Zhiwei Jia

Blocking the Function of Inflammatory Cytokines and Mediators by Using IL-10 and TGF-β: A Potential Biological Immunotherapy for Intervertebral Disc Degeneration in a Beagle Model

The debilitating effects of lower back pain are a major health issue worldwide. A variety of factors contribute to this, and oftentimes intervertebral disk degeneration (IDD) is an underlying cause of this disorder. Inflammation contributes to IDD, and inflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β, play key roles in the pathology of IDD. Therefore, the development of treatments that inhibit the expression and/or effects of TNF-α and IL-1β in IDD patients should be a promising therapeutic approach to consider. This study characterized the potential to suppress inflammatory cytokine production in degenerative intervertebral disc (NP) cells by treatment with IL-10 and TGF-β in a canine model of IDD. IDD was induced surgically in six male beagles, and degenerative NP cells were isolated and cultured for in vitro studies on cytokine production. Cultured degenerative NP cells were divided into four experimental treatment groups: untreated control, IL-10-treated, TGF-β-treated, and IL-10- plus TGF-β-treated cells. Cultured normal NP cells served as a control group. TNF-α expression was evaluated by fluorescence activated cell sorting (FACS) analysis and enzyme-linked immunosorbent assay (ELISA); moreover, ELISA and real-time PCR were also performed to evaluate the effect of IL-10 and TGF-β on NP cell cytokine expression in vitro. Our results demonstrated that IL-10 and TGF-β treatment suppressed the expression of IL-1β and TNF-α and inhibited the development of inflammatory responses. These data suggest that IL-10 and TGF-β should be evaluated as therapeutic approaches for the treatment of lower back pain mediated by IDD.

Hybrid surgery for multilevel cervical degenerative disc diseases: a systematic review of biomechanical and clinical evidence

PurposeThe optimal surgical technique for multilevel cervical degenerative disc diseases (DDD) remains controversial. Hybrid surgery (HS) incorporating anterior cervical discectomy and fusion (ACDF) and cervical disc replacement (CDR) is increasingly performed for cervical DDD. This study aims to evaluate the biomechanical and clinical evidence available for HS and to provide a systematic review of current understanding of HS.MethodsThis systematic review was undertaken by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. Multiple databases and online registers of clinical trials were searched up to February 2014. The biomechanical and clinical studies on HS for cervical DDD written in English were included. Two authors independently assessed methodological quality and extracted data.ResultsFifteen studies including eight biomechanical studies and seven clinical studies were indentified. The biomechanical studies showed that HS was benefit to motion preservation of the operative levels and revealed less adverse effect on adjacent segments. All clinical studies demonstrated improvement in validated functional scores after HS. Segment motion and immobilization were achieved at the arthroplasty level and arthrodesis level, respectively. Postoperative assessments and complication rate were similar or in favor of HS when comparing with ACDF or CDR. However, the overall quality of evidence for HS was low to very low.ConclusionsThere is a paucity of high quality evidence for HS. HS may be a safe and efficacious technique to benefit a select group of multilevel cervical DDD, which is needed to be confirmed by further prospective, randomized controlled trials.

The 50 Most-cited Articles in Orthopaedic Surgery From Mainland China

BackgroundCitation analysis has been widely used to evaluate the impact of articles in medical and surgical specialties. Although China is the most populous country in the world, and although more than 50,000 orthopaedic surgeons practice there, to our knowledge no formal citation analysis of Chinese orthopaedic articles has been performed.Questions/purposesWe identified the 50 most-cited orthopaedic articles from mainland China and evaluated these articles in terms of their language of publication, source journals, and topics.MethodsScience Citation Index Expanded was searched in July 31, 2014 for citations of articles published in 70 selected journals since the inception of the database. The 50 most-cited orthopaedic articles originating in mainland China were identified. Basic information, including title, authors, year of publication, article type, journal in which the work was published, city, institution, number of citations, decade published, and topic or subspecialty of the research were recorded.ResultsThe number of citations for the top 50 papers ranged from 181 to 31 (mean, 52). These articles were published between 1981 and 2010. The decade of 2000 to 2009 was the most prolific, with 36 of the top 50 articles published during this time. All articles were written in English and they were published in a total of 16 journals. The journal Spine published the largest number of articles (12), followed by Clinical Orthopaedics and Related Research® (seven). The journal Lancet had the highest impact factor (39.207 for 2013) among any of the journals that published articles we identified. The top 50 articles originated mainly from Beijing (16) and Shanghai (12), with basic research being the focus of the majority (27 of 50; 54%); the remaining were clinical studies. Bone was the most-investigated topic in basic research; the spine was the most-common topic among the identified clinical studies.ConclusionsThe 50 most-cited articles that we identified should be considered influential, although a large gap remains between mainland China and the global orthopaedic community in terms of citations per article. Nevertheless, insofar as the most-recent decade of our survey generated the most articles in this top-50 list, we would characterize mainland China’s effect on musculoskeletal research as increasing, and as funding increases to programs in mainland China, we anticipate this trend will continue in the future.

Fusion-nonfusion hybrid construct versus anterior cervical hybrid decompression and fusion: a comparative study for 3-level cervical degenerative disc diseases.

Study Design. A retrospective analysis. Objective. This study aimed to compare the safety and efficacy between the fusion-nonfusion hybrid construct (HC: anterior cervical corpectomy and fusion plus artificial disc replacement, ACCF plus cADR) and anterior cervical hybrid decompression and fusion (ACHDF: anterior cervical corpectomy and fusion plus discectomy and fusion, ACCF plus ACDF) for 3-level cervical degenerative disc diseases (cDDD). Summary of Background Data. The optimal anterior technique for 3-level cDDD remains uncertain. Long-segment fusion substantially induced biomechanical changes at adjacent levels, which may lead to symptomatic adjacent segment degeneration. Hybrid surgery consisting of ACDF and cADR has been reported with good results for 2-level cDDD. In this context, ACCF combining with cADR may be an alternative to ACHDF for 3-level cDDD. Methods. Between 2009 and 2012, 28 patients with 3-level cDDD who underwent HC (n = 13) and ACHDF (15) were retrospectively reviewed. Clinical assessments were based on Neck Disability Index, Japanese Orthopedic Association disability scale, visual analogue scale, Japanese Orthopedic Association recovery rate, and Odom criteria. Radiological analysis included range of motion of C2–C7 and adjacent segments and cervical lordosis. Perioperative parameters, radiological adjacent-level changes, and the complications were also assessed. Results. HC showed better Neck Disability Index improvement at 12 and 24 months, as well as Japanese Orthopedic Association and visual analogue scale improvement at 24 months postoperatively (P < 0.05). HC had better outcome according to Odom criteria but not significantly (P > 0.05). The range of motion of C2–C7 and adjacent segments was less compromised in HC (P < 0.05). Both 2 groups showed significant lordosis recovery postoperatively (P < 0.05), but no difference was found between groups (P > 0.05). The incidence of adjacent-level degenerative changes and complications was higher in ACHDF but not significantly (P > 0.05). Conclusion. HC may be an alternative to ACHDF for 3-level cDDD due to the equivalent or superior early clinical outcomes, less compromised C2–C7 range of motion, and less impact at adjacent levels. Level of Evidence: 3

Operative versus nonoperative treatment for complex proximal humeral fractures: a meta-analysis of randomized controlled trials.

Whether operative treatment for complex proximal humeral fractures has a greater benefit over nonoperative treatment is uncertain. The authors conducted a meta-analysis to include all randomized controlled trials (RCTs) to determine the advantages and disadvantages of operative vs nonoperative treatment. Multiple databases, online registries of RCTs, and proceedings from major meetings were systematically searched up to November 2012. Randomized controlled trials comparing operative and non-operative treatment for 3- and 4-part proximal humeral fractures were included. Two authors independently assessed methodological quality and extracted data. Seven articles with a total of 286 patients met inclusion criteria. No significant differences were found between operative and nonoperative treatment regarding Constant score, the Disabilities of the Arm, Shoulder and Hand score, American Shoulder and Elbow Surgeons score, Simple Shoulder Test, 15 Dimensions, and complications. Health-related quality of life according to the EuroQol-5D score in operative treatment showed statistically, but not clinically, significant improvement compared with nonoperative treatment. Operative treatment could significantly increase the incidence of additional surgery at 12- and 24-month follow-up compared with nonoperative treatment. However, sensitivity analysis showed a higher additional surgery rate at 12-month follow-up remained unstable. On the basis of current evidence, both operative and nonoperative treatment can achieve a similar treatment effect on complex proximal humeral fractures, but operative treatment may increase the occurrence of additional surgery. However, due to some limitations, the result of this meta-analysis should be cautiously interpreted, and further studies are needed.

Total disc replacement versus fusion for lumbar degenerative disc disease: a systematic review of overlapping meta-analyses.

PurposeAlthough many meta-analyses have been performed to compare total disc replacement (TDR) and fusion for treating lumbar degenerative disc disease (LDDD), their findings are inconsistent. This study aimed to conduct a systematic review of overlapping meta-analyses comparing TDR with fusion for treating LDDD, to assist decision makers in selection among conflicting meta-analyses, and to provide treatment recommendations based on the best available evidence.MethodsThis study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Multiple databases were comprehensively searched for meta-analyses comparing TDR with fusion for treating LDDD. Meta-analyses only comprising randomised controlled trials (RCTs) were included. Two authors independently assessed meta-analysis quality and extracted data. The Jadad decision algorithm was used to ascertain which meta-analyses represented the best evidence.ResultsA total of five meta-analyses were included. All these studies only included RCTs were determined as Level-II evidence. The scores of Assessment of Multiple Systematic Reviews (AMSTAR) ranged from 6 to 9 (median 7). A high-quality Cochrane review was chosen according to the Jadad algorithm. This best available evidence found that statistical significances were observed between TDR and fusion for LDDD regarding disability, pain relief, and pain in the short term, but it was not over clinically important differences. The prevent effects on adjacent segment and facet joint degeneration, as the primary goal of adopting TDR stated by the manufacturers, were not appropriately evaluated.ConclusionsThere is discord in results from meta-analyses that assessed TDR and fusion for LDDD. According to this systematic review of overlapping meta-analyses comparing TDR and fusion for LDDD, the current best available evidence suggests that TDR may be an effective technique for the treatment of selected patients with LDDD, and is at least equal to lumbar fusion in the short term. However, considering that disadvantages may appear after years, spine surgeons should be cautions about performing TDR on a large scale.

Is surgical intervention more effective than non-surgical treatment for acute Achilles tendon rupture? A systematic review of overlapping meta-analyses

OBJECTIVE There is discordance in the results from meta-analyses on surgical versus non-surgical treatment for acute Achilles tendon rupture. We systematically reviewed the overlapping meta-analyses on this topic to provide information that will be helpful to decision makers when selecting treatments based on the current best available evidence. METHODS We comprehensively searched multiple databases for systematic reviews that compared surgical and non-surgical treatments for acute Achilles tendon rupture. We only included meta-analyses that comprised randomized controlled trials (RCTs). The methodological quality and extracted data were assessed. The meta-analysis that offered the best evidence was ascertained with the Jadad decision algorithm. RESULTS Nine meta-analyses were included in our study and all of them included RCTs with Level-II evidence. Assessment of Multiple Systematic Reviews (AMSTAR) scores ranged from 5 to 10 (median 7). The Jadad decision algorithm was used to select a high-quality meta-analysis with more RCTs. The results from this study showed that when functional rehabilitation was used, non-surgical intervention was similar to surgical treatment regarding the incidence of range of motion, rerupture, calf circumference and functional outcomes, and the incidence of other complications was reduced. Non-surgical intervention significantly increased the rerupture rate if functional rehabilitation was not considered. CONCLUSIONS The findings of meta-analyses regarding surgical versus non-surgical treatment for acute Achilles tendon rupture are inconsistent. According to this systematic review of overlapping meta-analyses, the current best available evidence suggests that centers offering functional rehabilitation may prefer non-surgical intervention. Surgical treatment may be preferred at centers that do not have functional rehabilitation.

Functional Self-Assembled Peptide Nanofibers for Bone Marrow Mesenchymal Stem Cell Encapsulation and Regeneration in Nucleus Pulposus

Low back pain (LBP) is mainly caused by intervertebral disc degeneration (IDD). Recent studies have demonstrated that the transplantation of mesenchymal stem cells (MSCs) can regenerate regions that have undergone degeneration, and the regenerative effect can be enhanced by using a hydrogel carrier. This article describes an injectable functional hydrogel system manufactured by combining RADA16-I and RADA-KPSS (RADA-KPSS was manufactured by conjugating a bioactive motif derived from BMP-7 [KPSS] onto the C terminal of RADA16-I) at a volume ratio of 1:1. This hydrogel system can enhance the proliferation, differentiation, and chemotactic migration of BMSCs. In addition, the encapsulation of BMSCs with this system maintains cell viability for a long period after transplantation into an ex vivo cultured disc model. In conclusion, KPSS-conjugated RADKPS is an ideal encapsulation system for BMSCs in intervertebral disc (IVD) regeneration.

Erratum to: Biomechanical consideration of prosthesis selection in hybrid surgery for bi-level cervical disc degenerative diseases

Purpose Hybrid surgery (HS) coupling total disc replacement and fusion has been increasingly applied for multilevel cervical disc diseases (CDD). However, selection of the optimal disc prosthesis for HS in an individual patient has not been investigated. This study aimed to distinguish the biomechanical performances of five widely used prostheses (Bryan, ProDisc-C, PCM, Mobi-C, and Discover) in HS for the treatment of bi-level CDD. Methods A finite element model of healthy cervical spine (C3–C7) was developed, and five HS models using different disc prostheses were constructed by arthrodesis at C4–C5 and by arthroplasty at C5–C6. First, the rotational displacements in flexion (Fl), extension, axial rotation, and lateral bending in the healthy model under 1.0 Nm moments combined with 73.6 N follower load were achieved, and then the maximum rotations in each direction combined with the same follower load were applied in the surgical models following displacement control testing protocols. Results The range of motion (ROM) of the entire operative and adjacent levels was close to that of the healthy spine for ball-in-socket prostheses, that is, ProDisc-C, Mobi-C, and Discover, in Fl. For Bryan and PCM, the ROM of the operative levels was less than that of the healthy spine in Fl and resulted in the increase in ROMs at the adjacent levels. Ball-in-socket prostheses produced similar reaction moments (92–99 %) in Fl, which were close to that of the healthy spine. Meanwhile, Bryan and PCM required greater moments ([130 %). The adjacent intradiscal pressures (IDPs) in the models of ball-in-socket prostheses were close to that of the healthy spine. Meanwhile, in the models of Bryan and PCM, the adjacent IDPs were 25 % higher than that of the ball-in-socket models. The maximum facet stress in the model of Mobi-C was the greatest among all prostheses, which was approximately two times that of the healthy spine. Moreover, Bryan produced the largest stress on the bone–implant interface, followed by PCM, Mobi-C, ProDisc-C, and Discover. Conclusion Each disc prosthesis has its biomechanical advantages and disadvantages in HS and should be selected on an individual patient basis. In general, ProDisc-C, Mobi-C, and Discover produced similar performances in terms of spinal motions, adjacent IDPs, and driving moments, whereas Bryan and PCM produced similar biomechanical performances. Therefore, HS with Discover, Bryan, and PCM may be suitable for patients with potential risk of facet joint degeneration, whereas HS with ProDisc-C, Mobi-C, and Discover may be suitable for patients with potential risk of vertebral osteoporosis. & Yubo Fan yubofan@buaa.edu.cn 1 National Research Center for Rehabilitation Technical Aids, Beijing, People’s Republic of China 2 Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, International Joint Research Center of Aerospace Biotechnology and Medical Engineering of Ministry of Science and Technology, School of Biological Science and Medical Engineering, Beihang University, Beijing, People’s Republic of China 3 Department of Orthopaedics, The 306th Hospital of People’s Liberation Army, Beijing, People’s Republic of China 4 Interdisciplinary Division of Biomedical Engineering, The Hong Kong Polytechnic University, Hong Kong, SAR, People’s Republic of China

Age-Related Changes in Nucleus Pulposus Mesenchymal Stem Cells: An In Vitro Study in Rats

The functions of mesenchymal stem cells (MSCs) appear to decline with age due to cellular senescence, which could reduce the efficacy of MSCs-based therapies. Recently, MSCs have been identified in the nucleus pulposus, which offers great potential for intervertebral disc (IVD) repair. However, this potential might be affected by the senescence of nucleus pulposus MSCs (NPMSCs), but whether or not this exists remains unknown. The aim of this study was to investigate the age-related changes in NPMSCs. NPMSCs isolated from young (3-month-old) and old (14-month-old) Sprague-Dawley rats were cultured in vitro. Differences in morphology, proliferation, colony formation, multilineage differentiation, cell cycle, and expression of β-galactosidase (SA-β-gal) and senescent markers (p53, p21, and p16) were compared between groups. Both young and old NPMSCs fulfilled the criteria for definition as MSCs. Moreover, young NPMSCs presented better proliferation, colony-forming, and multilineage differentiation capacities than old NPMSCs. Old NPMSCs displayed senescent features, including significantly increased G0/G1 phase arrest, increased SA-β-gal expression, decreased S phase entry, and significant p53-p21-pRB pathway activation. Therefore, this is the first study demonstrating that senescent NPMSCs accumulate in IVD with age. The efficacy of NPMSCs is compromised by donor age, which should be taken into consideration prior to clinical application.