BackgroundAs of now, effective clinical treatments for burn-induced intestinal injury are still limited. Carbon dots (CDs), recognized for their unique biological activities, present a promising avenue for the development of innovative nanomedicine-based therapies aimed at addressing intestinal barrier dysfunction following burns.MethodsThis study reports the successful synthesis of a novel class of CDs—specifically derived from Sanguisorbae Radix carbonisata (SRC-CDs)—through a green, one-step pyrolysis method, using Sanguisorbae Radix as the sole precursor. A comprehensive suite of analytical techniques, including high-resolution transmission electron microscopy (HR-TEM), dynamic light scattering (DLS), fluorescence spectroscopy, and Fourier-transform infrared (FTIR) spectroscopy, was employed to meticulously characterize the physicochemical properties, particle morphology, surface chemistry, and optical features of the synthesized SRC-CDs. Furthermore, the intestinal protective efficacy of SRC-CDs fabricated at varying pyrolysis temperatures (260 °C, 310 °C, 360 °C, and 410 °C) was evaluated in a murine model of 30% total body surface area (TBSA) full-thickness scald injury. Assessments included intestinal permeability biomarkers, tight junction protein expression, inflammatory cytokine levels, and oxidative stress parameters.ResultsNotably, SRC-CDs synthesized across a spectrum of pyrolysis temperatures (260 °C, 310 °C, 360 °C, and 410 °C) consistently exhibited particle diameters within a defined nanoscale range (2.0–8.0 nm) and featured a rich surface chemistry characterized by diverse functional groups, irrespective of the specific thermal conditions employed. Importantly, in vivo administration of SRC-CDs conferred significant protection against burn-induced intestinal injury. This protective effect was manifested through the substantial mitigation of histopathological damage and the functional restoration of the intestinal barrier. Mechanistically, SRC-CDs treatment effectively restored intestinal barrier integrity, as demonstrated by a marked reduction in circulating levels of permeability markers, intestinal fatty acid binding protein (I-FABP) and diamine oxidase (DAO), coupled with a robust upregulation of key tight junction proteins, ZO-1 and occludin, within the intestinal mucosa. At a molecular level, SRC-CDs exerted pronounced anti-inflammatory and antioxidant actions, significantly suppressing the levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and the lipid peroxidation product malondialdehyde (MDA), while concurrently enhancing the activities of the endogenous antioxidant enzymes superoxide dismutase (SOD) and glutathione (GSH).ConclusionThis study developed biocompatible SRC-CDs via green pyrolysis, demonstrating their efficacy in mitigating burn-induced intestinal injury. SRC-CDs enhanced barrier integrity, reduced inflammation and oxidative stress, with the 360 °C-synthesized variant showing optimal bioactivity, thereby supporting the traditional use of SR and proposing a novel nanomaterial strategy for managing critical burn complications.

Background:Gastrointestinal (GI) dysfunction is a life-threatening complication following severe burn injury, significantly increasing risks of multi-organ failure and mortality. This study aimed to develop and validate the first machine learning (ML)-based clinical prediction model for GI dysfunction after severe burns by leveraging explainable artificial intelligence (AI) techniques to support early clinical intervention. Methods:In this retrospective multicenter study, 570 patients with severe burns were enrolled: 469 from Hospital A [randomly split into training (n = 328) and internal validation (n = 141) sets] and 101 from Hospital B (external validation set). Predictors of GI dysfunction were identified using least absolute shrinkage and selection operator (LASSO) regression and Boruta algorithm. Eight ML algorithms were developed and evaluated using a 7:3 training-validation split and external validation. Model performance was assessed by area under the curve (AUC), accuracy, specificity, and decision curve analysis (DCA). Model interpretability was provided using SHapley Additive exPlanations (SHAP). Results:Among 570 patients, the incidence of GI dysfunction was 35.61% (203/570). The XGBoost algorithm showed superior discrimination, with an AUC of 0.910 (95% CI: 0.878-0.941) in the training set, 0.851 (0.790-0.913) in the internal validation set, and 0.908 (0.837-0.979) in the external validation set. SHAP analysis identified five key predictors by importance: SOFA score, TBSA, inhalation injury, blood culture result, and hematuria. Conclusion:We developed and validated the first interpretable ML-based model for predicting GI dysfunction after severe burn injury, with XGBoost achieving high performance. This model could help identify high-risk patients for personalized pre-emptive management.

Deep sternal wound infection with osteomyelitis (DSWI-OM) is a severe complication after median sternotomy. This study aimed to identify key determinants of wound healing after initial combined platelet-rich plasma (PRP) and negative-pressure wound therapy (NPWT) in DSWI-OM patients, to guide individualized management. In a single-center retrospective cohort, 75 DSWI-OM patients treated with PRP-NPWT (2013–2021) were stratified by healing status at 2 weeks into Healed (n = 33) and Nonhealed (n = 42) groups. Univariate and multivariable logistic regression analyses identified risk factors from baseline characteristics, wound-specific factors (e.g., debridement history), and laboratory parameters. ROC curves established cut-off values. A novel sternal stability classification (Type A: stable, B: loosened, C: defective) integrated anatomical severity. The primary closure failure rate was significantly higher in DSWI-OM than DSWI-alone patients (56.0

The treatment of burn wounds is a complex and lengthy process, including infection control, inflammation modulation, tissue regeneration, and scar management. Although significant progress has been achieved, numerous clinical challenges persist, especially the increased bacterial resistance, the risk of wound sepsis, and the issue of serious hypertrophic scar. In recent years, nanozymes have emerged as a hotspot in materials research and increasingly been applied to promote burn wound healing. Possessing multiple enzyme-like activities, nanozymes can integrate antibacterial, anti-inflammatory, and pro-angiogenic effects, among others. Meanwhile, nanozymes offer advantages such as less prone to inducing drug resistance, high stability, and simple preparation, which indicate broad application prospects compared with antibiotics, natural enzymes, and traditional nanomaterials. This review provides a comprehensive overview of the pathophysiology involved in burn wounds and introduces nanozymes exhibiting a variety of enzyme-like activities including oxidase (OXD), peroxidase (POD), superoxide dismutase (SOD), catalase (CAT), haloperoxidase (HPO), nitrite reductase (NiRs), and hydrolase. The potential mechanisms by which nanozymes promote burn wound healing are summarized and elucidated from the aspects of anti-bacteria, anti-oxidative stress, anti-inflammation, pro-angiogenesis, and anti-scarring. Finally, we discuss the limitations of the current study and offer an outlook for future research, hoping to pave the way for the next generation nanozymes in the treatment of burn wounds.

Persistent hyperglycemia-induced mitochondrial oxidative stress causes mtDNA leakage, activating the STING signaling pathway in macrophages and eliciting sustained pro-inflammatory cytokine secretion, resulting in wound healing stagnation throughout the inflammatory phase. In this study, we developed a glucose/ROS-responsive hydrogel dressing (SG) employing dynamic crosslinking via boronate ester between chlorogenic acid (CGA)-conjugated gelatin and sodium alginate functionalized with 3-aminophenylboronic acid. Furthermore, the engineered macrophage-targeting phosphatidylserine (PS)-incorporated liposomes (HPSL), designed for the precise delivery of the STING inhibitor H151, were incorporated into the hydrogel (HPSL@SG). This hydrogel exhibits superior injectability, stretchability, self-healing properties, and adaptation to the irregular shapes of skin wounds. Upon injection into a diabetic wound, the as-prepared hydrogel disintegrated in response to elevated glucose and ROS, facilitating the on-demand release of CGA and HPSL. The CGA can directly scavenge ROS to alleviate oxidative stress, achieving a 79.9% reduction in superoxide anion levels; the HPSL specifically targets macrophages to prevent disturbance of immunologic homeostasis due to off-target effects. This process facilitates macrophage polarization towards an anti-inflammatory phenotype by inhibiting the STING signaling pathway, thereby suppressing the release of pro-inflammatory cytokines TNF-α and IL-6 and promoting the release of IL-10. The HPSL@SG hydrogel collectively enhances angiogenesis, evidenced by a 6.6-fold increase in CD31 levels and a 7.3-fold increase in VEGF levels, while also facilitating collagen deposition, with collagen content escalating from 32.6% to 69.3%. This procedure culminates in an 89.7% recovery within 10 days and nearly complete wound healing within 14 days, indicating its potential for clinical application in diabetic wound healing.

Background:Chronic nonhealing wounds are major complications in diabetic patients, with impaired angiogenesis playing a critical role in the delayed healing process. Current treatments for diabetic wounds are inadequate. The dysregulation of endothelial cell genes, particularly thrombospondin-1 (TSP-1), impairs neovascularization and delays wound repair. In recent years, hydrogel-based wound dressings have gained widespread application in biomedicine. The study introduced a new therapeutic approach, embedding miR-221-3p-loaded small extracellular vesicles (miR-221OE-sEVs) within gelatin methacryloyl (GelMA) hydrogels to reduce TSP-1 levels and improve healing in diabetic wounds. Methods:First, we observed upregulated TSP-1 expression in human umbilical vein endothelial cells (HUVECs) when cultured in a high-glucose (HG) environment. We employed small interfering RNA (siRNA) and miR-221-3p to suppress TSP-1 expression and then evaluate the functional effects on HUVECs. Subsequently, miR-221-3p was encapsulated in sEVs via lentiviral transfection. The effects of miR-221OE-sEVs on HUVECs under HG conditions were evaluated. Finally, miR-221OE-sEVs were incorporated into a GelMA hydrogel (G-miR-221OE-sEVs) and applied to a diabetic murine wound model to evaluate their effects on wound closure and angiogenesis. Results:Under HG conditions, the use of siTSP-1 to silence TSP-1 enhanced the proliferation, migration, and tube formation capabilities of HUVECs. Similarly, miR-221-3p treatment exerted proregenerative effects via the targeting of TSP-1. We successfully generated miR-221OE-sEVs that exhibited a 28-fold increase in miR-221-3p expression, which significantly enhanced HUVEC functionality under HG conditions. Encapsulation within the GelMA hydrogel enabled G-miR-221OE-sEVs to significantly accelerate diabetic wound healing via increased angiogenesis. Conclusions:This study demonstrated the successful fabrication of a novel bioactive wound dressing (G-miR-221OE-sEVs), which promotes diabetic wound healing by promoting angiogenesis through the regulation of TSP-1. This approach offers a potential therapeutic option for enhancing the management of diabetic wounds.

Perfect and rapid wound healing remains a clinical challenge, and appropriate wound dressing is the key to promoting wound healing. Bioactive hydrogels have gained widespread attention in the field of wound dressings because of their superior physicochemical properties. First, the stages of wound healing, including hemostasis, inflammation, proliferation, and remodeling, are outlined. Next, on the basis of their biological effects, hydrogel dressings are categorized into the following types: antibacterial, hemostatic and adhesive, anti-inflammatory, antioxidant, angiogenic, microenvironment-responsive, and conductive. Each category is thoroughly discussed with respect to its design strategies, underlying mechanisms of action, and practical applications. Finally, we provide a comprehensive overview of the key challenges confronting bioactive hydrogel dressing research, including sequential treatment needs, individualized treatment needs, advanced material preparation strategies, effective clinical translation and real-time wound monitoring. The corresponding promising solution strategies are also proposed and discussed in detail, offering a novel perspective for the development of hydrogel dressings.

Background Burns present a significant clinical challenge and are a critical global public health concern. Existing studies primarily focus on specific countries or regions, resulting in a lack of comprehensive global epidemiological data. This study aims to assess the disease burden of burns across various regions, providing crucial insights for policy decisions to mitigate their impact.Methods:This ecological time-series study utilized data from the Global Burden of Disease (GBD) Study 2021 to analyze the incidence and Years Lived with Disability (YLDs) for burn injuries categorized as “burns < 20%” (<20% total burned surface area without lower airway burns), “burns ≥ 20%” ( ≥20% TBSA or ≥10% if head/neck or hands/wrist involved, without lower airway burns), and “lower airway burns” from 1990 to 2021. We calculated percentage change (PC) and estimated annual percentage change (EAPC) to assess trends in age-standardized rates (ASRs). Spearman’s rank correlation coefficient was used to validate correlations between ASRs and the socio-demographic index (SDI). Gaussian curves were employed to analyze associations between EAPC rates and the SDI, while a Bayesian age-period-cohort (BAPC) model examined the effects of age, period, and cohort.Results:From 1990 to 2021, burns showed a significant decline in ASIR and ASR-YLDs, particularly for burns < 20% and burns ≥ 20%. In 2021, burns < 20% and lower airway burns correlated positively with the SDI, while burns ≥ 20% exhibited a negative correlation (P < 0.05). The predominant causes of burns include fire, heat, and hot substances. Based on current trends, projections suggest a continued global decline in both ASIR and ASR-YLDs for all types of burns from 2022 to 2035.Conclusions:This comprehensive study advances the epidemiological understanding of global burn injuries by providing detailed subgroup analyses that inform healthcare planning and targeted intervention strategies.

Infected wounds present a major clinical challenge due to the increasing prevalence of antibiotic resistance and the complex interplay of factors that impede tissue regeneration. To address this, we developed a pathologically responsive, sprayable hydrogel dressing incorporating gold-core silver-shell nanorod (Au@Ag NR) nanocomposites to accelerate infected wound healing. The hydrogel, composed of poly(vinyl alcohol) (PVA) and carboxylated chitosan (CCS), responds to elevated hydrogen peroxide (H2O2) levels characteristic of infected wound microenvironments. Upon exposure to pathological H2O2, the Ag shell of the Au@Ag NRs undergoes oxidative etching, releasing silver ions (Ag+) for potent antibacterial action while simultaneously exposing the Au core for subsequent photothermal therapy upon second near-infrared (NIR-II) irradiation. In vitro studies demonstrated significant antibacterial efficacy against both Escherichia coli and Staphylococcus aureus, while in vivo assessments using a mouse model of infected wound healing revealed enhanced angiogenesis, reduced inflammation, and accelerated wound closure compared to control treatments. Synergistic Ag+ release and NIR-triggered photothermal ablation led to superior antibacterial and wound healing outcomes. These findings suggest that the sprayable hydrogel shows promise as a clinically translatable strategy for the effective management of severely infected wounds.

NMR metabolomics faces critical sensitivity limitations when analyzing whole spectral profiles, particularly in clinical biomarker discovery where weak metabolite signals often elude detection. To address this challenge, we present NMR metabolomics convolutional neural network(NmCNN) as an interpretable 1D-convolutional neural network framework that innovatively integrates spectral translation invariance with explainable AI. Our approach presents a novel concept distinct from traditional machine learning methods, and the incorporation of an interpreter exhibits a higher sensitivity in detecting differential metabolites. The model incorporates translation invariance from CNN, facilitating efficient processing of spectra and effectively addressing issues pertaining to deviations in spectral peak alignment. Validated on sepsis biomarker discovery for whole blood and blood platelet samples, NmCNN achieved 90–95 % sensitivity, 80 %-85 % specificity and area under curve 0.83–0.96 The interpretability framework with SHapley Additive exPlanations (SHAP) identified previously undetected metabolic features, demonstrating sensitivity improvement over conventional quantification methods through its whole-spectrum utilization. Overall, our NmCNN model offers a distinctive approach that enhances the utilization of raw NMR-based spectral metabolomics profiles in AI-driven clinical research, thereby improving interpretability and sensitivity in metabolomics analysis.

BACKGROUND:This study aimed to summarize risk factors for complications of tissue expansion using a meta-analysis of cohort studies. METHODS:PubMed, Embase, and Cochrane Library were searched from January 1985 to January 2025 for retrospective cohort studies investigating at least one potential risk factor for complications of tissue expansion. The quality of individual studies was assessed using the Newcastle-Ottawa scale. We conducted meta-analysis with risk ratios calculated for complication event rates. RESULTS:This review included 19 studies involving 1,673 participants. Two distinct subgroups (children only, adults and children) were identified. Strong evidence indicated that lower limb (relative ratio, 1.73; 95% confidence interval, 1.27-2.37), burn (relative ratio, 1.45, 95% confidence interval, 1.07-1.95), and myelomeningocele (relative ratio, 1.82; 95% confidence interval, 1.22-2.70) were the risk factors for premature removal of expansion in both children and adults. CONCLUSION:This review identified lower limb, burn, and myelomeningocele are risk factors for complications of tissue expansion. Identifying modifiable risk factors is an urgent priority to improve prevention and treatment outcomes.

BACKGROUND:Mitochondrial DNA (mtDNA) plays a crucial role in inflammation regulation and can be passively or accidentally released in setting of cellular stress or traumatic injury. In this study, we try to evaluate the distribution and significance of mtDNA in blister fluid of paediatric small area intermediate depth burn wounds. METHODS:This trial was conducted as a follow-up analysis of a single-centre, prospective observational study that enrolled 62 children with small area partial-thickness thermal burns. The mtDNA in blister fluid was measured with a PCR-based assay. The levels of cytokines including interleukin-6 (IL-6), interleukin-8 (IL-8) and transforming growth factor β1 (TGF-β1) were evaluated by using ELISA. Association of mtDNA with inflammatory markers and wound healing outcome was analysed. RESULTS:The mtDNA copy number (mtDNA-CN) was determined as median (min, max) value of 76.30 (16.5, 219.1). Spearman rank correlation coefficient analysis showed that the levels of IL-6, IL-8, and TGF-β1 all exhibited significant correlations with mtDNA-CN in burn blister fluid samples (all P < 0.05). Moreover, a significant association between wound healing time and mtDNA-CN in blister fluid was observed (P < 0.05); Kaplan-Meier curves by log-rank test demonstrated that mtDNA-CN in blister fluid was significantly associated with for time to re-epithelialization (P < 0.05). CONCLUSION:Blister fluid mtDNA may serve to evaluate burn wound severity in children with small area intermediate-depth burns.

Chinese herbal medicines and their extracts will produce nano-components of charcoal drugs after high-temperature carbonization, and the process is similar to that of carbon dots (CDs). Chinese herbal medicine-derived CDs (CHM-CDs) are a new carbon-based nanomaterial with a particle size of less than 10 nm discovered in charcoal drugs in recent years. CHM-CDs possess a range of beneficial traits, such as minimal toxicity, strong water solubility, superior biocompatibility, and remarkable photoluminescence capabilities. Additionally, they exhibit multifaceted pharmacological activity in the absence of drug loading. Over the past half-decade, numerous publications have presented evidence suggesting that CHM-CDs exhibit a wide array of pharmacological effects. These primarily encompass hemostatic capabilities, neuroprotection, anti-infective, antitumor, immunomodulatory effects and hypoglycemic activity. Notably, they have been associated with circulatory system, digestive system, nervous system, immune system, endocrine system, urinary system and skeletal system. This article systematically reviews the modern pharmacological effects and potential mechanisms of CHM-CDs, offering insights into current challenges and proposing directions for future advancements. As such, it serves as a vital reference for the clinical application of CHM-CDs.

Background Hypernatremia represents a critical complication in patients with severe burns. This study aims to further investigate the etiology, clinical features, and therapeutic strategies for hypernatremia in this patient population. Methods We conducted daily measurements of serum sodium (Na), chloride (Cl), potassium (K), urea nitrogen (Un), creatinine (Cr) concentrations, procalcitonin (PCT) levels, and serum osmolality in 23 patients with total burn area ≥ 90% TBSA. Additionally, 24-hour urine output was recorded, and urinary excretion of Na, Cl, K, Un, and Cr was analyzed. Changes in wound status and systemic inflammatory response were also monitored. After wound treatment and repair, serum and 24-hour urine test indicators were reassessed. Patients were categorized into two groups based on their serum Na concentration: the normal group (N group) with serum Na ≤ 149 mmol/L, and the hypernatremia group (H group) with serum Na ≥ 150 mmol/L. Results Among the 10 patients in the H group, serum Na, Un, PCT, and serum osmolality were 158.09 ± 5.74 mmol/L, 27.43 ± 9.10 mmol/L, 1.40 ± 0.94 ng/mL, and 323.53 ± 8.46 mosm/kg, respectively, all significantly higher than those in the N group (P < 0.05). Urinary Na excretion in the H group was 105.95 ± 44.81 mmol/24 h, significantly lower than in the N group (p < 0.05). Urinary excretion of Un, Cr, and K increased in the H group, with Un excretion reaching 1339.08 ± 350.43 mmol/24 h, significantly higher than in the N group (P < 0.05). The H group exhibited signs of wound eschar dissolution and exacerbated systemic inflammatory response. Within 2 days post-wound treatment and repair, serum Na levels in the H group normalized, with 8 out of 10 patients achieving full recovery. All 13 patients in the N group recovered fully. Conclusions Some severely burned patients may experience increased systemic inflammatory response, leading to enhanced high catabolic metabolism, increased production and excretion of Un, and reduced urinary Na excretion, resulting in hypernatremia. Reduced urinary Na excretion is a significant cause of hypernatremia in severely burned patients. The primary basic treatment measure should be to treat and repair the wound, thereby controlling systemic inflammatory response, reducing high metabolism, and promoting urinary sodium excretion.

Burn injuries are underestimated trauma that moderate and severe burns are often associated with death. Early excision is the gold standard treatment for burn injuries to reduce the risk of infection, but is subject to scarce source and high cost of donor skin, complications of patients and battlefield environment. Cerium based materials are showing growing potential in biomedical field. Cerium nitrate have been used over the past 50 years, either alone or as adjunct to silver sulphadiazine, achieving improved outcomes in burn injuries. It not only strengthens the antibacterial effect of silver sulfadiazine, but also performs excellent anti-inflammation and immunoregulation capabilities, and has positive influence on eschars for postpone excision and grafting. Moreover, the superior redox properties of cerium oxide nanoparticles (CeO2 NPs), also known as nanoceria, make them good candidates in the treatment of excessive oxidative stress on burn wounds. The aim of this review is to give an overview and update about cerium-based materials in burn wound care, considering the history, applications, mechanisms and biosafety of cerium nitrate and CeO2 NPs in burn injuries, raising awareness of the ongoing development of this kind of promising material in burn wound healing in the future.

>The destruction of the skin barrier and the presence of necrotic tissue in large burns increase the risk of multiple infections, often leading to sepsis, bacteremia, and other complications.Infective endocarditis(IE) is a severe manifestation of organ damage, and if conservative medical treatment fails to control the infection, irreversible pathological changes may occur, including valvular redundancy.