中国汉族人群中20p12染色体上三个单核苷酸多态性与后纵韧带骨化发生及其严重程度的关系研究

Background Ossification of the posterior longitudinal ligament （OPLL） is characterized by the replacement of ligamentous tissue with new ectopic bone formation, and has a strong genetic background. Because of the abnormal bone metabolic features and the strong genetic component, osteoporosis is a related disorder with OPLL. Three polymorphisms on chromosome 20p12 were identified associated with the risk of osteoporosis and osteoporotic fracture.The rs996544 （C/T） ＂TT＂ and rs965291 （G/A） ＂AA＂ genotypes conferred higher risks for vertebral and hip fractures. The osteoporosis haplotype is defined by two polymorphisms, rs1116867 （A） and D35548 （T）. However, it remains unknown whether these three polymorphisms predispose to an increased frequency and severity of OPLL in Han Chinese patients.Methods A total of 420 OPLL patients and 506 age- and sex-matched controls were studied. Three single nucleotide polymorphisms （SNPs）, rs996544 （C/T）, rs965291 （G/A） and rs1116867 （A/G）, were analyzed by direct sequencing.Associations between these SNPs with the occurrence and extent of OPLL were statistically evaluated.Results There was no significant association between the rs996544 （C/T） polymorphism and the prevalence of OPLL.The rs1116867 （A/G） polymorphism ＂AG＂ genotype was associated with the occurrence of OPLL. The rs1116867 （A/G） polymorphism ＂G＂ allele was associated with the occurrence of OPLL, but not with the extent of OPLL. The rs965291 （G/A） polymorphism in female patients was statistically different between cases and controls （P 〈0.05）. The rs965291 （G/A） polymorphism ＂A＂ allele was associated with the occurrence of OPLL in female patients. For the rs965291 （G/A）polymorphism, patients with the ＂A＂ allele （genotype, ＂AG＂ or ＂AA＂） showed a significantly greater number of ossified cervical vertebrae than those without the ＂A＂ allele （genotype, ＂GG＂, P 〈0.05）, particularly in female patients.Conclusions The rs1116867 （A/G） and rs965291 （G/A） polymorphisms on chromosome 20p12 are associated with the occurrence and the extent of OPLL, at least in Han Chinese subjects. Our data should advance our understanding of the molecular etiology of OPLL and may guide approaches to prevent the onset of OPLL.     

Continuous epidural block of the cervical vertebrae for cervicogenic headache

Background Cervicogenic headache （CEH） is caused by a structural abnormality in the cervical spine. Available treatments for CEH include medical therapy, local botulinum toxin injection, cervical epidural corticosteroid injection, and surgery. The objective of this study was to investigate the safety and efficacy of a continuous epidural block of the cervical vertebra.
Methods Medical records were retrospectively analyzed for 37 patients diagnosed with CEH treated by a continuous epidural block of the cervical vertebra with lidocaine, dexamethasone, and saline （5 ml/min） for 3-4 weeks and triamcinolone acetonide 5 mg once weekly for 3-4 weeks. Pain was measured via the visual analogue scale （VAS） in combination with quality of life assessment. Outcome measures were patient-reported days with mild or moderate pain, occurrence of severe pain, and the daily oral dosages of non-steroidal anti-inflammatory drug use （NSAID）.
Results In the 3 months immediately preceding placement of the epidural catheter, the mean number of days with mild or moderate pain was 22.0±4.3. The mean occurrence of severe pain was （3.20±0.75） times and the mean oral dosage of NSAID was （1267±325） mg. During the first 6 months after epidural administration of lidocaine and corticosteroids, the mean number of days with mild or moderate pain, the mean occurrence of severe pain, and the mean daily oral dosages of NSAIDs were significantly decreased compared to 3-month period immediately preceding treatment （P 〈0.01）. By 12 months post-treatment, no significant difference in these three outcome measures was noted.
Conclusions Continuous epidural block of the cervical vertebra for patients with CEH is effective for at least six months. Further research is needed to elucidate mechanisms of action and to prolong this effect.     

Dynamic Radiographic Analysis of Sympathetic Cervical Spondylosis Instability

Objective To investigate the correlation between subaxial cervical spine instability and cervical spondylotic sympathetic symptoms as well as the difference of cervical spondylotic subaxial instability between male and female patients. Methods We analyzed retrospectively 318 surgical cases of cervical spondylosis treated at Department of Orthopedic Surgery of Peking Union Medical College Hospital between July 2003 and December 2007. All cases were divided into group A without sympathetic symptoms （n=284） and group B with sympathetic symptoms （n=34）. Angular and horizontal translation values between two adjacent vertebral bodies from C2 to C7 were measured separately on hyperflexion and hyperextension lateral cervical spine radiographs. Fisher＇s exact test was used to evaluate the correlation between subaxial cervical instability and sympathetic symptoms. Intragroup correlation between patient gender and subaxial cervical instability was also evaluated. Results Subaxial instability incidences in groups A and B were 21.8% （62/284） and 55.9% （19/34）, respectively. Statistical analysis indicated a definite correlation between subaxial cervical instability and sympathetic symptoms （P=0.000）. Among patients without sympathetic symptoms, subaxial instability incidences were 21.4% （37/173） in males and 22.5% （25/111） in females, respectively （P=0.883）. While among patients with sympathetic symptoms, sub axial instability incidences were 27.3% （3/11） in males and 69.6% （16/23） in females, respectively, indicating significant difference （P=0.030）. Subaxial instability was most commonly seen at C4-C5 intervertebral space in sympathetic cervical spondylosis patients. Conclusions High correlation exists between subaxial cervical spine instability and cervical spondylotic sympathetic symptoms, especially in female patients. Hyperextension and hyperflexion radiographs of cervical spine are important to assess sympathetic cervical spondylotic subaxial instability.     

Chordomas of the upper cervical spine: clinical characteristics and surgical management of a series of 21 patients

Background Chordomas of the upper cervical spine are rare and present unique surgical challenge.This study aimed to describe the clinical characteristics and surgical management of patients with chordomas of the upper cervical spine.Methods Twenty-one patients with chordomas of the upper cervical spine who were treated in Peking University Third Hospital from January 1999 to October 2012 were retrospectively analyzed.Survival was calculated by the Kaplan-Meier method and was compared between groups using the log-rank test.Results The postoperative diagnosis was classical chordoma in 20 cases and chondroid chordoma in one case.The mean operative time was 9.5 hours （range 6-17 hours）,and the mean blood loss was 2 812 ml （range 700-4 800 ml）.There were two postoperative deaths.Unilateral vertebral artery ligation was performed in six patients,cervical nerve roots were cut in six patients,and the external branch of the superior laryngeal nerve was repaired after being cut in one case.Two patients developed postoperative velopharyngeal incompetence,and loosening of the occipitocervical screws was observed in one patient.The recurrence rate was 66.7% （10/15） after a mean follow-up period of 46.8 months （range 14-150 months）.The 5-and 10-year overall survival rates were （39.8±13.1）% and （31.9±12.7）%,respectively.There was a significant difference in survival rate between patients who underwent surgery and those who did not.Conclusion In spite of the high rates of recurrence and complications after surgical treatment of chordomas of the upper cervical spine,intralesional resection combined with adjuvant radiotherapy remains the optimal treatment to prolong survival.     

Anatomy-related risk factors in Harm's mesh subsidence in cervical reconstruction after one-level corpectomy

Objective： To clarify anatomy-related factors in the cervical spine with subsidence of titanium mesh cage （TMC） after one-level cervical corpectomy and fusion. The effect of the cervical posture, segmental curvature and endplate gradient on this postoperative phenomenon was evaluated. Methods： Between August 2003 and March 2006, a total of the 236 patients underwent one-level corpectomy and TMC fusion. Their radiological examinations were reviewed and clinical outcomes evaluated. Results： In the patients who were followed up for 12 months, TMC subsidence occurred in 54 （28.6%） cases. C6 corpectomy had a significant higher risk （26/60, 43.3%） for TMC subsidence, which was correlated with the variation of the gradient of the vertebral endplates against cervical levels. Although the clinical outcome was comparable with those in the literature, the patients may have subsidence-related problems such as neck-shoulder pain, neurological deterioration and instrumental failure. Conclusion： To decrease the incidence of subsidence, TMC design should be optimized to be in line with anatomic characteristics of the cervical spine.     

Cerebrospinal fluid dynamics in Chiari malformation associated with syringomyelia

Background About 50%--70% of patients with Chiad malformation I （CMI） presented with syringomyelia （SM）, which is supposed to be related to abnormal cerebrospinal fluid （CSF） flow around the foramen magnum. The aim of this study was to investigate the cerebrospinal fluid dynamics at levels of the aqueduct and upper cervical spine in patients with CMI associated with SM, and to discuss the possible mechanism of formation of SM. Methods From January to Apdl 2004, we examined 10 adult patients with symptomatic CMI associated with SM and 10 healthy volunteers by phase-contrast MRI. CSF flow patterns were evaluated at seven regions of interest （ROI）： the aqueduct and ventral and dorsal subarachnoid spaces of the spine at levels of the cerebellar tonsil, C2-3, and C5-6. The CSF flow waveforms were analyzed by measuring CSF circulation time, durations and maximum velocities of cranial- and caudal-directed flows, and the ratio between the two maximum velocities. Data were analyzed by ttest using SPSS 11.5. Results We found no definite communication between the fourth ventricle and syringomyelia by MRI in the 10 patients. In both the groups, we observed cranial-directed flow of CSF in the early cardiac systolic phase, which changed the direction from cranial to caudal from the middle systolic phase to the early diastolic phase, and then turned back in cranial direction in the late diastolic phase. The CSF flow disappeared at the dorsal ROI at the level of C2-3 in 3 patients and 1 volunteer, and at the level of C5-6 in 6 patients and 3 volunteers. The durations of CSF circulation at all the ROIs were significantly shorter in the patients than those in the healthy volunteers （P=-0.014 at the midbrain aqueduct, P=-0.019 at the inferior margin of the cerebellar tonsil, P=-0.014 at the level of C2-3, and P=-0.022 at the level of C5-6）. No significant difference existed between the two groups in the initial point and duration of the caudal-directed CSF flow during a cardiac cycle at all the ROIs. The maximum velocities of both cranial- and caudal-directed CSF flows were significantly higher in the patients than those in the volunteers at the aqueduct （P=-0.018 and P=-0.007） and ventral ROI at the inferior margin of the cerebellar tonsil （P〈0.001 and P=-0.002）, as so did the maximum velocities of the caudal-directed flow in the ventral and dorsal ROIs at the level of C2-3 （P=-0.004; P=-0.007）. Conclusions The direction of CSF flow changes in accordance with cardiac cycle. The syringomyelia in patients with CMI may be due to the decreased circulation time and abnormal dynamics of the CSF in the upper cervical segment. The decompression of the foramen magnum with dural plasty is an alternative for patients with CMI associated with SM.     

Effects of single nucleotide polymorphisms 869 T/C and 915 G/C in the exon 1 locus of transforming growth factor-β1 gene on chronic obstructive pulmonary disease susceptibility in Chinese

Background The main risk factor for chronic obstructive pulmonary disease （COPD） is cigarette smoking. However, only 10%-20% of chronic heavy smokers develop systematic COPD. We hypothesized that the inheritance of gene polymorphisms could influence the development of COPD, which was investigated by studying two single nucleotide polymorphisms （SNP） in exon 1 of the transforming growth factor-β1 （TGF-β1） gene. Methods We enrolled 219 patients with COPD as the research group and 148 healthy people as the control group, all of whom were Chinese Han people. The polymorphisms of the TGF-β1 gene, 869T/C and 915G/C, were analyzed using the method of amplification refractory mutation system-polymerase chain reaction （ARMS-PCR）. Results The occurrence of the TGF-β1 gene 869T/C polymorphism in patients with COPD was significantly different from the control group （P 〈0.05）, in which the relative risk of this disease increased in cases who had the C allele （OR： 1.131, 95% CI： 1.101-1.539）. There was no increased frequency of TGF-β1 915G/C gene in COPD patients compared with control subjects （P 〉0.05）. Conclusions The polymorphism 869T/C in TGF-β1 gene has a significant association with disease occurrence in COPD patients and the C allele might be a risk factor. The homozygous wild-type CC of 869T/C on TGFβ1 could be a predisposing factor in COPD and those who carry the C allele might have particularly susceptibility to developing COPD.     

Clinic characteristics and surgical strategy of ossification of the posterior longitudinal ligament of thoracic spine

Objective To study the ossification of the posterior longitudinal ligament （OPLL） of thoracic spine which treated surgically, analysis the clinic characteristics and surgical strategy. Methods Fifty-five patients who had been treated surgically for thoracic OPLL were reviewed. There were 19 males and 36 females. The mean age was 51.9 years （ range, 35 - 73 years）. All cases were with neurological deficits. The treatment procedures consisted of anterior decompression with instrumentation （15 patients）, posterior removal of posterior wall of thoracic spinal canal （34 patients）,     

生物力学因素与BMP2单核苷酸多态性对颈椎后纵韧带骨化成骨作用的影响

目的 探讨生物力学因素与骨形态发生蛋白-2（bone morphogenetic protein 2,BMP2）单核苷酸多态性对颈椎后纵韧带骨化（ossification of the posterior longitudinal ligament,OPLL）成骨作用的影响,为进一步发现OPLL多因素共同致病的具体机制奠定基础.方法 采集颈椎OPLL病变组手术减压过程中骨化部位的后纵韧带和颈椎外伤等手术减压过程中的正常对照组后纵韧带.利用PCR和直接测序法分析BMP2上2个单核苷酸多态性位点109T＞G（rs2273073）,570A＞T（rs235768）基因型及等位基因型的分布.Masson三色染色观察组织学结构改变.免疫组织化学染色和Western blot法检测BMP2的分布和表达.用C3H10T1/2细胞做转染构建细胞模型：正常组、空载体组、BMP2野生型组、BMP2（rs2273073）单突变组、BMP2（rs235768）单突变组、BMP2（rs2273073,rs235768）双突变组.采用机械应力装置对接种于Flexercell板的细胞施加10％、0.5Hz的机械应力,持续加载24h.以同样接种于Flexereell板未施加机械应力的细胞作为对照组.采用Western blot法检测机械应力加载前后各组BMP2表达情况.结果 Masson三色染色组织学观察显示病变组有成骨结构改变,免疫组织化学染色和Western blot法显示病变组BMP2的表达增加.机械应力加载后,细胞转染模型BMP2（rs2273073）单突变组和BMP2（rs2273073,rs235768）双突变组的BMP2表达较未施加应力组明显增加,差异具有统计学意义（P＜0.05）.结论 BMP2单核苷酸多态性位点109T＞G（rs2273073）的突变不仅能提高人们对OPLL的易感性,同时能提高OPLL患者对机械应力的敏感度,从而加速OPLL的进展.     

A single nucleotide polymorphism in the human bone morphogenetic protein-2 gene (109T>G) affects the Smad signaling pathway and the predisposition to ossification of the posterior longitudinal ligament of the spine

Background Although various systemic and local factors such as abnormal carbohydrate or calcium metabolism,aging,and hormonal disturbances have been suggested as causes of ossification of the posterior...     

前路多节段椎体次全切除治疗严重颈椎后纵韧带骨化症

目的 探讨采用前路多节段椎体次全切除治疗严重颈椎后纵韧带骨化症的适应证、方法及其临床效果.方法 2006年4月至2008年3月,25例严重颈椎后纵韧带骨化症患者采用前路多节段椎体次全切除手术进行治疗,年龄42～75岁,平均53.2岁.骨化物分型包括局限型7例,分节型5例,连续型8例,混合型5例;骨化物范围涉及2～4个椎节,平均2.8个椎节;椎管狭窄率50%～97%,平均68.4%.所有患者均通过前路椎体次全切除术,切除骨化后纵韧带减压,并采用钛网植骨钢板固定重建颈椎稳定性.结果 本组两椎体次全切除16例,三椎体次全切除9例.随访2～18个月,患者神经功能JOA评分从术前平均9.3(5～12)分提高至术后平均14.2(11～16)分,恢复率22.2%～87.5%,平均63.2%.并发症包括6例脑脊液漏(4例间歇性脑脊液假性囊肿),2例神经根麻痹,1例血肿压迫,1例术后短期四肢肌力下降.结论 前路多椎体次全切除治疗严重颈椎后纵韧带骨化症有助于提高此类患者的手术疗效,但手术难度大,风险高.     

Clinics in diagnostic imaging (55). Ossification of the posterior longitudinal ligament

Ossification of the posterior longitudinal ligament (OPLL) of the cervical spine associated with diffuse idiopathic skeletal hyperostosis is described in a 70-year-old Caucasian man presenting with a rapidly progressive myelopathy. The acute nature of his myelopathic symptoms and cervical canal stenosis necessitated posterior decompressive surgery. Four other patients with OPLL are presented to illustrate the spectrum of imaging findings. The computed tomographic features of OPLL are distinctive.A 2-5 mm thick linear ossified strip along the posterior vertebral margin usually at mid cervical (C3 to C5) level characterises the condition. Magnetic resonance (MR) imaging is valuable in excluding possible cord damage and associated disc lesions prior to surgery. A calcified central sequestrated disc is the only condition that may be mistaken for the segmental and retrodiscal forms of OPLL In a clinical setting of compressive myelopathy, it is pertinent to distinguish between these two conditions since a sequestrated disc has a more favourable surgical prognosis. The merits and relevance of anterior and posterior surgery together with their possible complications are outlined.     

Clinics in diagnostic imaging (161). Cervical OPLL with cord compression

A 53-year-old man presented with acute cervical myelopathy following a fall. Cervical radiography and computed tomography showed ossification of the posterior longitudinal ligament (OPLL) from C2 to C6 level, with severe cervical canal stenosis and cord compression. Magnetic resonance imaging further showed increased T2-weighted signal in the spinal cord at the level of greatest central spinal canal stenosis. OPLL is a significant cause of myelopathy in Asian populations and is found in up to 25% of patients presenting with cervical compression myelopathy. The clinical presentation, radiological evaluation and management of OPLL are discussed.     

后路单开门椎管扩大成形术联合侧块钢板固定治疗颈椎后纵韧带骨化

目的: 研究颈椎后路减压单开门椎管扩大成形术联合侧块钢板固定治疗颈椎后纵韧带骨化的疗效。方法: 对41例临床病例进行回顾性研究,均有程度不等的脊髓压迫症状,全部行颈椎后路减压单开门椎管扩大成形术,侧块钢板固定术。术前术后神经功能评分采用JOA评分。结果: 随访12~16(14±2.0)个月,JOA评分较术前提高4.8分。结论: 颈椎后路减压单开门椎管扩大成形术合并颈椎侧块钢板内固定术治疗后纵韧带骨化,具有适应范围广、操作简单安全、固定牢固等优点,是治疗后纵韧带骨化的一种有效的方法。     

CYPIB1与北方地区汉族人群喉癌易感性多基因关联分析

目的：探讨代谢酶CYP1B1基因CYP1B1＊2142C／G,CYP1B1＊2355G／T,CYP1B1＊34326C／G多态性与北方地区汉族人群喉癌易感性的关系。方法：采用病例-对照研究的方法,运用多重聚合酶链反应方法（Multi—PCR）及基质辅助激光解析-飞行时间质谱分析技术（MALDI—TOFMS）对200例北方地区汉族人群喉癌患者和200例健康对照组外周血DNA中CYP1B1＊2142c／G、355G／T,CYP1B1＊34326c／G基因进行多态性研究,并分析上述基因位点之间及基因和烟酒的联合作用与喉癌发生风险的关联强度。结果：携带CYP1B1＊2355G／T突变型基因型的病例组惠病风险高于对照组（0R=2．281,95％CI：1．142～3．516,P〈0．001）,携带CYP1B1＊34326c／c突变型基因型的病例组患病风险低于对照组（0R=0．571,95％CI：0．370～0．882,P=-0．011）。C142T355C4326单倍体型具有协同效应,显著增加喉癌风险（AdjustedOR=3．180,95％CI：1．760～5．746,P〈0．001）。在非吸烟及吸烟者中携带CYP1B1＊2355G／T突变型等位基因的危险度OR分另U为2．080（95％CI：0．742—5．830）、6．322（95％CI：2．541～15．725,尸〈0．001）。结论：CYP1B1基因的多态性与喉癌患病风险密切相关。CYP1B1＊2355G／T突变型基因是喉癌的风险基因,CYP1B1＊34326C／G突变型基因是喉癌的保护基因。CYP1B1＊2142c／G基因多态性与喉癌易感性无相关性。基因与基因之间具有协同作用,风险基因越多惠癌风险越大。烟酒与基因之间无相互协同效应。     

基因多态性与脊柱后纵韧带骨化病发病机制的研究进展

后纵韧带骨化(ossification of the posterior longitudinal ligament,OPLL)是临床常见脊柱疾患,好发于颈椎,主要表现为神经压迫症状,严重损伤患者健康。其发病机制尚不明确,与遗传因素、基因多态性、机械刺激、代谢异常等多种因素有关,可能是多基因、多因素导致的疾病。该病具有鲜明的遗传特性,与多个基因单核苷酸多态性位点的改变相关。因此,本文就其发病相关基因(COL11A2、BMP-2、TGF-β1、TGF-β3、NPPS、COL6A1、Runx2)的多态性研究进展作一综述,为后续研究奠定基础。