Guixin Sun

Background: During the healing of skin wounds, excessive fibrosis and collagen remodeling disorders often lead to the formation of proliferative scars. Fisetin is a naturally occurring flavonoid compound with antioxidant and anti-fibrotic properties. However, its therapeutic effect and mechanism of action in wound healing and inhibition of scar formation are still unknown. Methods: This study used network pharmacological methods to identify potential targets and pathways related to wound healing and proliferative scar formation. Through protein-protein interaction analysis, Gene Ontology analysis and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG), its potential biological functions were clarified. In addition, molecular docking was also carried out to evaluate the binding affinity between fisetin and the core target. The effect of fisetin on wound closure and collagen deposition was evaluated using the full-thickness skin wound model in rats. In in vitro experiments, human dermal fibroblasts were used to study the effect of fisetin on collagen expression and the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Results: Network pharmacological analysis highlighted serine/threonine kinase 1 (AKT1) as a central target linking fisetin to wound repair and fibrosis. Functional enrichment indicated significant involvement of the PI3K/Akt pathway. Molecular docking further confirmed a strong binding affinity between fisetin and AKT1. In vivo experiments demonstrated that fisetin significantly accelerated wound closure, reduced inflammatory cell infiltration, and improved histological organization. Quantitative analysis showed decreased histological inflammation scores and a reduced the ratio of type I collagen (COL1A)/type III collagen (COL3A), indicating improved collagen remodeling and attenuated scar formation. Moreover, fisetin upregulated PTEN expression while suppressing transforming growth factor-beta1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) expression in wound tissues. In vitro experiments further confirmed that fisetin inhibited profibrotic marker expression and regulated PI3K/Akt signaling activity in HDFs. Conclusion: Fisetin promotes skin wound healing and attenuates proliferative scar formation by reducing inflammation, improving collagen remodeling, and suppressing fibrotic signaling. Mechanistically, fisetin upregulates PTEN and inhibits the PI3K/Akt/TGF-β1 axis, thereby limiting fibroblast activation and pathological extracellular matrix deposition. These findings suggest fisetin as a promising therapeutic candidate for wound management and scar prevention.

Background: Inflammaging, an immune status characterized by a sustained increase in pro-inflammatory markers and a decline in anti-inflammatory mechanisms, is a critical risk factor in the development of sarcopenia. Landscapes of the causal relationships between immunity and sarcopenia are needed to understand the mechanism of sarcopenia and provide novel treatments comprehensively.Methods: We used Mendelian Randomization (MR) as the basic method in this study. By setting immune proteins, immune cells, and sarcopenia as exposures and outcomes alternatively, and then combining them in different directions, we potentially estimated their causal relationships and directions and subsequently mapped the comprehensive causal landscape based on this information efficiently. To further understand the network, we developed a method based on rank-sums to integrate multiple algorithms and identify the key immune cells and proteins.Results: More than 1,000 causal relationships were identified between immune cell phenotypes, proteins, and sarcopenia traits (p < 0.05), and the causal maps of these linkages were established. In the threshold of FDR < 0.05, hundreds of causal linkages were still significant. The final comprehensive map included 13 immune cell phenotypes and 8 immune proteins. The star factors in the final map included EM CD8br %CD8br, EM DN (CD4- CD8-) %DN, SIRT2, and so on.Conclusion: By reading the landscapes in this study, we may not only find the factors and the pathways that have been reported and proven but also identify multiple novel immunity cell phenotypes and proteins with enriched upstream and downstream pathways.

Effect of inflammatory response on joint function after hip fracture in elderly patients: A clinical study

Background: Cytokines and growth factors may serve as a bridge in studying the causal relationships between inflammaging and sarcopenia due to their roles in inflammaging. In this study, we aim to explore the causal association of cytokines with sarcopenia and aging traits and further identify the significant inflammation factors.Methods: Bidirectional Mendelian randomization (MR) analysis was used to identify the causality. Forty‐one kinds of circulation cytokines and growth factors were set as exposures, and the data were from a summary genome‐wide association study (GWAS) containing three cohorts with 8293 healthy participants of European ancestry from 1983 to 2011. Hand grip strength, adjusted appendicular lean mass (AALM), usual walking pace, moderate‐to‐vigorous physical activity (MVPA) levels, able to walk or cycle unaided for 10 min (AWCU10) and telomere length were selected as outcomes. Data for outcomes were obtained from meta‐GWAS and the UK Biobank, and sample sizes ranged from 69 537 to 472 174. Low hand grip strength was defined by the European Working Group on Sarcopenia in Older People (EWGSOP) and Foundation for the National Institutes of Health (FNIH) cut‐off points, respectively. Other outcome traits were defined and measured according to the UK Biobank and raw cohorts' criteria. We set two significance thresholds for single nucleotide polymorphisms (SNPs) associated with exposures to obtain adequate SNPs (5 × 10⁻⁶ and 5 × 10⁻⁸). Inverse‐variance weighted, MR‐Egger and weighted median were employed to estimate the causality.Results: Twenty‐seven factors were identified to relate to sarcopenia and aging traits causally, and most were associated with only one outcome trait. IL16 (interleukin‐16), CTACK (cutaneous T‐cell attracting chemokine), MIP1b (macrophage inflammatory protein 1b) and PDGFbb (platelet‐derived growth factor BB) were proven to relate causally to at least one sarcopenia and aging trait in both analyses with two significance thresholds. IL16 was causally associated with hand grip strength (0.977 [0.956–0.998] for EWGSOP and 0.933 [0.874–0.996] for FNIH), AALM (0.991 [0.984, 0.998]), MVPA (0.997 [0.995–1.000]) and AWCU10 (1.008 [1.003–1.013]). CTACK was proven to relate causally to hand grip strength (1.013 [1.007–1.019] for EWGSOP and 1.090 [1.041–1.142] for FNIH), AWCU10 (0.990 [0.986–0.994]) and telomere length (0.998 [0.983–0.994]). The results indicated that MIP1b has a causal effect on hand grip strength (1.032 [1.001–1.063] for EWGSOP), AWCU10 (0.994 [0.988–1.000] and 0.993 [0.988–0.998]) and telomere length (1.006 [1.000–1.012]). PDGFbb may causally relate to AALM (1.016 [1.001–1.030]) and telomere length (1.011 [1.007–1.015]). Reserve MR analyses also proved their unidirectional causal effects.Conclusions: Twenty‐seven factors were causally related to sarcopenia and aging traits, and the causal effects of IL16, CTACK, MIP1b and PDGFbb were proven in both analyses with two significance thresholds.

Background Dorsal Barton's fracture is a distinct type of distal radius fracture. The treatment of dorsal Barton's fracture is contentious and may lead to severe complications like traumatic arthritis and fracture malunion. Furthermore, there is a scarcity of clinical studies on dorsal Barton's fractures. This study aims to use three-dimensional (3D) CT scans to more intuitively and clearly depict the characteristics and patterns of dorsal Barton fractures. The objective is to deepen the understanding of such fractures, providing reference significance for clinical treatment. Methods The patients with dorsal Barton's fracture who met the inclusion criteria in our hospital were retrospectively analyzed. 3D models of dorsal Barton's fracture were established by high-quality CT scanning, and the relevant data of different sections were measured to obtain the fracture characteristics of dorsal Barton's fracture. Results This study included 122 patients, comprising 39 males and 83 females. The average age for males was 55.21 years (range: 19–87 years), and for females, it was 63.88 years (range: 42–89 years). Among the 39 cases of dorsal Barton's fractures, 27 were single dorsal fractures, including 22 cases of dorsal ulnar Barton's fractures, 3 cases of dorsal radial Barton's fractures, and 2 cases of dorsal horizontal Barton's fractures. Twelve cases presented with 2 dorsal fractures, but none had 3 dorsal fractures. Among the 83 cases of female dorsal Barton's fractures, 59 were single dorsal fractures, including 55 cases of dorsal ulnar Barton's fractures, 3 cases of dorsal radial Barton's fractures, and 1 case of dorsal horizontal Barton's fracture. Twenty-two cases had 2 dorsal fractures, and 2 cases had 3 dorsal fractures. Conclusions Dorsal Barton fractures exhibit variability in fracture line and number, showing morphological distinctions. The 3D fracture line map of dorsal Barton's fracture, derived from CT 3D reconstruction, not only reveals relevant characteristics but also aids in basic research and the determination of an appropriate surgical plan based on fracture line distribution.

Bone defects or bone discontinuities caused by trauma, infection, tumours and other diseases have led to an increasing demand for bone grafts and biomaterials. Autologous bone grafts, bone grafts with vascular tips, anastomosed vascular bone grafts and autologous bone marrow components are all commonly used in clinical practice, while oversized bone defects require the use of bone tissue engineering-related biomaterials to repair bone defects and promote bone regeneration. Currently, inorganic components such as polysaccharides and bioceramics, as well as a variety of bioactive proteins, metal ions and stem cells can be loaded into hydrogels or 3D printed scaffold materials to achieve better therapeutic results. In this review, we provide an overview of the types of materials, applications, potential mechanisms and current developments in the repair of bone defects.