Mechanism of icariin for the treatment of osteoarthritis based on network pharmacology and molecular docking method.

BACKGROUND: Icarin's mechanism of action in osteoarthritis (OA) was explored using network pharmacology and the GEO database, and then further validated using molecular docking. METHODS: GEO database using network pharmacology identified differential genes in OA based on Icariin's possible targets predicted by pharmmapper database. Combining the differentially expressed genes in OA with the OA-related targets, the overlapping targets were removed. In order to determine what Icariin's core targets are for treating OA, PPI network analysis was performed using OA-related targets and possible Icariin targets. Furthermore, molecular docking was used to verify the chemical's binding to the targets. Final steps included Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Cytoscape was used to construct a network of compound-target-pathway-disease. RESULTS: Protein-protein interactions between overlapping targets revealed 151 intersection targets based on a network analysis. The top ten targets with the highest enrichment scores were SRC, MAPK1, HSP90AA1, AKT1, PTPN11, ESR1, EGFR, RhoA, JAK2, and MAPK14. KEGG enrichment analysis showed that the pathways at which Icariin intervention occurs include the OA including FOXO signaling pathway, and estrogen signaling pathway. The GO analysis result showed that various biologic processes such as proteolysis, angiogenesis, innate immune response, and positive regulation of inflammatory response were involved in treatment. Molecular docking analysis confirmed that Icariin could bind well to the targets through intermolecular forces. CONCLUSION: With its multi-targeting and multi-pathway characteristics, Icariin is a promising candidate drug for treating OA.

Causal relationship between thyroid dysfunction and hallux valgus: A two-sample Mendelian randomization study.

Introduction: Previous observational studies have reported that thyroid dysfunction is associated with hallux valgus (HV). However, the causal effect of thyroid dysfunction on hallux valgus is still unknown. To assess whether there is a causal relationship between thyroid dysfunction and hallux valgus, we performed a two-sample Mendelian randomization (MR) study. Methods: The data of the two-sample Mendelian randomization study were obtained from public databases. In this study, hypothyroidism, hyperthyroidism, free thyroxine (FT4), and thyrotropin (TSH) were chosen as exposures. The single nucleotide polymorphisms (SNP) of hypothyroidism and hyperthyroidism were from the genome-wide association studies (GWAS) of the IEU database, including 337,159 subjects. Data for FT4 and TSH (72,167 subjects) were extracted from the ThyroidOmics Consortium. HV was used as the outcome. The SNPs associated with HV were selected from a GWAS of 202,617 individuals in the fignngen database. The inverse variance weighted (IVW) method was used as the primary analysis. Four complementary methods were applied, including MR-presso, MR-Egger, and weighted median. In addition, Cochran's Q test, MR-presso, MR-Egger regression, and the leave-one-out test were used as sensitivity analysis, and the MR-pleiotropy test was performed to examine pleiotropy. Results: According to the results of IVW, we found that there was a causal relationship between hypothyroidism and HV, and hypothyroidism increased the incidence of HV (OR = 2.838 (95% CI: 1.116-7.213); p = 0.028). There were no significant causal effects of hyperthyroidism, FT4, and TSH on HV (p > 0.05). Sensitivity analyses showed that the results were robust and reliable, and no horizontal pleiotropy was detected. Conclusions: Our findings provided genetic support that hypothyroidism might increase the risk of HV. It will predict the occurrence of HV in patients with hypothyroidism and provide suggestions for early prevention and intervention.

Establishment and Validation of a Predictive Nomogram for Hallux Valgus with Pain Under the Second Metatarsal.

Objective: To investigate the risk factors for hallux valgus complicated with pain under the second metatarsal and construct an effective model and method for predicting hallux valgus complicated with pain under the second metatarsal based on risk factors. Methods: A total of 545 patients with hallux valgus who were admitted to our hospital were divided randomly into a training set and a validation set. The demographic characteristics, imaging indices and gait test indices of the patients were collected. The risk factors were identified by univariate and multivariate logistic regression analyses. A risk prediction model for hallux valgus with pain under the second metatarsal was established, and the area under the curve (AUC) of the receiver operating characteristic and a decision curve analysis were used for verification and identification. The value of the model was tested in the verification group. Results: Second metatarsal length, second metatarsal peak pressure, hallux valgus angle (HVA), intermetatarsal angle 1-2 (IMA1-2) and weight were the risk factors for hallux valgus complicated with pain under the second metatarsal. Based on the weighting of these seven risk factors, a prediction model was established. The AUC of the prediction model was 0.84 (95% confidence interval [CI]: 0.802~0.898, P < 0.05), and the results of a Hosmer-Lemeshow test showed a good degree of calibration (χ 2 = 10.62, P > 0.05). The internal validation of the AUC was 0.83 (95% CI: 0.737-0.885, P < 0.05). The model had obvious net benefits when the threshold probability was 10%-70%. Conclusion: Second metatarsal length, second metatarsal peak pressure, HVA, IMA1-2 and weight were the risk factors for hallux valgus combined with second metatarsal pain. The risk prediction model for hallux valgus complicated with pain under the second metatarsal based on these seven variables was proven effective. Level of Evidence: Level III, retrospective comparative study.

Clinical effectiveness of arthroscopic vs open ankle arthrodesis for advanced ankle arthritis: A systematic review and meta-analysis.

BACKGROUND: Ankle fusion is the primary treatment for advanced ankle arthritis. With the advancement of arthroscopy technology, ankle arthroscopy fusion has shown many advantages over traditional surgery. However, there are few related studies globally, and evidence-based medicine is needed to verify the reliability and feasibility of ankle arthroscopy fusion. OBJECTIVE: To compare the clinical efficacy and safety of arthroscopic ankle arthrodesis and open ankle arthrodesis. METHODS: We searched the databases of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure [CNKI], Wanfang Database, and VIP Database for published prospective or retrospective controlled studies of arthroscopic-assisted ankle fusion in the treatment of advanced ankle arthritis. The dates were limited from the construction of the library to June 30, 2019. Literature was included based on the principles and methods of evidence-based medicine. Literature retrieval, data extraction, and quality assessment were performed by 2 independent reviewers using the Cochrane 5.1 risk bias assessment tool. The methodological bias of the literature was evaluated, and a meta-analysis was using by RevMan 5.3 software. RESULTS: A total of 18 studies and 1102 patients were included in the study, including 551 in the arthroscopic surgery group and 551 in the open surgery group. Arthroscopy-assisted surgery for advanced ankle arthritis was more effective than open surgery in terms of fusion rate (odd ratio[OR] = 3.32, 95% confidence interval[CI]:2.16, 5.10), fusion time (mean difference[MD] = -2.31, 95% CI:-4.63, -2.21), intraoperative blood loss (MD = -43.37, 95%CI: -48.49, -38.25), hospital stay (MD = -1.80, 95%CI: -2.28, -1.33), and visual analog scale score (MD = -1.75, 95%CI: -2.04, -1.46). In addition, rate of complications (OR = 0.33, 95%CI: 0.21, 0.52) was superior to open ankle fusion (P < .00001). CONCLUSION: Arthroscopic ankle arthrodesis has more advantages than open ankle arthrodesis in improving the fusion rate and reducing complications, which is worthy of clinical application. PROSPERO REGISTRATION NUMBER: CRD42020195727.

Bland-Altman Analysis of Different Radiographic Measurements of the Hallux Valgus Angle and the Intermetatarsal Angle After Distal Osteotomy.

OBJECTIVE: The aim of the present study was to evaluate commonly used approaches for detection of radiographic angles in hallux valgus deformity patients. METHODS: This retrospective study was conducted in patients with hallux valgus deformity at Wangjing Hospital of China Academy of Chinese Medical Sciences from January 2016 to January 2019. The inclusion criteria were: (i) postoperative dorsoplantar weight-bearing radiographs for the feet of patients with the hallux valgus; (ii) patients had been managed with a distal osteotomy of the first metatarsal and the osteotomized bone ends recovered. The exclusion criteria applied were as follows: (i) age > 65 years or < 18 years old; (ii) blurry image; (iii) previous history of severe foot trauma and surgery. Postoperative radiographs for hallux valgus were analyzed using six methods: by a line drawn through the long axis of the first metatarsal bone (method 1); an extended line drawn to bisect the shaft of the metatarsal at two levels with joined points of bisection (method 2); a line drawn to connect the center of the articular surface of the metatarsal head and the center of the proximal articulation (method 3); a line drawn from the center of the head of the first metatarsal head through the center of the base of the first metatarsal bone (method 4); a line drawn through the center of the head and the center of the proximal shaft (method 5); and a line drawn from the center of the head of the first metatarsal head through the center of the proximal articulation (method 6). The measurement results obtained were subjected to Bland-Altman analysis and consistency evaluation. RESULTS: A total number of 20 radiographs were collected for measurement. No statistically significant differences were found in the measurement values among the six methods (P > 0.05). The lowest values of the average measurement, standard deviation, and confidence interval were established in method 3, followed by those in methods 1 and 4. The standard deviation of the measurement value and the confidence interval in method 2 were the largest. Methods 1 and 4 had similar confidence intervals and were with a high consistency. Due to the nature of the retrospective study, no follow-up and complications were applicable in the present study. CONCLUSION: Line drawn through the long axis of the first metatarsal bone (method 1) and line drawn from the center of the head of the first metatarsal head through the center of the base of the first metatarsal bone (method 4) were reliable and well repeatable, and may be used for postoperative radiographs.