Advanced glycation end products induce nucleus pulposus cell apoptosis by upregulating TXNIP via inhibiting glycolysis pathway in intervertebral disc degeneration.

Accumulation of advanced glycation end products (AGEs) causes apoptosis in human nucleus pulposus cells (NPCs), contributing to intervertebral disc degeneration (IVDD). The purpose of this study was to determine the roles of thioredoxin-interacting protein (TXNIP) in the mechanisms underlying AGE-induced apoptosis of NPCs. TXNIP was silenced or overexpressed in HNPCs exposed to AGEs. Glycolysis was assessed using extracellular acidification rate (ECAR), ATP level, GLUT1, and GLUT4 measurements. AGEs, TXNIP, GLUT1, and GLUT4 levels in IVDD patients were measured as well. In NPCs, AGEs reduced cell viability, induced apoptosis, inhibited glycolysis, and increased TXNIP expression. Silencing TXNIP compromised the effects of AGEs on cell viability, apoptosis, and glycolysis in NPCs. Furthermore, TXNIP overexpression resulted in decreased cell viability, increased apoptotic cells, and glycolysis suppression. Furthermore, co-treatment with a glycolysis inhibitor improved TXNIP silencing's suppressive effects on AGE-induced cell injury in NPCs. In IVDD patients with Pfirrmann Grades II-V, increasing trends in AGEs and TXNIP were observed, while decreasing trends in GLUT1 and GLUT4. AGE levels had positive correlations with TXNIP levels. Both AGE and TXNIP levels correlated negatively with GLUT1 and GLUT4. Our study indicates that TXNIP plays a role in mediating AGE-induced cell injury through suppressing glycolysis. The accumulation of AGEs, the upregulation of TXNIP, and the downregulation of GLUT1 and GLUT4 are all linked to the progression of IVDD.

Atlantoaxial intra-articular cage fusion by posterior intermuscular approach for treating reducible atlantoaxial dislocation: a technique note with case series.

PURPOSE: To evaluate the clinical feasibility of atlantoaxial intra-articular cage (AIC) fusion via intermuscular approach for treating reducible atlantoaxial dislocation (AAD). METHODS: An analysis was conducted on the data of 10 patients who underwent C1-C2 segmental fixation and AIC fusion for AAD by unilateral intermuscular approach and contralateral open approach. Outcome assessments included Japanese Orthopaedic Association score (JOA) and Visual Analog Scale Score for Neck Pain (VASSNP). The duration of surgical exposure, screw insertion and cage insertion, and postoperative drainage volume were also compared between two approaches. Bone fusion was evaluated through computed tomography (CT) reconstruction. Postoperative paravertebral tissue edema was evaluated by paravertebral tissue cross-sectional area (CSA) and signal intensity on T2 weighted sequence of magnetic resonance imaging (MRI) at 3 days postoperatively. RESULTS: The intermuscular approach exhibited a longer exposure time but lower drainage postoperatively compared to the open approach (P < 0.05). After operation, JOA scores significant improved (P < 0.05), while VASSNP scores significantly decreased (P < 0.05). There was no significant difference in preoperative CSA between two approaches (P > 0.05). However, compared to the open approach, the intermuscular approach exhibited less CSA (P < 0.05) and lower T2 signal intensity on MRI postoperatively, indicating less invasive to the paravertebral tissues. CONCLUSIONS: AIC fusion by intermuscular approach is an effective and safe technique in the treatment of reducible AAD. Intermuscular approach could reduce the postoperative drainage volume and the extent of paravertebral tissue edema compared to open approach.

Rolipram plays an anti-fibrotic effect in ligamentum flavum fibroblasts by inhibiting the activation of ERK1/2.

BACKGROUND: Fibrosis is an important factor and process of ligamentum flavum hypertrophy. The expression of phosphodiesterase family (PDE) is related to inflammation and fibrosis. This article studied the expression of PDE in hypertrophic ligamentum flavum fibroblasts and investigated whether inhibition of PDE4 activity can play an anti-fibrotic effect. METHODS: Samples of clinical hypertrophic ligamentum flavum were collected and patients with lumbar disc herniations as a control group. The collagenase digestion method is used to separate fibroblasts. qPCR is used to detect the expression of PDE subtypes, type I collagen (Col I), type III collagen (Col III), fibronectin (FN1) and transforming growth factor ß1 (TGF-ß1). Recombinant TGF-ß1 was used to stimulate fibroblasts to make a fibrotic cell model and treated with Rolipram. The morphology of the cells treated with drugs was observed by Sirius Red staining. Scratch the cells to observe their migration and proliferation. WB detects the expression of the above-mentioned multiple fibrotic proteins after drug treatment. Finally, combined with a variety of signaling pathway drugs, the signaling mechanism was studied. RESULTS: Multiple PDE subtypes were expressed in ligamentum flavum fibroblasts. The expression of PDE4A and 4B was significantly up-regulated in the hypertrophic group. Using Rolipram to inhibit PDE4 activity, the expression of Col I and TGF-ß1 in the hypertrophic group was inhibited. Col I recovered to the level of the control group. TGF-ß1 was significantly inhibited, which was lower than the control group. Recombinant TGF-ß1 stimulated fibroblasts to increase the expression of Col I/III, FN1 and TGF-ß1, which was blocked by Rolipram. Rolipram restored the increased expression of p-ERK1/2 stimulated by TGF-ß1. CONCLUSION: The expressions of PDE4A and 4B in the hypertrophic ligamentum flavum are increased, suggesting that it is related to the hypertrophy of the ligamentum flavum. Rolipram has a good anti-fibrosis effect after inhibiting the activity of PDE4. This is related to blocking the function of TGF-ß1, specifically by restoring normal ERK1/2 signal.

TRIM32 triggers ß-catenin signaling through ubiquitylation of AXIN1 to promote inflammatory factor-induced apoptosis of rat nucleus pulposus cells.

The dysregulation of ubiquitin ligase is the cause of many human diseases. Tripartite motif protein 32 (TRIM32) is an E3 ubiquitin ligase whose role in nucleus pulposus (NP) cell apoptosis is unclear. The expression of TRIM family protein and ß-catenin in 40 NP tissue samples was detected by RT-PCR. Interleukin (IL)-1ß or tumor necrosis factor (TNF)-α was used to treat rat NP cells. Knockdown and overexpression of Trim32 were achieved using specific siRNA and recombinant plasmids. Western blotting, RT-PCR, and flow cytometry were used to assess the expression of TRIM32/ß-catenin and the apoptosis rate of NP cells. Coimmunoprecipitation was adopted to analyze the possible interactions between AXIN1 and TRIM32. In clinical samples, TRIM32 expression was of positive relevance with the expression of CTNNB1 (ß-catenin). In vitro, apoptosis of IL-1ß- or TNF-α-treated rat NP cells was induced through upregulated Trim32 expression and activated ß-catenin signaling, whereas Trim32 siRNA and inhibition of ß-catenin reversed the induction effect of cytokines. Further studies indicated that TRIM32 activated the ß-catenin signaling pathway through ubiquitination of AXIN1, thereby regulating apoptosis. Collectively, this study reveals that TRIM32 promotes inflammatory factor-induced apoptosis of rat NP cells, in part by direct degradation of AXIN1 to trigger ß-catenin signaling.

A new decompression technique for upper lumbar fracture with neurologic deficit-comparison with traditional open posterior surgery.

BACKGROUND: Surgery is usually recommended for thoracolumbar fracture with neurologic deficit. However, traditional open posterior approach requires massive paraspinal muscles stripping, and the canal decompression may be limited and incomplete. We aimed to investigate a new approach via the Wiltse approach and the Kambin's Triangle. METHODS: Twenty-one consecutive patients with traumatic upper lumbar fracture who received this new approach surgery between January 2015 and January 2016 constituted the new approach group. Twenty-nine patients received the traditional open posterior surgery between January 2014 and January 2015 were classified as the traditional posterior surgery group. Surgical informations including operative time, blood loss, drainage volume, hospitalization days were collected and compared among the two groups. The American Spinal Injury Association (ASIA) impairment scale and Visual Analog Score (VAS) were evaluated preoperatively, postoperatively and at 12 months follow-up. RESULTS: Patients in the new approach group had fewer operation time (128.3 ± 25.1 vs 151 ± 32.2 min, P = 0.01), less blood loss (243.8 ± 135.5 vs 437.8 ± 224.9 ml, P = 0.001) and drainage volume (70.7 ± 57.2 vs 271.7 ± 95.5 ml, P < 0.001), as well as shorter hospitalization stay than the traditional posterior surgery group (6.6 ± 1.8 vs 8.5 ± 2.4 d, P = 0.004). Similar neurologic recovery according to ASIA grade was achieved in both groups (Recovery index: 0.90 ± 0.53 vs 0.86 ± 0.51, P = 0.778). While the pain level was significantly lower in the new approach group postoperatively (2.6 ± 0.7 vs 3.5 ± 0.9, P < 0.001) and at 12 months follow-up (1.4 ± 0.9 vs 2.4 ± 0.8, P < 0.001). CONCLUSION: The present new approach was successfully applied in the treatment of upper lumbar fracture with neurologic deficit. It can reduce iatrogenic trauma and achieve similar or better outcomes compared to the traditional posterior surgery.

Tumor Necrosis Factor Alpha Promotes Osteoclast Formation Via PI3K/Akt Pathway-Mediated Blimp1 Expression Upregulation.

Tumor necrosis factor alpha (TNF-α)-induced osteoclastogenesis have profound effects in states of inflammatory osteolysis such as rheumatoid arthritis, periprosthetic implant loosening, and periodontitis. However, the exact mechanisms by which TNF-α promotes RANKL-induced osteoclast formation remains poorly understood. B lymphocyte-induced maturation protein-1 (Blimp1) is a transcriptional repressor that plays crucial roles in the differentiation and/or function of various kinds of cells including osteoclasts. A novel mechanism was identified where TNF-α-mediated Blimp1 expression, which contributed to RANKL-induced osteoclastogenesis. It is shown that TNF-α could promote the level of Blimp1 expression during osteoclast differentiation. Silencing of Blimp1 in osteoclast precursor cells obviously attenuated the stimulatory effect of TNF-α on osteoclastogenesis. Mechanistically, TNF-α-induced Blimp1 expression was markedly rescued by blocking the PI3K/Akt signaling pathway, which suggested that PI3K/Akt signaling was involved in the regulation of TNF-α-stimulated Blimp1 expression. Taken together, the results established a molecular mechanism of TNF-α-induced osteoclasts differentiation, and provided insights into the potential contribution of Blimp1 in the regulation of osteoclastogenesis by TNF-α. J. Cell. Biochem. 118: 1308-1315, 2017. © 2016 Wiley Periodicals, Inc.

Multilevel anterior cervical discectomy and fusion with plate fixation for juvenile unilateral muscular atrophy of the distal upper extremity accompanied by cervical kyphosis.

STUDY DESIGN: A retrospective clinical study was conducted and related literatures were reviewed. OBJECT: This study aimed to evaluate outcome of multilevel anterior cervical discectomy and fusion with plate fixation for juvenile unilateral muscular atrophy of the distal upper extremity accompanied by cervical kyphosis. SUMMARY OF BACKGROUND DATA: Juvenile unilateral muscular atrophy of the distal upper extremity is a rare disease. Traditional treatment uses a neck collar to immobilize neck motion. However, if the disease is accompanied by cervical kyphosis, conservative treatment is difficult to correct cervical kyphosis and the prognosis is worsened. Therefore, it is important to initially apply surgical treatment for juvenile unilateral muscular atrophy accompanied with cervical kyphosis. METHODS: From March 2008 to May 2010, 4 patients were transferred to our spine medical center because of a history of slowly progressive distal weakness and atrophy of their hands and forearms. Four patients were diagnosed with Hirayama disease accompanied with cervical kyphosis based on their clinical representations and radiologic findings. After conservative treatment failed, these patients underwent multilevel anterior cervical discectomy and fusion with plate fixation. The clinical outcomes were retrospectively evaluated with follow-up ranging from 1.5 to 3 years. RESULTS: The clinical and radiologic follow-up indicated satisfactory clinical relief from symptoms, cervical sagittal alignment and cervical spinal canal volume, for all the patients. Within 6 months after surgery, the JOA score improved from a preoperative average of 14 to a postoperative average of 16.3; JOA recovery rates of all patients were more than good level. The muscle strengths of intrinsic muscles, wrist flexors and extensors, and biceps and triceps muscle improved on average by 1 grade. No complications occurred. CONCLUSIONS: Hirayama disease is a rare disease, a proper diagnosis of which can be made based on significant clinical symptoms and neurological imaging (dynamic MRI). The primary results from this study showed the tendency that multilevel anterior cervical discectomy and fusion with plate fixation is a preferred treatment for patients showing anterior effacement and apparent cervical kyphosis.

The Impact of Cervical Degeneration and Sagittal Balance on Retro-Odontoid Soft-Tissue Thickness.

OBJECTIVE: To investigate whether retro-odontoid soft-tissue thickness (ROSTT) is associated with cervical degeneration, cervical spine mobility, and sagittal balance of cervical spine. METHODS: The data of 151 patients who presented at our hospital with cervical spondylosis were reviewed. The ROSTT was measured using T1-weighted sagittal cervical magnetic resonance imaging findings. The assessment of the degree of cervical intervertebral disc degeneration (IVDD) was conducted using sagittal T2-weighted imaging. The T1 slope (T1S), C0-C2 angle, C1-C2 angle, C2-C7 angle, C1-C7 sagittal vertical axis and C2-C7 sagittal vertical axis were measured. The range of motion was assessed by measuring the flexion-extension radiographs. According to the ROSTT, those measuring less than 3 mm were classified as normal group and those measuring larger than 3 mm were classified as thickened group. RESULTS: The thickened group had larger cervical IVDD grade, age, C2-C7 angle, and T1S compared to the normal group (all P < 0.05). Additionally, the C0-C2 angle was significantly smaller in the thickened group than in the normal group (P < 0.05). ROSTT showed a negative correlation with C0-C2 angle (r = -0.181, P < 0.05), but positive correlations with both C2-C7 angle (r = 0.255, P < 0.05) and T1S (r = 0.240, P < 0.05). Furthermore, ROSTT was positively correlated with age (r = 0277, P < 0.05) and cervical IVDD grade (Spearman, r = 0.299, P < 0.05). CONCLUSIONS: Cervical sagittal balance and cervical degeneration have a significant impact on ROSTT. Patients with a higher T1S and severe cervical degeneration are more likely to result in greater ROSTT.

Influence of the type of atlantoaxial dislocation secondary to os odontoideum on sagittal alignment and balance of the subaxial cervical spine after posterior atlantoaxial fusion.

OBJECTIVE: This retrospective study aims to investigate the effect of the type of atlantoaxial dislocation due to os odontoideum on the sagittal alignment and balance of the cervical spine after posterior atlantoaxial fusion. METHODS: Data of 48 consecutive patients who underwent posterior C1-C2 fusion to treat atlantoaxial dislocation/instability due to os odontoideum were retrospectively reviewed. Radiographic variables, namely the T1 slope (T1S), C1-C2 angle, C2-C7 angle, C1-C2 sagittal vertical axis (SVA), C2-C7 SVA, and modified atlas-dens interval (MADI), were measured preoperatively, immediate postoperatively, and at final follow-up. Patients were divided into three groups based on the preoperative MADI. Differences within and between groups in radiographic variables and relationships between the investigated variables were analyzed. RESULTS: The MADI was correlated with the preoperative to postoperative changes in the C1-C2 angle (r = 0.776, P < 0.05) and C2-C7 angle (r = - 0.357, P < 0.05). In the group with anterior atlantoaxial dislocation, the C1-C2 angle and C2-C7 SVA were significantly enlarged at final follow-up (P < 0.05), while the C2-C7 angle was significantly reduced (P < 0.05). The changes in C1-C2 angle and C2-C7 angle were opposite between the posterior group and the anterior dislocation group. CONCLUSION: The direction/type of atlantoaxial subluxation correlates with the changes in lower cervical curvature after atlantoaxial fusion. Patients with atlantoaxial posterior dislocation and atlantoaxial instability are less likely than those with atlantoaxial anterior dislocation to develop loss of lordosis after posterior atlantoaxial fusion.

C1 Transposterior Arch Lateral Mass Screws Combined With C2 Pedicle Screw and Rod Fixation for Pediatric Atlantoaxial Subluxation: A Minimal 10-Year Follow-up Outcome Analysis.

BACKGROUND AND OBJECTIVES: Although the short-term outcomes of the 1-step reduction and fixation technique using C1 transposterior arch lateral mass screws combined with C2 pedicle screw and rod fixation system for the treatment of pediatric atlantoaxial subluxation (AAS) have been satisfactory, its long-term outcomes and impact on spinal development are not well studied. This study was intended to assess the long-term reliability of this technique for pediatric AAS. METHODS: A retrospective case series study was conducted to analyze the minimum 10-year follow-up outcomes from 7 pediatric patients with AAS who underwent atlantoaxial fusion using the aforementioned technique. Quality of life and cervical range of motion were both measured thoroughly. In addition, vertical growth within the fusion construct (C1-2), overall cervical alignment, and subaxial cervical spine degeneration were evaluated radiographically. RESULTS: The mean age of the 7 patients was 8.14 ± 2.41 (6-12) years at the time of surgery. The mean follow-up period was 11.00 ± 1.15 (10-13) years. No patients presented identifiable intervertebral disk degeneration or segmental instability in the subaxial cervical spine except for 1 patient who showed mild intervertebral disk degeneration. Vertical growth did continue within the atlantoaxial complex after surgery (11.90% ± 2.37%); however, there was a decrease in the percentage of vertical growth compared with the corresponding normal populations of the same age and sex. Moreover, there was a significant decrease in the range of cervical extension and rotation motion, and the overall cervical alignment straightened at the latest follow-up. CONCLUSION: The 1-step reduction and fixation technique is a relatively reliable surgical technique for pediatric AAS, which does not adversely affect the postoperative quality of life or the subaxial cervical degeneration. Nevertheless, certain limitations, such as decreased cervical range of motion and changes in cervical alignment, should be concerned.

Posterior Reduction and Temporary Fixation Through Intermuscular Approach for Odontoid Fracture.

BACKGROUND AND OBJECTIVE: Posterior reduction and temporary fixation (PRTF) through open approach can effectively avoid the loss of C1-C2 motion caused by posterior atlantoaxial fusion in the treatment of odontoid fracture. PRTF through intermuscular approach can preserve the integrity of the paravertebral muscle. However, its contribution to the preservation of C1-C2 rotation remains unassessed in the context of fresh odontoid fractures. METHODS: The data of 31 patients with odontoid fractures who underwent PRTF through intermuscular approach were retrospectively reviewed. Operation time, intraoperative blood loss, the time of ambulation and surgery-related complications were recorded. After fracture healing, the instrumentation was removed. The Japanese Orthopedic Association score, Visual Analog Scale score for neck pain, and patient satisfaction were recorded. The range of motion in rotation of C1-C2 was calculated 1 month after removing the instrumentation. RESULTS: Fracture healing was observed in all patients, and the instrumentation was removed. After removing the instrumentation, the range of motion of C1-C2 in rotation was returned to 35.6° ± 4.8°. Patient satisfaction was improved (P < .05). There was no significant difference in Japanese Orthopedic Association scores and Visual Analog Scale score for neck pain between 2 values before and after removing the instrumentation (P > .05). No osteoarthritis was observed at the C1-C2 lateral mass joints. There were no perioperative complications. CONCLUSION: PRTF through intermuscular approach can be used as a salvage treatment of an odontoid fracture with an intact transverse ligament in cases of failure of, or contraindication to, anterior screw fixation. This minimally invasive technique can effectively preserve the rotational function of the atlantoaxial complex.

Posterior Release, Reduction, and Intra-Articular Fusion for Irreducible Type III Atlantoaxial Rotary Fixation.

BACKGROUND AND OBJECTIVES: For irreducible atlantoaxial rotary fixation (AARF), anterior or posterior release was often needed before posterior reduction and fusion. Anterior atlantoaxial joint release has potential complications such as retropharyngeal abscess, persistent hoarseness, and infection. This study aims to assess the efficacy of posterior release, reduction, and intra-articular fusion without resecting the C2 nerve root on irreducible type III AARF. METHODS: The data of 9 pediatric patients diagnosed with AARF who underwent posterior atlantoaxial release, reduction, and intra-articular fusion without resecting the C2 nerve root were retrospectively reviewed. Japanese Orthopaedic Association scores and Visual Analog Scale for Neck Pain were used to assess outcomes. The preoperative and follow-up assessments of atlantodens interval (ADI) were documented to evaluate the reduction of atlantoaxial joint. The patient demographics, surgery time, blood loss, bone fusion time, follow-up period, and surgery-related complications were meticulously documented. RESULTS: The mean follow-up duration was 35.1 ± 11.5 months. Complete reduction was achieved in 8 patients, while one patient did not achieve complete reduction. The ADI decreased significantly from 8.7 ± 2.2 mm before surgery to 2.1 ± 1.3 mm at the final follow-up. All patients demonstrated successful bone fusion, with an average fusion period of 3.7 ± 1.3 months. The Visual Analog Scale for Neck Pain at the final follow-up exhibited a significant decrease compared with preoperative values (P < .05), while no significant difference was observed in Japanese Orthopaedic Association scores. There were no complications related to surgery. CONCLUSION: Posterior atlantoaxial release, reduction, and intra-articular fusion with a C2 nerve root preservation technique is effective in the treatment of irreducible type III AARF.

Clinical and radiological outcomes of spinal cord injury without radiologic evidence of trauma with cervical disc herniation.

PURPOSE: To verify the relationship between neurologic deficit after spinal cord injury without radiologic evidence of trauma (SCIWORET) and coexisting cervical disc herniation (CDH). METHODS: A retrospective review was made to compare the neurologic and radiological outcomes in SCIWORET patients with and without CDH. The neurologic deficit was evaluated by the American Spinal Injury Association (ASIA) scale at admission and last follow-up. The radiological evaluation was performed with magnetic resonance imaging to determine the maximum canal compromise (MCC) and maximum spinal cord compression (MSCC). RESULTS: Prevalence of CDH was 37.1 % among all 70 SCIWORET cases. There was no significant difference between the CDH and non-CDH group in the ASIA grade at admission and last follow-up and the improvement. Patients with CDH had more substantial MSCC (P < 0.05) but not MCC than those without CDH. No significant correlation was noted between the extent of MSCC or MCC and the initial and final neurologic functions. 12 of 26 patients with CDH underwent anterior cervical discectomy fusion, while the remaining 14 received anterior cervical corpectomy fusion. No significant difference was noted in the neurologic outcomes between the two techniques. CONCLUSIONS: CDH in most patients with SCIWORET likely occurred before rather than after trauma. CDH caused more severe cord compression but did not aggravate the neurologic injury. The extent of MSCC had no association with the initial neurologic deficit or final recovery.

Clinical and radiological follow-up of single-level Prestige LP cervical disc replacement.

OBJECTIVE: To evaluate the clinical outcomes and radiographic results of patients who underwent single-level cervical arthroplasty using the Prestige LP. METHOD: Thirty-one patients with single-level cervical disc disease received the Prestige LP disc replacement from June 2008 to December 2009. The neck disability index (NDI), Japanese Orthopedic Association score (JOA) and visual analogue scale (VAS) were used to assessed clinical outcomes pre-operatively and post-operatively at 24 months. The overall cervical alignment (C2-7 Cobb angle), the functional segmental unit (FSU) curvature, the range of motion (ROM) of treated and adjacent levels were measured, and the evidence of heterotopic ossification (HO) was observed from static and dynamic radiographs. RESULTS: There was a statistically significant improvement in the NDI from 20.2 ± 7.5 to 6.4 ± 3.5 (P < 0.000), JOA from 12.8 ± 2.2 to 16.6 ± 0.6 (P < 0.000), the neck VAS score from 4.1 ± 2.5 to 1.4 ± 1.1 (P < 0.000), the arm VAS score from 4.6 ± 2.5 to 0.7 ± 1.1 (P < 0.000). The post-operative overall cervical alignment (9.3° ± 7.2°), ROM of treated level (7.6°) and adjacent level (upper level 9.4° ± 3.1°, lower level 9.1° ± 3.5°) are well maintained. The FSU were 0.2° ± 5.4° and 1.9° ± 5.5° at pre-operation and final follow-up with statistical significance (P = 0.011). Heterotopic ossification was evidenced in five operated segment (16 %). CONCLUSIONS: The Prestige LP disc arthroplasty maintains favorable clinical outcomes, preserves the overall cervical alignment, FSU curvature, ROM of treated level and adjacent levels.

Hydroxycamptothecin liposomes inhibit collagen secretion and induce fibroblast apoptosis in a postlaminectomy rabbit model.

OBJECTIVE: To design and attest the role of hydroxycamptothecin liposomes (L-HCPT) as a new delivery system to prevent epidural scar adhesions after laminectomy in a rabbit model. METHODS: Lumbar laminectomies at L6 were performed on 18 mature male New Zealand rabbits. The rabbits were randomly divided into three groups: (I) a cotton pad soaked with 0.05 % hydroxycamptothecin (HCPT) solution was kept on the laminectomy area for 5 min before the layers were sutured (HCPT group); (II) 25 mg of liposomes containing 0.01 % HCPT was implanted on the laminectomy area (L-HCPT group); and (III) the laminectomy area was flushed with saline (control group). The rabbits were killed 4 weeks after the operation. Macroscopic evaluation and histological analysis of epidural scar adhesion were employed with hematoxylin-eosin and Masson staining, followed by hydroxyproline (Hyp) quantification and magnetic resonance imaging (MRI) of postoperative rabbit scar tissues. The epidural scar area and number of fibroblasts in the scar tissue were also evaluated. RESULTS: In the laminectomy sites of rabbits treated with HCPT or L-HCPT, the dura mater and nerve root were clean without evident scar adhesion. Hyp concentration was significantly lower in these two groups compared with the saline-control group. On the other hand, the MRI of postoperative rabbits showed apparent decreased fibrosis around the dura mater in these two groups compared with the control group. In addition, the epidural scar area and the number of fibroblasts were significantly lower in the two groups compared with the control group. CONCLUSION: These results demonstrate that the treatment of postlaminectomy wounds with L-HCPT may reduce and prevent the severity of adhesion.

New Subtype of Atlantoaxial Rotatory Fixation (Type IIIa).

OBJECTIVE: Some atlantoaxial rotatory fixations (AARFs) cannot be classified according to the Fielding and Hawkins classification. This study aimed to introduce a new subtype of AARF (type IIIa AARF) with a C1 anterior displacement >5 mm, but with one lateral mass being displaced anteriorly and another posteriorly. METHODS: Data from 10 cases of AARF with anterior C1 displacement of >5 mm were retrospectively reviewed. The exclusion criteria were as follows: 1) type I, II, or IV AARF according to the Fielding and Hawkins classification; 2) cases caused by trauma, tumor, or infection; 3) AARF with os odontoideum or odontoid fracture; and 4）age ≥18 years. Imaging features were analyzed. The atlanto-dental interval was measured to evaluate C1 anterior displacement. RESULTS: Three cases that did not match type III AARF were classified under type IIIa AARF. They had the following common imaging features: 1) atlanto-dental interval of >5 mm, being similar to type III AARF; 2) one lateral mass of C1 displaced anteriorly and the other posteriorly (the most important feature distinguishing the type from type III AARF in which both C1 lateral masses displaced anteriorly); and 3) C1-C2 separation angle (mean 44.2 ± 2.9°) being larger than that in type III AARF. CONCLUSIONS: AARF with anterior C1 displacement of >5 mm, but with one lateral mass displaced anteriorly and the other posteriorly, was defined as type IIIa AARF. It should not be confused with type III AARF because these 2 types differ in biomechanics and imaging parameters.

Posterior Reduction and Intra-Articular Cage Fusion With a C2 Nerve Root Preservation Technique for Treating Posterior Atlantoaxial Dislocation Secondary to Os Odontoideum.

BACKGROUND AND OBJECTIVES: Posterior C1-C2 interlaminae compression fusion with iliac bone graft may lead to donor site complications and recurrent C1 posterior dislocation for posterior atlantoaxial dislocation (AAD) secondary to os odontoideum. C1-C2 intra-articular fusion often needs C2 nerve ganglion transection to facilitate exposing and manipulating the facet joint, leading to bleeding from the venous plexus and suboccipital numbness or pain. Therefore, this study was conducted to evaluate the outcomes of posterior C1-C2 intra-articular fusion with a C2 nerve root preservation technique in the treatment of posterior AAD secondary to os odontoideum. METHODS: Data of the 11 patients who underwent C1-C2 posterior intra-articular fusion because of posterior AAD secondary to os odontoideum were retrospectively reviewed. Posterior reduction was performed using C1 transarch lateral mass screws and C2 pedicle screws. Intra-articular fusion was performed using a polyetheretherketone cage filled with autologous bone from the caudal edge of the C1 posterior arch and cranial edge of the C2 laminar. Outcomes were evaluated by using the Japanese Orthopaedics Association score, Neck Disability Index, and visual analog scale for neck pain. Bone fusion was evaluated by using computed tomography and 3-dimensional reconstruction. RESULTS: The average follow-up duration was 43.9 ± 9.5 months. All patients achieved good reduction and bone fusion, without transection of the C2 nerve roots. The mean bone fusion time was 4.3 ± 1.1 months. There was no complication related to the surgical approach and instrumentation. Function of the spinal cord manifested by the Japanese Orthopaedics Association score significantly improved ( P < .05). The Neck Disability Index score and visual analog scale for neck pain markedly decreased (all P < .05). CONCLUSION: Posterior reduction and intra-articular cage fusion with a C2 nerve root preservation technique was a promising treatment of posterior AAD secondary to os odontoideum.

Exosomes derived from Mouse Bone Marrow Mesenchymal Stem Cells Attenuate Nucleus Pulposus Cell Apoptosis via the miR-155- 5p/Trim32 Axis.

BACKGROUND: Lower back pain, shown to be strongly associated with IVDD, affects approximately 60%-80% of adults and has a considerable societal and economic impact. Evidence suggests that IVDD, caused by abnormal apoptosis of nucleus pulposus cells (NPCs), can be treated using MSC-derived exosomes. OBJECTIVE: This study aimed to evaluate the role of miR155-5p/Trim32 in intervertebral disc disease (IVDD) and elucidate the underlying molecular mechanisms. Deregulating miR-155 has been shown to promote Fas-mediated apoptosis in human IVDD. Evidence also suggests that tripartite motif (TRIM)-containing protein 32 (Trim32) is regulated by miR-155. However, the role of miR155-5p/Trim32 in IVDD remains unclear. METHODS: Cell viability was checked using CCK-8 kits, and flow cytometry was used to analyze cell cycle and apoptosis. Cell migration was measured with a Transwell assay, while a luciferase assay was adopted to study how miR-155-5p interacts with Trim32. The roles of Trim32 and miR-155-5p were studied by silencing or up-regulating them in NPCs, while qPCR and immunoblots were used to evaluate mRNA and protein changes, respectively. RESULTS: TNF-α treatment significantly inhibited cell viability but promoted Trim32 expression in primary mouse NPCs. Administration of bone marrow mesenchymal stem cells (BMSCs) attenuated primary NPC cell cycle arrest and apoptosis induced by TNFα. BMSCs-derived exosomes could be taken up by NPCs to inhibit TNF-α-induced cell cycle arrest and apoptosis through miR-155-5p. Examination of the underlying mechanism showed that miR-155-5p targeted Trim32. Moreover, Trim32 overexpression inhibited the effect of BMSCs-derived exosomes on primary mouse NPC cell apoptosis induced by TNF-α. CONCLUSION: Overall, these findings suggest that exosomes from BMSCs can suppress TNF-α-induced cell cycle arrest and apoptosis in primary mouse NPCs through the delivery of miR-155-5p by targeting Trim32. This study provides a promising therapeutic strategy for IVDD.

Biocompatible Gallium Nanodots against Drug-Resistant Bacterial Pneumonia and Liver Abscess.

Resistant bacterial infection remains a severe public health threat, and conventional antibiotic drugs work poorly in effectively treating infectious diseases. Here, we developed gallium-based nanodots (Ga NDs), consisting of specific disruption of bacterial iron ability, to treat multidrug-resistant (MDR) Gram-negative bacteria-infected diseases. The Ga NDs significantly suppress the proliferation of two typical MDR bacteria strains (P. aeruginosa and ESBL E. coli) compared with clinically used antibacterial drugs, including penicillin and levofloxacin. Ga NDs could also disrupt the biofilms of these two bacterial strains. In P. aeruginosa infected pneumonia and ESBL E. coli infected acute liver abscess models, the Ga NDs enable substantial inhibition of bacterial growth and reduce the organs' inflammation that resulted in significant improvement of survival. Further, the Ga NDs demonstrated excellent biocompatibility and biosafety characteristics. Together, we believe that our gallium containing nanotherapeutics are expected to be developed into promising alternative therapies to combat drug-resistant bacterial infection.

C2 Dome-Like Expansive Laminoplasty Versus C2 Open-Door Laminoplasty for Treating Multilevel Cervical Ossification of the Posterior Longitudinal Ligament Involving C2.

BACKGROUND: There are controversies over the treatment of cervical ossification of the posterior longitudinal ligament (OPLL) involving C2. OBJECTIVE: To compare the outcomes of C2 dome-like expansive laminoplasty (C2DL) and C2 open-door laminoplasty (C2OL) for treating cervical OPLL involving C2. METHODS: The data of 36 patients undergoing C2OL and 40 patients treated with C2DL because of cervical OPLL involving C2 were retrospectively analyzed. The functional outcomes of the Japanese Orthopedic Association score, Neck Disability Index, 36-Item Short Form Health Survey score, and visual analog scale score for neck pain were compared between the 2 groups. The C2-C7 Cobb angle, cervical range of motion (ROM), and space available for the spinal cord at C2 were measured. RESULTS: At the final follow-up, the Japanese Orthopedic Association score, Neck Disability Index, and 36-Item Short Form Health Survey score significantly improved in both groups (all P < .05), but with no significant intergroup differences (all P > .05). The visual analog scale score for neck pain reduced significantly in both groups (P < .05), but the patients in the C2OL group experienced more severe neck axial pain (P < .05). The C2-C7 Cobb angle and cervical ROM reduced greatly in both groups (P < .05), but those in the C2OL group decreased more (P < .05). The spinal cord at C2 significantly improved in both groups (P < .05), with no significant intergroup differences (P > .05). CONCLUSION: C2DL was superior to C2OL in maintaining the cervical alignment and ROM and reducing neck axial pain for treating OPLL involving C2.