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.
Purpose: The objective of this study was to conduct the latest meta-analysis of randomized controlled trials (RCTs) that compare clinical results between surgery and conservative therapy of acute primary patellar dislocation (APPD), focusing on medial patellofemoral ligament (MPFL) reconstruction. Methods: We performed a literature search in Embase, The Cochrane Library, PubMed, and Medline to identify RCTs comparing APPD surgical treatment with conservative treatment from the establishment of each database to January 2019. The methodological quality of each RCT was assessed independently by the two authors through the Cochrane Collaboration's "Risk of Bias" tool. Mean differences of continuous variables and risk ratios of dichotomous variables were computed for the pooled data analyses. The I 2 statistic and the χ 2 test were used to evaluate heterogeneity, with the significance level set at I 2 > 50% or P < 0.10. Results: Ten RCTs with a sum of 569 patients (297 receiving surgical treatment and 263 receiving conservative treatment) met the inclusion criteria for meta-analysis. Pooled data analysis showed no statistical difference in the field of subluxation rate, Kujala score, patient satisfaction, and frequency of reoperation between the two groups. Tegner activity score and recurrent dislocation rate in the conservative group were significantly higher than those in the surgically treated group. Conclusions: Conservative treatment may produce better outcomes than surgery for APPD in consideration of Tegner activity score. However, in view of limited research available, the interpretation of the discoveries should be cautious. More convincing evidence is required to confirm the effect of MPFL reconstruction.
Background: Rheumatoid arthritis (RA) is a common autoimmune disease characterized by progressive, destructive polyarthritis. However, the cause and underlying molecular events of RA are not clear. Here, we applied integrated bioinformatics to identify tissue-specific expressed hub genes involved in RA and reveal potential targeted drugs.Methods: Three expression profiles of human microarray datasets involving fibroblast-like synoviocytes (FLS) were downloaded from the Gene Expression Omnibus (GEO) database, the differentially expressed mRNAs (DEGs), miRNAs (DEMs), and lncRNAs (DELs) between normal and RA synovial samples were screened using GEO2R tool. BioGPS was used to identified tissue-specific expressed genes. Functional and pathway enrichment analyses were performed for common DEGs using the DAVID database, and the protein-protein interaction (PPI) network of common DEGs was constructed to recognize hub genes by the STRING database. Based on receiver operating characteristic (ROC) curve, we further investigated the prognostic values of tissue-specific expressed hub genes in RA patients. Connectivity Map (CMap) was run to identify novel anti-RA potential drugs. The DEM–DEG pairs and ceRNA network containing key DEMs were established by Cytoscape.Results: We obtain a total of 418 DEGs, 23 DEMs and 49 DELs. 64 DEGs were verified as tissue-specific expressed genes, most derive from the hematologic/immune system (20/64, 31.25%). GO term and KEGG pathway enrichment analysis showed that DEGs focused primarily on immune-related biological process and NF-κB pathway. 10 hub genes were generated via using MCODE plugin. Among them, SPAG5, CUX2, and THEMIS2 were identified as tissue-specific expressed hub genes, these 3 tissue-specific expressed hub genes have superior diagnostic value in the RA samples compared with osteoarthritis (OA) samples. 5 compounds (troleandomycin, levodopa, trichostatin A, LY-294002, and levamisole) rank among the top five in connectivity score. In addition, 5 miRNAs were identified to be key DEMs, the lncRNA–miRNA–mRNA network with five key DEMs was formed. The networks containing tissue-specific expressed hub genes are as follows: ARAP1-AS2/miR-20b-3p/TRIM3, ARAP1-AS2/miR-30c-3p/FRZB.Conclusion: This study indicates that screening for identify tissue-specific expressed hub genes and ceRNA network in RA using integrated bioinformatics analyses could help us understand the mechanism of development of RA. Besides, SPAG5 and THEMIS2 might be candidate biomarkers for diagnosis of RA. LY-294002, trichostatin A, and troleandomycin may be potential drugs for RA.
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