Identification of autophagy-related genes in osteoarthritis articular cartilage and their roles in immune infiltration.

Background: Autophagy plays a critical role in the progression of osteoarthritis (OA), mainly by regulating inflammatory and immune responses. However, the underlying mechanisms remain unclear. This study aimed to investigate the potential relevance of autophagy-related genes (ARGs) associated with infiltrating immune cells in OA. Methods: GSE114007, GSE169077, and ARGs were obtained from the Gene Expression Omnibus (GEO) database and the Human Autophagy database. R software was used to identify the differentially expressed autophagy-related genes (DEARGs) in OA. Functional enrichment and protein-protein interaction (PPI) analyses were performed to explore the role of DEARGs in OA cartilage, and then Cytoscape was utilized to screen hub ARGs. Single-sample gene set enrichment analysis (ssGSEA) was used to conduct immune infiltration analysis and evaluate the potential correlation of key ARGs and immune cell infiltration. Then, the expression levels of hub ARGs in OA were further verified by the GSE169077 and qRT-PCR. Finally, Western blotting and immunohistochemistry were used to validate the final hub ARGs. Results: A total of 24 downregulated genes and five upregulated genes were identified, and these genes were enriched in autophagy, mitophagy, and inflammation-related pathways. The intersection results identified nine hub genes, namely, CDKN1A, DDIT3, FOS, VEGFA, RELA, MAP1LC3B, MYC, HSPA5, and HSPA8. GSE169077 and qRT-PCR validation results showed that only four genes, CDKN1A, DDT3, MAP1LC3B, and MYC, were consistent with the bioinformatics analysis results. Western blotting and immunohistochemical (IHC) showed that the expression of these four genes was significantly downregulated in the OA group, which is consistent with the qPCR results. Immune infiltration correlation analysis indicated that DDIT3 was negatively correlated with immature dendritic cells in OA, and FOS was positively correlated with eosinophils. Conclusion: CDKN1A, DDIT3, MAP1LC3B, and MYC were identified as ARGs that were closely associated with immune infiltration in OA cartilage. Among them, DDIT3 showed a strong negative correlation with immature dendritic cells. This study found that the interaction between ARGs and immune cell infiltration may play a crucial role in the pathogenesis of OA; however, the specific interaction mechanism needs further research to be clarified. This study provides new insights to further understand the molecular mechanisms of immunity involved in the process of OA by autophagy.

Influence of Patient-Reported Outcome Measures by Surgical Versus Conservative Management in Adult Ankle Fractures: A Systematic Review and Meta-Analysis.

Background and Objective: This meta-analysis was performed to compare the effectiveness of surgical treatment and conservative treatment in adult ankle fractures. Methods: Pubmed, Embase, and Cochrane-Library databases were searched to retrieve prospective randomized-controlled studies that compared the efficacy of surgical treatment and conservative treatment in adult ankle fractures. The meta package in R language was used to organize and analyze the obtained data. Results: A total of eight studies involving 2081 patients was considered eligible, including 1029 patients receiving surgical treatment and 1052 receiving conservative treatment. This systematic review and meta-analysis was prospectively registered on PROSPERO, and the registration number is CRD42018520164. Olerud and Molander ankle-fracture scores (OMAS) and the health survey 12-item Short-Form (SF-12) were used as main outcome indicators, and the follow-up outcomes were grouped according to the follow-up time. Meta-analysis results showed significantly higher OMAS scores in patients receiving surgical treatment than those with conservative treatment at six months (MD = 1.50, 95% CI: 1.07; 1.93) and over 24 months (MD = 3.10, 95% CI: 2.46; 3.74), while this statistical significance was absent at 12-24 months (MD = 0.08, 95% CI: -5.80; 5.96). At six months and 12 months after treatment, patients receiving surgical treatment exhibited significantly higher SF12-physical results than those receiving conservative treatment (MD = 2.40, 95% CI: 1.89; 2.91). The MD of SF12-mental data at six months after meta-analysis was -0.81 (95% CI: -1.22; 0.39), and the MD of SF12-mental data at 12+ months was -0.81 (95% CI: -1.22; 0.39). There was no significant difference in SF12-mental results between the two treatment methods after six months, but after 12 months, the SF12-mental results of patients receiving surgical treatment were significantly lower than those of conservative treatment. Conclusions: In the treatment of adult ankle fractures, surgical treatment is more efficacious than conservative treatment in improving early and long-term joint function and physical health of patients, but it is associated with long-term adverse mental health.

Is metaphyseal ulnar shortening osteotomy superior to diaphyseal ulnar shortening osteotomy in the treatment of ulnar impaction syndrome? A meta-analysis.

BACKGROUND: Although metaphyseal ulnar shortening osteotomy (MUSO) is safer for the treatment of ulnar impaction syndrome (UIS) than diaphyseal ulnar shortening osteotomy (DUSO), DUSO is widely used for UIS treatment. AIM: To evaluate the effectiveness of DUSO and MUSO for UIS treatment and determine the factors that should be considered when choosing surgical treatment for UIS. METHODS: Articles comparing the effectiveness of DUSO and MUSO for UIS treatment were systematically retrieved from MEDLINE (Ovid), PubMed, EMBASE, and Cochrane Library. The demography, incidence of complications, secondary operation rate, postoperative DASH score, wrist pain on the visual analogue scale, and grip strength improvement were also evaluated. In addition, the correlation between the improvement of grip strength and the shortening of osteotomy length of ulna was analyzed. The outcome of the patient was discontinuous, and the odds ratio, risk ratio (RR), and 95%CI were calculated and analyzed via RevMan5.3 software. RESULTS: Six studies, including 83 patients receiving MUSO (experimental group) and 112 patients receiving DUSO (control group), were included in the meta-analysis. The second operation rate was significantly higher after DUSO than after MUSO. The DASH scores were slightly lower in the MUSO group than in the DUSO group. The patients receiving MUSO had slightly better pain relief effect than patients receiving DUSO. However, the incidence of complications and improvement of grip strength were not significantly different between the two groups. CONCLUSION: Although DUSO and MUSO provide similar effects for UIS, MUSO is associated with a lower secondary operation rate, slightly lower postoperative DASH scores and slightly better pain relief effect than DUSO, indicating that MUSO can effectively be used for UIS treatment.

Coexistence of anomalous muscle, persistent median artery, bifid median nerve causing carpal tunnel syndrome: A case report and literature review.

Carpal tunnel syndrome (CTS) is an upper extremity median nerve entrapment disorder that is rare in children and adolescents. Anatomical variations of the wrist, such as anomalous muscles, persistent median artery (PMA), and bifid median nerves (BMN), are rare etiology of CTS. Coexistence of all three variants combined with CTS in adolescents has been rarely reported. Case description: A 16-year-old right-hand dominant male presented to our clinic with several years of bilateral thenar muscle atrophy and weakness but no paresthesia or pain in his both hands. Ultrasonography showed that the right median nerve become significantly thinner, and the left median nerve was split into two branches by PMA. Magnetic resonance imaging (MRI) revealed that anomalous muscles in the bilateral wrist extending to the carpal tunnel, causing compression of the median nerve. Considering the possibility of CTS clinically, the patient underwent bilateral open carpal tunnel release without resection of anomalous muscles and PMA. The patient has no discomfort after 2 years. This suggests that anatomical variations of the carpal tunnel may contribute to CTS, which can be confirmed by preoperative ultrasonography and MRI, and the possibility of carpal tunnel anatomical variations should be considered when CTS occurs in adolescents. Open carpal tunnel release is an effective treatment for juvenile CTS without the need to resect abnormal muscle and PMA during the operation.

Cerebral Gray Matter Volume Changes in Patients with Neuropathic Pain from Total Brachial Plexus Injury.

INTRODUCTION: Total brachial plexus injury not only significantly affects the motor and sensory function of the affected upper limbs but also causes further physical and mental damage to patients with long-term intractable pain. Previous studies mainly focused on the surgical treatment, while only a few paid attention to the intractable neuropathic pain caused by this injury. Changes in the volume of gray matter in the brain are thought to be associated with chronic neuropathic pain. METHODS: Voxel-based morphometry analysis was used to compare the difference in cerebral gray matter volume between total brachial plexus injury patients with neuropathic pain and healthy controls. Correlations between pain duration, pain severity, and GM changes were analyzed. RESULTS: The volume of cerebral gray matter in the patient group was decreased significantly in multiple regions, including the parahippocampal gyrus, paracentric lobule, inferior frontal gyrus, auxiliary motor cortex, middle occipital gyrus, right middle temporal gyrus, while it was increased in the insular, pons, middle frontal gyrus, cingulate gyrus, inferior parietal lobule, bilateral thalamus, and globus pallidus. There were no significant correlations between pain duration and rGMV changes, while a positive correlation was observed between pain severity and rGMV changes in one specific region, involving the anterior cingulate cortex. CONCLUSION: Total brachial plexus injury patients with chronic pain have widespread regions of gray matter atrophy and hypertrophy. The only positive correlation was observed between pain severity and rGMV changes in one specific region, suggesting that nociceptive stimuli trigger a variety of nonpain-specific processes, which confirms the multidimensional nature of pain.

Corrigendum to "Andrographolide Enhances Proliferation and Prevents Dedifferentiation of Rabbit Articular Chondrocytes: An In Vitro Study".

[This corrects the article DOI: 10.1155/2015/984850.].

Changes in bone density, intraosseous pressure of distal femoral articular cartilage and subchondral bone after proximal femoral medullary cavity cement filling in rabbits.

Bone cement is widely used, particularly in hip replacements, but the potential clinical complications of its use have been largely unrecognized. The purpose of the present study was to investigate the effects of bone cement in the proximal femoral medullary cavity (PFMC) on bone mineral density (BMD), intraosseous pressure (IOP), articular cartilage and subchondral bone in the distal femurs of rabbits. A total of 32 New Zealand white rabbits were randomly numbered and the left hind limb of the odd-numbered rabbits and the right hind limb of the even numbered rabbits were selected as the experimental side. For each rabbit, the non-experimental hind limb was labeled as the control side by the principal investigator. An intramedullary injection of polymethyl methacrylate was made into the experimental hindlimb of each rabbit and the PFMC filled with bone cement. BMD and IOP of the distal femur of the bilateral hindlimb were measured at 4 and 16 weeks after surgery, and histological and ultra-fine structural features were examined by light and transmission electron microscopy, respectively. At week 4 after the operation, IOP in the experimental limb was significantly higher and BMD lower compared with the control limb. At the 16th week after operation, the IOP in the experimental limb was lower than at the 4th week after operation, but still higher compared with controls, and the BMD was significantly higher than the controls. In the controls, IOP and BMD was not significantly different between the 4th and 16th week after operation. Compared with controls, the cartilage in the experimental group was thinner, the chondrocytes partially necrotic and the trabecular structure of the subchondral bone broken. Analysis of ultra-fine structural features in the experimental group showed chondrocytes with necrotic cytoplasm and pyknotic nuclei relative to controls. The results indicated that blockage of the PFMC with bone cement resulted in an increase in the IOP in the distal femur, a change in BMD and damage to the subchondral bone and articular cartilage.

Anlotinib suppresses metastasis and multidrug resistance via dual blockade of MET/ABCB1 in colorectal carcinoma cells.

Anlotinib, a highly selective multi-targeted tyrosine kinase inhibitor (TKI) has therapeutic effects on non-small-cell lung cancer (NSCLC). In this study, the anti-tumor activity and molecular mechanism of anlotinib in metastatic colorectal cancer (mCRC) was explored. The anti-angiogenesis, anti-metastasis, anti-proliferative, and anti-multidrug resistance efficacy of anlotinib were analyzed by using in vitro and in vivo models of human CRC cells. The results indicated that anlotinib boosted chemo-sensitivity of CRC cells, and restrained its proliferation. Besides the suppression of the MET signaling pathway, anlotinib also inhibited invasion and migration of CRC cells. Furthermore, anlotinib prevented VEGF-induced angiogenesis, N-cadherin (CDH2)-induced cell migration, and reversed ATP-binding cassette subfamily B member 1 (ABCB1) -mediated CRC multidrug resistance in CRC. The CRC liver metastasis and subcutaneously implanted xenograft model testified that anlotinib could inhibit proliferation and liver metastasis in CRC cells. Such an observation suggested that a combination of anlotinib with anti-cancer drugs could attenuate angiogenesis, metastasis, proliferative, and multidrug resistance, which constitutes a novel treatment strategy for CRC patients with metastasis.

Individualized Drug Repositioning For Rheumatoid Arthritis Using Weighted Kolmogorov-Smirnov Algorithm.

BACKGROUND: Existing drugs are far from enough for investigators and patients to administrate the therapy of rheumatoid arthritis. Drug repositioning has drawn broad attention by reusing marketed drugs and clinical candidates for new uses. PURPOSE: This study attempted to predict candidate drugs for rheumatoid arthritis treatment by mining the similarities of pathway aberrance induced by disease and various drugs, on a personalized or customized basis. METHODS: We firstly measured the individualized pathway aberrance induced by rheumatoid arthritis based on the microarray data and various drugs from CMap database, respectively. Then, the similarities of pathway aberrances between RA and various drugs were calculated using a Kolmogorov-Smirnov weighted enrichment score algorithm. RESULTS: Using this method, we identified 4 crucial pathways involved in rheumatoid arthritis development and predicted 9 underlying candidate drugs for rheumatoid arthritis treatment. Some candidates with current indications to treat other diseases might be repurposed to treat rheumatoid arthritis and complement the drug group for rheumatoid arthritis. CONCLUSION: This study predicts candidate drugs for rheumatoid arthritis treatment through mining the similarities of pathway aberrance induced by disease and various drugs, on a personalized or customized basis. Our framework will provide novel insights in personalized drug discovery for rheumatoid arthritis and contribute to the future application of custom therapeutic decisions.