Zhongju Shi

Effectiveness of Teriparatide on Fracture Healing: A Systematic Review and Meta-Analysis.

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.

The roles of microRNAs in spinal cord injury

ABSTRACT 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.

Exploring the key genes and pathways of osteosarcoma with pulmonary metastasis using a gene expression microarray

Osteosarcoma is a common and highly malignant tumour in children and teenagers that is characterized by drug resistance and high metastatic potential. Patients often develop pulmonary metastasis and have a low survival rate. However, the mechanistic basis for pulmonary metastasis remains unclear. To identify key gene and pathways associated with pulmonary metastasis of osteosarcoma, the authors downloaded the gene expression dataset GSE85537 and obtained the differentially expressed genes (DEGs) by analyzing high-throughput gene expression in primary tumours and lung metastases. Subsequently, the authors performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses and a protein-protein interaction (PPI) network was constructed and analyzed by Cytoscape software. In total, 2,493 genes were identified as DEGs. Of these, 485 genes (19.45%) were upregulated, and the remaining 2,008 genes (80.55%) were downregulated. The authors identified the predominant GO categories and KEGG pathways that were significantly over-represented in the metastatic OS samples compared with the non-metastatic OS samples. A PPI network was constructed, and the results indicated that ALB, EGFR, INS, IL6, CDH1, FYN, ERBB2, IL8, CXCL12 and RAC2 were the top 10 core genes. The enrichment analyses of the genes involved in the top three significant modules demonstrated that the DEGs were principally related to neuroactive ligand-receptor interaction, the Rap1 signaling pathway, and protein digestion and absorption. Together, these data elucidated the molecular mechanisms of OS patients with pulmonary metastasis and provide potential therapeutic targets. However, further experimental studies are needed to confirm these results.

The Effectiveness of Transforaminal Versus Caudal Routes for Epidural Steroid Injections in Managing Lumbosacral Radicular Pain: A Systematic Review and Meta-Analysis.

AbstractEpidural 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.

The emerging role of long non-coding RNA in spinal cord injury

Spinal cord injury (SCI) is a significant health burden worldwide which causes permanent neurological deficits, and there are approximately 17,000 new cases each year. However, there are no effective and current treatments that lead to functional recovery because of the limited understanding of the pathogenic mechanism of SCI. In recent years, the biological roles of long non‐coding RNAs (lncRNAs) in SCI have attracted great attention from the researchers all over the world, and an increasing number of studies have investigated the regulatory roles of lncRNAs in SCI. In this review, we summarized the biogenesis, classification and function of lncRNAs and focused on the investigations on the roles of lncRNAs involved in the pathogenic processes of SCI, including neuronal loss, astrocyte proliferation and activation, demyelination, microglia activation, inflammatory reaction and angiogenesis. This review will help understand the molecular mechanisms of SCI and facilitate the potential use of lncRNAs as diagnostic markers and therapeutic targets for SCI treatment.

Exploring the key genes and pathways in enchondromas using a gene expression microarray

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.

MicroRNA-29a regulates neural stem cell neuronal differentiation by targeting PTEN.

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 NSCs 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.

Aquatic Exercises in the Treatment of Low Back Pain: A Systematic Review of the Literature and Meta-analysis of Eight Studies

Objective 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. Design 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. Results 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). Conclusions 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.

Investigation of candidate long noncoding RNAs and messenger RNAs in the immediate phase of spinal cord injury based on gene expression profiles

Spinal cord injury (SCI) is a serious devastating condition and it has a high mortality rate and morbidity rate. The early pathological changes in the immediate phase of SCI may play a major part in the development of secondary injury. Alterations in the expression of many long noncoding RNAs (lncRNAs) have been shown to play fundamental roles in the diseases of the central nervous system. However, the roles of lncRNAs and messenger RNAs (mRNAs) in the immediate phase of SCI are not clear. We examined the expression of mRNAs and lncRNAs in a rat model at 2 h after SCI and identified the differentially expressed lncRNAs (DE lncRNAs) and differentially expressed mRNAs (DE mRNAs) using microarray analysis. 772 DE lncRNAs and 992 DE mRNAs were identified in spinal cord samples in the immediate phase following SCI compared with control samples. Moreover, Gene Ontology (GO) term annotation results showed that CXCR chemokine receptor binding, neutrophil apoptotic process, neutrophil migration, neutrophil extravasation, macrophage differentiation, monocyte chemotaxis and cellular response to interleukin-1 (IL-1) were the main significantly enriched GO terms. The results of Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the DEGs were enriched in toll-like receptor signaling pathway, p53 signaling pathway, MAPK signaling pathway and Jak-STAT signaling pathway. IL6, MBOAT4, FOS, TNF, JUN, STAT3, CSF2, MYC, CCL2 and FGF2 were the top 10 high-degree hub nodes and may be important targets in the immediate phase of SCI. The current study on provides novel insights into how lncRNAs and mRNAs regulate the pathogenesis of the immediate phase after SCI.

Identification of differentially expressed proteins in rats with spinal cord injury during the transitional phase using an iTRAQ-based quantitative analysis

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.