Objective:To evaluate the effects of a piceatannol-loaded self-nanoemulsifying drug delivery system(PIC-SNEDDS)on wound healing in diabetic rats and its mechanisms of wound healing action.Methods:Diabetes was induced ...Objective:To evaluate the effects of a piceatannol-loaded self-nanoemulsifying drug delivery system(PIC-SNEDDS)on wound healing in diabetic rats and its mechanisms of wound healing action.Methods:Diabetes was induced in rats using streptozotocin,after which full-thickness excisional wounds were created.Piceatannol was administered topically either as a raw hydrogel or formulated into a PIC-SNEDDS,which was prepared using an optimized oil-surfactant mixture and incorporated into a hydrogel for application.Wound healing activity was assessed through measurements of wound contraction,oxidative stress biomarkers,and collagen content,along with histological and immunohistochemical evaluation of inflammatory,angiogenic,and remodeling markers.Results:PIC-SNEDDS markedly enhanced diabetic wound healing by promoting epithelial regeneration,granulation tissue formation,epidermal proliferation,and keratinization.The formulation also reduced the expression of pro-inflammatory markers(interleukin-6,nuclear factor-kappa B,and tumor necrosis factor-α)while increasingα-smooth muscle actin,transforming growth factor-β1,vascular endothelial growth factor-A,and hydroxyproline levels.Additionally,it improved antioxidant status by lowering malondialdehyde levels and boosting superoxide dismutase and catalase activity,along with upregulation of COL1A1 mRNA expression.Conclusions:PIC-SNEDDS promotes the healing of diabetic wounds and exhibits anti-inflammatory,antioxidant,pro-collagen,and angiogenic properties.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)present a significant clinical challenge due to their high prevalence and profound impact on morbidity.Ultrasound-assisted wound debridement(UAWD)has emerged as a potential therape...BACKGROUND Diabetic foot ulcers(DFUs)present a significant clinical challenge due to their high prevalence and profound impact on morbidity.Ultrasound-assisted wound debridement(UAWD)has emerged as a potential therapeutic modality to improve healing outcomes in DFU management.AIM To evaluate the efficacy of UAWD in treating DFUs on wound closure rates,treatment duration,and quality of life outcomes.METHODS This systematic review and meta-analysis followed PRISMA guidelines,systematically searching PubMed,Embase,Web of Science,and the Cochrane Library with no date restrictions.Randomized controlled trials(RCTs)that evaluated the efficacy of UAWD in DFU treatment were included.Data were independently extracted by two reviewers,with discrepancies resolved through consensus or third-party consultation.The risk of bias was assessed using the Cochrane tool.χ2 and I2 statistics assessed heterogeneity,informing the use of fixed or random-effects models for meta-analysis,supplemented by sensitivity analysis and publication bias assessment through funnel plots and Egger's test.RESULTS From 1255 articles,seven RCTs met the inclusion criteria.The studies demonstrated that UAWD significantly reduced DFU healing time(standardized mean difference=-0.78,95%CI:-0.97 to-0.60,P<0.001)and increased healing rates(odds ratio=9.96,95%CI:5.99 to 16.56,P<0.001)compared to standard care.Sensitivity analysis confirmed the stability of these results,and no significant publication bias was detected.CONCLUSION UAWD is a promising adjunctive treatment for DFUs,significantly reducing healing times and increasing healing rates.These findings advocate for the integration of UAWD into standard DFU care protocols.展开更多
Magnesium and its alloys have garnered significant attention as promising materials for bone tissue engineering,owing to their bone-like density and elastic modulus,favorable mechanical properties,biodegradability,bio...Magnesium and its alloys have garnered significant attention as promising materials for bone tissue engineering,owing to their bone-like density and elastic modulus,favorable mechanical properties,biodegradability,biocompatibility,and diverse biological activities.However,rapid degradation,subcutaneous gas formation from H_(2)release,and osteolysis caused by elevated Mg concentrations have limited its widespread clinical application.In this study,Mg-3.0Gd-1Zn-0.4Zr(GZ31K)alloy with desirable uniform degradation and stress corrosion resistance under extruded and drawn condition was used as internal fixation implants for fracture healing,while the commercially available WE43 alloy was used as control.Results revealed that GZ31K alloy exhibited refined grain structure,nanoscale distributed stacking faults and superior corrosion resistance compared to WE43 alloy.The corrosion rate of the extruded GZ31K and WE43 alloys are 0.25 mm/year and 0.35 mm/year,meeting the corrosion tolerance threshold for orthopedic implants(<0.5 mm/year).In vitro study demonstrated that GZ31K alloy exhibited pronounced biocompatibilities and osteogenic bioactivities towards rat bone marrow mesenchymal stem cells(rBMSCs)compared with WE43 alloy,as evidenced by the enhanced ALP activity level,mineralized nodule formation and expression of osteogenicrelated marker genes.In vivo results confirmed that GZ31K alloy retained its above 87.1%structural integrity for up to 8 weeks postimplantation and exhibited better corrosion resistance compared to the WE43 alloy(80.9%).Besides,the Sprague-Dawley rats administrated with GZ31K alloy exhibited greater bone volume,trabecular thickness,satisfactory load-bearing performance and surface degradation behavior at 8 weeks post-fracture healing compared to the Kirschner wire and the WE43 alloy.Taken together,these findings highlighted that GZ31K alloy with slower degradation rate,enhanced structural stability,exceptional biocompatibilities and osteogenic potential might provide sustained structural integrity and mechanical support throughout the fracture healing process,positioning it as a strong candidate for next-generation orthopedic implants.展开更多
Diabetes mellitus is an escalating global health issue,with 463 million adults affected in 2019.Without intervention,this number is projected to increase to 578 million by 2030 and 700 million by 2045[1].Diabetic woun...Diabetes mellitus is an escalating global health issue,with 463 million adults affected in 2019.Without intervention,this number is projected to increase to 578 million by 2030 and 700 million by 2045[1].Diabetic wound,a significant complication,is characterized by delayed healing,high disability rates,and elevated mortality[2].The challenges of wound healing in diabetic patients,compounded by their high morbidity and mortality rates,have drawn growing attention in biomedical research.展开更多
Wound management continues to present major clinical challenges,often necessitating therapeutic strategies that extend beyond conventional dressings,which provide only passive protection.Magnesium(Mg),a biologically i...Wound management continues to present major clinical challenges,often necessitating therapeutic strategies that extend beyond conventional dressings,which provide only passive protection.Magnesium(Mg),a biologically indispensable element,has attracted considerable attention for its multifaceted role in wound repair,including modulation of inflammatory responses,stimulation of fibroblast and keratinocyte proliferation,promotion of angiogenesis,and enhancement of collagen synthesis.However,the direct application of Mg formulations is limited by uncontrolled Mg ion(Mg^(2+))release,localized cytotoxicity at elevated concentrations,and inadequate mechanical stability at the wound site.To address these challenges,Mg-incorporated polymeric scaffolds have been developed as advanced delivery platforms.These systems integrate the regenerative capacity of Mg with the tunable properties of polymers,enabling controlled degradation,mechanical reinforcement,and sustained Mg^(2+)release to establish a favorable microenvironment for tissue repair.This review critically examines the role of Mg in wound healing and the effectiveness of polymeric matrices for controlled Mg^(2+)delivery.It further provides a comprehensive evaluation of recent advances in Mg-incorporated polymeric scaffolds,including nanofibers,hydrogels,and sponges,with emphasis on fabrication strategies,structural characteristics,and therapeutic efficacy.Key challenges,such as optimizing ion release kinetics,enhancing scaffold stability,and facilitating clinical translation,are also discussed.Collectively,this work underscores the potential of Mg-polymeric scaffolds as a next-generation platform for advanced wound care and highlights perspectives for future research and development.展开更多
The development of highly efficient and multifunctional nanozymes holds promise for addressing the challenges posed by drugresistant bacteria.Here,copper single-atom-loaded MoS_(2) nanozymes(CuSAs/MoS_(2))were develop...The development of highly efficient and multifunctional nanozymes holds promise for addressing the challenges posed by drugresistant bacteria.Here,copper single-atom-loaded MoS_(2) nanozymes(CuSAs/MoS_(2))were developed to effectively combat drug-resistant bacteria by synergistically integrating the triple strategies of oxidative damage,cuproptosis-like death and disruption of cell wall synthesis.Density functional theory revealed that each Cu center coordinated with three sulfur ligands,enhancing the adsorption of H_(2)O_(2),which reduced the activation energy of the key step by 17%,thereby improving peroxidase-like(PODlike)activity.The generation of reactive oxygen species in combination with CuSAs/MoS_(2) glutathione peroxidase-like(GSH-Px-like)for glutathione scavenging resulted in an imbalance in redox homeostasis within bacteria.CuSAs/MoS_(2),which act as nanopioneers,drive oxidative stress to initiate the process of cuproptosis-like death,leading to abnormal aggregation of lipoylated proteins and inactivation of iron-sulfur cluster proteins.Moreover,CuSAs/MoS_(2) inhibited the biosynthesis of the peptidoglycan synthesis precursors D-glutamate and m-diaminopimelic acid and disrupted the peptidoglycan cross-linking process mediated by penicillin-binding proteins,effectively blocking the compensatory cell wall remodeling pathway ofβ-lactam-resistant bacteria.Overall,CuSAs/MoS_(2) with multiple functions can not only efficiently kill bacteria but also decelerate the development of bacterial resistance to combat drug-resistant bacterial infections.展开更多
Burn infection is one of the most common and severe complications in burn patients and a major factor contributing to high mortality rates.The loss of skin barrier function and the immunosuppressive state following bu...Burn infection is one of the most common and severe complications in burn patients and a major factor contributing to high mortality rates.The loss of skin barrier function and the immunosuppressive state following burns make patients highly susceptible to wound infections,which can progress to systemic sepsis.Although burn wounds are initially sterile,they are rapidly colonized by Gram-positive bacteria(e.g.,Staphylococcus aureus)within a short period,followed by colonization with Gram-negative bacteria(e.g.,Pseudomonas aeruginosa),thereby increasing therapeutic challenges.Current clinical management relies on a multidisciplinary collaborative approach,combining conventional antibiotics,emerging therapies,and comprehensive care strategies.Among these methods,early intervention,precise treatment administration,and prevention and control are critical to improving patient survival and prognosis.In recent years,drug-loaded hydrogels,as a class of wound repair materials characterized by biocompatibility,controlled drug release,and multifunctional integration,have demonstrated significant advantages in the treatment of burn infections.They can effectively inhibit pathogenic microorganisms,alleviate inflammation,and promote tissue regeneration.This review systematically summarizes recent research advances in the application of drug-loaded hydrogels for the treatment of infected burn wounds,aiming to provide a reference for their further development and clinical translation.展开更多
Delayed wound healing following radical gastrectomy remains an important yet underappreciated complication that prolongs hospitalization,increases costs,and undermines patient recovery.In An et al’s recent study,the ...Delayed wound healing following radical gastrectomy remains an important yet underappreciated complication that prolongs hospitalization,increases costs,and undermines patient recovery.In An et al’s recent study,the authors present a machine learning-based risk prediction approach using routinely available clinical and laboratory parameters.Among the evaluated algorithms,a decision tree model demonstrated excellent discrimination,achieving an area under the curve of 0.951 in the validation set and notably identifying all true cases of delayed wound healing at the Youden index threshold.The inclusion of variables such as drainage duration,preoperative white blood cell and neutrophil counts,alongside age and sex,highlights the pragmatic appeal of the model for early postoperative monitoring.Nevertheless,several aspects warrant critical reflection,including the reliance on a postoperative variable(drainage duration),internal validation only,and certain reporting inconsistencies.This letter underscores both the promise and the limitations of adopting interpretable machine learning models in perioperative care.We advocate for transparent reporting,external validation,and careful consideration of clinically actionable timepoints before integration into practice.Ultimately,this work represents a valuable step toward precision risk stratification in gastric cancer surgery,and sets the stage for multicenter,prospective evaluations.展开更多
Objective:To analyze the clinical application value of autologous periosteum graft combined with platelet-rich plasma(PRP)in the treatment of long bone fractures in the extremities.Methods:A total of 40 patients with ...Objective:To analyze the clinical application value of autologous periosteum graft combined with platelet-rich plasma(PRP)in the treatment of long bone fractures in the extremities.Methods:A total of 40 patients with long bone fractures in the extremities admitted to Santai Hospital Affiliated to North Sichuan Medical College from January 2023 to January 2025 were included,including cases of upper extremity forearm fractures and lower extremity femoral and tibial fractures.The patients were evenly divided using a random number table,with the control group undergoing open reduction and internal fixation(ORIF)combined with autologous periosteum graft,and the observation group undergoing ORIF,autologous periosteum graft,and PRP injection.Surgical indicators,complication rates,excellent fracture healing rates,functional satisfaction,and joint range of motion were compared between the two groups.Results:The surgical indicators in the observation group were similar to those in the control group(p>0.05).The complication rate in the observation group was lower than that in the control group,while the excellent fracture healing rate and functional satisfaction were higher in the observation group(p<0.05).Conclusion:Autologous periosteum graft combined with PRP technology is safe and reliable for the treatment of long bone fractures in the extremities,with satisfactory clinical outcomes.展开更多
This study presents a physics-informed modelling framework that combines finite element method(FEM)simulations and supervised machine learning(ML)to predict the self-healing performance of microbial concrete.A FEniCS-...This study presents a physics-informed modelling framework that combines finite element method(FEM)simulations and supervised machine learning(ML)to predict the self-healing performance of microbial concrete.A FEniCS-based FEM platform resolves multiphysics phenomena including nutrient diffusion,microbial CaCO_(3) precipitation,and stiffness recovery.These simulations,together with experimental data,are used to train ML models(Random Forest yielding normalized RMSE≈0.10)capable of predicting performance over a wide range of design parameters.Feature importance analysis identifies curing temperature,calcium carbonate precipitation rate,crack width,bacterial strain,and encapsulation method as the most influential parameters.The coupled FEM-ML approach enables sensitivity analysis,design optimization,and prediction beyond the training dataset(consistently exceeding 90%healing efficiency).Experimental validation confirms model robustness in both crack closure and strength recovery.This FEM–ML pipeline thus offers a generalizable,interpretable,and scalable strategy for the design of intelligent,self-adaptive construction materials.展开更多
To evaluate circulating IL9 in inflammatory bowel disease and disease-associated anemia/cachexia and assess its potential as a mucosal healing marker.METHODSSerum IL9 as well as other cytokines (IL1β, IL6, IL13, IFN...To evaluate circulating IL9 in inflammatory bowel disease and disease-associated anemia/cachexia and assess its potential as a mucosal healing marker.METHODSSerum IL9 as well as other cytokines (IL1β, IL6, IL13, IFNγ, TNFα, and VEGF-A) were determined in 293 individuals: 97 patients with Crohn’s disease (CD) and 74 with ulcerative colitis (UC) and in 122 apparently healthy controls. The clinical activity of CD and UC was expressed in terms of the Crohn’s Disease Activity Index (CDAI) and the Mayo Scoring System (MDAI), respectively, and the severity of bowel inflammation in UC patients was assessed using Mayo endoscopic score. Cytokine concentrations were measured by a flow cytometry-based method using Luminex xMAP<sup>®</sup> technology. High-sensitive C-reactive protein concentrations (hsCRP) were determined in CD and UC patients using the enhanced immunoturbidimetric method.RESULTSSystemic IL9 was significantly lower in healthy individuals [9 pg/mL (95%CI: 8.2-10)] than in patients with inflammatory bowel disease (IBD): both inactive [14.3 pg/mL (11.9-19.9)] and active [27.6 pg/mL (24.5-32), P < 0.0001]. Cytokine concentrations were significantly higher in active CD [27.4 pg/mL (23.4-32.2)] and in active UC [32.7 pg/mL (27-38.9)] compared to inactive diseases [15.9 pg/mL (10.8-23.4) in CD and 19.4 pg/mL (13.9-27.1) in UC, P = 0.001]. IL9 correlated weakly with CDAI (ρ = 0.32, P = 0.003) and MDAI (ρ = 0.35, P = 0.002) and strongly with endoscopic inflammation in UC (ρ = 0.74, P < 0.0001). As a negative marker of mucosal healing (MH), IL9 had an accuracy superior to hsCRP and IL6 [97% (P < 0.0001), 67% (P = 0.071), and 55% (P = 0.525), respectively]. IL9 was significantly higher in cachectic IBD patients [30.25 pg/mL (24.4-37.5) vs 21.88 pg/mL (18-26.5), P = 0.026] and negatively correlated with hemoglobin concentrations (ρ = -0.27, P < 0.001). Multiple regression showed IL1β and IL13 to be the independent predictors of circulating IL9 in healthy individuals, IFNγ or IL6 in active and inactive UC, respectively, and IL13 and VEGF-A in both active and inactive CD.CONCLUSIONThe systemic IL9 level is higher in IBD and corresponds with endoscopic inflammation, suggesting its possible application as a negative marker of mucosal healing in UC.展开更多
AIM:To provide a specifi c review and meta-analysis of the available evidence for continuous wound infusion of local anaesthetic agents following midline laparoto-my for major colorectal surgery. METHODS: Medline, Emb...AIM:To provide a specifi c review and meta-analysis of the available evidence for continuous wound infusion of local anaesthetic agents following midline laparoto-my for major colorectal surgery. METHODS: Medline, Embase, trial registries, conference proceedings and article reference lists were searched to identify randomised, controlled trials of continuous wound infusion of local anaesthetic agents following colorectal surgery. The primary outcomes were opioid consumption, pain visual analogue scores (VASs), return to bowel function and length of hospital stay. Weighted mean difference were calculated for continuous outcomes. RESULTS: Five trials containing 542 laparotomy wounds were eligible for inclusion. There was a sig- nificant decrease in post-operative pain VAS at rest on day 3 (weighted mean difference: -0.43; 95% CI: -0.81 to -0.04; P = 0.03) but not on post-operative day 1 and 2. Local anaesthetic infusion was associated with a signifi cant reduction in pain VAS on movement on all three post-operative days (day 1 weighted mean difference: -1.14; 95% CI: -2.24 to -0.041; P = 0.04, day 2 weighted mean difference: -0.97, 95% CI: -1.91to -0.029; P = 0.04, day 3 weighted mean difference: -0.61; 95% CI: 1.01 to -0.20; P = 0.0038). Local an- aesthetic wound infusion was associated with a signifi - cant decrease in total opioid consumption (weighted mean difference: -40.13; 95% CI: -76.74 to -3.53; P = 0.03). There was no signifi cant decrease in length of stay (weighted mean difference: -20.87; 95% CI: -46.96 to 5.21; P = 0.12) or return of bowel function (weighted mean difference: -9.40; 95% CI: -33.98 to 15.17; P = 0.45). CONCLUSION: The results of this systematic re- view and meta-analysis suggest that local anaesthetic wound infusion following laparotomy for major color- ectal surgery is a promising technique but do not pro- vide conclusive evidence of benefi t. Further research is required including cost-effectiveness analysis.展开更多
Mucosal healing(MH)has emerged as a key therapeutic target in inflammatory bowel disease(IBD),and achievement of this goal is documented by endoscopy with biopsy.However,colonoscopy is burdensome and invasive,and subs...Mucosal healing(MH)has emerged as a key therapeutic target in inflammatory bowel disease(IBD),and achievement of this goal is documented by endoscopy with biopsy.However,colonoscopy is burdensome and invasive,and substitution with an accurate noninvasive biomarker is desirable.AIM To summarize published data regarding the performance of noninvasive biomarkers in assessing MH in IBD patients.METHODS We conducted a systematic review of studies that reported the performance of biomarkers in diagnosing MH in patients with IBD.The main outcome measure was to review the diagnostic accuracy of serum and fecal markers that showed promising utility in assessing MH.RESULTS We screened 1301 articles,retrieved 46 manuscripts and included 23 articles for full-text analysis.The majority of the included manuscripts referred to fecal markers(12/23),followed by circulatory markers(8/23);only 3/23 of the included manuscripts investigated combined markers(serum and/or fecal markers).Fecal calprotectin(FC)was the most investigated fecal marker for assessing MH.In ulcerative colitis,for cutoff levels ranging between 58 mcg/g and 490 mcg/g,the sensitivity was 89.7%-100%and the specificity was 62%-93.3%.For Crohn’s disease,the cutoff levels of FC ranged from 71 mcg/g to 918 mcg/g(sensitivity 50%-95.9%and specificity 52.3%-100%).The best performance for a serum marker was observed for the endoscopic healing index,which showed a comparable accuracy to the measurement of FC and a higher accuracy than the measurement of serum C-reactive protein.CONCLUSION Several promising biomarkers of MH are emerging but cannot yet substitute for endoscopy with biopsy due to issues with reproducibility and standardization assessing MH.In ulcerative colitis,for cutoff levels ranging between 58 mcg/g and 490 mcg/g,the sensitivity was 89.7%-100%and the specificity was 62%-93.3%.For Crohn’s disease,the cutoff levels of FC ranged from 71 mcg/g to 918 mcg/g(sensitivity 50%-95.9%and specificity 52.3%-100%).The best performance for a serum marker was observed for the endoscopic healing index,which showed a comparable accuracy to the measurement of FC and a higher accuracy than the measurement of serum C-reactive protein.CONCLUSION Several promising biomarkers of MH are emerging but cannot yet substitute for endoscopy with biopsy due to issues with reproducibility and standardization.展开更多
The complication of diabetes,which is known as diabetic foot ulcer(DFU),is a significant concern due to its association with high rates of disability and mortality.It not only severely affects patients’quality of lif...The complication of diabetes,which is known as diabetic foot ulcer(DFU),is a significant concern due to its association with high rates of disability and mortality.It not only severely affects patients’quality of life,but also imposes a substantial burden on the healthcare system.In spite of efforts made in clinical practice,treating DFU remains a challenging task.While mesenchymal stem cell(MSC)therapy has been extensively studied in treating DFU,the current efficacy of DFU healing using this method is still inadequate.However,in recent years,several MSCs-based drug delivery systems have emerged,which have shown to increase the efficacy of MSC therapy,especially in treating DFU.This review summarized the application of diverse MSCs-based drug delivery systems in treating DFU and suggested potential prospects for the future research.展开更多
BACKGROUND Tranexamic acid(TXA)has been used as an anti-fibrinolytic drug for over half a century and has received much attention in recent decades.AIM To evaluate the efficacy of topical vs intravenous TXA in reducin...BACKGROUND Tranexamic acid(TXA)has been used as an anti-fibrinolytic drug for over half a century and has received much attention in recent decades.AIM To evaluate the efficacy of topical vs intravenous TXA in reducing blood loss and promoting wound healing in bone surgery.METHODS From the electronic resources,PubMed,Cochrane Library,Embase,ISI,and Scopus were used to perform a literature search over the last 10 years between 2010 and 2020.EndNote™X8 was used for managing the electronic resource.Searches were performed with mesh terms.The data were retracted blindly by two independent reviewers.Random effects were used to deal with potential heterogeneity and I2 showed heterogeneity.Chi-square(I2)tests were used to quantify the extent of heterogeneity(P<0.01 was considered statistically significant).The efficacy of topical TXA in reducing blood loss and promoting wound healing in bone surgery was compared with intravenous TXA and placebo.RESULTS According to the research design,1360 potentially important research abstracts and titles were discovered in our electronic searches,and 18 papers remained in agreement with our inclusion criteria.It was found that TXA reduced 277.51 mL of blood loss compared to placebo,and there was no significant difference between topical TXA and IV TXA in reducing blood loss in bone surgery.Our analyses also showed that TXA significantly reduced blood transfusion compared to placebo and there was no significant difference between topical TXA and IV TXA.CONCLUSION The use of both topical and intravenous TXA are equally effective in reducing blood loss in bone surgery,which might be beneficial for wound healing after surgery.展开更多
基金funded by the Deanship of Scientific Research at King Abdulaziz University,Jeddah,under Grant No.G:534-140-1443.
文摘Objective:To evaluate the effects of a piceatannol-loaded self-nanoemulsifying drug delivery system(PIC-SNEDDS)on wound healing in diabetic rats and its mechanisms of wound healing action.Methods:Diabetes was induced in rats using streptozotocin,after which full-thickness excisional wounds were created.Piceatannol was administered topically either as a raw hydrogel or formulated into a PIC-SNEDDS,which was prepared using an optimized oil-surfactant mixture and incorporated into a hydrogel for application.Wound healing activity was assessed through measurements of wound contraction,oxidative stress biomarkers,and collagen content,along with histological and immunohistochemical evaluation of inflammatory,angiogenic,and remodeling markers.Results:PIC-SNEDDS markedly enhanced diabetic wound healing by promoting epithelial regeneration,granulation tissue formation,epidermal proliferation,and keratinization.The formulation also reduced the expression of pro-inflammatory markers(interleukin-6,nuclear factor-kappa B,and tumor necrosis factor-α)while increasingα-smooth muscle actin,transforming growth factor-β1,vascular endothelial growth factor-A,and hydroxyproline levels.Additionally,it improved antioxidant status by lowering malondialdehyde levels and boosting superoxide dismutase and catalase activity,along with upregulation of COL1A1 mRNA expression.Conclusions:PIC-SNEDDS promotes the healing of diabetic wounds and exhibits anti-inflammatory,antioxidant,pro-collagen,and angiogenic properties.
基金Hubei Province Top Medical Youth Talent Program,Wuhan Knowledge Innovation Special Basic Research Project,No.2023020201020558Clinical Research Project of Affiliated Hospital of Guangdong Medical University,No.LCYJ2021B004 and No.LCYJ2019B010Science and Technology Plan Project of Zhanjiang,No.2022A01191.
文摘BACKGROUND Diabetic foot ulcers(DFUs)present a significant clinical challenge due to their high prevalence and profound impact on morbidity.Ultrasound-assisted wound debridement(UAWD)has emerged as a potential therapeutic modality to improve healing outcomes in DFU management.AIM To evaluate the efficacy of UAWD in treating DFUs on wound closure rates,treatment duration,and quality of life outcomes.METHODS This systematic review and meta-analysis followed PRISMA guidelines,systematically searching PubMed,Embase,Web of Science,and the Cochrane Library with no date restrictions.Randomized controlled trials(RCTs)that evaluated the efficacy of UAWD in DFU treatment were included.Data were independently extracted by two reviewers,with discrepancies resolved through consensus or third-party consultation.The risk of bias was assessed using the Cochrane tool.χ2 and I2 statistics assessed heterogeneity,informing the use of fixed or random-effects models for meta-analysis,supplemented by sensitivity analysis and publication bias assessment through funnel plots and Egger's test.RESULTS From 1255 articles,seven RCTs met the inclusion criteria.The studies demonstrated that UAWD significantly reduced DFU healing time(standardized mean difference=-0.78,95%CI:-0.97 to-0.60,P<0.001)and increased healing rates(odds ratio=9.96,95%CI:5.99 to 16.56,P<0.001)compared to standard care.Sensitivity analysis confirmed the stability of these results,and no significant publication bias was detected.CONCLUSION UAWD is a promising adjunctive treatment for DFUs,significantly reducing healing times and increasing healing rates.These findings advocate for the integration of UAWD into standard DFU care protocols.
基金supported by Nanjing Health Bureau Medical Science and Technology Development Foundation(grant number:YKK21106)the National Natural Science Foundation of China(52071175)the Key Research&Development Plan(Social Development)of Jiangsu Province(BE2020702).
文摘Magnesium and its alloys have garnered significant attention as promising materials for bone tissue engineering,owing to their bone-like density and elastic modulus,favorable mechanical properties,biodegradability,biocompatibility,and diverse biological activities.However,rapid degradation,subcutaneous gas formation from H_(2)release,and osteolysis caused by elevated Mg concentrations have limited its widespread clinical application.In this study,Mg-3.0Gd-1Zn-0.4Zr(GZ31K)alloy with desirable uniform degradation and stress corrosion resistance under extruded and drawn condition was used as internal fixation implants for fracture healing,while the commercially available WE43 alloy was used as control.Results revealed that GZ31K alloy exhibited refined grain structure,nanoscale distributed stacking faults and superior corrosion resistance compared to WE43 alloy.The corrosion rate of the extruded GZ31K and WE43 alloys are 0.25 mm/year and 0.35 mm/year,meeting the corrosion tolerance threshold for orthopedic implants(<0.5 mm/year).In vitro study demonstrated that GZ31K alloy exhibited pronounced biocompatibilities and osteogenic bioactivities towards rat bone marrow mesenchymal stem cells(rBMSCs)compared with WE43 alloy,as evidenced by the enhanced ALP activity level,mineralized nodule formation and expression of osteogenicrelated marker genes.In vivo results confirmed that GZ31K alloy retained its above 87.1%structural integrity for up to 8 weeks postimplantation and exhibited better corrosion resistance compared to the WE43 alloy(80.9%).Besides,the Sprague-Dawley rats administrated with GZ31K alloy exhibited greater bone volume,trabecular thickness,satisfactory load-bearing performance and surface degradation behavior at 8 weeks post-fracture healing compared to the Kirschner wire and the WE43 alloy.Taken together,these findings highlighted that GZ31K alloy with slower degradation rate,enhanced structural stability,exceptional biocompatibilities and osteogenic potential might provide sustained structural integrity and mechanical support throughout the fracture healing process,positioning it as a strong candidate for next-generation orthopedic implants.
基金supported by a grant from General Scientific Research Project of Zhejiang Provincial Department of Education(No.Y202455614).
文摘Diabetes mellitus is an escalating global health issue,with 463 million adults affected in 2019.Without intervention,this number is projected to increase to 578 million by 2030 and 700 million by 2045[1].Diabetic wound,a significant complication,is characterized by delayed healing,high disability rates,and elevated mortality[2].The challenges of wound healing in diabetic patients,compounded by their high morbidity and mortality rates,have drawn growing attention in biomedical research.
文摘Wound management continues to present major clinical challenges,often necessitating therapeutic strategies that extend beyond conventional dressings,which provide only passive protection.Magnesium(Mg),a biologically indispensable element,has attracted considerable attention for its multifaceted role in wound repair,including modulation of inflammatory responses,stimulation of fibroblast and keratinocyte proliferation,promotion of angiogenesis,and enhancement of collagen synthesis.However,the direct application of Mg formulations is limited by uncontrolled Mg ion(Mg^(2+))release,localized cytotoxicity at elevated concentrations,and inadequate mechanical stability at the wound site.To address these challenges,Mg-incorporated polymeric scaffolds have been developed as advanced delivery platforms.These systems integrate the regenerative capacity of Mg with the tunable properties of polymers,enabling controlled degradation,mechanical reinforcement,and sustained Mg^(2+)release to establish a favorable microenvironment for tissue repair.This review critically examines the role of Mg in wound healing and the effectiveness of polymeric matrices for controlled Mg^(2+)delivery.It further provides a comprehensive evaluation of recent advances in Mg-incorporated polymeric scaffolds,including nanofibers,hydrogels,and sponges,with emphasis on fabrication strategies,structural characteristics,and therapeutic efficacy.Key challenges,such as optimizing ion release kinetics,enhancing scaffold stability,and facilitating clinical translation,are also discussed.Collectively,this work underscores the potential of Mg-polymeric scaffolds as a next-generation platform for advanced wound care and highlights perspectives for future research and development.
基金supported by the National Natural Science Foundation of China(82372552)the Excellent Youth of Natural Science Research Projects in Anhui Province Universities(2023AH030060)+1 种基金Anhui Provincial Natural Science Foundation(2408085Y016)Anhui Province Excellent Research and Innovation Team Project(2024AH010013)。
文摘The development of highly efficient and multifunctional nanozymes holds promise for addressing the challenges posed by drugresistant bacteria.Here,copper single-atom-loaded MoS_(2) nanozymes(CuSAs/MoS_(2))were developed to effectively combat drug-resistant bacteria by synergistically integrating the triple strategies of oxidative damage,cuproptosis-like death and disruption of cell wall synthesis.Density functional theory revealed that each Cu center coordinated with three sulfur ligands,enhancing the adsorption of H_(2)O_(2),which reduced the activation energy of the key step by 17%,thereby improving peroxidase-like(PODlike)activity.The generation of reactive oxygen species in combination with CuSAs/MoS_(2) glutathione peroxidase-like(GSH-Px-like)for glutathione scavenging resulted in an imbalance in redox homeostasis within bacteria.CuSAs/MoS_(2),which act as nanopioneers,drive oxidative stress to initiate the process of cuproptosis-like death,leading to abnormal aggregation of lipoylated proteins and inactivation of iron-sulfur cluster proteins.Moreover,CuSAs/MoS_(2) inhibited the biosynthesis of the peptidoglycan synthesis precursors D-glutamate and m-diaminopimelic acid and disrupted the peptidoglycan cross-linking process mediated by penicillin-binding proteins,effectively blocking the compensatory cell wall remodeling pathway ofβ-lactam-resistant bacteria.Overall,CuSAs/MoS_(2) with multiple functions can not only efficiently kill bacteria but also decelerate the development of bacterial resistance to combat drug-resistant bacterial infections.
基金Supported by Natural Science Foundation of Guangxi(2025GXNSFHA069111,2020GXNSFAA159033,2019GXNSFAA245078)National Undergraduate Innovation and Entrepreneurship Training Program(202410601054).
文摘Burn infection is one of the most common and severe complications in burn patients and a major factor contributing to high mortality rates.The loss of skin barrier function and the immunosuppressive state following burns make patients highly susceptible to wound infections,which can progress to systemic sepsis.Although burn wounds are initially sterile,they are rapidly colonized by Gram-positive bacteria(e.g.,Staphylococcus aureus)within a short period,followed by colonization with Gram-negative bacteria(e.g.,Pseudomonas aeruginosa),thereby increasing therapeutic challenges.Current clinical management relies on a multidisciplinary collaborative approach,combining conventional antibiotics,emerging therapies,and comprehensive care strategies.Among these methods,early intervention,precise treatment administration,and prevention and control are critical to improving patient survival and prognosis.In recent years,drug-loaded hydrogels,as a class of wound repair materials characterized by biocompatibility,controlled drug release,and multifunctional integration,have demonstrated significant advantages in the treatment of burn infections.They can effectively inhibit pathogenic microorganisms,alleviate inflammation,and promote tissue regeneration.This review systematically summarizes recent research advances in the application of drug-loaded hydrogels for the treatment of infected burn wounds,aiming to provide a reference for their further development and clinical translation.
文摘Delayed wound healing following radical gastrectomy remains an important yet underappreciated complication that prolongs hospitalization,increases costs,and undermines patient recovery.In An et al’s recent study,the authors present a machine learning-based risk prediction approach using routinely available clinical and laboratory parameters.Among the evaluated algorithms,a decision tree model demonstrated excellent discrimination,achieving an area under the curve of 0.951 in the validation set and notably identifying all true cases of delayed wound healing at the Youden index threshold.The inclusion of variables such as drainage duration,preoperative white blood cell and neutrophil counts,alongside age and sex,highlights the pragmatic appeal of the model for early postoperative monitoring.Nevertheless,several aspects warrant critical reflection,including the reliance on a postoperative variable(drainage duration),internal validation only,and certain reporting inconsistencies.This letter underscores both the promise and the limitations of adopting interpretable machine learning models in perioperative care.We advocate for transparent reporting,external validation,and careful consideration of clinically actionable timepoints before integration into practice.Ultimately,this work represents a valuable step toward precision risk stratification in gastric cancer surgery,and sets the stage for multicenter,prospective evaluations.
文摘Objective:To analyze the clinical application value of autologous periosteum graft combined with platelet-rich plasma(PRP)in the treatment of long bone fractures in the extremities.Methods:A total of 40 patients with long bone fractures in the extremities admitted to Santai Hospital Affiliated to North Sichuan Medical College from January 2023 to January 2025 were included,including cases of upper extremity forearm fractures and lower extremity femoral and tibial fractures.The patients were evenly divided using a random number table,with the control group undergoing open reduction and internal fixation(ORIF)combined with autologous periosteum graft,and the observation group undergoing ORIF,autologous periosteum graft,and PRP injection.Surgical indicators,complication rates,excellent fracture healing rates,functional satisfaction,and joint range of motion were compared between the two groups.Results:The surgical indicators in the observation group were similar to those in the control group(p>0.05).The complication rate in the observation group was lower than that in the control group,while the excellent fracture healing rate and functional satisfaction were higher in the observation group(p<0.05).Conclusion:Autologous periosteum graft combined with PRP technology is safe and reliable for the treatment of long bone fractures in the extremities,with satisfactory clinical outcomes.
基金funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Grant Agreement No.945478(SASPRO2)supported by the ReBuilt project:Circular and Digital Renewal of Central Europe Construction and Building Sector CE0100390 ReBuiltthe Slovak Research and Development Agency under APVV-23-0383 and the Slovak Grant Agency VEGA No.2/0080/24.
文摘This study presents a physics-informed modelling framework that combines finite element method(FEM)simulations and supervised machine learning(ML)to predict the self-healing performance of microbial concrete.A FEniCS-based FEM platform resolves multiphysics phenomena including nutrient diffusion,microbial CaCO_(3) precipitation,and stiffness recovery.These simulations,together with experimental data,are used to train ML models(Random Forest yielding normalized RMSE≈0.10)capable of predicting performance over a wide range of design parameters.Feature importance analysis identifies curing temperature,calcium carbonate precipitation rate,crack width,bacterial strain,and encapsulation method as the most influential parameters.The coupled FEM-ML approach enables sensitivity analysis,design optimization,and prediction beyond the training dataset(consistently exceeding 90%healing efficiency).Experimental validation confirms model robustness in both crack closure and strength recovery.This FEM–ML pipeline thus offers a generalizable,interpretable,and scalable strategy for the design of intelligent,self-adaptive construction materials.
基金Supported by National Science Center,No.DEC-2011/01/D/NZ5/02835
文摘To evaluate circulating IL9 in inflammatory bowel disease and disease-associated anemia/cachexia and assess its potential as a mucosal healing marker.METHODSSerum IL9 as well as other cytokines (IL1β, IL6, IL13, IFNγ, TNFα, and VEGF-A) were determined in 293 individuals: 97 patients with Crohn’s disease (CD) and 74 with ulcerative colitis (UC) and in 122 apparently healthy controls. The clinical activity of CD and UC was expressed in terms of the Crohn’s Disease Activity Index (CDAI) and the Mayo Scoring System (MDAI), respectively, and the severity of bowel inflammation in UC patients was assessed using Mayo endoscopic score. Cytokine concentrations were measured by a flow cytometry-based method using Luminex xMAP<sup>®</sup> technology. High-sensitive C-reactive protein concentrations (hsCRP) were determined in CD and UC patients using the enhanced immunoturbidimetric method.RESULTSSystemic IL9 was significantly lower in healthy individuals [9 pg/mL (95%CI: 8.2-10)] than in patients with inflammatory bowel disease (IBD): both inactive [14.3 pg/mL (11.9-19.9)] and active [27.6 pg/mL (24.5-32), P < 0.0001]. Cytokine concentrations were significantly higher in active CD [27.4 pg/mL (23.4-32.2)] and in active UC [32.7 pg/mL (27-38.9)] compared to inactive diseases [15.9 pg/mL (10.8-23.4) in CD and 19.4 pg/mL (13.9-27.1) in UC, P = 0.001]. IL9 correlated weakly with CDAI (ρ = 0.32, P = 0.003) and MDAI (ρ = 0.35, P = 0.002) and strongly with endoscopic inflammation in UC (ρ = 0.74, P < 0.0001). As a negative marker of mucosal healing (MH), IL9 had an accuracy superior to hsCRP and IL6 [97% (P < 0.0001), 67% (P = 0.071), and 55% (P = 0.525), respectively]. IL9 was significantly higher in cachectic IBD patients [30.25 pg/mL (24.4-37.5) vs 21.88 pg/mL (18-26.5), P = 0.026] and negatively correlated with hemoglobin concentrations (ρ = -0.27, P < 0.001). Multiple regression showed IL1β and IL13 to be the independent predictors of circulating IL9 in healthy individuals, IFNγ or IL6 in active and inactive UC, respectively, and IL13 and VEGF-A in both active and inactive CD.CONCLUSIONThe systemic IL9 level is higher in IBD and corresponds with endoscopic inflammation, suggesting its possible application as a negative marker of mucosal healing in UC.
文摘AIM:To provide a specifi c review and meta-analysis of the available evidence for continuous wound infusion of local anaesthetic agents following midline laparoto-my for major colorectal surgery. METHODS: Medline, Embase, trial registries, conference proceedings and article reference lists were searched to identify randomised, controlled trials of continuous wound infusion of local anaesthetic agents following colorectal surgery. The primary outcomes were opioid consumption, pain visual analogue scores (VASs), return to bowel function and length of hospital stay. Weighted mean difference were calculated for continuous outcomes. RESULTS: Five trials containing 542 laparotomy wounds were eligible for inclusion. There was a sig- nificant decrease in post-operative pain VAS at rest on day 3 (weighted mean difference: -0.43; 95% CI: -0.81 to -0.04; P = 0.03) but not on post-operative day 1 and 2. Local anaesthetic infusion was associated with a signifi cant reduction in pain VAS on movement on all three post-operative days (day 1 weighted mean difference: -1.14; 95% CI: -2.24 to -0.041; P = 0.04, day 2 weighted mean difference: -0.97, 95% CI: -1.91to -0.029; P = 0.04, day 3 weighted mean difference: -0.61; 95% CI: 1.01 to -0.20; P = 0.0038). Local an- aesthetic wound infusion was associated with a signifi - cant decrease in total opioid consumption (weighted mean difference: -40.13; 95% CI: -76.74 to -3.53; P = 0.03). There was no signifi cant decrease in length of stay (weighted mean difference: -20.87; 95% CI: -46.96 to 5.21; P = 0.12) or return of bowel function (weighted mean difference: -9.40; 95% CI: -33.98 to 15.17; P = 0.45). CONCLUSION: The results of this systematic re- view and meta-analysis suggest that local anaesthetic wound infusion following laparotomy for major color- ectal surgery is a promising technique but do not pro- vide conclusive evidence of benefi t. Further research is required including cost-effectiveness analysis.
文摘Mucosal healing(MH)has emerged as a key therapeutic target in inflammatory bowel disease(IBD),and achievement of this goal is documented by endoscopy with biopsy.However,colonoscopy is burdensome and invasive,and substitution with an accurate noninvasive biomarker is desirable.AIM To summarize published data regarding the performance of noninvasive biomarkers in assessing MH in IBD patients.METHODS We conducted a systematic review of studies that reported the performance of biomarkers in diagnosing MH in patients with IBD.The main outcome measure was to review the diagnostic accuracy of serum and fecal markers that showed promising utility in assessing MH.RESULTS We screened 1301 articles,retrieved 46 manuscripts and included 23 articles for full-text analysis.The majority of the included manuscripts referred to fecal markers(12/23),followed by circulatory markers(8/23);only 3/23 of the included manuscripts investigated combined markers(serum and/or fecal markers).Fecal calprotectin(FC)was the most investigated fecal marker for assessing MH.In ulcerative colitis,for cutoff levels ranging between 58 mcg/g and 490 mcg/g,the sensitivity was 89.7%-100%and the specificity was 62%-93.3%.For Crohn’s disease,the cutoff levels of FC ranged from 71 mcg/g to 918 mcg/g(sensitivity 50%-95.9%and specificity 52.3%-100%).The best performance for a serum marker was observed for the endoscopic healing index,which showed a comparable accuracy to the measurement of FC and a higher accuracy than the measurement of serum C-reactive protein.CONCLUSION Several promising biomarkers of MH are emerging but cannot yet substitute for endoscopy with biopsy due to issues with reproducibility and standardization assessing MH.In ulcerative colitis,for cutoff levels ranging between 58 mcg/g and 490 mcg/g,the sensitivity was 89.7%-100%and the specificity was 62%-93.3%.For Crohn’s disease,the cutoff levels of FC ranged from 71 mcg/g to 918 mcg/g(sensitivity 50%-95.9%and specificity 52.3%-100%).The best performance for a serum marker was observed for the endoscopic healing index,which showed a comparable accuracy to the measurement of FC and a higher accuracy than the measurement of serum C-reactive protein.CONCLUSION Several promising biomarkers of MH are emerging but cannot yet substitute for endoscopy with biopsy due to issues with reproducibility and standardization.
基金Supported by Science and Health Joint Medical Research Project of Chongqing,No.2022MSXM133Natural Science Foundation of Chongqing,No.CSTB2022NSCQ-MSX1522,No.CSTB2023NSCQ-MSX0246,No.CSTB2022NSCQ-MSX1271+1 种基金The First Batch of Key Disciplines on Public Health in Chongqing and ScienceHealth Joint Project of Dazu District Science and Technology Bureau,No.DZKJ,2022CCC1001.
文摘The complication of diabetes,which is known as diabetic foot ulcer(DFU),is a significant concern due to its association with high rates of disability and mortality.It not only severely affects patients’quality of life,but also imposes a substantial burden on the healthcare system.In spite of efforts made in clinical practice,treating DFU remains a challenging task.While mesenchymal stem cell(MSC)therapy has been extensively studied in treating DFU,the current efficacy of DFU healing using this method is still inadequate.However,in recent years,several MSCs-based drug delivery systems have emerged,which have shown to increase the efficacy of MSC therapy,especially in treating DFU.This review summarized the application of diverse MSCs-based drug delivery systems in treating DFU and suggested potential prospects for the future research.
文摘BACKGROUND Tranexamic acid(TXA)has been used as an anti-fibrinolytic drug for over half a century and has received much attention in recent decades.AIM To evaluate the efficacy of topical vs intravenous TXA in reducing blood loss and promoting wound healing in bone surgery.METHODS From the electronic resources,PubMed,Cochrane Library,Embase,ISI,and Scopus were used to perform a literature search over the last 10 years between 2010 and 2020.EndNote™X8 was used for managing the electronic resource.Searches were performed with mesh terms.The data were retracted blindly by two independent reviewers.Random effects were used to deal with potential heterogeneity and I2 showed heterogeneity.Chi-square(I2)tests were used to quantify the extent of heterogeneity(P<0.01 was considered statistically significant).The efficacy of topical TXA in reducing blood loss and promoting wound healing in bone surgery was compared with intravenous TXA and placebo.RESULTS According to the research design,1360 potentially important research abstracts and titles were discovered in our electronic searches,and 18 papers remained in agreement with our inclusion criteria.It was found that TXA reduced 277.51 mL of blood loss compared to placebo,and there was no significant difference between topical TXA and IV TXA in reducing blood loss in bone surgery.Our analyses also showed that TXA significantly reduced blood transfusion compared to placebo and there was no significant difference between topical TXA and IV TXA.CONCLUSION The use of both topical and intravenous TXA are equally effective in reducing blood loss in bone surgery,which might be beneficial for wound healing after surgery.
