A nomogram for predicting cerebral white matter lesions in elderly men.

Objective: This study aimed to develop a nomogram tool to predict cerebral white matter lesions (WMLs) in elderly men. Methods: Based on a retrospective cohort from January 2017 to December 2019, a multivariate logistic analysis was performed to construct a nomogram for predicting WMLs. The nomogram was further validated using a follow-up cohort between January 2020 and December 2022. The calibration curve, receiver operating characteristics (ROC) curves, and the decision curves analysis (DCA) were used to evaluate discrimination and calibration of this nomogram. Result: A total of 436 male patients were enrolled in this study, and all 436 patients were used as the training cohort and 163 follow-up patients as the validation cohort. A multivariate logistic analysis showed that age, cystatin C, uric acid, total cholesterol, platelet, and the use of antiplatelet drugs were independently associated with WMLs. Based on these variables, a nomogram was developed. The nomogram displayed excellent predictive power with the area under the ROC curve of 0.951 [95% confidence interval (CI), 0.929-0.972] in the training cohort and 0.915 (95% CI, 0.864-0.966) in the validation cohort. The calibration of the nomogram was also good, as indicated by the Hosmer-Lemeshow test with p-value of 0.594 in the training cohort and 0.178 in the validation cohort. The DCA showed that the nomogram holds good clinical application value. Conclusion: We have developed and validated a novel nomogram tool for identifying elderly men at high risk of WMLs, which exhibits excellent predictive power, discrimination, and calibration.

Hierarchically Assembled Nanofiber Scaffolds with Dual Growth Factor Gradients Promote Skin Wound Healing Through Rapid Cell Recruitment.

To address current challenges in effectively treating large skin defects caused by trauma in clinical medicine, the fabrication, and evaluation of a novel radially aligned nanofiber scaffold (RAS) with dual growth factor gradients is presented. These aligned nanofibers and the scaffold's spatial design provide many all-around "highways" for cell migration from the edge of the wound to the center area. Besides, the chemotaxis induced by two growth factor gradients further promotes cell migration. Incorporating epidermal growth factor (EGF) aids in the proliferation and differentiation of basal layer cells in the epidermis, augmenting the scaffold's ability to promote epidermal regeneration. Concurrently, the scaffold-bound vascular endothelial growth factor (VEGF) recruits vascular endothelial cells at the wound's center, resulting in angiogenesis and improving blood supply and nutrient delivery, which is critical for granulation tissue regeneration. The RAS+EGF+VEGF group demonstrates superior performance in wound immune regulation, wound closure, hair follicle regeneration, and ECM deposition and remodeling compared to other groups. This study highlights the promising potential of hierarchically assembled nanofiber scaffolds with dual growth factor gradients for wound repair and tissue regeneration applications.

Identification of a potential bioinformatics-based biomarker in keloids and its correlation with immune infiltration.

Keloid formation is a pathological consequence resulting from cutaneous irritation and injury, primarily attributed to excessive collagen matrix deposition and fibrous tissue proliferation. Chronic inflammation, left uncontrolled over an extended period, also stands as a substantial contributing factor. The precise mechanisms underlying keloid formation remain unclear. Therefore, this study aimed to identify key genes for diagnostic purposes. To achieve this, we used two Gene Expression Omnibus (GEO) data sets to identify differentially expressed genes. We identified one particular gene, homeobox C9 (HOXC9), using a thorough strategy involving two algorithms (least absolute shrinkage and selection operator and support vector machine-recursive feature elimination) and weighted gene co-expression network analysis. We then assessed its expression in normal and keloid tissues. In addition, we explored its temporal expression patterns via Mfuzz time clustering analysis. In our comprehensive analysis, we observed that immune infiltration, as well as cell proliferation, are crucial to keloid formation. Thus, we investigated immune cell infiltration in the keloid and normal groups, as well as the correlation between HOXC9 and these immune cells. It was found that HOXC9 was closely associated with the immune microenvironment of keloids. This shows that HOXC9 can serve as a potential biomarker and therapeutic target for keloids.

Biomimetic nanoparticles of platelet membranes carrying bFGF and VEGFA genes promote deep burn wound healing.

INTRODUCTION: The treatment of burn wounds, especially deep burn wounds, remains a major clinical challenge. Growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor A (VEGFA) show great potential in promoting the healing of damaged tissues. This study explored wound healing following targeted delivery of bFGF and VEGFA genes into deep burn wounds through a novel platelet membrane-coated nanoparticle (PM@gene-NP) complex delivery system. METHODS: First, bFGF and VEGFA genes were inserted into plasmid (pEGFP-N1) vectors. Subsequently, the assembled plasmids were loaded onto nanoparticles to form gene-loaded nanoparticle complexes, which were then wrapped with extracted platelet membrane, fully simulating the characteristics of platelets, in order to actively target sites of inflammatory damage. After administration of PM@gene-NP complexes through the tail vein of rats, a series of experiments were conducted to evaluate wound healing. RESULTS: The PM@gene-NP complexes effectively targeted the burn sites. After the administration of the PM@gene-NP complexes, the rats exhibited increased blood flow in the burn wounds, which also healed faster than control groups. Histological results showed fewer inflammatory cells in the burned skin tissue after treatment. After the wounds healed, the production of hair follicles, sebaceous glands and other skin accessories in the skin tissue increased. CONCLUSION: Our results showed that the PM@gene-NP complexes can effectively deliver gene therapy to the injured area, and this delivery system should be considered as a potential method for treating deep burns.

Evaluation of Platelet Distribution Width as an Early Predictor of Acute Kidney Injury in Extensive Burn Patients.

Background: The extensive burns devastate trauma. The research was designed to analyse the predictive value of early platelet (PLT) indices on the development of acute kidney injury (AKI) after severe burns. Methods and Results: 186 patients with extensive burns (burn area ≥30%) were eventually involved. Multivariate analyses pointed out that platelet distribution width (PDW) in the first 24 h after admission was an independent risk factor for AKI, severe AKI, and RRT requirement in patients with severe burns, and AKI risk showed an increase of 30.9% per increase of 1% in PDW (OR = 1.309, CI, 1.075-1.594, and P = 0.007). It was found that the area under the ROC curve (AUC) of PDW predicting AKI was 0.735 and that the AUC value was 0.81 for AKI after combining PDW and blood urea nitrogen (BUN). Based on the cut-off value PDW = 17.7%, patients were divided into high- (PDW ≥17.7%) and low-risk (PDW <17.7%) groups. In the KM analysis, there was a higher cumulative incidence of AKI if patients were in a high-risk group (in 30 days); and the stages of AKI showed a linear upward trend (chi-square test for linear trend P < 0.001) as there was an increase in the risk level. Conclusion: The PDW level in the early stage serves as an important risk factor for AKI, severe AKI, and RRT requirement in extensive burns. When PDW >17.7%, burn patients are not only at a higher risk for AKI but may also have higher AKI severity. Due to low cost and wide availability, PDW has the potential to be the tool that can predict AKI in extensive burn patients.

Identification of nanoparticle-mediated siRNA-ASPN as a key gene target in the treatment of keloids.

Background: Keloid, also known as connective tissue hyperplasia, is a benign proliferative disorder with a global distribution. The available therapeutic interventions are steroid injections, surgical removal of keloids, radiotherapy, compression therapy, the application of cryosurgery, and many other methods. Objectives: Existing treatments or approaches for keloids may lead to similar or even larger lesions at the site of keloid excision, leading to a high recurrence rate. Therefore, this study aims at identifying a new gene-based therapy for the treatment of keloids. Methods: An ASPN-siRNA/nanoparticle combination (si-ASPN) and a negative siRNA/nanoparticle complex (NC) was developed on the basis of bioinformatics studies and used in vitro and in vivo experiments. Results: The results showed a strong correlation between the development of keloids and high expression of ASPN protein. With the expression of ASPN protein greatly reduced in keloid fibroblasts and nude mice allografts after treatment with si-ASPN, the collagen and fibroblasts were also uniform, thinner, parallel and regular. Conclusion: All the above experimental results suggest that keloid and ASPN are closely related and both fibroblast growth and metabolism of keloid are inhibited after silencing ASPN. Therefore, ASPN-siRNA delivered via nanoparticles can serve as a novel intervention therapy for the treatment of keloids.

Chitosan degradation products promote healing of burn wounds of rat skin.

Burns can impair the barrier function of the skin, and small burns can also cause high mortality. The WHO has described that over 180,000 people die of burns worldwide each year. Thus, the treatment of burn wounds is a major clinical challenge. Chitooligosaccharides (COS) are alkaline amino oligosaccharides with small molecular weights obtained by enzyme or chemical degradation of chitosan. With the characteristics of biocompatibility, water solubility and degradability, it has attracted increasing attention in the fields of biomedicine. In the present study, we used COS to treat deep second-degree burn wounds of rat skin and found that COS was able to promote wound healing. We also revealed that COS could promote fibroblast proliferation. Transcriptome sequencing analysis was performed on COS-treated fibroblasts to identify the underlying mechanisms. The results showed that COS was able to promote wound healing through regulation of the mitogen-activated protein kinase (MAPK) pathway and growth factor Hepatocyte Growth Factor (HGF). Our results provide a potential drug for burn wound therapy and the related molecular mechanism.

Effects of nanoparticle-mediated Co-delivery of bFGF and VEGFA genes to deep burn wounds: An in vivo study.

Deep burns are a common form of trauma worldwide, and they are hard to be cured in a short time and enhance psychological pressure of the patients. How to effectively promote the healing of wounds after burns is a continuing challenge currently faced by burn physicians. Various strategies of promoting wound healing of deep burns have been developed, including gene therapy and growth factor therapy. In this study, we developed a combined therapy using PLGA nanoparticles as carriers to deliver bFGF and VEGFA genes to promote healing of burn wounds. We first inserted the bFGF and VEGFA genes into pEGFP-N1 vectors and loaded the mixed generated plasmids into PLGA nanoparticles. Next, we injected the nanoparticle/plasmid complexes into the rats intracutaneously and found that the complexes were successfully transfected in vivo one week later. Finally, we injected the nanoparticle/plasmid complexes containing bFGF and VEGFA around burn wounds. We found that the percentage of wound healing of rats treated with nanoparticles/bFGF+ VEGFA plasmid complexes was higher than that of rats in the scald control group, and the early percentage of wound complete epithelialization was also higher. Therefore, combining gene therapy with nanoparticles may be an effective biological strategy for wound repair.