CD44在大鼠急性颈脊髓损伤后肺水肿中的作用

[目的]探讨大鼠急性颈脊髓损伤后不同时间节点血清及肺泡灌洗液中CD44含量的变化与肺水肿的关系.[方法]成年Wistar大鼠40只,体重240 ～ 250 g,雌雄不限.大鼠随机分为实验组和对照组,每组20只,每组又分为造模后24 h、3d、1、2周共4个时间点,每个时间点5只大鼠.实验组采用C7段脊髓改良Allen’s打击法制作大鼠脊髓损伤模型,打击力度为10×2.5 g·cm;对照组只暴露C7脊髓.在不同时间点处死大鼠,检测各时间点两组大鼠血清和肺泡灌洗液中CD44含量和蛋白浓度,计算肺通透指数.[结果]急性脊髓损伤大鼠伤后肺泡灌洗液的CD44无明显变化,血清CD44含量于伤后24 h开始下降,伤后3d达最低值,伤后1周含量开始回升,伤后24 h和3d实验组大鼠血清CD44含量与假手术组有显著差异性.CD44含量变化周期与SCI后肺水肿及肺病理变化周期呈负相关.[结论]血清CD44含量变化周期与SCI后肺水肿及肺病理变化周期呈负相关,急性脊髓损伤后肺水肿的形成过程可能与SCI后血清CD44含量下降有关.     

Overexpression of Hepatocyte growth factor and its soluble receptor (s-cMet) in the serum of patients with different grades of meningioma

ObjectivesMeningiomas are the most common primary intracranial tumor. Hepatocyte growth factor (HGF) and its receptor, cMet, were shown to be involved in meningioma. This study was aimed to determine the concentration of HGF and soluble cMet (s-cMet) in the serum of patients with different grades of meningioma.MethodsNinety serum samples from different grades of meningioma patients (42 cases of grade I, 28 grade II, 20 grade III) and 51 controls were included in this study. The serum total protein concentration (TPC) was measured by a Bio-Rad protein assay and serum concentration of HGF and s-cMet by enzyme linked immunosorbent assay (ELISA).ResultsNo significant change in the serum TPC of patients was seen as compared to controls. We also showed that serum HGF and s-cMet concentration in meningioma patients was higher than in controls. The results showed that starting from grades I to III meningioma, a significant increase in HGF and s-cMet serum concentration was observed (HGF; 380 ± 57.69, 430.27 ± 48.72, 596.36 ± 104.49 pg/ml, respectively, as compared to controls which was 327.72 ± 49.68 pg/ml and for s-cMet was 274.45 ± 45.05, 314.81 ± 38.71, 433.54 ± 51.81 ng/ml, respectively, as compared to controls which was 213.72 ± 29.13 ng/ml). The results showed that a high concentration of HGF and s-cMet is associated with advanced grades of meningioma.ConclusionIt is concluded that HGF and s-cMet serum levels increased in meningioma patients and their concentration was significantly higher in more advanced grades of the disease. It is also suggested that HGF/s-cMet might be involved in the progression of meningioma.     

Tumor Necrosis Factor-α– and Interleukin-1β–Dependent Matrix Metalloproteinase-3 Expression in Nucleus Pulposus Cells Requires Cooperative Signaling via Syndecan 4 and Mitogen-Activated Protein Kinase–NF-κB Axis: Implications in Inflammatory Disc Disease

Matrix metalloproteinase-3 (MMP-3) plays an important role in intervertebral disc degeneration, a ubiquitous condition closely linked to low back pain and disability. Elevated expression of syndecan 4, a cell surface heparan sulfate proteoglycan, actively controls disc matrix catabolism. However, the relationship between MMP-3 expression and syndecan 4 in the context of inflammatory disc disease has not been clearly defined. We investigated the mechanisms by which cytokines control MMP-3 expression in rat and human nucleus pulposus cells. Cytokine treatment increased MMP-3 expression and promoter activity. Stable silencing of syndecan 4 blocked cytokine-mediated MMP-3 expression; more important, syndecan 4 did not mediate its effects through NF-κB or mitogen-activated protein kinase (MAPK) pathways. However, treatment with MAPK and NF-κB inhibitors resulted in partial blocking of the inductive effect of cytokines on MMP-3 expression. Loss-of-function studies confirmed that NF-κB, p38α/β2/γ/δ, and extracellular signal–regulated kinase (ERK) 2, but not ERK1, contributed to cytokine-dependent induction of MMP3 promoter activity. Similarly, inhibitor treatments, lentiviral short hairpin-p65, and short hairpin-IκB kinase β significantly decreased cytokine-dependent up-regulation in MMP-3 expression. Finally, we show that transforming growth factor-β can block the up-regulation of MMP-3 induced by tumor necrosis factor (TNF)-α by counteracting the NF-κB pathway and syndecan 4 expression. Taken together, our results suggest that cooperative signaling through syndecan 4 and the TNF receptor 1–MAPK–NF-κB axis is required for TNF-α–dependent expression of MMP-3 in nucleus pulposus cells. Controlling these pathways may slow the progression of intervertebral disc degeneration and matrix catabolism.Low back pain is one of the most prevalent and costly health problems facing the world population, with occurrence in 84% of the population; the total costs exceed $100 billion per year in the United States alone.^1,2 Intervertebral disc degeneration (IVDD) is one of the major contributors of low back and neck pain and associated disability.^3,4 Nucleus pulposus (NP) cells, which primarily secrete proteoglycan aggrecan and fibrillar collagens to form the complex extracellular matrix (ECM), are key in maintaining a healthy disc.⁵ Loss of NP cells and their dysfunction, resulting in decreased proteoglycan synthesis, increased expression of catabolic enzymes, and a shift toward synthesis of fibrotic matrix, are hallmarks of disc degeneration. All these pathological changes diminish the water-binding capacity of the disc, leading to failure to resist compressive loads in the spine.⁶Despite the ubiquitous nature of the spinal pathologies, the molecular mechanisms of low back pain–associated IVDD have not been well investigated. Many studies have demonstrated that there was an increase in expression and activity of a range of matrix-degrading enzymes in IVDD, including the matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS) families.^7–9 The MMP is a family of metal-dependent proteases capable of degrading all components of the ECM of connective tissues.¹⁰ It was demonstrated by many studies that elevated MMPs 1, 2, 3, and 13 have been found in degenerated IVD.^8–11 Active MMP-3 has the ability to degrade core proteins of disc and cartilage connective matrix components, such as proteoglycans, fibronectin, laminin, elastin,^12–14 and collagens II, IX, and X.¹⁵ Noteworthy, MMP-3 can indirectly affect the degradation of cartilagenous matrix by proteolysis of latent MMPs, including pro–MMP-1, pro–MMP-7, and pro–MMP-9 into the active forms,^16–18 suggesting that MMP-3 may be important in disc pathologies.Elevated levels of the proinflammatory cytokines, including tumor necrosis factor (TNF)-α and IL-1β, have been reported in IVDD.^19–21 Recent studies have shown that, in disc cells, MMP-3 expression is induced by these cytokines.^22–27 However, only a handful of these studies have examined the mechanism of regulation of MMP-3 by cytokines.^14,28 Likewise, little is known about the intricacies of the signaling pathways controlling cytokine-mediated MMP-3 expression during IVDD.²⁹ TNF-α–dependent elevated expression of syndecan 4 (SDC4), a cell surface heparan sulfate proteoglycan, plays a major role in matrix catabolism through activation of ADAMTS-5.^19,30,31 Although synergistic actions of SDC4 on activity of several chemokines and cytokines have been demonstrated,^32–34 in the context of inflammatory disc disease, it is not yet known if SDC4 contributes to the cellular actions of TNF-α and if a regulatory relationship exists between MMP-3 expression and SDC4. In the present study, using genetic approaches, we investigate the mechanisms by which cytokines TNF-α and IL-1β control expression of MMP-3 in human and rat NP cells. Our results indicate that, in addition to mitogen-activated protein kinase (MAPK)–NF-κB axis downstream of cytokine receptor, cell surface SDC4 is required for TNF-α– and IL-1β–dependent MMP-3 expression in NP cells.     

Clinical and radiological results of total disc replacement in the cervical spine with preoperative reducible kyphosis

Purpose

To investigate the clinical and radiological results of total disc replacement (TDR) in the cervical spine with preoperative reducible kyphosis, and discuss when TDR is indicated for the patients with preoperative kyphosis.

Methods

Fifty-two patients who underwent single-level cervical TDR from June 2008 to May 2010 were included in this study. TDR was indicated for patients with preoperative lordosis or reducible kyphosis, and the patients were divided into a lordotic group (preoperative global angle of ≥0°) and kyphotic group (preoperative global angle of <0°). Clinical results were evaluated using the Japanese Orthopaedic Association (JOA) score, visual analog scale (VAS) score and Neck Disablity Index (NDI). For radiological evaluation, the global and functional spinal unit (FSU) angles and the global and FSU range of motion were measured preoperatively and postoperatively.

Results

The mean NDI in the kyphotic group was significantly higher than that in the lordotic group preoperatively and at six months postoperatively, but the groups showed no significant differences in JOA score, VAS score and NDI at the two year follow-up. The mean global and FSU angles in the kyphotic group were significantly lower than those in the lordotic group preoperatively and at six months postoperatively, but they gradually improved postoperatively. The differences lost significance at the two year follow-up.

Conclusions

Postoperative cervical kyphosis had adverse effects on the NDI after TDR. Artificial discs, symptom relief, and neck functional exercises may contribute to correction of preoperative reducible kyphosis at different stages after cervical TDR. Preoperative reducible kyphosis should not be an independent contraindication for cervical TDR.     

Unaffected contralateral S1 transfer for the treatment of lumbosacral plexus avulsion

Introduction

This study describes a new surgical strategy for lumbosacral plexus avulsion by transfer of the unaffected contralateral S1 nerve root.

Methods

A surgical reconstruction of the sacral nerve was performed on a 10-year-old boy with left lumbosacral plexus avulsion. The unaffected S1 nerve root (right side) is severed extradurally for transfer. A 25-cm long nerve graft from the common peroneal nerve of the affected side was used as donor nerve. One end of the nerve graft was anastomosed to the proximal stump of the right-sided extradural S1 nerve. The distal end of the nerve graft was divided into two fascicles and anastomosed to the left-sided inferior gluteal nerve and the branch of the sciatic nerve innervating the left-sided hamstrings.

Results

According to motor score of the British Medical Research Council (MRC) system, the strength of glutei and hamstrings improved to the level of M3 1.5 years after surgery.

Conclusions

The extradural S1 nerve root in the unaffected side can be considered as a suitable donor nerve for transfer in patients with root avulsion of the lumbar or sacral nerve plexus.     

Chordomas: A review with emphasis on their pathophysiology,pathology, molecular biology,and genetics

Chordomas are uncommon, bone, axial, or (rarely) extra-axial tumors that are malignant and frequently recur but less commonly metastasize. They usually affect adults, with a very small proportion being pediatric tumors. For children, such tumors present a different biology, since they are more common as scull rather than sacral tumors, with aggressive histological features, including a loss of SMARCB1/INI1 and a dismal prognosis. Histologically, chordomas, believed to derive from notochordal tissue, characteristically show physaliphorous cells in a myxoid or chondroid matrix. Dedifferentiated and poorly differentiated forms can be observed. Moreover, a grading scale for chordomas has been proposed. Cytokeratin, EMA, S100, and brachyury are expressed by most chordomas. These are chemo-resistant tumors, for which surgical resection and/or radiotherapy are the treatments of choice. In this review, the histological, immunohistochemical, molecular, and clinical data of chordomas are discussed.     

几丁糖阿霉素缓释药粒治疗骨巨细胞瘤的临床初步观察

为了观察骨巨细胞瘤刮除术后局部应用几丁糖阿霉素缓释药粒的疗效及全身反应，对４例骨巨细胞瘤刮除术后残腔应用４倍于常规静脉阿霉素用量的几丁糖阿霉素缓释药粒，检测术后１，２及５天血浆中阿霉素含量，以及术后１周、１个月及６个月的肝肾功能。结果表明，术后１，２及５天血浆中阿霉素含量分别为（１４３．０５±２７．５５）ｎｇ／ｍｌ、（５２．１７±１１．２８）ｎｇ／ｍｌ及（４．２５±３．０７）ｎｇ／ｍｌ，术后１周、１个月及６个月的肝肾功能均正常。随访７个月～１９个月，无局部复发、全身反应及Ｘ线片复发表现。认为，几丁糖阿霉素缓释药粒用于骨巨细胞瘤刮除术后是安全、有效的。     

神经节苷脂治疗大鼠脊髓半切综合征运动功能恢复的机制

目的单唾液酸四己糖神经节苷脂(GM-1)可促进神经再生,有助于运动功能恢复,评价GM-1对颈髓半切综合征(BSS)的治疗效果。方法取SD大鼠55只,随机抽签法分成对照组、损伤组、治疗组;直视下半切大鼠颈髓1/2C5-7阶段;治疗组在伤后15,90,180min,2,3d分别腹腔内注射GM-110mg/kg,损伤组注射生理盐水。伤后1,6,24h,1,6周时各取损伤组合治疗组大鼠各2只伤区颈髓组织送光镜和电镜检查,并进行Rivlin斜板试验以评价大鼠运动功能。结果正常对照组大鼠在自制斜板上停留的最大角度为82°,损伤组术后1周平均为55°,6周时有一定程度的增加65°;而治疗组术后增加较快,6周时接近正常。治疗组半切处出血减轻,周围白质大部相连,髓鞘修复,大量重组的少突胶质细胞增生,运动功能恢复90%。结论GM-1对BSS脊髓有保护作用,并促进其恢复。     

Treatment and outcome of metastatic paraganglioma of the spine

Background

Spinal metastatic paraganglioma (MPG) is rare and only reported in individual case reports. The low incidence makes it difficult to define appropriate therapy and prognosis. Our study illustrated the largest series to discuss the possible treatment and outcomes of patients with spinal MPG.

Methods

A retrospective study of 15 patients with spinal MPG who were surgically treated between 2005 and 2014 was performed. Three surgical modalities were applied, and radiotherapy and chemotherapy were utilized as adjuvant therapy.

Results

The mean patients age was 40.9 (range 23–58) years. The period between primary surgery and spinal metastasis averaged 8.2 (0.5–15) years. Lesions were mainly located in cervical spine (2), thoracic spine (8), lumbar spine (3), and sacrum (2). The mean follow-up period was 35.0 months. Lesion progression was detected in nine patients, whereas five patients (33.3%) passed away. For solitary spine, multiple bone and both bone and nonosseous metastasis cases, the mean progression-free survival was 41 (range 9–56), 22.5 (range 12–38) and 8.3 (range 3–18) months, respectively.

Conclusions

The cases presented in the current study highlight the crucial role of surgery. Total en bloc for solitary spinal MPG could result in a satisfying prognosis and piecemeal total resection with postoperative radiotherapy could be an alternative therapy. Radiotherapy and chemotherapy were advocated, especially for the multiple metastasis.