Qile Gao

Monocyte chemoattractant protein-1 in spinal tuberculosis: -362G/C genetic variant and protein levels in Chinese patients.

The objective of the study is to explore the possible association of the monocyte chemoattractant protein (MCP)-1-362G/C genetic polymorphism and plasma levels of MCP-1 in patients with spinal tuberculosis (TB). The MCP-1-362G/C (rs2857656) polymorphism and blood levels of MCP-1 in patients with spinal TB and healthy subjects were evaluated and compared. Three hundred thirty-two patients and 336 healthy subjects were genotyped using polymerase chain reaction and Sanger DNA sequencing technology. MCP-1 plasma levels were measured by a solid-phase enzyme-linked immunosorbent assay. When comparisons were made between patients and controls, the frequency of the MCP-1-362*C minor allele (55.4% versus 47.5%, P = 0.004, odds ratio [OR] = 1.376, 95% confidence interval [CI]: 1.109-1.706) and the carriers of the MCP-1-362*C allele (80.7% versus 71.4%, P = 0.005, OR = 1. 657, 95% CI: 1.167-2.403) were over-represented in patients. The mean MCP-1 plasma level in spinal TB patients was significantly higher than in controls (154.44 ± 68.81 pg/mL versus 36.69 ± 21.71 pg/mL, t = -5.85, P < 0.001). The patients with the CC genotype had the highest MCP-1 level (150.63 ± 73.89 pg/mL), followed by those with the GC genotype (108.63 ± 52.09 pg/mL, t = 2.351, P = 0.022) and GG (91.29 ± 54.31 pg/mL, t = 3.091, P = 0.003) homozygotes. We report the association of the -362G/C genetic polymorphism and increased plasma levels of MCP-1 in patients with spinal TB and nominate the -362*C minor allele as a risk factor for spinal TB in the Chinese population.

The Clinical Outcomes of Surgical Treatment of Noncontiguous Spinal Tuberculosis: A Retrospective Study in 23 Cases

Study design A retrospective clinical study. Objective To evaluate the clinical efficacy of the surgical treatment of noncontiguous spinal tuberculosis (NSTB), and to discuss its therapeutic strategies. Methods We performed a retrospective review of clinical and radiographic data that were prospectively collected on 550 consecutive spinal tubercular patients including 27 patients who were diagnosed and treated as NSTB in our institution from June 2005 to June 2011. Apart from 4 patients being treated conservatively, the remainder received surgery by posterior transforaminal debridement, interbody fusion with instrumentation, posterior instrumentation and anterior debridement with fusion in a single or two-stage operation. The clinical outcomes were evaluated before and after treatment in terms of hematologic and radiographic examinations, bone fusion and neurologic status. The Oswestry Disability Index score was determined before treatment and at the last follow-up visit. Results 23 patients (15 M/8F), averaged 44.6±14.2 years old (range, 19 to 70 yd), who received surgical treatment, were followed up after surgery for a mean of 52.5±19.5 months (range, 24 to 72 months). The kyphotic angle was changed significantly between pre- and postoperation (P<0.05). The mean amount of correction was 12.6±7.2 degrees, with a small loss of correction at last follow-up. All patients achieved solid bone fusion. No patients with neurological deficit deteriorated postoperatively. Neither mortalities nor any major complications were found. There was a significant difference of Oswestry Disability Index scores between preoperation and the final follow-up. Conclusion The outcomes of follow-up showed that posterior and posterior-anterior surgical treatment methods were both viable surgical options for NSTB. Posterior transforaminal debridement, interbody fusion and posterior instrumentation, as a less invasive technique, was feasible and effective to treat specific tubercular foci.

Comparison of Three Surgical Approaches for Thoracic Spinal Tuberculosis in Adult: Minimum 5-year Follow Up

Study Design. Retrospective study. Objective. To assess the minimum 5-year follow up outcomes of the surgical management of adults with thoracic tuberculosis by comparing posterior only (PO), anterior only (AO), and combined posterior and anterior (AP) surgical approaches. Summary of Background Data. Surgeons use multiple methods to treat spinal tuberculosis, including an anterior, posterior, and combined anterior and posterior approach. However, there are a few reports comparing the mid- and long-term outcomes of these surgical methods. Methods. The medical records for 184 patients treated for thoracic tuberculosis between January 2003 and November 2010 were retrospectively reviewed. Among them, 62 patients were treated with a single-stage posterior debridement and interbody fusion with instrumentation (Group A), 65 patients with posterior instrumentation, anterior debridement, and bone graft in a single or two-stage procedure (Group B), and 57 patients with anterior debridement and strut grafting with instrumentation (Group C). Operative time, blood loss, Visual Analog Scale for pain, complications, recovery of neurological function, Cobb angle, correction rate, and loss angle were compared among all groups. Results. Groups A, B, and C were followed for 72.7 ± 3.8 months, 74.3 ± 4.2 months, and 73.6 ± 4.5 months, respectively. The operative time, blood loss, and rate of complications for Group A were significantly less than Groups B and C (P < 0.05). The correction rate and loss angle were superior in Groups A and B compared with C, whereas the Visual Analog Scale for pain and fusion time showed no statistically significant difference among the groups (P > 0.05). Conclusion. For patients with thoracic tuberculosis, use of the AO approach should be limited. Although the AP approach produced satisfactory outcomes, it remains more traumatic. Therefore, the PO approach is recommended, not only because it achieves good results, but because it has reduced complications, operative time, and blood loss. Level of Evidence: 3

Debridement, interbody graft using titanium mesh cages, posterior instrumentation and fusion in the surgical treatment of multilevel noncontiguous spinal tuberculosis in elderly patients via a posterior-only

PURPOSE To analyse the efficacy and feasibility of surgical management for elderly patients with multilevel non-contiguous spinal tuberculosis(MNSTB)by using one-stage posterior focus debridement, interbody graft using titanium mesh cages, posterior instrumentation and fusion. METHODS From September 2009 to October 2013, 15 elderly patients with MNSTB were treated with one-stage posterior focus debridement, interbody graft using titanium mesh cages, posterior instrumentation and fusion. There were 10 males and 5 females with a mean age of 63.2 years (range: 60-68 years) at the time of surgery. The mean follow-up time was 40 months(range 26-68 months). Patients were evaluated before and after surgery in terms of erythrocyte sedimentation rate(ESR), neurological status, pain and kyphotic angle. RESULTS The spinal tuberculosis was completely cured, and the grafted bones were fused in all 15 patients. There were no recurrent tuberculous infections. The ESR reached a normal level within 3 months in all patients. The ASIA neurological classification improved in all cases, and pain relief was reported by all patients. The average preoperative kyphosis was 20.1° (range 8-38°) and decreased to 7.6° (range 1-18°) postoperatively. There was no significant loss of the correction at the latest follow-up. CONCLUSIONS Our results showed that one-stage posterior focus debridement, interbody graft using titanium mesh cages, posterior instrumentation and fusion was an effective treatment for elderly patients with MNSTB. It is characterized by minimum surgical trauma, good neurological recovery, and good correction of kyphosis.

Estradiol via estrogen receptor beta inhibits chondrogenesis of mouse vertebral growth plate in vitro.

PurposeAbnormal growth of vertebral growth plate (VGP) was considered as one of the etiologic factors in adolescent idiopathic scoliosis (AIS). Previous studies described that estrogen played an important role in the pathogenesis of AIS. The present study was aimed to investigate the effect of estrogen/estrogen receptor axis on mouse VGP chondrocytes in vitro.MethodsChondrocytes were isolated from mouse VGP and treated with or without 17β-estradiol (E2). Cell proliferation was measured by the cell growth rate assay. Gene expression of collagen type II and aggrecan were evaluated by real-time PCR. Expression of the proliferating cell nuclear antigen (PCNA), Sox9, and Smad4 were detected by Western blotting.ResultsEstradiol inhibited the proliferation of VGP chondrocytes and the gene expression of collagen type II and aggrecan and downregulated the protein expression of PCNA, Sox9, and Smad4. In addition, the inhibitory effect of estradiol was reversed by ERβ small interfering RNA (siRNA) or PHTPP, an ERβ antagonist.ConclusionsEstradiol via estrogen/estrogen receptor β axis inhibits the proliferation and differentiation of VGP chondrocytes, which might give some new insight into the regulatory mechanism of bone development.

Posterior-only surgical correction of dystrophic scoliosis in 31 patients with neurofibromatosis Type 1 using the multiple anchor point method

OBJECTIVE The objective of this study was to evaluate the clinical efficacy of posterior-only surgical correction of dystrophic scoliosis in patients with neurofibromatosis Type 1 (NF1) using a multiple anchor point method (MAPM). METHODS From 2005 to 2014, 31 patients (mean age 13.5 years old, range 10-22 years old) suffering from dystrophic scoliosis associated with NF1 underwent posterior-only surgical correction using a MAPM. The apex of the deformity was thoracic (n = 25), thoracolumbar (n = 4), and lumbar (n = 2). The mean preoperative coronal Cobb angle was 69.1° (range 48.9°-91.4°). The mean Cobb angle on the side-bending radiograph of the convex side was 58.2° (range 40°-79.8°). The mean flexibility and apical vertebral rotation (AVR) were 15.6% (range 8.3%-28.2%) and 2.5° (range 2°-3°), respectively. The mean angle of sagittal kyphosis was 58.3° (range 34.1°-79.6°). RESULTS The mean follow-up period was 53 months (range 12-96 months). The mean postoperative coronal Cobb angle was 27.4° (range 16.3°-46.7°). Postoperatively, the mean AVR and angle of sagittal kyphosis were 1.2° (range 1°-2°) and 22.4° (range 4.2°-36.3°), respectively. All patients showed good correction of all indices postoperatively. The mean postoperative correction rate was 58.7% (range 46.3%-74.1%). At the final follow-up evaluation, the corrective loss rate of the Cobb angle was only 2.3%. Only 1 patient required revision surgery. No severe complications such as spinal cord, neural, or large vascular injury occurred during the operation. CONCLUSIONS Posterior-only surgical correction of dystrophic scoliosis in patients with NF1 using a MAPM could yield satisfactory clinical efficacy of correction and fusion.

Polymorphisms in the SP110 and TNF-α Gene and Susceptibility to Pulmonary and Spinal Tuberculosis among Southern Chinese Population

Objective To investigate the association of single-nucleotide polymorphisms (SNPs) in SP110 gene and TNF-α gene among pulmonary TB (PTB) and spinal TB (STB) patients. Methods In a total of 190 PTB patients, 183 STB patients were enrolled as the case group and 362 healthy individuals at the same geographical region as the control group. The SP110 SNPs (rs722555 and rs1135791) and the promoter -308G>A (rs1800629) and -238G>A (rs361525) polymorphisms in TNF-α were genotyped. Results. TNF-α -238G>A polymorphism was involved in susceptibility to STB, but not to PTB. The TNF-α -238 A allele was a protective factor against STB (A versus G: OR [95% CI] = 0.331 [0.113–0.972], P = 0.044). Furthermore, the presence of the -238 A allele was considered a trend to decrease the risk of STB (AG versus GG: P = 0.062, OR [95% CI] = 0.352 [0.118–1.053]; AA + AG versus GG: P = 0.050, OR [95CI%] = 0.335 [0.113–0.999]). However, SP110 SNPs (rs722555 and rs1135791) and TNF-α -308G>A (rs1800629) showed no association with PTB and STB in all genetic models. Conclusion The TNF-α -238 A allele appeared a protective effect against STB, whereas the SP110 SNPs (rs722555 and rs1135791) and TNF-α -308G>A (rs1800629) showed no association with susceptibility to PTB and STB patients in southern China.

Correlation between Serum Level of Monocyte Chemoattractant Protein-1 and Postoperative Recurrence of Spinal Tuberculosis in the Chinese Han Population

Objective To correlate serum level of monocyte chemoattractant protein-1 (MCP-1) with postoperative recurrence of spinal tuberculosis in the Chinese Han population. Methods Patients of Han nationality with newly diagnosed spinal tuberculosis were consecutively included in this study. At different time points postoperatively, serum level of MCP-1 was determined using an enzyme linked immunosorbent assay. Recurrence of spinal tuberculosis after surgery and during the follow-up period was recorded. The correlation between serum MCP-1 level and recurrence of spinal tuberculosis was analyzed. Results A total of 169 patients with spinal tuberculosis were included in the study and followed up for an average of2.2±1.3 years (range, 1–5 years). Of these patients, 11 had postoperative recurrence of spinal tuberculosis. The patients’ serum level of MCP-1 increased significantly after postoperative recurrence of spinal tuberculosis. Once the symptoms of recurrence were cured, the serum level of MCP-1 decreased significantly and it did not differ from patients without disease recurrence. Conclusion Postoperative recurrence of spinal tuberculosis is likely to increase the serum level of MCP-1.

P2X7 receptor in spinal tuberculosis: Gene polymorphisms and protein levels in Chinese Han population

Spinal tuberculosis (TB) accounts for 1%-5% of all TB infections. Host genetic variation influences susceptibility to Mycobacterium tuberculosis (MTB). P2X7 receptor (P2X7R) expressed on cells has been identified as a regulatory molecule in cell death/apoptosis, killing of intercellular pathogens, and bone turnover. This study investigated the P2X7 gene polymorphisms and protein levels in spinal TB. P2X7 gene -762C>T and 489C>T polymorphisms were genotyped. The expression of P2X7R in bone or intervertebral disc (ID) tissues was analyzed by Western blot assay. The -762C>T and 489C>T polymorphisms were associated with susceptibility to spinal TB. Having the -762CC genotype and -762C allele increased the risk of developing spinal TB (CC vs. TT: P=0.031, OR [95%CI]=1.865 [1.053-3.304]; C vs. T: P=0.028, OR [95%CI]=1.355 [1.034-1.775]). The presence of the 489T allele was associated with an increased risk of developing spinal TB (TT vs. CC: P=0.004, OR [95%CI]=2.248 [1.283-3.939]; CT vs. CC: P=0.044, OR [95%CI]=1.755 [1.011-3.047]; T vs. C: P=0.004, OR [95%CI]=1.482 [1.134-1.936]; TT+CT vs. CC: P=0.010, OR [95%CI]=1.967 [1.171-3.304]; TT vs. CT+CC: P=0.037, OR [95%CI]=1.489 [1.023-2.167]). The expression of P2X7R in TB-induced bone lesions increased significantly among spinal TB patients (t=0.011). Carrying the P2X7 -762CC genotype and 489T allele is associated with an increased risk of developing spinal TB in a Southern Chinese Han population.

Knockdown of Indian hedgehog protein induces an inhibition of cell growth and differentiation in osteoblast MC3T3‑E1 cells

Indian hedgehog protein (Ihh) is evolutionarily conserved and serves important roles in controlling the differentiation of progenitor cells into osteoblasts. Ihh null mutant mice exhibit a failure of osteoblast development in endochondral bone. Although studies have demonstrated that Ihh signaling is a potent local factor that regulates osteoblast differentiation, the specific transcription factors that determine osteoblast differentiation remain unclear. Further studies are required to determine the precise mechanism through which Ihh regulates osteoblast differentiation. In the present study, Ihh was knocked down in osteoblast MC3T3-E1 cells using short hairpin RNA, to investigate the function of Ihh in osteoblast proliferation and differentiation and to examine the potential mechanism through which Ihh induces osteoblast apoptosis and cell cycle arrest. It was observed that the knockdown of Ihh induced a marked inhibition of cell growth and increased the apoptosis rate compared with the negative control osteoblasts. Downregulation of Ihh resulted in a cell cycle arrest at the G1 to S phase boundary in osteoblasts. In addition, the knockdown of Ihh decreased the alkaline phosphatase activity and mineral deposition of osteoblasts. The inhibitory roles of Ihh downregulation in osteoblast growth and differentiation may be associated with the transforming growth factor-β/mothers against decapentaplegic homolog and tumor necrosis factor receptor superfamily member 11B/tumor necrosis factor ligand superfamily member 11 signaling pathways. Manipulating either Ihh expression or its signaling components may be of benefit for the treatment of skeletal diseases.