Exploring the potential relationship between frozen shoulder and Dupuytren's disease through bioinformatics analysis and machine learning.

Background: Frozen shoulder (FS) and Dupuytren's disease (DD) are two closely related diseases, but the mechanism of their interaction is unknown. Our study sought to elucidate the molecular mechanism of these two diseases through shared gene and protein interactions. Methods: GSE75152 and GSE140731 data were downloaded from the Gene Expression Omnibus (GEO) database, and shared genes between FS and DD were selected by using R packages. Then, we used Cytoscape software and the STRING database to produce a protein-protein interaction (PPI) network. Important interaction networks and hub genes were selected through MCODE and cytoHubba algorithms. To explore the potential mechanisms of the development of the two diseases, the hub genes were further enriched by GO and KEGG analyses. We predicted the transcription factors (TFs) of hub genes with Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TRRUST). Moreover, we identified candidate genes for FS with DD with cytoHubba and machine learning algorithms. Finally, we analyzed the role of immunocyte infiltration in FS and constructed the relationship between candidate genes and immunocytes in FS. Results: We identified a total of 321 shared genes. The results of GO and KEGG enrichment of shared genes showed that extracellular matrix and collagen fibril tissue play a certain role in the occurrence and development of disease. According to the importance of genes, we constructed the key PPI network of shared genes and the top 15 hub genes for FS with DD. Then, we predicted that five TFs are related to the hub genes and are highly expressed in the FS group. Machine learning results show that the candidate genes POSTN and COL11A1 may be key for FS with DD. Finally, immune cell infiltration revealed the disorder of immunocytes in FS patients, and expression of candidate genes can affect immunocyte infiltration. Conclusion: We identified a PPI network, 15 hub genes, and two immune-related candidate genes (POSTN and COL11A1) using bioinformatics analysis and machine learning algorithms. These genes have the potential to serve as diagnostic genes for FS in DD patients. Furthermore, our study reveals disorder of immunocytes in FS.

Correlations between gut microbiota and lichen planus: a two-sample Mendelian randomization study.

Purpose: Several existing studies have revealed that the occurrence of lichen planus (LP) is relevant to the gut microbiota, and the causal relationship between gut microbiota and LP was analyzed using the Mendelian randomization (MR) method. Methods: Through the two-sample MR method, single nucleotide polymorphisms (SNPs) relevant to gut microbiota were selected as instrument variables (IVs) to evaluate the causal association between gut microbiota and the risk of LP. Results: According to the selection criteria of inverse-variance weighted (IVW), six bacterial genera were found to be significantly linked to the initiation of LP; The IVW results suggested that Oxalobacteraceae, Victivallaceae, and Actinobacteria could restrain the initiation of LP, showing protective effects against LP. Desulfovibrio, Veillonella, and Ruminococcus gauvreauii groups were demonstrated to have casual correlations with the onset of LP. Conclusion: The relationship between gut microbiota and LP was not a single positive or inverse relationship. Investigation of the causal relationship of these gut microbiota with LP could further provide evidence for the intestine-skin axis theory. However, the specific mechanism of microorganisms affecting the skin remains to be clarified. In this paper, the protective effects and mechanisms of Oxalobacteraceae, Victivallaceae, and Actinobacteria on LP require further exploration.

Characterization of immune microenvironment infiltration and m6A regulator-mediated RNA methylation modification patterns in osteoarthritis.

Background: Few studies have been reported the potential role of N6-methyladenosine (m6A) modification in osteoarthritis (OA). We investigated the patterns of m6A modification in the immune microenvironment of OA. Methods: We evaluated the m6A modification patterns based on 22 m6A regulators in 139 OA samples and systematically associated these modification patterns with immune cell infiltration characteristics. The function of m6A phenotype-related differentially expressed genes (DEGs) was investigated using gene enrichment analysis. An m6A score model was constructed using principal component analysis (PCA), and an OA prediction model was established based on the key m6A regulators. We used real-time PCR analysis to detect the changes of gene expression in the cell model of OA. Results: Healthy and OA samples showed significant differences in the expression of m6A regulators. Nine key m6A regulators, two m6A modification patterns, m6A-related genes and two gene clusters were identified. Some m6A regulators had a strong correlation with each other. Gene clusters and m6A clusters have high similarity, and cluster A corresponds to a high m6A score. Immunocytes infiltration differed significantly between the two clusters, with the m6A cluster B and gene cluster B having more types of infiltrating immunocytes than cluster A. The predictive model can also predict the progression of OA through m6A regulators expression. The results of real-time PCR analysis showed that the gene expression in the cell model of OA is similar to that of the m6A cluster B. Conclusions: Our study reveals for the first time the potential regulatory mechanism of m6A modification in the immune microenvironment of OA. This study also sheds new light on the pathogenesis of OA.

Silencing of miR-483-5p alleviates postmenopausal osteoporosis by targeting SATB2 and PI3K/AKT pathway.

Postmenopausal osteoporosis (PMOP) poses a significant threat to women's health worldwide. However, detailed molecular mechanism and therapeutic strategy for PMOP remain insufficient. Accumulating evidence suggests that miR-48-5p is implicated in the pathogenesis of osteoporosis. The present study aimed to determine the role and mechanism of miR-483-5p in PMOP. Results from PMOP patients demonstrated that miR-483-5p was up-regulated and SATB2 was down-regulated. Luciferase reporter assay identified SATB2 as a direct target gene of miR-483-5p. Experiments in MC3T3-E1 cells indicated that miR-483-5p mimic markedly inhibited cell viability as well as the expressions of OPG, RUNX2 and BMP2. And miR-483-5p inhibitor, SATB2-overexpressed lentiviruses (Lv-SATB2) or LY294002 (PI3K/AKT inhibitor) significantly reversed the above results. Similarly, PI3K/AKT signaling was activated by miR-483-5p mimic, and was inhibited in miR-483-5p inhibitor, Lv-SATB2 or LY294002 treated cells. In vivo experiments showed that miR-483-5p inhibitor significantly increased the bone mineral density and biomechanical parameters of femurs in ovariectomized (OVX) rats by targeting SATB2. In addition, the osteogenic differentiation and PI3K/AKT signaling were also regulated by miR-483-5p-SATB2 axis. Taken together, our findings indicated that miR-483-5p contributed to the pathogenesis of PMOP by inhibiting SATB2 and activating PI3K/AKT pathway. MiR-483-5p/SATB2 could be selected as a potential therapeutic target for PMOP.

The effects of teriparatide and bisphosphonates on new fractures in postmenopausal women with osteoporosis: A protocol for systematic review and meta-analysis.

BACKGROUND: To systematically evaluate the efficacy of teriparatide and bisphosphonates in preventing fractures in postmenopausal women with osteoporosis. MATERIALS AND METHODS: We performed a systematic search of PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) that compared teriparatide and bisphosphonates for osteoporosis treatment. Searches were performed without language restrictions and included studies from beginning of time to March 2019. Two authors independently screened and extracted the selected article. The quality of the included studies was evaluated using the Cochrane system evaluation method. Data were extracted and analysed using RevMan 5.2 software. RESULTS: Nine RCTs were included for a total of 2990 postmenopausal women with osteoporosis. Of these, 1515 patients were treated with teriparatide and 1475 were treated with bisphosphonates. After pooling the data of 9 studies, there were significant differences between teriparatide and bisphosphonates [relative risk (RR): 0.61, 95% confidence interval (CI) (0.51, 0.74)] in the prevention of fractures according to different follow-up durations (P < .05), whatever alendronate [RR: 0.51, 95% CI (0.27, 0.95)] and other bisphosphonates [RR: 0.63, 95% CI (0.51, 0.77)]. In addition, we found significant differences between teriparatide and bisphosphonates in the prevention of vertebral fractures [RR: 0.47, 95% CI (0.35, 0.64)] and non-vertebral fractures [RR: 0.76, 95% CI (0.58,0.99)]. There were no significant differences in adverse effects between teriparatide and bisphosphonates [RR: 0.89, 95% CI (0.76, 1.03)]. CONCLUSIONS: Based on the results of our meta-analysis, teriparatide was better than bisphosphonates in preventing fractures in postmenopausal women with osteoporosis both in the short-term and long-term follow-up periods. Teriparatide was superior to bisphosphonates in preventing vertebral and non-vertebral fractures. These drugs did not differ in terms of their adverse effects. More high-quality studies are needed to compare other factors such as costs and adverse reactions.

Anterior cruciate ligament reconstruction with the use of adductor canal block can achieve similar pain control as femoral nerve block.

PURPOSE: Moderate-to-severe postoperative pain remains a challenge for both patients and surgeons after anterior cruciate ligament reconstruction (ACLR). The purpose of this study was to systematically review the current evidence in the literature to compare adductor canal block (ACB) with femoral nerve block (FNB) in the treatment of ACLR. METHODS: A comprehensive search of the published literature in PubMed, Scopus, EMBASE, and Cochrane Library databases was performed. Only English randomized clinical trials (RCTs) were included in this study. The primary outcome was pain score. Secondary outcome measures included opioid consumption, postoperative adverse events, patient satisfaction, and quadriceps strength. RESULTS: Eight RCTs with a total of 587 patients were included. No statistically significant difference was observed between the ACB and FNB groups in pain scores at 6 h, 12 h, 24 h, or 48 h; cumulative opioid consumption at 24 h or 48 h; patient satisfaction at 24 or 48 h; and postoperative adverse event. However, ACB showed superior quadriceps strength in the early postoperative period. CONCLUSIONS: Both treatments provided similar overall pain relief after ACLR. The potential benefits of quadriceps preservation with ACB are worthy of future study. Therefore, ACB is recommended as an attractive alternative to FNB as the peripheral nerve block of choice for ACLR. LEVEL OF EVIDENCE: Meta-analysis of Level 1 was performed in this study.

MiR-151a-3p Promotes Postmenopausal Osteoporosis by Targeting SOCS5 and Activating JAK2/STAT3 Signaling.

Postmenopausal osteoporosis, the most common type of primary osteoporosis, poses a significant threat to women's health worldwide. However, detailed molecular mechanism and therapeutic strategy for postmenopausal osteoporosis remain insufficient. Increasing evidence suggests that microRNAs contributed to the pathogenesis of osteoporosis and could be considered as potential therapeutic targets. In this study, we found that miR-151a-3p was upregulated in osteoporosis samples. Experiments in MC3T3-E1 cells indicated that miR-151a-3p significantly inhibited cell viability and promoted lactate dehydrogenase release, as well as increased RANKL/OPG ratio and decreased Runx2 and BMP2 expressions. SOCS5 was identified as a direct target gene of miR-151a-3p, which was confirmed by luciferase reporter assay. Moreover, an inverse correlation between miR-151a-3p and SOCS5 was observed in osteoporosis femurs. In addition, JAK2/STAT3 pathway was found to be involved in the progress of osteoporosis mediated by miR-151a-3p-SOCS5 axis. In vivo, ovariectomized (OVX) rat model was established to simulate postmenopausal osteoporosis. The results revealed that miR-151a-3p significantly decreased the bone mineral density and biomechanical parameters of femurs in OVX rats by targeting SOCS5, and that JAK2/STAT3 pathway is a downstream target of miR-151a-3p-SOCS5 axis in OVX rats. In conclusion, our findings suggested that miR-151a-3p contributed to the pathogenesis of postmenopausal osteoporosis, and promoted its progress by targeting SOCS5 and activating JAK2/STAT3 signaling. Thus, anti-miR-151a-3p could be a potential therapeutic strategy for postmenopausal osteoporosis.