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Summary Objective Low back pain (LBP) is the predominant cause of disc degeneration in patients, which brings serious social problems and economic burdens. Increasing evidence has indicated that intervertebral disc degeneration (IDD) is one of the most common causes triggering LBP. Accumulating evidence has shown that circRNAs are involved in the pathological process of IDD. Nevertheless, the circRNA-mediated IDD pathogenesis still remains unknown. This study explored the potential mechanism and functions of circ-FAM169A in NPCs. Methods Bioinformatics analysis was conducted to identify key circRNA, miRNA and mRNA and predict their potential role in IDD. Dual-luciferase reporter assay, western blot, qRT-PCR, and fluorescence in situ hybridisation (FISH) were used to demonstrate the interaction among circ-FAM169A, miR-583 and Sox9 in NPCs. Results Herein, we identified circ-FAM169A, which was dramatically up-regulated in degenerative nucleus pulposus (NP) tissues and negatively correlated with expression levels of miR-583. We constructed a circ-FAM169A-miR-583-mRNAs co-expression network and predicted circ-FAM169A-miR-583 pathway predominantly involved in extracellular matrix metabolism and cell apoptosis etc. FISH experiments confirmed circ-FAM169A and miR-583 co-existence in the cytoplasm of NPCs. Luciferase reporter assay illustrated that circ-FAM169A was directly bound to miR-583 and Sox9 was the directly target gene of miR-583. Additionally, miR-583 negatively regulated Sox9 mRNA and protein levels in NPCs. Conclusion Findings of this study indicated that circ-FAM169A-miR-583 pathway may play a significant role in the regulation of IDD, which will provide novel diagnostic biomarkers and develop effective treatment strategy of IDD diseases. The translational potential of this article This study suggested that circ-FAM169A-miR-583 pathway may regulate NPCs apoptosis and extracellular matrix synthesis and catabolism by targeting Sox9. It provides a novel therapeutic target and strategy for IVDD diseases.

BackgroundChina has the largest population of traumatic spinal cord injury (TSCI), but has not yet performed a national-level study on its epidemiological and clinical features, treatment status, and economic burden.MethodsA total of 14 754 patients were recruited between January 2013 and December 2018 from 37 hospitals in 11 provinces and municipalities, which represented all geographical divisions of China. The percentage of TSCI in hospitalized patients and the percentage of TSCI in hospitalized patients through the orthopaedic departments were calculated. The treatment status, total and daily costs were collected.ResultsThe percentage of TSCI in hospitalized patients and the percentage of TSCI in hospitalized patients through the orthopaedic departments did not change significantly overall (APC= -0.5%, 95% CI: -3.0 to 2.1 and -1.6%, -4.9 to 1.8, respectively). A total of 10 918 (74.0%) patients received surgery after TSCI. However, only 3.0% of patients underwent surgery received surgery less than 24 hours after injury. A total of 2 084 (14.1%) patients were treated with methylprednisolone sodium succinate/methylprednisolone (MPSS/MP) at a high dose (≥500 mg) and 641 (4.3%) patients receiving it within 8 hours. The total costs for acute TSCI decreased (-4.8%, -6.2 to -3.4), while the daily costs did not change significantly (0.5%, -1.2 to 2.2).ConclusionsThis study revealed epidemiological and clinical features, treatment status, and economic burden of TSCI that occurred in China from 2013 to 2018.FundingNational Key Research and Development Project of Stem Cell and Transformation Research (2019YFA0112100).

Epigenetic modifications play an important role in central nervous system disorders. As a widespread posttranscriptional RNA modification, the role of the m5C modification in cerebral ischemia-reperfusion injury (IRI) remains poorly defined. Here, we successfully constructed a neuronal oxygen-glucose deprivation/reoxygenation (OGD/R) model and obtained an overview of the transcriptome-wide m5C profiles using RNA-BS-seq. We discovered that the distribution of neuronal m5C modifications was highly conserved, significantly enriched in CG-rich regions and concentrated in the mRNA translation initiation regions. After OGD/R, modification level of m5C increased, whereas the number of methylated mRNA genes decreased. The amount of overlap of m5C sites with the binding sites of most RNA-binding proteins increased significantly, except for that of the RBM3-binding protein. Moreover, hypermethylated genes in neurons were significantly enriched in pathological processes, and the hub hypermethylated genes RPL8 and RPS9 identified by the protein-protein interaction network were significantly related to cerebral injury. Furthermore, the upregulated transcripts with hypermethylated modification were enriched in the processes involved in response to stress and regulation of apoptosis, and these processes were not identified in hypomethylated transcripts. In final, we verified that OGD/R induced neuronal apoptosis in vitro using TUNEL and western blot assays. Our study identified novel m5C mRNAs associated with ischemia-reperfusion in neurons, providing valuable perspectives for future studies on the role of the RNA methylation in cerebral IRI.

Lower back pain (LBP) is one of the most common reasons for seeking medical advice in orthopedic clinics. Increasingly, research has shown that symptomatic intervertebral disc degeneration (IDD) is mostly related to LBP. This review first outlines the research and findings of studies into IDD, from the physiological structure of the intervertebral disc (IVD) to various pathological cascades. The vicious cycles of IDD are re-described in relation to the analysis of the relationship among the pathological mechanisms involved in IDD. Interestingly, a ‘chief molecule’ was found, hypoxia-inducible factor-1α (HIF-1α), that may regulate all other mechanisms involved in IDD. When the vicious cycle is established, the low oxygen tension activates the expression of HIF-1α, which subsequently enters into the hypoxia-induced HIF pathways. The HIF pathways are dichotomized as friend and foe pathways according to the oxygen tension of the IVD microenvironment. Combined with clinical outcomes and previous research, the trend of IDD development has been predicted in this paper. Lastly, an early precautionary diagnosis and treatment method is proposed whereby nucleus pulposus tissue for biopsy can be obtained through IVD puncture guided by B-ultrasound when the patient is showing symptoms but MRI imaging shows negative results. The assessment criteria for biopsy and the feasibility, superiority and challenges of this approach have been discussed. Overall, it is clear that HIF-1α is an indispensable reference indicator for the accurate diagnosis and treatment of IDD.

Neural stem cells (NSCs) are self-renewing, pluripotent, and undifferentiated cells which have benefits as candidates for central nervous system (CNS) injury. However, the transplanted NSCs usually maintain their undifferentiated characteristics, or differentiated potentially along the glial lineage after transplantation. MicroRNAs (miRNAs) are small, non-coding RNAs that play key roles in cell differentiation. However, it is unknown whether miR-29a could play a role in the process of NSC's differentiation. Primary NSCs were derived from rat embryonic cortex. Lentiviral vector-mediated miR-29a (LV-miR-29a) and negative control (LV-null) were infected into NSCs. Quantitative real-time PCR was used to detect expression of miR-29a and PTEN. Immunocytochemistry was used to stain neurons, astrocytes, and oligodendrocytes. Dual luciferase assay to study the interaction between miR-29a and PTEN. The current study showed that the expression of miR-29a was upregulated during NSC differentiation, while the expression of PTEN was downregulated during NSC differentiation. After infection with LV-miR-29a, MAP-2-positive neurons significantly increased, and GFAP-positive astrocytes significantly decreased. Furthermore, we demonstrated that PTEN is a molecular target of miR-29a. miR-29a promote the neuronal differentiation and decrease the astrocytes differentiation of NSCs via targeting PTEN. This may give insight into a novel mechanism of NSC differentiation and provide a promising therapeutic target.

Long non-coding RNAs (lncRNAs) are widely accepted as key players in various biological processes. However, the roles of lncRNA in peripheral nerve regeneration remain completely unknown. Thus, in this study, we performed microarray analysis to measure lncRNA expression in the distal segment of the sciatic nerve at 0, 3, 7 and 14 days following injury. We identified 5,354 lncRNAs that were differentially expressed: 3,788 lncRNAs were differentially expressed between days 0 and 3; 3,314 lncRNAs were differentially expressed between days 0 and 7; and 2,400 lncRNAs were differentially expressed between days 0 and 14. The results of RT-qPCR of two dysregulated lncRNAs were consistent with those of microarray analysis. Bioinformatics approaches, including lncRNA classification, gene ontology (GO) analysis and target prediction, were utilized to investigate the functions of these dysregulated lncRNAs in peripheral nerve damage. Importantly, we predicted that several lncRNA-mRNA pairs may participate in biological processes related to peripheral nerve injury. RT-qPCR was performed for the preliminary verification of three lncRNA-mRNA pairs. The overexpression of NONMMUG014387 promoted the proliferation of mouse Schwann cells. Thus, the findings of our study may enhance our knowledge of the role of lncRNAs in nerve injury.

Valproic acid (VPA), an anticonvulsant and mood-stabilizing drug, can induce neuronal differentiation, promote neurite extension and exert a neuroprotective effect in central nervous system (CNS) injuries; however, comparatively little is known regarding its action on mouse embryonic neural stem cells (NSCs) and the underlying molecular mechanism. Recent studies suggested that c-Jun N-terminal kinase (JNK) is required for neurite outgrowth and neuronal differentiation during neuronal development. In the present study, we cultured mouse embryonic NSCs and treated the cells with 1 mM VPA for up to 7 days. The results indicate that VPA promotes the neuronal differentiation of mouse embryonic NSCs and neurite outgrowth of NSC-derived neurons; moreover, VPA induces the phosphorylation of c-Jun by JNK. In contrast, the specific JNK inhibitor SP600125 decreased the VPA-stimulated increase in neuronal differentiation of mouse embryonic NSCs and neurite outgrowth of NSC-derived neurons. Taken together, these results suggest that VPA promotes neuronal differentiation of mouse embryonic NSCs and neurite outgrowth of NSC-derived neurons. Moreover, JNK activation is involved in the effects of VPA stimulation.

Osteoprotegerin (OPG) is implicated in the pathogenesis of postmenopausal osteoporosis, and other metabolic bone diseases caused by estrogen deficiency. Previous studies have demonstrated that estrogen may stimulate OPG expression in osteoblast cells at the transcriptional level; however, whether estrogen can regulate OPG expression at a post-transcriptional level remains elusive. The present study aimed to investigate the role of microRNA (miRNA) in estrogen‑mediated OPG production in human osteoblast‑like MG‑63 cells. The results from ELISA, western blotting and reverse transcription-quantitative polymerase chain reaction (RT‑qPCR) confirmed that estrogen may upregulate OPG expression. Mechanistic studies indicated that estrogen increased the activity of a luciferase reporter harboring the OPG 3'‑untranslated region (3'‑UTR). Bioinformatics analysis demonstrated that there is a potential targeting site in the OPG 3'‑UTR for miRNA (miR)‑145, which is associated with osteoblast differentiation. The results of an RT‑qPCR suggested that estrogen suppressed miR‑145 expression. In addition, dual‑luciferase assay, RT‑qPCR and western blot analysis indicated that miR‑145 directly targets and negatively regulates OPG expression. Furthermore, transfection of cells with miR‑145 mimics was able to partially inhibit the induction of OPG expression by estrogen, thus confirming the role of miR‑145 in estrogen‑mediated OPG induction. Taken together, the results of the present study demonstrated that estrogen may post-transcriptionally regulate OPG expression through suppression of miR-145 expression.

Background The aim of the present study was to evaluate whether vertebral augmentation technology increases the occurrence of adjacent vertebral fractures in patients with osteoporotic vertebral compression fractures (OVCFs). Materials and Methods Databases, including MEDLINE, EMBASE and Cochrane library, were retrieved via PRISMA covering 1987 to 2015. The number of patients who suffered from adjacent secondary vertebral fractures was calculated. A meta-analysis, using indexes of odds ratios (OR) and 95% confidence intervals (95% CI), was conducted with STATA software. Subgroup investigations were conducted according to the operation methods and the duration of observation. Sensitivity analysis and publication bias were also evaluated. Results Ten randomized controlled trials (RCTs) met our inclusion criteria. Our results indicated there was no statistically significant difference in the occurrence rate of adjacent vertebral fractures between manipulation of vertebral augmentation and non-surgical treatment (OR = 0.89, 95% CI = 0.58–1.37). Neither subgroup investigations based on selection of operation nor duration of follow-up time showed marked differences. A sensitivity analysis did not identify specific trails seriously deflected. No obvious publication bias was identified. Conclusion Despite various limitations in the present study, our data demonstrated that using vertebral augmentation was not related to increasing incidence of subsequent adjacent vertebral fractures.

The present study aimed to explore the role of the PTEN/Akt/mTOR signaling pathway in the neurite outgrowth and apoptosis of cortical neurons. Cortical neurons were seeded on or adjacent to chondroitin sulfate proteoglycans. The length, number and crossing behavior of the neurites were calculated. Immunohistochemical staining and TUNEL data were analyzed. Neurites treated with PTEN inhibitor exhibited significant enhancements in elongation, initiation and crossing abilities when they encountered chondroitin sulfate proteoglycans in vitro. These effects disappeared when the PTEN/Akt/mTOR signaling pathway was blocked. Neurons exhibited significant enhancements in survival ability following PTEN inhibition. The present study demonstrated that PTEN inhibition can promote axonal elongation and initiation in cerebral cortical neurons, as well as the ability to cross the chondroitin sulfate proteoglycan border. In addition, PTEN inhibition is useful for protecting the neuron from apoptosis. The PTEN/Akt/mTOR signaling pathway is an important signaling pathway.

Introduction: The purpose of this study was to provide a comprehensive understanding of gene expression during Wallerian degeneration and axon regeneration after peripheral nerve injury. Methods: A microarray was used to detect gene expression in the distal nerve 0, 3, 7, and 14 days after sciatic nerve crush. Bioinformatic analysis was used to predict function of the differentially expressed mRNAs. Microarray results and the key pathways were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: Differentially expressed mRNAs at different time-points (3, 7, and 14 days) after injury were identified and compared with a control group (0 day). Nine general trends of changes in gene expression were identified. Key signal pathways and 9 biological processes closely associated with nerve regeneration were identified and verified. Conclusions: Differentially expressed genes and biological processes and pathways associated with axonal regeneration may elucidate the molecular-biological mechanisms underlying peripheral nerve regeneration. Muscle Nerve 55: 373–383, 2017

Neural stem cells (NSCs) are characterized by their potential for self-renewal and ability to differentiate into neurons, astrocytes, and oligodendrocytes. They are of great value to scientific studies and clinical applications. Culturing NSCs in vitro is important for characterizing their properties under controlled environmental conditions that may be modified and monitored accurately. The present study explored a modified, detailed and efficient protocol for the isolation, culture and cryopreservation of rat embryonic NSCs. In particular, the viability, nestin expression, and self-renewal and multi-differentiation capabilities of NSCs cryopreserved for various periods of time (7 days, or 1, 6 or 12 months) were characterized and compared. Rat embryonic NSCs were successfully obtained and maintained their self-renewal and multipotent differentiation capabilities even following long-term cryopreservation (for up to 12 months).

Spinal cord injury (SCI) is a highly severe disease and it can lead to the destruction of the motor and sensory function resulting in temporary or permanent disability. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nt that play a critical role in central nervous system (CNS) injury. However, the exact roles of lncRNAs and messenger RNAs (mRNAs) in the early acute phase of SCI remain to be elucidated. We examined the expression of mRNAs and lncRNAs in a rat model at 2 days after SCI and identified the differentially expressed lncRNAs (DE lncRNAs) and differentially expressed mRNAs (DE mRNAs) using microarray analysis. Subsequently, a comprehensive bioinformatics analysis was also performed to clarify the interaction between DE mRNAs. A total of 3,193 DE lncRNAs and 4,308 DE mRNAs were identified between the injured group and control group. Classification, length distribution, and chromosomal distribution of the dysregulated lncRNAs were also performed. The gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed to identify the critical biological processes and pathways. A protein-protein interaction (PPI) network indicated that IL6, TOP2A, CDK1, POLE, CCNB1, TNF, CCNA2, CDC20, ITGAM, and MYC were the top 10 core genes. The subnetworks from the PPI network were identified to further elucidate the most significant functional modules of the DE mRNAs. These data may provide novel insights into the molecular mechanism of the early acute phase of SCI. The identification of lncRNAs and mRNAs may offer potential diagnostic and therapeutic targets for SCI.

Background Spinal cord injury (SCI) is a disease associated with high disability and mortality rates. The transitional phase from subacute phase to intermediate phase may play a major role in the process of secondary injury. Changes in protein expression levels have been shown to play key roles in many central nervous system (CNS) diseases. Nevertheless, the roles of proteins in the transitional phase of SCI are not clear. Methods We examined protein expression in a rat model 2 weeks after SCI and identified differentially expressed proteins (DEPs) using isobaric tagging for relative and absolute protein quantification (iTRAQ). Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEPs were performed. Furthermore, we constructed a protein-protein interaction (PPI) network, and the top 10 high-degree core nodes were identified. Meanwhile, we validated protein level changes of five high-degree core regulated proteins using Western blots. Results A total of 162 DEPs were identified between the injury group and the control, of which 101 (62.35%) were up-regulated and 61 (37.65%) were down-regulated in the transitional phase of SCI. Key molecular function, cellular components, biological process terms and pathways were identified and may be important mechanisms in the transitional phase of SCI. Alb, Calm1, Vim, Apoe, Syp, P4hb, Cd68, Eef1a2, Rab3a and Lgals3 were the top 10 high-degree core nodes. Western blot analysis performed on five of these proteins showed the same trend as iTRAQ results. Conclusion The current study may provide novel insights into how proteins regulate the pathogenesis of the transitional phase after SCI.

Aim: To explore neurite growth/regeneration and spinal cord injury repair after PTEN silencing via lentivirus-mediated RNAi. Materials & methods: Cortical neurons were seeded on or adjacent to chondroitin sulfate proteoglycans. The length, number and crossing behavior of neurites were calculated. Lentivirus was locally injected into spinal cord contusion rats. The functional recovery and immunohistochemical staining were analyzed. Results: Neurites with PTEN silencing exhibited significant enhancements in elongation, initiation and crossing ability when they encountered chondroitin sulfate proteoglycans in vitro. In vivo PTEN silencing improved functional recovery significantly, and promoted axon and synapse formation, but not scar formation. Conclusions: PTEN silencing may be promising for spinal cord injury repair.

Spinal cord injury (SCI) is difficult to treat because of secondary injury. Valproic acid (VPA) is clinically approved for mood stabilization, but also counteracts secondary damage to functionally rescue SCI in animal models by improving neuroprotection and neurogenesis via inhibition of HDAC and GSK-3. However, a comprehensive review summarizing the therapeutic benefits and mechanisms of VPA for SCI and the issues affecting clinical trials is lacking, limiting future research on VPA and impeding its translation into clinical therapy for SCI. This article presents the current status of VPA treatment for SCI, emphasizing interactions between enhanced neuroprotection and neurogenesis. Crucial issues are discussed to optimize its clinical potential as a safe and effective treatment for SCI.

Multipotent neural stem cells (NSCs) are currently under investigation as a candidate treatment for central nervous system (CNS) injury because of their potential to compensate for neuronal damage and to reconstruct disrupted neuronal connections. To maximize the regenerative effect of the derived neurons and to minimize the side effects of the derived astrocytes, it is necessary to regulate the fate determination of NSCs to produce more neurons and fewer astrocytes. Both valproic acid (VPA) and all-trans-retinoic acid (ATRA), two clinically established drugs, induce neuronal differentiation and facilitate neurite outgrowth at the expense of astrocytic differentiation in NSCs. However, the time-dependent activities and the long-term treatment effects of these drugs have not been explored in NSCs. More importantly, the efficacies of VPA and ATRA in neuronal promotion and astrocytic suppression remain unclear. In this study, we compare the time-dependent characteristics of VPA and ATRA in NSC differentiation and neurite outgrowth in vitro and, for the first time, demonstrate the improved efficacy of their combined application in neuronal induction and astrocytic suppression. These significant effects are closely coupled to the altered expression of a neurogenic transcription factor, a Wnt signaling component, a cell cycle regulator and a neural growth factor, indicating an underlying cross-talk between the mechanisms of action of ATRA and VPA. These findings indicate that a novel strategy combining these two therapeutic drugs may improve the restorative effect of NSC transplantation by altering the expression of their interconnected targets for fate determination.

Low back pain is the most common musculoskeletal condition with a high prevalence. There was no sufficient evidence to recommend that aquatic exercise was potentially beneficial to patients with low back pain. The aim of this study was to systematically analyze all evidence available in the literature about effectiveness of the aquatic exercise.A comprehensive search of PubMed, the Cochrane Library, Embase, and Cumulative Index to Nursing and Allied Health was conducted from their inceptions to November 2016 for randomized controlled trials, which concerned the therapeutic aquatic exercise for low back pain. The results were expressed in terms of standardized mean difference and the corresponding 95% confidence interval.Eight trials involving 331 patients were included in the meta-analysis, and the results showed a relief of pain (standardized mean difference = -0.65, 95% confidence interval = -1.16 to -0.14) and physical function (standardized mean difference = 0.63, 95% confidence interval = 0.17 to 1.09) after aquatic exercise. However, there was no significant effectiveness with regard to general mental health in aquatic group (standardized mean difference = 0.46; 95% confidence interval = -0.22 to 1.15).Aquatic exercise can statistically significantly reduce pain and increase physical function in patients with low back pain. Further high-quality investigations on a larger scale are required to confirm the results.

Background and purpose: Spinal cord injury (SCI) involves serious damage that can result in abnormal or absent motor and sensory functions and a disruption of autonomic function, and a series of pathological reactions occur after the injury. As a type of small non-coding RNA, microRNAs (miRNAs) have been verified to inhibit gene expression via post-transcriptional regulation. This review mainly focuses on recent advances regarding the roles of miRNAs following SCI. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were adopted. The studies regarding the roles of miRNAs following SCI were identified through PubMed, Embase and Web of Science. We summarise the changes in expression levels of miRNAs and discuss the roles of miRNAs after SCI. Results: A total of 77 empirical studies meeting the inclusion criteria were identified. Existing studies showed that miRNAs were temporally altered and had effects on apoptosis, inflammation, angiogenesis, astrogliosis, oligodendrocyte development, axonal regeneration and remyelination after SCI. The alteration of miRNAs and the regulative action of pathological reactions can also provide opportunities for potential therapeutic interventions. “miRNA replacement therapy” aims to transfer miRNAs into diseased cells via delivery techniques and improve targeting effectiveness in cells, and this novel therapeutic tool provides a promising technique to promote the repair of SCI and reduces functional deficits. Conclusions: This review is helpful for understanding the underlying mechanisms of SCI and the potential clinical value of miRNAs. miRNAs have the potential to be attractive tools and targets for novel diagnostic and therapeutic approaches of SCI.

// Zhongju Shi 1, * , Hengxing Zhou 1, * , Bin Pan 1, * , Lu Lu 1 , Yi Kang 1 , Lu Liu 1 , Zhijian Wei 1 and Shiqing Feng 1 1 Department of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, PR China * These authors have contributed equally to this work Correspondence to: Shiqing Feng, email: sqfeng@tmu.edu.cn Keywords: enchondromas, microarray, differentially expressed genes, pathways, protein–protein interaction Received: December 01, 2016 Accepted: March 06, 2017 Published: March 30, 2017 ABSTRACT Enchondromas are the most common primary benign osseous neoplasms that occur in the medullary bone; they can undergo malignant transformation into chondrosarcoma. However, enchondromas are always undetected in patients, and the molecular mechanism is unclear. To identify key genes and pathways associated with the occurrence and development of enchondromas, we downloaded the gene expression dataset GSE22855 and obtained the differentially expressed genes (DEGs) by analyzing high-throughput gene expression in enchondromas. In total, 635 genes were identified as DEGs. Of these, 225 genes (35.43%) were up-regulated, and the remaining 410 genes (64.57%) were down-regulated. We identified the predominant gene ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways that were significantly over-represented in the enchondromas samples compared with the control samples. Subsequently the top 10 core genes were identified from the protein-protein interaction (PPI) network. The enrichment analyses of the genes mainly involved in two significant modules showed that the DEGs were principally related to ribosomes, protein digestion and absorption, ECM-receptor interaction, focal adhesion, amoebiasis and the PI3K-Akt signaling pathway. Together, these data elucidate the molecular mechanisms underlying the occurrence and development of enchondromas and provide promising candidates for therapeutic intervention and prognostic evaluation. However, further experimental studies are needed to confirm these results.

Purpose Nowadays, the efficacy of teriparatide in treating osteoporosis was widely accepted, but the discussion about using teriparatide to enhance fracture healing hasn’t come to an agreement. This meta-analysis was conducted to evaluate the effectiveness of teriparatide for fracture healing. Methods We searched PubMed, the Cochrane Library, and Embase in August 2016 for randomized controlled trials (RCTs) which concerned the treatment of teriparatide for fracture healing. Results Finally, a total of 380 patients were randomly assigned in the 5 trials included in this meta-analysis. There was a significant effectiveness with regards to function improvement in patients following fracture, however, there was no significant effectiveness with regards to time of radiographic fracture healing, fracture healing rate and reduction in pain. Conclusions This analysis showed that administration of teriparatide following fracture lacked the effectiveness for fracture healing. Moreover, teriparatide administration had no apparent adverse effects. These results should be interpreted with caution because of some clear limitations. If we want to confirm whether teriparatide improves fracture healing, more high-quality randomized controlled trials are needed.

With laminectomy being widely accepted as the treatment for lumbar disorders, epidural fibrosis (EF) is a common complication for both the patients and the surgeons alike. Currently, EF is thought to cause recurrent postoperative pain after laminectomy or after discectomy.Angelica sinensisis a traditional Chinese medicine which has shown anti-inflammatory, antifibrotic, and antiproliferative properties. The object of this study was to investigate the effects ofAngelica sinensison the prevention of post-laminectomy EF formation in a rat model. A controlled double-blinded study was conducted in sixty healthy adult Wistar rats that underwent laminectomy at the L1-L2 levels. They were divided randomly into 3 groups according to the treatment method, with 20 in each group: (1)Angelica sinensistreatment group, (2) saline treatment group, and (3) sham group (laminectomy without treatment). All rats were euthanized humanely 4 weeks after laminectomy. The hydroxyproline content, Rydell score, vimentin cells density, fibroblasts density, inflammatory cells density, and inflammatory factors expressions all suggested better results inAngelica sinensisgroup than the other two groups. Topical application ofAngelica sinensiscould inhibit fibroblasts proliferation and TGF-β1 and IL-6 expressions and prevent epidural scar adhesion in postlaminectomy rat model.

Objective This meta-analysis was performed to determine the effects of minimally invasive percutaneous plate osteosynthesis (MIPO) versus conventional fixation techniques (CFT) for treating distal tibial fractures. Methods A literature search was performed in EMBASE, Medline, the Cochrane Library, and Web of Science. The trials searched were evaluated for eligibility. The Cochrane Collaboration's Review Manager software was used to perform meta-analyses. Results Eight studies were enrolled, including five randomized controlled trials, one control-matched trial and two retrospective cohort trials. The meta-analysis revealed that MIPO has a longer operating time, longer radiation time and higher incidence rate of soft tissue irritation symptoms than those of CFT. There was no significant difference between the two techniques with regard to union time, the American Orthopedic Foot and Ankle Society (AOFAS), infection rate and various other complications. Conclusions The present meta-analysis showed that MIPO did not have obvious advantages over CFT in the treatment of distal tibia fracture. However, more rigorous randomized controlled trials are required in the future.

Skeletal cryptococcosis, an aspect of disseminated cryptococcal disease or isolated skeletal cryptococcal infection, is a rare but treatable disease. However, limited information is available regarding its clinical features, treatment, and prognosis. This systematic review examined all cases published between April 1977 and May 2013 with regard to the factors associated with this disease, including patient sex, age, and epidemiological history; affected sites; clinical symptoms; underlying diseases; laboratory tests; radiological manifestations; and delays in diagnosis, treatment, follow-up assessments, and outcomes. We found that immune abnormality is a risk factor but does not predict mortality; these observations are due to recent Cryptococcus neoformans var gattii (CNVG) outbreaks (Chaturvedi and Chaturvedi, 2011). Dissemination was irrespective of immune status and required combination therapy, and dissemination carried a worse prognosis. Therefore, a database of skeletal cryptococcosis cases should be created.

The costs of spinal cord injury and its complications are high in personal, social and financial terms. Complications include bladder cancer, for which the risk is 16-28 times higher than that of the general population, There is currently little consensus regarding the cause of this discrepancy. As microRNAs are stable biomarkers and potential therapeutic targets of cancer, the present study aimed to explore the underlying mechanisms of this phenomenon by examining changes in the microRNAome. Rats were used to produce models of spinal cord injury. Microarrays and bioinformatics were used to investigate the cancer-associated microRNAs that are upregulated in rat bladders following spinal cord injury. In order to validate the results, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry were performed. The expression of miR-1949 was found to be deregulated and abundant in the rat bladder following spinal cord injury. Bioinformatics demonstrated that retinoblastoma 1, which is involved in tumorigenesis, is a target gene of miR-1949. qRT-PCR, western blotting and immunohistochemistry confirmed the results of the microarray analysis. In addition, it was shown that miR-1949 expression was not influenced by aging. Furthermore, the expression of miR-1949 was stable until the third month following spinal cord injury, after which it significantly increased. If this increase was prolonged, the expression of retinoblastoma 1 may decline to a carcinogenic level. The present study suggests a role for miR-1949 in the translational regulation of retinoblastoma 1 and in subsequent bladder tumorigenesis following spinal cord injury.

After spinal cord injury (SCI), the rapidly upregulated chondroitin sulfate proteoglycans (CSPGs), the prominent chemical constituents and main repulsive factors of the glial scar, play an important role in the extremely limited ability to regenerate in adult mammals. Although many methods to overcome the inhibition have been tested, no successful method with clinical feasibility has been devised to date. It was recently discovered that receptor protein tyrosine phosphatase sigma (RPTPσ) is a functional receptor for CSPGs-mediated inhibition. In view of the potential clinical application of RNA interference (RNAi), here we investigated whether silencing RPTPσ via lentivirus-mediated RNA interference can promote axon regeneration and functional recovery after SCI. Neurites of primary rat cerebral cortical neurons with depleted RPTPσ exhibited a significant enhancement in elongation and crossing ability when they encountered CSPGs in vitro. A contusion model of spinal cord injury in Wistar rats (the New York University (NYU) impactor) was used for in vivo experiments. Local injection of lentivirus encoding RPTPσ shRNA at the lesion site promoted axon regeneration and synapse formation, but did not affect the scar formation. Meanwhile, in vivo functional recovery (motor and sensory) was also enhanced after RPTPσ depletion. Therefore, strategies directed at silencing RPTPσ by RNAi may prove to be a beneficial, efficient and valuable approach for the treatment of SCI.

Epidural steroid injection (ESI) is one of the most commonly used treatments for radiculopathy. Previous studies have described the effectiveness of ESI in the management of radiculopathy. However, controversy exists regarding the route that is most beneficial and effective with respect to the administration of epidural steroids, as both transforaminal (TF) and caudal (C) routes are commonly used.This analysis reviewed studies comparing the effectiveness of TF-ESIs with that of C-ESIs in the treatment of radiculopathy as a means of providing pain relief and improving functionality. This meta-analysis was performed to guide clinical decision-making.The study was a systematic review of comparative studies.A systematic literature search was performed using the PubMed, EMBASE, and Cochrane Library databases for trials written in English. The randomized trials and observational studies that met our inclusion criteria were subsequently included. Two reviewers, respectively, extracted data and estimated the risk of bias. All statistical analyses were performed using Review Manager 5.3.Six prospective and 2 retrospective studies involving 664 patients were included. Statistical analysis was performed utilizing only the 6 prospective studies. Although slight pain and functional improvements were noted in the TF-ESI groups compared with the C-ESI groups, these improvements were neither clinically nor statistically significant.The limitations of this meta-analysis resulted primarily from the weaknesses of the comparative studies and the relative paucity of patients included in each study.Both the TF and C approaches are effective in reducing pain and improving functional scores, and they demonstrated similar efficacies in the management of lumbosacral radicular pain.

Background Although cryptococcosis mainly occurs in the central nervous system and lungs in immunocompromised hosts, it can involve any body site or structure. Here we report the first case of primary cryptococcosis of a lumbar vertebra without involvement of the central nervous system or lungs in a relatively immunocompromised individual with rheumatoid arthritis and scleroderma. Case presentation A 40-year-old Chinese woman with rheumatoid arthritis diagnosed 1 year beforehand and with a subsequent diagnosis of scleroderma was found to have an isolated cryptococcal infection of the fourth lumbar vertebra. Her main complaints were severe low back and left leg pain. Cryptococcosis was diagnosed by CT-guided needle biopsy and microbiological confirmation; however, serum cryptococcal antigen titer was negative. After 3 months of antifungal therapy with fluconazole the patient developed symptoms and signs of scleroderma, which was confirmed on laboratory tests. After taking fluconazole for 6 months, the progressive destruction of the lumbar vertebral body had halted and the size of an adjacent paravertebral mass had decreased substantially. On discharge symptoms had resolved and at an annual follow-up there was no evidence of recurrence on the basis of symptoms, signs or imaging investigations. Conclusion Although cryptococcosis of the lumbar vertebra is extremely rare, it should be considered in the differential diagnosis for patients with lumbar vertebral masses to avoid missed diagnosis, misdiagnosis and diagnostic delay. Early treatment with antifungals proved to be a satisfactory alternative to surgery in this relatively immunocompromised patient. Any residual spinal instability can be treated later, once the infection has resolved.