Imbalanced Protein Expression Patterns of Anabolic,Catabolic, Anti-Catabolic and Inflammatory Cytokines in Degenerative Cervical Disc Cells: New Indications for Gene Therapeutic Treatments of Cervical Disc Diseases

Degenerative disc disease (DDD) of the cervical spine is common after middle age and can cause loss of disc height with painful nerve impingement, bone and joint inflammation. Despite the clinical importance of these problems, in current publications the pathology of cervical disc degeneration has been studied merely from a morphologic view point using magnetic resonance imaging (MRI), without addressing the issue of biological treatment approaches. So far a wide range of endogenously expressed bioactive factors in degenerative cervical disc cells has not yet been investigated, despite its importance for gene therapeutic approaches. Although degenerative lumbar disc cells have been targeted by different biological treatment approaches, the quantities of disc cells and the concentrations of gene therapeutic factors used in animal models differ extremely. These indicate lack of experimentally acquired data regarding disc cell proliferation and levels of target proteins. Therefore, we analysed proliferation and endogenous expression levels of anabolic, catabolic, ant-catabolic, inflammatory cytokines and matrix proteins of degenerative cervical disc cells in three-dimensional cultures. Preoperative MRI grading of cervical discs was used, then grade III and IV nucleus pulposus (NP) tissues were isolated from 15 patients, operated due to cervical disc herniation. NP cells were cultured for four weeks with low-glucose in collagen I scaffold. Their proliferation rates were analysed using 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide. Their protein expression levels of 28 therapeutic targets were analysed using enzyme-linked immunosorbent assay. During progressive grades of degeneration NP cell proliferation rates were similar. Significantly decreased aggrecan and collagen II expressions (P<0.0001) were accompanied by accumulations of selective catabolic and inflammatory cytokines (disintegrin and metalloproteinase with thrombospondin motifs 4 and 5, matrix metalloproteinase 3, interleukin-1β, interleukin-1 receptor) combined with low expression of anti-catabolic factor (metalloproteinase inhibitor 3) (P<0.0001). This study might contribute to inhibit inflammatory catabolism of cervical discs.     

单节段颈椎人工椎间盘置换术治疗颈椎病的临床研究

目的:探讨单节段颈椎人工椎间盘置换术(CDA)治疗颈椎病的临床效果。方法:选择2013年5月到2015年5月在我院收治的80例颈椎病患者,按手术方式不同分为颈椎人工椎间盘置换组(CDA组)和前路颈椎减压融合组(ACDF组),各40例。两组患者均于术前、术后3个月、术后6个月及术后1年进行末期随访时,采用颈椎功能障碍指数(NDI)评价患者颈部功能,采用颈痛视觉模拟评分(VAS)和上肢痛VAS评价患者颈部疼痛,采用X线片在过伸和过屈位测量患者术前和术后手术节段相邻节段的活动度。结果:两组患者术后3个月、6个月及术后1年时的NDI评分、颈痛VAS及上肢痛VAS均明显低于术前,差异具有统计学意义(P0.05),然而两组间比较差异无统计学意义(P0.05)。CDA组患者术后3个月、6个月及术后1年时的手术相邻上节段活动度和手术相邻下节段活动度与术前比较差异无统计学意义(P0.05),而ACDF组患者术后3个月、6个月及术后1年时均明显高于术前及同期CDA组,差异具有统计学意义(P0.05)。结论:单节段CDA治疗颈椎病的临床疗效与ACDF相近,另外其不会引起手术相邻节段活动度的增加,值得在临床上推广应用。     

Mid- to Long-Term Outcomes of Cervical Disc Arthroplasty versus Anterior Cervical Discectomy and Fusion for Treatment of Symptomatic Cervical Disc Disease: A Systematic Review and Meta-Analysis of Eight Prospective Randomized Controlled Trials

Purpose

This study aimed to investigate the mid- to long-term outcomes of cervical disc arthroplasty (CDA) versus anterior cervical discectomy and fusion (ACDF) for the treatment of 1-level or 2-level symptomatic cervical disc disease.

Methods

Medline, Embase, and the Cochrane Central Register of Controlled Trials databases were searched to identify relevant randomized controlled trials that reported mid- to long-term outcomes (at least 48 months) of CDA versus ACDF. All data were analyzed by Review Manager 5.3 software. The relative risk (RR) and 95% confidence intervals (CIs) were calculated for dichotomous variables. The weighted mean difference (WMD) and 95%CIs were calculated for continuous variables. A random effect model was used for heterogeneous data; otherwise, a fixed effect model was used.

Results

Eight prospective randomized controlled trials (RCTs) were retrieved in this meta-analysis, including 1317 and 1051 patients in CDA and ACDF groups, respectively. Patients after an ACDF had a significantly lower rate of follow-up than that after CDA. Pooled analysis showed patients in CDA group achieved significantly higher rates of overall success, Neck Disability Index (NDI) success, neurological success and significantly lower rates of implant/surgery-related serious adverse events and secondary procedure compared with that in ACDF group. The long-term functional outcomes (NDI, Visual Analog Scale (VAS) neck and arm pain scores, the Short Form 36 Health Survey physical component score (SF-36 PCS)), patient satisfaction and recommendation, and the incidence of superior adjacent segment degeneration also favored patients in CDA group with statistical difference. Regarding inferior adjacent segment degeneration, patients in CDA group had a lower rate without statistical significance.

Conclusions

This meta-analysis showed that cervical disc arthroplasty was superior over anterior discectomy and fusion for the treatment of symptomatic cervical disc disease in terms of overall success, NDI success, neurological success, implant/surgery-related serious adverse events, secondary procedure, functional outcomes, patient satisfaction and recommendation, and superior adjacent segment degeneration.     

Cervical Total Disc Replacement is Superior to Anterior Cervical Decompression and Fusion: A Meta-Analysis of Prospective Randomized Controlled Trials

Background

Despite being considered the standard surgical procedure for symptomatic cervical disc disease, anterior cervical decompression and fusion invariably accelerates adjacent segment degeneration. Cervical total disc replacement is a motion-preserving procedure developed as a substitute to fusion. Whether cervical total disc replacement is superior to fusion remains unclear.

Methods

We comprehensively searched PubMed, EMBASE, Medline, and the Cochrane Library in accordance with the inclusion criteria to identify possible studies. The retrieved results were last updated on December 12, 2014. We classified the studies as short-term and midterm follow-up.

Results

Nineteen randomized controlled trials involving 4516 cases were identified. Compared with anterior cervical decompression and fusion, cervical total disc replacement had better functional outcomes (neck disability index [NDI], NDI success, neurological success, neck pain scores reported on a numerical rating scale [NRS], visual analog scales scores and overall success), greater segmental motion at the index level, fewer adverse events and fewer secondary surgical procedures at the index and adjacent levels in short-term follow-up (P < 0.05). With midterm follow-up, the cervical total disc replacement group indicated superiority in the NDI, neurological success, pain assessment (NRS), and secondary surgical procedures at the index level (P < 0.05). The Short Form 36 (SF-36) and segmental motion at the adjacent level in the short-term follow-up showed no significant difference between the two procedures, as did the secondary surgical procedure rates at the adjacent level with midterm follow-up (P > 0.05).

Conclusions

Cervical total disc replacement presented favorable functional outcomes, fewer adverse events, and fewer secondary surgical procedures. The efficacy and safety of cervical total disc replacement are superior to those of fusion. Longer-term, multicenter studies are required for a better evaluation of the long-term efficacy and safety of the two procedures.     

两种微创方法治疗颈椎间盘突出症的疗效比较

目的:比较经皮激光椎间盘减压术(PLDD)和经皮颈椎间盘等离子消融术治疗单节段突出的神经根型颈椎间盘突出症的临床疗效及安全性。方法:回顾2007年6月至2011年5月的颈椎间盘突出症住院患者36例。其中PLDD治疗17例(A组),等离子消融治疗19例(B组)。根据VAS评分和JOA评分,评价术前和术后一月内的疗效,同时记录两组患者的不良反应和并发症。结果:所有病例均成功穿刺并完成随访。两组手术后一月内各观察点的VAS评分和JOA评分均明显优于术前(P<0.05),其中B组患者术后3d和7d的VAS评分低于A组(P<0.05),而两组间术后JOA评分无明显差异。两组均未发生严重并发症。结论:与经皮激光椎间盘减压术相比,经皮椎间盘等离子消融术治疗颈椎间盘突出症患者症状消失更快。     

两种微创方法治疗颈椎间盘突出症的疗效比较

目的:比较经皮激光椎间盘减压术( PLDD)和经皮颈椎间盘等离子消融术治疗单节段突出的神经根型颈椎间盘突出症的临床疗效及安全性.方法:回顾2007年6月至2011年5月的颈椎间盘突出症住院患者36例.其中PLDD治疗17例(A组),等离子消融治疗19例(B组).根据VAS评分和JOA评分,评价术前和术后一月内的疗效,同时记录两组患者的不良反应和并发症.结果:所有病例均成功穿刺并完成随访.两组手术后一月内各观察点的VAS评分和JOA评分均明显优于术前(P＜0.05),其中B组患者术后3d和7d的VAS评分低于A组(P＜0.05),而两组间术后JOA评分无明显差异.两组均未发生严重并发症.结论:与经皮激光椎间盘减压术相比,经皮椎间盘等离子消融术治疗颈椎间盘突出症患者症状消失更快.     

Bryan颈椎间盘假体置换术对脊髓型颈椎病患者疗效及颈椎生物力学的影响

目的:探讨Bryan颈椎间盘假体置换术对脊髓型颈椎病患者疗效及颈椎生物力学的影响。方法:选取2015年1月到2016年12月期间在我院接受治疗的脊髓型颈椎病患者48例,根据手术方式的不同将其分为植骨融合组(25例)和假体置换组(23例),其中植骨融合组采用颈椎前路减压植骨融合术进行治疗,假体置换组采用Bryan颈椎间盘假体置换术进行治疗。比较两组患者的日本骨科协会(JOA)颈椎评分、颈椎功能障碍指数(NDI)评分、视觉模拟疼痛量表(VAS)评分、颈椎生理曲度、颈椎活动度、手术节段活动度、上邻近节段活动度、下邻近节段活动度,并比较两组患者的并发症情况。结果:术后12个月假体置换组的NDI评分明显低于植骨融合组(P0.05);术后6个月、术后12个月植骨融合组的颈椎活动度低于假体置换组(P0.05);术后1个月、术后3个月、术后6个月、术后12个月假体置换组的手术节段活动度高于植骨融合组(P0.05);术后12个月植骨融合组的上邻近节段活动度、下邻近节段活动度高于假体置换组(P0.05);两组患者随访期间颈部轴性症状发生率比较差异有统计学意义(P0.05)。结论:与颈椎前路减压植骨融合术比较,Bryan颈椎间盘假体置换术对脊髓型颈椎病患者的远期疗效更佳,可更好的改善患者的颈椎生物力学,降低颈部轴性症状发生率,值得临床推广应用。     

Bryan人工椎间盘置换术治疗颈椎病的研究进展

Bryan人工椎间盘置换术是治疗颈椎椎间盘退行性变的有效手段,与传统的颈前路植骨融合内固定术比较,颈椎人工椎间盘置换的最大优势在于在有效减压的同时重建节段的运动功能,使整个颈椎运动学特征最大程度地接近于置换前的生理状态,减少传统融合术后由于融合节段运动功能丧失所造成的相邻节段过度运动和应力集中,从而避免相邻节段退变的发生和发展.但没有统一的适应症标准、缺乏远期的临床观察、昂贵的费用等问题阻碍了其在临床上的广泛应用,该文着重进行颈椎人工椎间盘的生物力学特点、适应症与禁忌症、临床疗效以及并发症的文献综述.     

人工颈椎间盘置换与颈前路减压植骨融合术治疗脊髓型颈椎病近期疗效的回顾性研究

摘要 目的：回顾性分析人工颈椎间盘置换（ADR）与颈前路减压植骨融合术（ACDF）治疗脊髓型颈椎病（CSM）的近期疗效。方法：回顾性选取2016年7月~2018年12月期间我院收治的CSM患者120例,上述患者根据手术方式的不同分为A组（n=58,ACDF治疗）和B组（n=62,ADR治疗）,比较两组患者疗效、围术期指标、生活质量简表（SF-12）评分、日本矫形外科协会（JOA）评分、颈椎活动度及并发症发生情况。结果：B组术后12个月的优良率为74.19%（46/62）,高于A组的53.45%（31/58）（P<0.05）。两组患者术后6个月、术后12个月躯体健康评分、精神健康评分均较术前升高,且B组高于A组（P<0.05）。B组术后1个月、术后3个月、术后6个月、术后12个月JOA评分和颈椎活动度均高于A组（P<0.05）。B组住院时间、术后颈托固定时间、术后恢复工作时间均短于A组（P<0.05）。两组术后并发症发生率比较差异无统计学意义（P>0.05）。结论：与ACDF治疗相比,ADR治疗CSM的近期疗效显著,可有效改善患者脊椎功能及生活质量,且安全性较好,临床应用价值较高。     

Genetic and Functional Studies of the Intervertebral Disc: A Novel Murine Intervertebral Disc Model

Intervertebral disc (IVD) homeostasis is mediated through a combination of micro-environmental and biomechanical factors, all of which are subject to genetic influences. The aim of this study is to develop and characterize a genetically tractable, ex vivo organ culture model that can be used to further elucidate mechanisms of intervertebral disc disease. Specifically, we demonstrate that IVD disc explants (1) maintain their native phenotype in prolonged culture, (2) are responsive to exogenous stimuli, and (3) that relevant homeostatic regulatory mechanisms can be modulated through ex-vivo genetic recombination. We present a novel technique for isolation of murine IVD explants with demonstration of explant viability (CMFDA/propidium iodide staining), disc anatomy (H&E), maintenance of extracellular matrix (ECM) (Alcian Blue staining), and native expression profile (qRT-PCR) as well as ex vivo genetic recombination (mT/mG reporter mice; AdCre) following 14 days of culture in DMEM media containing 10% fetal bovine serum, 1% L-glutamine, and 1% penicillin/streptomycin. IVD explants maintained their micro-anatomic integrity, ECM proteoglycan content, viability, and gene expression profile consistent with a homeostatic drive in culture. Treatment of genetically engineered explants with cre-expressing adenovirus efficaciously induced ex vivo genetic recombination in a variety of genetically engineered mouse models. Exogenous administration of IL-1ß and TGF-ß3 resulted in predicted catabolic and anabolic responses, respectively. Genetic recombination of TGFBR1^fl/fl explants resulted in constitutively active TGF-ß signaling that matched that of exogenously administered TGF-ß3. Our results illustrate the utility of the murine intervertebral disc explant to investigate mechanisms of intervertebral disc degeneration.     

Mild Obesity,Physical Activity,Calorie Intake,and the Risks of Cervical Intraepithelial Neoplasia and Cervical Cancer

Objective

We investigated whether obesity, physical activity, and calorie intake are associated with the risks of cervical intraepithelial neoplasia (CIN) and cervical cancer.

Methods

We enrolled 1125 women (age, 18–65 years) into a human papillomavirus cohort study established from 2006 to 2012. Multinomial logistic regression models were used to estimate crude and multivariate odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs), and to assess whether body mass index (BMI), height, weight, total calorie intake, and physical activity were associated with the risks of CIN and cervical cancer.

Results

Cervical cancer risk was positively associated with BMI and inversely associated with physical activity. When compared with women with a normal BMI (18.5–23 kg/m²), the multivariate ORs (95% CIs) for those overweight (23–25 kg/m²) and mild obesity (≥25 kg/m²) were 1.25 (0.79–2.00) and 1.70 (1.10–2.63), respectively. When compared with women with the lowest tertile of physical activity (<38.5 MET-hours/week), the ORs (95% CIs) for cervical cancer were 0.95 (0.61–1.48) and 0.61 (0.38–0.98) for women with medium physical activity (38.5–71.9 MET-hours/week) and those with high physical activity (72 MET-hours/week), respectively (p for linear trend  = 0.03). The CIN2/3 risk was inversely associated with physical activity after adjustment for confounders. Compared with women with low physical activity (< 38.5 MET-hours/week), the ORs (95% CIs) for CIN2/3 were 0.64 (0.40–1.01) and 0.58 (0.36–0.93) for the medium and high physical activity groups, respectively (p for linear trend  = 0.02). Total calorie intake was not statistically associated with the risks of CIN and cervical cancer after adjustment for confounders.

Conclusion

Our results indicate that in addition to screening for and treatment of CIN, recommendations on the maintenance of an appropriate BMI with an emphasis on physical activity could be an important preventive strategy against the development of cervical cancer.     

腰椎间盘突出症260例临床分析

目的:总结腰椎间盘突出症的临床特点及诊治要点。方法:回顾性分析260例腰椎间盘突出症手术患者的临床资料。结果:直腿抬高与影像学检查结果符合率为100%,治疗优良率达88.08%,有效率100%。结论:腰、下肢和臀部疼痛、下肢麻木、体位改变、运动障碍、感觉障碍、肌萎缩都是腰椎间盘突出症的主要临床表现;直腿抬高试验高试验可作为早期诊断的重要参考指标,要要根据惠者体征、病程等具体情况选择适合的最佳治法。     

Cervical cancer development,chemoresistance, and therapy: a snapshot of involvement of microRNA

Cervical cancer (CC) is one of the leading causes of death in women due to cancer and a major concern in the developing world. Persistent human papilloma virus (HPV) infection is the major causative agent for CC. Besides HPV infection, genetic and epigenetic factors including microRNA (miRNA) also contribute to the malignant transformation. Earlier studies have revealed that miRNAs participate in cell proliferation, invasion and metastasis, angiogenesis, and chemoresistance processes by binding and inversely regulating the target oncogenes or tumor suppressor genes. Based on functions and mechanistic insights, miRNAs have been identified as cellular modulators that have an enormous role in diagnosis, prognosis, and cancer therapy. Signatures of miRNA could be used as diagnostic markers which are necessary for early diagnosis and management of CC. The therapeutic potential of miRNAs has been shown in CC; however, more comprehensive clinical trials are required for the clinical translation of miRNA-based diagnostics and therapeutics. Understanding the molecular mechanism of miRNAs and their target genes has been useful to develop miRNA-based therapeutic strategies for CC and overcome chemoresistance. In this review, we summarize the role of miRNAs in the development, progression, and metastasis of CC as well as chemoresistance. Further, we discuss the diagnostic and therapeutic potential of miRNAs to overcome chemoresistance and treatment of CC.

     

Population-Level Scale-Up of Cervical Cancer Prevention Services in a Low-Resource Setting: Development,Implementation, and Evaluation of the Cervical Cancer Prevention Program in Zambia

Background

Very few efforts have been undertaken to scale-up low-cost approaches to cervical cancer prevention in low-resource countries.

Methods

In a public sector cervical cancer prevention program in Zambia, nurses provided visual-inspection with acetic acid (VIA) and cryotherapy in clinics co-housed with HIV/AIDS programs, and referred women with complex lesions for histopathologic evaluation. Low-cost technological adaptations were deployed for improving VIA detection, facilitating expert physician opinion, and ensuring quality assurance. Key process and outcome indicators were derived by analyzing electronic medical records to evaluate program expansion efforts.

Findings

Between 2006-2013, screening services were expanded from 2 to 12 clinics in Lusaka, the most-populous province in Zambia, through which 102,942 women were screened. The majority (71.7%) were in the target age-range of 25–49 years; 28% were HIV-positive. Out of 101,867 with evaluable data, 20,419 (20%) were VIA positive, of whom 11,508 (56.4%) were treated with cryotherapy, and 8,911 (43.6%) were referred for histopathologic evaluation. Most women (87%, 86,301 of 98,961 evaluable) received same-day services (including 5% undergoing same-visit cryotherapy and 82% screening VIA-negative). The proportion of women with cervical intraepithelial neoplasia grade 2 and worse (CIN2+) among those referred for histopathologic evaluation was 44.1% (1,735/3,938 with histopathology results). Detection rates for CIN2+ and invasive cervical cancer were 17 and 7 per 1,000 women screened, respectively. Women with HIV were more likely to screen positive, to be referred for histopathologic evaluation, and to have cervical precancer and cancer than HIV-negative women.

Interpretation

We creatively disrupted the ''no screening'' status quo prevailing in Zambia and addressed the heavy burden of cervical disease among previously unscreened women by establishing and scaling-up public-sector screening and treatment services at a population level. Key determinants for successful expansion included leveraging HIV/AIDS program investments, and context-specific information technology applications for quality assurance and filling human resource gaps.