inflammation, and decreased ECM synthesis. The expression of SIAH1 was significantly elevated in NPCs of IDD patients, and SIAH1 knockdown reversed senescence, apoptosis, elevated levels of inflammation, and decreased ECM synthesis in NPCs of IDD patients. CO-IP and ubiquitination assays indicated that SIAH1 can target and ubiquitinate XIAP. Besides, MeRIP-qPCR and actinomycin experiments showed that METTL3-mediated m6A can methylate SIAH1 mRNA. CONCLUSION: In IDD patients, SIAH1 can target and ubiquitinate XIAP, thereby mediating senescence, apoptosis, increased inflammation, and decreased ECM synthesis of NPCs, while METTL3-mediated m6A can methylate SIAH1 mRNA, producing harmful effects.

Efficacy and safety of tolperisone versus baclofen among Chinese patients with spasticity associated with spinal cord injury: a non-randomized retrospective study.

There are many medications available to treat spasticity, but the tolerability of medications is the main issue for choosing the best treatment. The objectives of this study were to compare the efficacy and adverse effects of tolperisone compared to baclofen among patients with spasticity associated with spinal cord injury. Patients received baclofen plus physical therapy (BAF+PT, n=135) or tolperisone plus physical therapy (TOL+PT, n=116), or physical therapy alone (PT, n=180). The modified Ashworth scale score, the modified Medical Research Council score, the Barthel Index score, and the Disability Assessment scale score were improved (P<0.05 for all) in all the patients at the end of 6 weeks compared to before interventions. After 6 weeks, the overall coefficient of efficacy of the intervention(s) in the BAF+PT, TOL+PT, and PT groups were 1.15, 0.45, and 0.05, respectively. The patients of the BAF+PT group reported asthenia, drowsiness, and sleepiness and those of the TOL+PT group reported dyspepsia and epigastric pain as adverse effects. When comparing drug interventions to physical therapy alone, both baclofen plus physical therapy and tolperisone plus physical therapy played a significant role in the improvement of daily activities of patients. Nonetheless, baclofen plus physical therapy was tentatively effective. Tolperisone plus physical therapy was slightly effective. In addition, baclofen caused adverse effects related to the sedative manifestation (Level of Evidence: III; Technical Efficacy Stage: 4).

Efficacy and safety of tolperisone versus baclofen among Chinese patients with spasticity associated with spinal cord injury: a non-randomized retrospective study

There are many medications available to treat spasticity, but the tolerability of medications is the main issue for choosing the best treatment. The objectives of this study were to compare the efficacy and adverse effects of tolperisone compared to baclofen among patients with spasticity associated with spinal cord injury. Patients received baclofen plus physical therapy (BAF+PT, n=135) or tolperisone plus physical therapy (TOL+PT, n=116), or physical therapy alone (PT, n=180). The modified Ashworth scale score, the modified Medical Research Council score, the Barthel Index score, and the Disability Assessment scale score were improved (P<0.05 for all) in all the patients at the end of 6 weeks compared to before interventions. After 6 weeks, the overall coefficient of efficacy of the intervention(s) in the BAF+PT, TOL+PT, and PT groups were 1.15, 0.45, and 0.05, respectively. The patients of the BAF+PT group reported asthenia, drowsiness, and sleepiness and those of the TOL+PT group reported dyspepsia and epigastric pain as adverse effects. When comparing drug interventions to physical therapy alone, both baclofen plus physical therapy and tolperisone plus physical therapy played a significant role in the improvement of daily activities of patients. Nonetheless, baclofen plus physical therapy was tentatively effective. Tolperisone plus physical therapy was slightly effective. In addition, baclofen caused adverse effects related to the sedative manifestation (Level of Evidence: III; Technical Efficacy Stage: 4).

Treatment of cervical disc herniation through percutaneous minimally invasive techniques.

PURPOSE: The goal of this study is to compare the therapeutic effectiveness of percutaneous cervical discectomy, percutaneous cervical disc nucleoplasty, and a combination of the two for the treatment of cervical disc herniation and the effective stabilization of the cervical vertebral column. METHODS: A retrospective study was performed from February 2003 to April 2011. One hundred and seventy-one cervical disc herniation patients with a mean age of 47.8 years (ranging from 21 to 74 years) participated in the study and were treated with the three types of percutaneous minimally invasive techniques: percutaneous cervical discectomy (PCD, 97 cases), percutaneous cervical disc nucleoplasty (PCN, 50 cases), and a combination of the two (PCDN, 24 cases). After treatment, the postoperative clinical results and the stability of the cervical vertebral columns of these three groups were evaluated and compared. RESULTS: Patients in the PCD group received follow-up care for approximately 4.1 years (ranging from 0.2 to 8.5 years), while those in the PCN group received only an average of 2.6 years (ranging from 0.3 to 7.8 years), and the PCDN group received an average of 3.3 years (ranging from 0.2 to 8 years of follow-up). According to the Japanese Orthopedic Association scoring system, the functional scores (JOA scores) differed significantly between the pre- and postoperative patients within the three groups (PCD t = 21.849, P = <0.05; PCN t = 14.503, P < 0.05; PCDN t = 8.555, P < 0.05). All patients had been successfully operated on by the same spinal surgeon team. According to the Odom criterion, the clinical outcomes were not significantly different for any of the three groups (the recovery rate using the JOA standard evaluation, F = 2.19, P = 0.116, P > 0.05). The percentages of each procedure that received either an excellent or a good rating were PCD at 81.35 %, PCN at 82.44 % and PCDN at 83.19 %. In addition, the clinical success rates among the three were not significantly different (P > 0.05). Notably, there was no postoperative instability of the cervical vertebral column in any of the patients (P > 0.05), and there was no difference in the pre- or postoperative stability of the cervical vertebral columns in each group. CONCLUSIONS: Each group achieved good clinical outcomes with this safe, minimally invasive spinal surgery for the treatment of cervical disc herniation. In addition, no postoperative risk of cervical instability was found.

Digital three-dimensional model of lumbar region 4-5 and its adjacent structures based on a virtual Chinese human.

OBJECTIVE: To study the methods for constructing a digitized three-dimensional (3D) model of a virtual lumbar region and its adjacent structures in order to assist anatomical study and virtual surgery. METHODS: Images of DSCF5375-p1 to DSCF5745-p1 were taken from the database of the digitized Virtual Chinese human of Southern Medical University in Guangzhou. This region encompasses the superior facet joint of L4 to the inferior edge of the intervertebral body of L5. The regions of interest were interactively segmented from the images utilizing Adobe Photoshop software. The images were further processed using format conversion and segmentation. Finally, a 3D model of the L4-5 region and its neighboring structures was reconstructed with the assistance of Mimics 10.01 software. RESULTS: A digitized 3D model of this part of the virtual lumbar spine and its adjacent structures was reconstructed. This model allows all constructed structures to be displayed individually or jointly, moved or rotated arbitrarily, setting of different transparencies and convenient measurement of the diameters and angles of the reconstructed structures. The 3D model precisely displays the anatomical relationships between all structures and provides a reliable 3D model for a spinal endoscopic surgery simulation system. CONCLUSION: Visualization of the digitized 3D reconstruction of the virtual lower lumbar region displays this region and its adjacent structures stereoscopically and in actuality, thus providing morphological data concerning anatomy, image diagnosis and virtual operations in this region.