Roles of extra-cellular signal-regulated protein kinase 5 signaling pathway in the development of spinal cord injury / 中华医学杂志(英文版)

BACKGROUND@#In consideration of characteristics and functions, extra-cellular signal-regulated protein kinase 5 (ERK5) signaling pathway could be a new target for spinal cord injury (SCI) treatment. Our study aimed to evaluate the roles of ERK5 signaling pathway in secondary damage of SCI.@*METHODS@#We randomly divided 70 healthy Wistar rats into five groups: ten in the blank group, 15 in the sham surgery + BIX02188 (sham + B) group, 15 in the sham surgery + dimethyl sulfoxide (DMSO; sham + D) group, 15 in the SCI + BIX02188 (SCI + B) group, and 15 in the SCI + DMSO (SCI + D) group. BIX02188 is a specific inhibitor of the ERK5 signaling pathway. SCI was induced by the application of vascular clips (with the force of 30 g) to the dura on T10 level, while rats in the sham surgery group underwent only T9-T11 laminectomy. BIX02188 or DMSO was intra-thecally injected at 1, 6, and 12 h after surgery or SCI. Spinal cord samples were taken for testing at 24 h after surgery or SCI.@*RESULTS@#Expression of phosphorylated-ERK5 (p-ERK5) significantly increased after SCI. Application of BIX02188 indeed inhibited ERK5 signaling pathway and reduced the degree of spinal cord tissue injury, neutrophil infiltration and proinflammatory cytokine expression, nuclear factor-κB (NF-κB) activation and apoptosis (measured by TdT-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling, expression of Fas-ligand, BCL2-associated X [Bax], and B-cell lymphoma-2 [Bcl-2]). Double immunofluorescence revealed activation of ERK5 in neurons and microglia after SCI.@*CONCLUSION@#ERK5 signaling pathway was activated in spinal neurons and microglia, contributing to secondary injury of SCI. Moreover, inhibition of ERK5 signaling pathway could alleviate the degree of SCI, which might be related to its regulation of infiltration of inflammatory cells and release of inflammatory cytokines, expression of NF-κB and cell apoptosis.

Roles of extra-cellular signal-regulated protein kinase 5 signaling pathway in the development of spinal cord injury / 中华医学杂志(英文版)

Background@#In consideration of characteristics and functions, extra-cellular signal-regulated protein kinase 5 (ERK5) signaling pathway could be a new target for spinal cord injury (SCI) treatment. Our study aimed to evaluate the roles of ERK5 signaling pathway in secondary damage of SCI.@*Methods@#We randomly divided 70 healthy Wistar rats into five groups: ten in the blank group, 15 in the sham surgery + BIX02188 (sham + B) group, 15 in the sham surgery + dimethyl sulfoxide (DMSO; sham + D) group, 15 in the SCI + BIX02188 (SCI + B) group, and 15 in the SCI + DMSO (SCI + D) group. BIX02188 is a specific inhibitor of the ERK5 signaling pathway. SCI was induced by the application of vascular clips (with the force of 30 g) to the dura on T10 level, while rats in the sham surgery group underwent only T9-T11 laminectomy. BIX02188 or DMSO was intra-thecally injected at 1, 6, and 12 h after surgery or SCI. Spinal cord samples were taken for testing at 24 h after surgery or SCI.@*Results@#Expression of phosphorylated-ERK5 (p-ERK5) significantly increased after SCI. Application of BIX02188 indeed inhibited ERK5 signaling pathway and reduced the degree of spinal cord tissue injury, neutrophil infiltration and proinflammatory cytokine expression, nuclear factor-κB (NF-κB) activation and apoptosis (measured by TdT-mediated 2′-deoxyuridine 5′-triphosphate nickend labeling, expression of Fas-ligand, BCL2-associated X [Bax], and B-cell lymphoma-2 [Bcl-2]). Double immunofluorescence revealed activation of ERK5 in neurons and microglia after SCI.@*Conclusion@#ERK5 signaling pathway was activated in spinal neurons and microglia, contributing to secondary injury of SCI. Moreover, inhibition of ERK5 signaling pathway could alleviate the degree of SCI, which might be related to its regulation of infiltration of inflammatory cells and release of inflammatory cytokines, expression of NF-κB and cell apoptosis.

Radiological Analysis of Thoracolumbar Junctional Degenerative Kyphosis in Patients with Lumbar Degenerative Kyphosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Thoracolumbar junction (TLJ) is the transitional area between the lower thoracic spine and the upper lumbar spine. Vertebral compression fractures and proximal junctional kyphosis following spine surgery often occur in this area. Therefore, the study of development and mechanisms of thoracolumbar junctional degeneration is important for planning surgical management. This study aimed to review radiological parameters of thoracolumbar junctional degenerative kyphosis (TLJDK) in patients with lumbar degenerative kyphosis and to analyze compensatory mechanisms of sagittal balance.</p><p><b>METHODS</b>From January 2016 to March 2017, patients with lumbar degenerative kyphosis were enrolled in this radiographic study. Patients were divided into two groups according to thoracolumbar junctional angle (TLJA): the non-TLJDK (NTLJDK) group (TLJA <10°) and the TLJDK group (TLJA ≥10°). Complete spinopelvic radiographic parameters were analyzed and compared between two groups. Pearson or Spearman correlation coefficients and independent two-sample t-test or Mann-Whitney U-test were used.</p><p><b>RESULTS</b>A total of 77 patients with symptomatic sagittal imbalance due to lumbar degenerative kyphosis were enrolled in this study. There were 34 patients in NTLJDK group (TLJA <10°) and 43 patients in TLJDK group (TLJA ≥10°). The median angle of lumbar lordosis (LL) in the NTLJDK or TLJDK groups was 23.40° (18.50°, 29.48°) or 19.50° (13.30°, 24.55°), respectively. The median TLJAs in all patients and both groups were -11.20° (-14.60°, -4.80°), -3.70° (-7.53°, -1.73°), and -14.30° (-17.45°, -13.00°), respectively. In the NTLJDK group, LL was correlated with thoracic kyphosis (TK; r = -0.400, P = 0.019), sacral slope (SS; r = 0.681, P < 0.001), and C7-sagittal vertical axis (r = -0.402, P = 0.018). In the TLJDK group, LL was correlated with TK (r = -0.345, P = 0.024), SS (r = 0.595, P < 0.001), and pelvic tilt (r = -0.363, P = 0.017). There were significant differences in LL, TLJA, TK, SS, and pelvic incidence (PI) between two groups.</p><p><b>CONCLUSIONS</b>Although TLJDK is common in patients with lumbar degenerative kyphosis, it might be generated by special characteristics of morphology and biomechanics of the TLJ. To maintain sagittal balance, pelvis back tilt might be more important in patients with TLJDK, whereas thoracic curve changes might be more important in patients without TLJDK.</p>

Effects of intrathecal injection of methylprednisolone sodium succinate in acute spinal cord injury rabbits / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effects and apoptosis of intrathecal injection of Methylprednisolone Sodium Succinate (MPss) for acute spinal cord injury (SCI) in New Zealand rabbits.</p><p><b>METHODS</b>Seventy-two healthy New Zealand rabbits were used for the procedure and were randomly divided into two groups: SCI group and SHAM group, which was both divided into 6 subgroups, such as the vehicle group, the MPss intrathecal injection groups (1.5 mg/kg, 3.0 mg/kg, 6.0 mg/kg group), the MPss intravenous injection group and the combined injection group. TARLOV score was tested daily to evaluate the motor function. The rabbits were sacrificed 7 days after the surgery and the thoracic spinal cord sections and the sacral sections where MPss was injected were harvested for HE and TUNEL staining. Two-Factors Repeated Measures analysis of variance for TARLOV scores tested at various times and One-Way ANOVA analysis of variance for data between groups were used.</p><p><b>RESULT</b>Seven days after surgery in SCI group, there was no statistical difference between the TARLOV scores of intrathecal injection of MPss 3.0 mg/kg group, 6.0 mg/kg group and MPss intravenous injection group (P > 0.05), which were all better than the vehicle group (F = 4.762, P < 0.05). Referring to the lymphocyte infiltration at the injury site in SCI group, there was statistical difference between MPss intrathecal injection 6.0 mg/kg group (1.33 ± 0.21) and the vehicle group (2.67 ± 0.21) (F = 5.793, P < 0.05) and no statistical difference between intrathecal injection of MPss 6.0 mg/kg group and MPss intravenous injection group (P > 0.05). As for the lymphocyte infiltration at the intrathecal injection site in SHAM group, there was statistical difference between MPss intrathecal injection 6.0 mg/kg group (2.50 ± 0.55) and the vehicle group (0.50 ± 0.55) (F = 17.333, P < 0.05). TUNEL staining in SCI group showed statistical difference between MPss intrathecal injection 6.0 mg/kg group (6.3 ± 1.5) and the vehicle group (20.3 ± 2.2) (F = 71.279, P < 0.05).</p><p><b>CONCLUSIONS</b>Intrathecal injection of MPss can improve the functional recovery of lower limb and decrease apoptosis of neuron cells,which can provide same effects as the traditional intravenous injection of MPss in New Zealand rabbits.</p>

Comparison of Topping-off and posterior lumbar interbody fusion surgery in lumbar degenerative disease: a retrospective study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Topping-off surgery is a newly-developed surgical technique which combines rigid fusion with an interspinous process device in the adjacent segment to prevent adjacent segment degeneration. There are few reports on Topping-off surgery and its rationality and indications remains highly controversial. Our study aims to investigate the short-term and mid-term clinical results of Topping-off surgery in preventing adjacent segment degeneration when mild or moderate adjacent segment degeneration existed before surgery.</p><p><b>METHODS</b>The 25 cases that underwent L5-S1 posterior lumbar interbody fusion (PLIF) + L4-L5 interspinous process surgeries between April 2008 and March 2010 formed Topping-off group. The 42 cases undergoing L5-S1 PLIF surgery formed PLIF group. Both groups matched in gender, age, body mass index and Pfirrmann grading (4 to 6). The patients were evaluated with visual analogue scale (VAS) and Japanese orthopaedic association (JOA) scores before surgery and in the last follow-up. Modic changes of endplates were recorded.</p><p><b>RESULTS</b>The follow-up averaged 24.8 and 23.7 months. No symptomatic or radiological adjacent segment degeneration was observed. There was no significant difference in intraoperative blood loss or postoperative drainage. VAS and lumbar JOA scores improved significantly in both groups (t = 12.1 and 13.5, P < 0.05). Neither anterior nor posterior disc height was significantly changed. Segmental lordosis of L4-L5 and total lordosis were all increased significantly (Topping-off group: t = -2.30 and -2.24,P < 0.05; PLIF group: t = -2.76 and -1.83, P < 0.01). In the hyperextension and hyperflexion view, Topping-off group's range of motion (ROM) and olisthesis in the L4-L5 segment did not significantly change in flexion, but decreased in extension. In PLIF group, ROM (t = -7.82 and -4.90, P < 0.01) and olisthesis (t = -15.67 and -18.58, P < 0.01) both significantly increased in extension and flexion.</p><p><b>CONCLUSIONS</b>Compared with single segment PLIF surgery, Topping-off surgery can achieve similar symptomatic improvement in cases with pre-existing mild or moderate adjacent segment degeneration, restrict the adjacent segment's ROM in extension and prevent excessive olisthesis of adjacent segment in both extension and flexion.</p>

The efficacy and complication analysis of interspinous dynamic device (Wallis) in patients of degenerative lumbar disease / 中华外科杂志

<p><b>OBJECTIVES</b>To review degenerative lumbar disease treated with Wallis and the re-herniation cases after the implantation of Wallis, so as to evaluate the effect of the device.</p><p><b>METHODS</b>From January 2009 to June 2010, a retrospective analysis was done and 48 patients (30 males and 18 females) with an average age of 43 years (ranging from 17 to 69 years), who received stabilization of the segment using the Wallis device, were reviewed. The involved segments included: 4 cases at L(3-4), 38 cases at L(4-5), 6 cases at L(5)-S(1). Preoperative and postoperative visual analogue scales (VAS) and Oswestry disability index (ODI) were recorded to evaluate the clinical efficiency, imageology diversity was assessed by X-rays and MRI.</p><p><b>RESULTS</b>All cases received fenestration and the implantation of Wallis. No surgery related complications were recorded. There were 48 cases were followed up. The average follow-up period was (20 ± 4) months (12 - 30 months). The average ODI score dropped from 46 ± 10 to 24 ± 7 (t = 12.765, P < 0.05). The average VAS for back and leg pain dropped from 8.1 ± 1.6 to 2.1 ± 1.1(t = 21.881, P < 0.05). Six patients with recurrent lower back and leg pain were diagnosed by MRI, as recurrent herniation (6/48, 12.5%). All re-herniation occurred at L(4-5) level, between 2 and 13 months after the surgery. Three of the 6 patients underwent additional discectomy and fusion, others received conservative treatment.</p><p><b>CONCLUSIONS</b>Although existing problems such as recurrence after surgery, the clinical outcome of Wallis in treating protrusion of lumbar intervertebral disc and lumbar stenosis is satisfied in middle-early stage.</p>

The effect of Topping-off surgery on preventing adjacent segment degeneration, a retrospective study / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the early-middle stage clinical results of Topping-off surgery in preventing adjacent segment degeneration when mild or moderate adjacent segment degeneration exists before surgery.</p><p><b>METHODS</b>All the cases that received L(5)-S(1) posterior lumbar interbody fusion (PLIF)+L(4)-L(5) interspinous process (ISP) surgeries between April 2008 and March 2010 (Topping-off group) were analyzed retrospectively. The cases received L(5)-S(1) PLIF surgery and whose intervertebral disc degeneration using modified Pfirrmann's grading system were grade 4 - 6 were analyzed retrospectively at the same time (PLIF group). Both groups matched in gender, age, body mass index and Pfirrmann's grading of disc. All the patients were evaluated with visual analogue scale (VAS) and Japanese orthopaedic association (JOA) scores before the surgery and in the last follow-up. The X-ray films before and after surgery were measured.</p><p><b>RESULTS</b>There were 25 patients in Topping-off group and 42 patients in PLIF group were included in the final analysis. The follow-up averaged 24.8 and 23.7 months. No symptomatic or radiological adjacent segment degeneration was observed. The average surgery time was (120 ± 24) min and (106 ± 21) min. There was no significant difference in the blood loss during surgery or post-operation drainage (P > 0.05). VAS and lumbar JOA score improved in both groups (P < 0.01). In the lateral view of lumbar spine, neither of anterior or posterior disk height was significantly changed (P > 0.05), segmental lordosis of L(4)-L(5), total lordosis were all increased (Topping-off group: t = -2.30 and -2.24, P < 0.05; PLIF group: t = -2.76 and -1.83, P < 0.05). In the hyperextension and hyperflexion view, Topping-off group's range of motion (ROM) and olisthesis in the L(4-5) segment did not significantly change in flexion (P > 0.05), but decreased in extension (t = 5.83 and 4.92, P < 0.01). In PLIF group, the ROM (t = -7.82 and -4.90, P < 0.01) and olisthesis (t = -15.67 and -18.58, P < 0.01) both significantly increased in extension and flection.</p><p><b>CONCLUSIONS</b>Compared with single segmental PLIF surgery, Topping-off surgery can achieve similar symptomatic improvement in cases with pre-existing mild or moderate adjacent segment degeneration, restrict the adjacent segment's range of motion in extension and prevent excessive olisthesis of adjacent segment in both extension and flexion. Topping-off surgery has a potential effect of preventing adjacent segmental degeneration.</p>

Clinical outcomes of Hybrid-surgery to treat the two-level cervical disease / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the clinical and radiologic outcomes of the Hybrid surgery (cervical artificial disc replacement combined with anterior cervical discectomy and fusion (ACDF)) and the effective of the adjacent segment.</p><p><b>METHODS</b>Between December 2007 to June 2010, 34 patients underwent 2-level cervical disc surgery. There were 17 patients underwent Hybrid surgery (Hybrid group), 17 patients underwent 2-level ACDF (ACDF group). Japanese orthopaedic association (JOA), neck disability index (NDI), and Odom's standards were evaluated. Dynamic flexion and extension lateral cervical radiographs were obtained in the standing position before surgery and at routine postoperative intervals of 1, 3, 6 months.</p><p><b>RESULTS</b>Both of the two groups had significantly improvement than preoperative in JOA (t = -8.790 - -5.803, P < 0.05) and NDI scores (t = 10.717 - 13.514, P < 0.05), but no significantly difference between the two groups (P > 0.05). Both of the two groups had significantly decreased in the mean C(2-7) range of motion (ROM). The Hybrid group decreased from 46° ± 11° preoperative to 41° ± 8° at the 6 mouths after surgery (t = 3.170, P < 0.05). The ACDF group decreased from 45° ± 13° preoperative to 38° ± 15° at the 6 mouths after surgery (t = 6.709, P < 0.05). But there were no significantly difference between the two groups (P > 0.05). In the Hybrid group, both the superior adjacent segment ROM and the inferior adjacent segment ROM were decreased in the follow-up, there had significantly difference at the 1 and 3 months after surgery (superior adjacent segment: t = 5.622 and 4.032, P < 0.05; inferior adjacent segment: t = 2.879 and 2.207, P < 0.05), but no significantly difference after 6 months (P > 0.05). In the ACDF group, the ROM of the inferior adjacent segment was significantly increased at 3 and 6 months after surgery (t = -7.038 and -13.540, P < 0.05), the ROM of the superior adjacent segment was significantly increased at 6 months after surgery (t = -2.453, P < 0.05).</p><p><b>CONCLUSIONS</b>Hybrid surgery has excellent clinical results and decreases the ROM of the adjacent segment in the following 6 months, meanwhile 2-level ACDF increases the ROM of the adjacent segment. The long-term clinical outcomes of the Hybrid surgery need more study.</p>

Surgical treatment of multilevel lumbar degenerative spondylolisthesis / 中华外科杂志

<p><b>OBJECTIVE</b>To discuss the surgical treatment of multilevel lumbar degenerative spondylolisthesis.</p><p><b>METHODS</b>From March 2005 to September 2008, 25 cases of multilevel lumbar degenerative spondylolisthesis were treated with total laminectomy, reduction of spondylolisthesis and 360 degrees circumferential fusion through interbody (PLIF), transverse process (PLF) and pedicle screw fixation. All cases were followed up for 0.5 - 4 years. The Lenke grading system was used to assess the spinal fusion and Henderson grading system was used to assess the clinical outcomes.</p><p><b>RESULTS</b>Complete reduction of spondylolisthesis was achieved in all cases. The bone fusion was grade A in 23 cases, grade B in 2 cases. The clinical outcome was excellent in 16 cases, good in 6 cases and poor in 3 cases.</p><p><b>CONCLUSIONS</b>The pathogenesis of lumbar degenerative multilevel spondylolisthesis is different from that of single-level spondylolisthesis. Complete decompression, reduction of spondylolisthesis sufficient fusion and reliable pedicle screw fixation can provide successful interbody fusion and satisfactory clinical results.It's crucial to reduce multilevel spondylolisthesis by proper techniques based on different types of listhesis.</p>