The dual role of CCND1 in heterotopic ossification: A Non-canonical Pathway for Celecoxib treatment.

Objective: To explore the effective targets of Celecoxib in the treatment of heterotopic ossification using network pharmacology methods. Methods: Potential molecules related to heterotopic ossification were obtained by retrieving the GEO and CTD databases and intersecting them. Potential binding targets of Celecoxib were acquired from the STITCH database. A protein-protein interaction network was constructed between potential binding targets of Celecoxib and potential related molecules of heterotopic ossification using the STRING database. Molecules in the protein-protein interaction network were further analyzed using GO and KEGG enrichment analysis in R software, followed by enrichment analysis of active molecules in the Celecoxib-heterotopic ossification target dataset. Hub genes were selected based on the "degree" value and enrichment within the protein-protein interaction network. The binding affinity of hub genes to Celecoxib was observed using molecular docking techniques. Finally, in vitro experiments were conducted to validate the effectiveness of hub genes and explore their regulatory role in the progression of heterotopic ossification. Additionally, the therapeutic effect of Celecoxib, which modulates the expression of the hub genes, was investigated in the treatment of heterotopic ossification. Results: 568 potential molecules related to heterotopic ossification and 76 potential binding targets of Celecoxib were identified. After intersection, 13 potential functional molecules in Celecoxib's treatment of heterotopic ossification were obtained. KEGG analysis suggested pathways such as Rheumatoid arthritis, NF-kappa B signaling pathway, Pathways in cancer, Antifolate resistance, MicroRNAs in cancer play a role in the treatment of heterotopic ossification by Celecoxib. Further enrichment analysis of the 13 potential functional molecules identified 5 hub genes: IL6, CCND1, PTGS2, IGFBP3, CDH1. Molecular docking results indicated that Celecoxib displayed excellent binding affinity with CCND1 among the 5 hub genes. Experimental validation found that CCND1 is highly expressed in the progression of heterotopic ossification, promoting heterotopic ossification in the early stages and inhibiting it in the later stages, with Celecoxib's treatment of heterotopic ossification depending on CCND1. Conclusion: In the process of treating heterotopic ossification with Celecoxib, immune and inflammatory signaling pathways play a significant role. The therapeutic effect of Celecoxib on heterotopic ossification depends on the hub gene CCND1, which plays different roles at different stages of the progression of heterotopic ossification, ultimately inhibiting the occurrence of heterotopic ossification.

Cartilage decellularized matrix hydrogel loaded with protocatechualdehyde for targeted epiphycan treatment of osteoarthritis.

Osteoarthritis (OA) is a prevalent chronic disease, characterized by chronic inflammation and cartilage degradation. This study aims to deepen the understanding of OA's pathophysiology and to develop novel therapeutic strategies. Our study underscores the pivotal role of Epiphycan (EPYC) and the IL-17 signaling pathway in OA. EPYC, an essential extracellular matrix constituent, has been found to exhibit a positive correlation with the severity of OA. We have discovered that EPYC modulates the activation of the IL-17 signaling pathway within chondrocytes by regulating the interaction between IL-17A and its receptor, IL-17RA. This regulatory mechanism underscores the intricate interplay between the extracellular matrix and immune signaling in the pathogenesis of OA Another finding of our study is the therapeutic effectiveness of protocatechualdehyde (PAH) in OA. PAH significantly reduces chondrocyte hypertrophy and supports cartilage tissue recovery.by targets EPYC. To reduce the side effects of orally administered PAH and maintain its effective drug concentration, we have developed a decellularized matrix hydrogel loaded with PAH for intra-articular injection. This novel drug delivery system is advantageous in minimizing drug-related side effects and ensuring sustained release PAH within the joint cavity.

Extracellular matrix hydrogels with fibroblast growth factor 2 containing exosomes for reconstructing skin microstructures.

Decellularized extracellular matrix hydrogel (ECM hydrogel), a natural material derived from normal tissue with unique biocompatibility properties, is widely used for tissue repair. However, there are still problems such as poor biological activity and insufficient antimicrobial property. To overcome these drawbacks, fibroblast growth factor 2 (FGF 2) containing exosome (exoFGF 2) was prepared to increase the biological activity. Furthermore, the antimicrobial capacity of ECM hydrogel was optimised by using copper ions as a ligand-bonded cross-linking agent. The decellularized extracellular matrix hydrogel, intricately cross-linked with copper ions through ligand bonds and loaded with FGF 2 containing exosome (exoFGF 2@ECM/Cu2+ hydrogel), has demonstrated exceptional biocompatibility and antimicrobial properties. In vitro, exoFGF 2@ECM/Cu2+ hydrogel effectively promoted cell proliferation, migration, antioxidant and inhibited bacterial growth. In vivo, the wound area of rat treated with exoFGF 2@ECM/Cu2+ hydrogels were significantly smaller than that of other groups at Day 5 (45.24% ± 3.15%), Day 10 (92.20% ± 2.31%) and Day 15 (95.22% ± 1.28%). Histological examination showed that exoFGF 2@ECM/Cu2+ hydrogels promoted angiogenesis and collagen deposition. Overall, this hydrogel has the potential to inhibit bacterial growth and effectively promote wound healing in a variety of clinical applications.

Enhanced Surgical Outcomes of Popliteal Cyst Excision: A Retrospective Study Comparing Arthroscopic Debridement with and without Methylene Blue Injection.

BACKGROUND This retrospective study of 42 patients with popliteal cysts (or Baker cysts) aimed to compare the effects on duration and outcomes of arthroscopic surgical debridement with and without the use of cyst injection with methylene blue (MB). MATERIAL AND METHODS Medical records of patients who underwent conventional arthroscopic surgery (n=20) or arthroscopic surgery after MB injection (n=22) for popliteal cysts between 2018 and 2021 were reviewed. The MB group underwent arthroscopic popliteal cystectomy with MB as the marker, and the control group underwent conventional arthroscopic popliteal cystectomy. Surgical time of cyst resection, postoperative bruising extent, complication rate, and cyst recurrence rate of the 2 groups were compared. RESULTS The MB group had a faster surgical cyst removal time (16.5±1.5 min) than the control group (24.5±1.6 min; P<0.05). The MB group had less postoperative bruising (1 case, 4.5%) than the control group (5 cases, 25%; P<0.05). The surgical results were similar in both groups, with a Lysholm score of 87.23±1.80 in the MB group and 87.23±1.62 (P>0.05) in the control group. CONCLUSIONS This study showed that preoperative injection of MB for popliteal cysts before arthroscopic debridement improved cyst localization and ease and accuracy of surgery and reduced operative time, adjacent tissue damage, postoperative complications, and recurrence rate.

Clinical Outcomes of Arthroscopic Surgery in Patients with Gluteal Muscle Contracture: Single-Institution Results from a High-Volume Cohort.

BACKGROUND The aim of this study was to assess clinical outcomes of arthroscopic surgery for gluteal muscle contracture (GMC) with at least 2 years of follow-up in a large sample. MATERIAL AND METHODS A total of 665 patients who underwent arthroscopic release procedure at our institution between March 2014 and December 2018 and met the inclusion criteria were included in this study. All the patients were operated on by the same surgeon and the surgeon released the contracture band from anterior to posterior starting from the anterior edge of the ITB, the contracture band of the gluteus maximus, and vastus medialis tensor. After exclusion, 544 patients (218 males and 326 females) were finally included. Clinical outcomes at 2 years of postoperative follow-up were evaluated by a combination of several methods, including a new criterion we proposed for postoperative assessment, which included the cross-leg test, difficulty in squatting with legs together, and abnormal gait, the visual analogue scale (VAS), the modified Harris hip score (mHHS), and the satisfaction of patients. RESULTS The average follow-up time was 48.2±14.9 months. Based on the new criteria, 513 (94.3%) patients were evaluated as good, 25 (4.6%) as fair, and 6 (1.1%) as poor. The mHHS increased from 72.1±6.0 (range, 56.0-81.3) to 97.3±2.2 (range, 92.3-100.0) (P<0.001). The VAS decreased from 3.3±1.1 (range, 0-5) to 0.062±0.13 (range, 0-1) (P<0.001). For subjective satisfaction, 526 (96.7%) patients were satisfied, 14 (2.6%) patients were neutral, and 4 (0.7%) patients were dissatisfied. CONCLUSIONS In a large sample, favorable and durable clinical outcomes were observed after the arthroscopic procedure. Clinical symptoms and mHHS showed significant improvement with a minimum 2-year follow-up.

Comparative analysis and prediction of avian influenza in Shangrao city, China from 2016 to 2022.

The aim of this study was to investigate the effects of vaccination, COVID-19 pandemic and migration of migratory birds on the avian influenza positivity rate in Shangrao City and to predict the future avian influenza positivity rate. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to detect nucleic acids of avian influenza A viruses. 1795 samples were collected between 2016 and 2022, of which 1086 were positive. In addition, there were seven human cases of avian influenza. The results showed that the positivity rate of H9 subtype in Shangrao City was higher than usual during the COVID-19 pandemic and migratory birds. Predictions suggest that the H9 subtype positivity rate in Shangrao City will be on the rise in the future. In recent years, the H5 positivity rate has gradually increased. Migratory birds and the COVID-19 pandemic have led to an increase in H9 subtype positivity. Therefore, the prevention and control of them should be strengthened.

Innovation Clustering Analysis of Accurate Support Path for CSE under the Environment of Big Data.

Facing the severe employment situation and social environment, the employment of college students has become a very important issue. The big data analysis plays a positive role in entrepreneurship, which can not only improve the success rate of entrepreneurial path selection, but also accumulate a lot of innovative practical experience for college students. Based on the importance of big data technology for entrepreneurial path, this paper proposes an innovative model of accurate support path for college students' entrepreneurship (CSE), in which the K-means algorithm is applied to the analysis of entrepreneurial support path. Finally, this paper makes an experimental analysis on the model, and the results show that K-means can greatly reduce the computational complexity of the algorithm, and the precision, recall, and F parameter of the model can be effectively improved. The model is of great significance in improving the feasibility of college students' entrepreneurial support policies.