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
Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic ...Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic management,DFUs,foot lesions,proper care for injuries,diet,and surgery.Certain reasonably priced treatments,such as hyperbaric oxygen and vacuum-assisted closure therapy,are also available for DFUs,along with modern wound care products and techniques.Nonetheless,DF care(cleaning,applying antimicrobial cream when wounded,and foot reflexology),blood glucose monitoring to control diabetes,and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs.Between 50%and 80%of DF infections are preventable.Regardless of the intensity of the lesion,it needs to be treated carefully and checked daily during infection.Tissue regeneration can be aided by cleaning,dressing,and application of topical medicines.The choice of shoes is also important because it affects blood circulation and nerve impulses.In general,regular check-ups,monitoring of the patient’s condition,measuring blood glucose levels,and providing frequent guidance regarding DFU care are crucial.Finally,this important clinical problem requires involvement of multiple professionals to properly manage it.展开更多
BACKGROUND Pain often predisposes patients with diabetic foot ulcers(DFUs)to negative emotional states,such as anxiety and depression,which can significantly impair treatment outcomes and recovery.However,very few stu...BACKGROUND Pain often predisposes patients with diabetic foot ulcers(DFUs)to negative emotional states,such as anxiety and depression,which can significantly impair treatment outcomes and recovery.However,very few studies have explored the relationship between anxiety,depression,and pain in DFUs,as well as the associated risk factors.AIM To analyze the correlation between anxiety,depression,and pain in patients with DFUs and to identify the associated risk factors.METHODS This study included 106 patients diagnosed with DFUs who were admitted to Tiantai County People’s Hospital between March 2022 and March 2024.The patients’anxiety levels were evaluated using Zung’s self-rating anxiety scale(SAS),depression status was assessed using Zung’s self-rating depression scale(SDS),and pain intensity was assessed using the visual analog scale(VAS).Subsequently,correlations between SAS,SDS,and VAS scores were analyzed.Univariate and multivariate analyses were conducted to explore the risk factors that contributed to anxiety and depression in patients with DFUs.RESULTS Among the 106 patients,39.62%exhibited anxiety and 43.40%presented with depression.Most patients experiencing anxiety or depression exhibited mild symptoms,with no severe cases observed.Compared with asymptomatic patients,those with anxiety or depression had significantly higher VAS scores.Correlation analysis indicated a significant positive relationship between both SAS and SDS scores and the VAS score.Univariate analysis identified sex,age,Wagner’s grade,presence of other complications,and smoking history as factors significantly associated with anxiety and depression.Multivariate analysis further confirmed that younger age,higher Wagner’s grade,and higher VAS scores were independent predictors of anxiety and depression.CONCLUSION This study reveals a significant positive correlation between anxiety,depression,and pain in patients with DFUs.This finding suggests that timely and effective pain intervention may be beneficial in alleviating negative emotions such as anxiety and depression.In addition,younger age(<50 years),higher Wagner’s grade,and higher VAS scores increase the risk of developing anxiety and depression in this patient population.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)are a significant challenge in diabetic care,and the efficacy of negative pressure wound therapy(NPWT)in treating them remains a subject of continuous investigation.AIM To provide ...BACKGROUND Diabetic foot ulcers(DFUs)are a significant challenge in diabetic care,and the efficacy of negative pressure wound therapy(NPWT)in treating them remains a subject of continuous investigation.AIM To provide a comprehensive meta-analysis of the role of NPWT in the manage-ment of DFUs.METHODS A systematic review was performed based on Preferred Reporting Items for Sys-tematic Reviews and Meta-Analyses guidelines,searching databases like PubMed,Embase,Web of Science,and the Cochrane Library.Randomized clinical trials(RCTs)were included to compare NPWT to other dressings for DFUs.Outcomes measured were wound healing time and rate,granulation tissue formation time,amputation rate,and adverse events.Study quality was evaluated using Coch-rane's risk of bias tool.Analyses utilizedχ2,I2,fixed or random-effects models via Stata v17.RESULTS Of the 1101 identified articles,9 RCTs were selected for meta-analysis.Studies spanned from 2005 to 2020 and originated from countries including the United States,Chile,Pakistan,Italy,India,and Germany.Meta-analysis demonstrated a significant improvement in wound healing rate[risk ratio(RR)=1.46,95%CI:1.22-1.76,P<0.01]and a reduction in amputation rate(RR=0.69,95%CI:0.50-0.96,P=0.006)with NPWT.Furthermore,the time for granulation tissue formation was significantly reduced by an average of 19.54 days.However,the incidence of adverse events did not significantly differ between NPWT and control treatments.CONCLUSION NPWT significantly improves wound healing rates and reduces amputation rates in DFUs.It also hastens the formation of granulation tissue.However,the therapy does not significantly alter the risk of adverse events compared to alternate treatments.展开更多
Diabetic foot ulcers(DFUs)represents a significant public health issue,with a rising global prevalence and severe potential complications including amputation.Traditional treatments often fall short due to various lim...Diabetic foot ulcers(DFUs)represents a significant public health issue,with a rising global prevalence and severe potential complications including amputation.Traditional treatments often fall short due to various limitations such as high recurrence rates and extensive resource utilization.This editorial explores the innovative use of acellular fish skin grafts as a transformative approach in DFU management.Recent studies and a detailed case report highlight the efficacy of acellular fish skin grafts in accelerating wound closure,reducing dressing changes,and enhancing patient outcomes with a lower socio-economic burden.Despite their promise,challenges such as limited availability,patient acceptance,and the need for further research persist.Addressing these through more extensive randomized controlled trials and fostering a multidisciplinary treatment approach may optimize DFU care and reduce the global health burden associated with these complex wounds.展开更多
Diabetic foot ulcers are among the most severe complications of the lower limb in patients with diabetes.As the immune resistance decreases due to the long-term exposure to hyperglycemic microenvironment,the wound oft...Diabetic foot ulcers are among the most severe complications of the lower limb in patients with diabetes.As the immune resistance decreases due to the long-term exposure to hyperglycemic microenvironment,the wound often fails to heal,leading to a poor prognosis.Foot ulcers have a high risk of amputation and mortality rates making it a growing health concern.Recently,exosomes derived from adipose mesenchymal stem cells have been shown to promote tissue healing,making them a popular topic in cell-free therapies.This article focuses on the risk factors leading to the development of diabetic foot ulcers and the mechanisms of non-healing with the hope to provide new directions or targets for future diabetic foot ulcer treatment.Additionally,this article clarifies the potential mechanisms of action of exosomes from adipose-derived stem cells in promoting the healing of diabetic foot ulcers and discusses its clinical application and limitations.This review aims to provide effective scientific evidence for research on the mechanism and clinical application of exosomes from adipose-derived stem cells for the treatment of diabetic foot ulcers.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)represent a common and serious complication of diabetes,characterized by impaired wound healing and an increased risk of infection.These infections severely impact patient health,n...BACKGROUND Diabetic foot ulcers(DFUs)represent a common and serious complication of diabetes,characterized by impaired wound healing and an increased risk of infection.These infections severely impact patient health,necessitating extensive medical intervention,and increasing the risk of amputation.Vitamin D(VD)plays a critical role in immune regulation and tissue repair.AIM To investigate the effects of VD supplementation on infection rates,wound healing,and immune function in patients with DFUs.METHODS A randomized controlled trial was conducted involving 120 patients with DFUs.Participants were randomly assigned to either a control group(n=60),which received standard care without VD supplementation,or an intervention group(n=60),which received 2000 IU of oral VD3(cholecalciferol)daily for 12 weeks.The primary outcomes included the incidence and severity of infections,whereas the secondary outcomes included wound healing rate,serum 25-hydroxyvitamin D level,levels of immune markers(cathelicidin,interleukin-6 and tumor necrosis factor-α),and adverse events,such as hypercalcemia.RESULTS The incidence of infection was significantly lower in the VD supplementation group(25%)compared with the control group(45%)(P=0.01).Severe infections requiring systemic antibiotics or hospitalization were also less frequent in the VD supplementation group.Wound healing was notably enhanced in the VD supplementation group,with a 60%reduction in ulcer size compared with a 35%reduction in the control group(P<0.01).Serum 25(OH)D level significantly increased in the VD supplementation group(from 16.5 ng/mL to 35.2 ng/mL),confirming the efficacy of VD supplementation.Immune function improved,as demonstrated by a 30%rise in cathelicidin level and a 20%decline in levels of pro-inflammatory cytokines.No adverse effects,including hypercalcemia,were reported.CONCLUSION The VD supplementation effectively reduced infection rate,promoted wound healing,and strengthened immune responses in patients with DFUs.These findings support the incorporation of VD as a safe and effective adjunctive therapy in the clinical management of DFUs.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)are a major complication of diabetes mellitus,and anemia is commonly observed in diabetic patients.However,the relationship between anemia and the risk of developing DFUs remains u...BACKGROUND Diabetic foot ulcers(DFUs)are a major complication of diabetes mellitus,and anemia is commonly observed in diabetic patients.However,the relationship between anemia and the risk of developing DFUs remains unclear.AIM To investigate the relationship between anemia and the risk of DFUs in diabetic patients through a meta-analysis.METHODS A systematic search was conducted across PubMed,Embase,and Web of Science databases to identify studies that reported the co-occurrence of anemia and DFUs in diabetic patients.The primary outcome was an association between anemia and DFU risk,expressed as odds ratios(ORs).Secondary outcomes included the risk of DFU per 1-g/dL decrease in hemoglobin and the difference in hemoglobin le-vels between patients with and without DFU.Statistical analyses were performed using random-effects models to account for heterogeneity.RESULTS Sixteen studies involving 170,949 diabetic patients were included in the analysis.The results indicated a significant association between anemia and an increased risk of DFUs(eight studies,n=166173,OR:2.72,95%CI:1.73–4.25,P<0.001;I2=93%).Subgroup analyses sup-ported consistent findings across various patient characteristics,analytic models,and study quality scores(P for subgroup differences,all>0.05).Additionally,each 1-g/dL decrease in hemoglobin was associated with an excess risk of DFUs(four studies,n=2543,OR:1.65,95%CI:1.21–2.27,P=0.002;I2=68%).Furthermore,diabetic patients with DFUs exhibited significantly lower hemoglobin levels compared to those without DFUs(nine studies,n=3986,mean difference:-2.13 g/dL,95%CI:-2.58 to-1.68,P<0.001;I2=90%).CONCLUSION Anemia can be associated with an increased risk of DFUs in diabetic patients.Monitoring and managing anemia in diabetic population may help mitigate the risk of DFUs,emphasizing the need for early interventions.Further research is required to investigate the underlying mechanisms and potential therapeutic strategies.展开更多
Diabetic foot ulcers(DFUs)are a serious complication of diabetes mellitus and are associated with high morbidity,risk of amputation,and increasedmortality.AlthoughDFUs typically remain a chronic,non-healing wound,a sm...Diabetic foot ulcers(DFUs)are a serious complication of diabetes mellitus and are associated with high morbidity,risk of amputation,and increasedmortality.AlthoughDFUs typically remain a chronic,non-healing wound,a small portion of DFUsmay undergomalignant transformation.The subsequentmalignancies are skin cancers such as squamous cell carcinoma(SCC),basal cell carcinoma,or melanoma.Understanding the pathophysiology of DFUs and themolecular and clinical determinants that contribute to theirpotentialmalignant transformationif crucial for clinical management.Chronic inflammation,dysregulation of cytokine signaling,faulty immune surveillance,and impaired wound healing all play a role in creating a tumor-permissive environment for the diabetic foot.This review highlights molecularmechanisms driving this transformation,including,vascular endothelial growth factor(VEGF)and plateletderived growth factor(PDGF)pathway dysregulation,hypoxia-inducible factor 1-alpha(HIF-1α)mediated angiogenic signaling,chronic osteomyelitis,and oxidative stress,which can collectively promote progression to malignancies,most notably cutaneous squamous cell carcinoma.Classic examples like Marjolin’s ulcer demonstrate how chronic injury can drive carcinogenesis,reinforcing the importance of vigilant DFU management.Connecting findings across clinical reports and mechanistic studies reveals that understandingDFUcarcinogenesis is essential for earlier detection,informed targeted treatment,and improved patient outcomes.展开更多
BACKGROUND Diabetic foot ulcers(DFU)are estimated to affect about 18.6 million people worldwide annually.The pathogenesis of DFU is complex,and the available drugs are not effective.Dl-3-n-butylphthalide(NBP)is a synt...BACKGROUND Diabetic foot ulcers(DFU)are estimated to affect about 18.6 million people worldwide annually.The pathogenesis of DFU is complex,and the available drugs are not effective.Dl-3-n-butylphthalide(NBP)is a synthetic mixture of racemates used in China for the treatment of ischemic stroke.It was initially isolated from the seeds of Apium graveolens Linn,with studies showing its potential role in treating diabetes and its complications.AIM To predict and validate the mechanism by which NBP treats DFU.METHODS Network pharmacological analysis was performed to identify pharmacological targets and signaling pathways mediating the treatment effect of NBP on DFU.In vivo and in vitro experiments were conducted to validate the therapeutic effects and mechanisms of NBP on DFU.RESULTS Network pharmacology analysis identified 26 pharmacological targets of NBP and predicted that NBP could treat DFU partially by modulating apoptosis and vascular signaling pathways.Results from animal experiments showed that NBP significantly improved DFU by increasing neovascularization and fibroblast proliferation.In vitro tests demonstrated that NBP treatment promoted the migration and proliferation of human umbilical vein endothelial cells and human dermal fibroblasts,while inhibiting the apoptosis of human umbilical vein endothelial cells,human dermal fibroblasts,and human keratinocytes cells.CONCLUSION This study found that NBP could treat DFU by decreasing the rate of apoptosis and increasing angiogenesis via the advanced glycation end products-receptor of advanced glycation end products signaling pathway and binding to the heme oxygenase 1,caspase 3,B cell leukemia/lymphoma 2,brain derived neurotrophic factor,and nuclear factor erythroid 2 L2 genes.展开更多
BACKGROUND Aloe vera has been used as a traditional herbal therapy for wound management and dermatological conditions worldwide for thousands of years.Scientific evidence has confirmed that acemannan,the bioactive com...BACKGROUND Aloe vera has been used as a traditional herbal therapy for wound management and dermatological conditions worldwide for thousands of years.Scientific evidence has confirmed that acemannan,the bioactive compound in aloe vera gel,exhibits significant anti-inflammatory and immunomodulatory properties that enhance tissue regeneration.This case report describes the successful application of an innovative acemannan-enriched glycolipid sphere dressing derived from aloe vera gel in diabetic foot ulcer(DFU)treatment,which achieved a clinically remarkable outcome.CASE SUMMARY An 80-year-old female patient with a 20-year history of type 2 diabetes mellitus experienced recurrent diabetic foot pain for 15 years.She had multiple hospitalizations due to acute infections and poorly controlled hyperglycemia.Long-term treatments included metformin and gliclazide.Upon presentation,she had a nonhealing wound on her left dorsal foot,diagnosed as a severe DFU(Texas classification:Grade II,stage D).She declined amputation and opted for conservative treatment.The medical team applied an acemannan-enriched glycolipid sphere dressing five times daily to the left calf and foot,avoiding the wound area.Frequency was reduced to three times daily after scab formation.Weight-bearing on the injured foot was avoided.Through in-person and online consultations,the team managed her lifestyle and diet,emphasizing natural foods.After 5 months,the DFU healed without significant scarring or functional loss.No recurrence was observed during the 2-year follow-up.Acemannan-enriched glycolipid sphere dressings promote DFU healing.This suggests the potential of these dressings for treating other refractory wounds.展开更多
BACKGROUND Diabetic foot ulcer(DFU)is a common and serious complication among individuals with diabetes.However,the co-occurrence of DFU with overlap syndrome,particularly involving anti-synthetase syndrome(ASS)and sy...BACKGROUND Diabetic foot ulcer(DFU)is a common and serious complication among individuals with diabetes.However,the co-occurrence of DFU with overlap syndrome,particularly involving anti-synthetase syndrome(ASS)and systemic sclerosis(SSc),is exceptionally rare.CASE SUMMARY We report a case of overlap syndrome(ASS and SSc)with diabetes manifesting as biped gangrene.The patient,a 60-year-old female,presented with painful ulcers on both heels that had persisted for nine months.She was diagnosed with DFU,which was likely attributable to SSc,suboptimal long-term glycemic control,and glucocorticoid therapy.Following four months of treatment,the patient demonstrated significant improvement and was subsequently discharged.At the oneyear follow-up,the patient developed new cyanotic ulcers on the right 4^(th) and 5^(th) toes ten months post-discharge that resolved completely within 3 months following conservative management.The four-year follow-up revealed persistent intermittent cyanosis without ulcer recurrence,although progressive interstitial lung disease necessitated prolonged bed rest.CONCLUSION SSc-related foot ulcers demonstrate favorable outcomes when managed with conventional wound care combined with vasoactive agents.展开更多
Diabetic foot ulcer(DFU)is an increasing global burden due to the rising prevalence of diabetes,and no specific pharmacological targets or satisfactory drugs are currently available for this devastating ailment.In thi...Diabetic foot ulcer(DFU)is an increasing global burden due to the rising prevalence of diabetes,and no specific pharmacological targets or satisfactory drugs are currently available for this devastating ailment.In this study,naringenin(NAR)was found to accelerate diabetic wound healing in diabetic C57BL/6J wild-type(WT)mice by reducing oxidative stress,as assessed through histological assay.NAR also alleviated the inhibition of proliferation,inflammation,cell senescence,and apoptosis in HaCaT cells induced by high glucose(HG).Mechanistically,the beneficial effects of NAR on wound healing are dependent on the E3 ubiquitin-protein ligase parkin(Parkin/PRKN/Prkn).NAR upregulated the expression level of Parkin and promoted its mitochondrial translocation,thereby activating Parkin-mediated mitophagy and maintaining mitochondrial quality control(MQC).Moreover,the wound healingpromoting effects of NAR were significantly diminished in Parkin knockdown HaCaT cells and Prkn knockout(Prkn^(-/-))DFU mice.Inhibition of NAR binding to estrogen receptors(ERs)using tamoxifen(TAM)abolished the protective effects of NAR in HG-induced HaCaT cells.The luciferase reporter assay confirmed that NAR enhanced ERs binding to the estrogen response element(ERE),thereby upregulating Parkin transcription.Additionally,the cellular thermal shift assay(CETSA)revealed that NAR specifically bound to ERa.In conclusion,NAR promoted DFU wound healing by enhancing Parkin-mediated mitophagy via binding to ERa,highlighting its potential as a promising therapeutic candidate.展开更多
BACKGROUND Shifting from the inflammatory to the proliferative phase represents a pivotal step during managing diabetic foot ulcers(DFUs);however,existing medical interventions remain insufficient.MicroRNAs(miRs)highl...BACKGROUND Shifting from the inflammatory to the proliferative phase represents a pivotal step during managing diabetic foot ulcers(DFUs);however,existing medical interventions remain insufficient.MicroRNAs(miRs)highlight notable capacity for accelerating the repair process of DFUs.Previous research has demonstrated which miR-122-5p regulates matrix metalloproteinases under diabetic conditions,thereby influencing extracellular matrix dynamics.AIM To investigate the impact of miR-122-5p on the transition from the inflammatory to the proliferative stage in DFU.METHODS Analysis for miR-122-5p expression in skin tissues from diabetic ulcer patients and mice was analyzed using quantitative real-time polymerase chain reaction(qRT-PCR).A diabetic wound healing model induced by streptozotocin was used,with mice receiving intradermal injections of adeno-associated virus-DJ encoding empty vector or miR-122.Skin tissues were retrieved at 3,7,and 14 days after injury for gene expression analysis,histology,immunohistochemistry,and network studies.The study explored miR-122-5p’s role in macrophage-fibroblast interactions and its effect on transitioning from inflammation to proliferation in DFU healing.RESULTS High-throughput sequencing revealed miR-122-5p as crucial for DFU healing.qRT-PCR showed significant upregulation of miR-122-5p within diabetic skin among DFU individuals and mice.Western blot,along with immunohistochemical and enzyme-linked immunosorbent assay,demonstrating the upregulation of inflammatory mediators(hypoxia inducible factor-1α,matrix metalloproteinase 9,tumor necrosis factor-α)and reduced fibrosis markers(fibronectin 1,α-smooth muscle actin)by targeting vascular endothelial growth factor.Fluorescence in situ hybridization indicated its expression localized to epidermal keratinocytes and fibroblasts in diabetic mice.Immunofluorescence revealed enhanced increased presence of M1 macrophages and reduced M2 polarization,highlighting its role in inflammation.MiR-122-5p elevated inflammatory cytokine levels while suppressing fibrotic activity from fibroblasts exposed to macrophage-derived media,highlighting its pivotal role in regulating DFU healing.CONCLUSION MiR-122-5p impedes cutaneous healing of diabetic mice via enhancing inflammation and inhibiting fibrosis,offering insights into miR roles in human skin wound repair.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)in patients with type 2 diabetes(T2D)are associated with heightened risks of infection and amputation and thus require effective surgical interventions to enhance outcomes.Free ant...BACKGROUND Diabetic foot ulcers(DFUs)in patients with type 2 diabetes(T2D)are associated with heightened risks of infection and amputation and thus require effective surgical interventions to enhance outcomes.Free anterolateral thigh(ALT)perforator flap is a promising reconstructive method;however,diabetic vasculopathy challenges optimal perfusion.This study analyzes factors influencing intraoperative blood perfusion in ALT flap repair for DFUs.AIM To identify key factors affecting intraoperative blood perfusion during free ALT perforator flap repair in patients with T2D and DFUs,thereby providing insights to improve surgical outcomes.METHODS This retrospective case-control study included 100 patients with T2D who underwent ALT flap repair at our institution between June 2016 and June 2024.Patients were categorized into normal(n=50)and abnormal(n=50)blood perfusion groups based on intraoperative perfusion assessments.Data on demographics,clinical characteristics,vascular status,metabolic control,and preoperative laboratory parameters were collected.Statistical analyses,including univariate and multivariate logistic regression,were conducted to identify significant predictive factors for perfusion outcomes.RESULTS Old age,high body mass index,long diabetes duration,and presence of diabetic peripheral neuropathy were associated with impaired perfusion.Abnormal perfusion was correlated with poor ankle-brachial index and elevated glycated hemoglobin(HbA1c),creatinine,triglycerides,and partial pressure of carbon dioxide.Conversely,high hemoglobin,albumin,and prealbumin levels and partial pressure of oxygen(PaO_(2))were protective.Multivariate analysis identified diabetes duration,HbA1c,PaCO_(2),PaO_(2),and albumin as independent predictors of perfusion,underscoring the roles of metabolic control and vascular health.CONCLUSION Optimizing metabolic control,vascular health,and nutritional status was crucial to enhance intraoperative blood perfusion in diabetic patients undergoing ALT perforator flap repair for DFUs.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)present a significant healthcare challenge attributable to their high rates of disability and the limitations of applied traditional nursing approaches.Effective management is crit...BACKGROUND Diabetic foot ulcers(DFUs)present a significant healthcare challenge attributable to their high rates of disability and the limitations of applied traditional nursing approaches.Effective management is critical for uneventful health outcomes.AIM To investigate the effects of multidisciplinary team(MDT)nursing interventions and blood glucose control on the negative emotions and satisfaction of DFUhealing patients.METHODS This retrospective cohort study included 115 patients with DFUs,divided into MDT and blood glucose control intervention group(n=60)and standard care control group(n=55).The comparison factors were wound area,new granulation tissue coverage area,wound healing rate,2-hour postprandial blood glucose level,fasting plasma glucose level,Hamilton Anxiety Scale score,Hamilton Depression Scale score,and nursing satisfaction.RESULTS After 4 weeks,the average wound area reduced from 22.04±6.48 cm^(2)to 11.96±3.63 cm^(2)(P<0.05).New granulation tissue coverage area reached 52.85±18.39 cm^(2) for the intervention group and 28.39±9.94 cm^(2)(P<0.05)in the control group,respectively.The healing rate was significantly higher in the intervention group than in the control group(91.7%vs 76.4%,P<0.05).Fasting plasma glucose decreased more sharply in the intervention group(from 8.36±0.98 mmol/L to 6.91±1.23 mmol/L)than in the control group(8.41±1.05 mmol/L to 7.81±1.27 mmol/L),with the intervention group maintaining significantly lower levels(P<0.05).The intervention group demonstrated a significantly greater reduction in 2-hour postprandial blood glucose levels(11.35±2.67 mmol/L to 7.52±1.38 mmol/L)compared to the control group(11.61±3.01 mmol/L to 8.72±1.63 mmol/L;P<0.05).Hamilton Anxiety Scale and Hamilton Depression Scale scores were significantly lower in the intervention group(P<0.05).Patient satisfaction with nursing was 93.33%and 74.55%in the intervention and control groups,respectively(P<0.05).CONCLUSION MDT combined with blood glucose control enhanced healing rates and positively influenced emotional well-being and satisfaction among patients.This strategy holds potential for application in clinical practice.展开更多
BACKGROUND Chronic nonhealing wounds,such as diabetic foot ulcer(DFU),suffer from delayed healing.Identifying effective biomarkers or targets is crucial for managing these refractory wounds.While N7-methylguanosine(m7...BACKGROUND Chronic nonhealing wounds,such as diabetic foot ulcer(DFU),suffer from delayed healing.Identifying effective biomarkers or targets is crucial for managing these refractory wounds.While N7-methylguanosine(m7G)methylation is important in RNA modification,its connection to chronic nonhealing wounds is poorly understood.AIM To assess the potential m7G biomarkers in DFU and their underlying molecular mechanisms.METHODS Differential expression analysis and weighted gene coexpression network analysis identified key genes in DFU.Hub genes were determined through m7G-DFU intersection,and gene set enrichment analysis was conducted.Diagnostic potential of hub genes was assessed using receiver operating characteristic curves.The hub gene’s expression(decapping scavenger enzyme,DCPS)was confirmed using quantitative reverse transcription polymerase chain reaction and immunofluorescence.In vitro,normal human epidermal keratinocyte models were knocked down for DCPS,and the function was assessed through flow cytometry,western blotting,immunofluorescence,Transwell assays,and scratch assays.RESULTS Weighted gene coexpression network analysis and differential expression analysis revealed links between DFU datasets and methylation processes,identifying hub gene DCPS as a candidate biomarker.Notably,its diagnostic value was confirmed with a test set and receiver operating characteristic curve,achieving an area under the curve of 0.98 and 0.99.Quantitative reverse transcription polymerase chain reaction and immunofluorescence analyses showed significantly reduced expression of DCPS in the wound skin of DFU patients and streptozotocin-induced diabetic mice,indicating its role as a regulatory factor of m7G in diabetic wounds.Mechanistically,in vitro studies showed that DCPS knockdown significantly reduced cyclin-dependent kinase 6 and cyclin D1 expression,disrupted the epithelial cell cycle,inhibited cell proliferation and migration,and increased apoptosis rates.CONCLUSION DCPS was identified as a promising DFU biomarker and therapeutic target,regulating m7G to affect cell cycle,proliferation,and epithelial cell migration during DFU wound healing.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)are a severe complication of diabetes and a leading cause of lower limb amputation due to impaired wound healing.Adipose-derived mesenchymal stem cells(ADSCs)have emerged as a prom...BACKGROUND Diabetic foot ulcers(DFUs)are a severe complication of diabetes and a leading cause of lower limb amputation due to impaired wound healing.Adipose-derived mesenchymal stem cells(ADSCs)have emerged as a promising therapeutic option for DFUs because of their angiogenic,immunomodulatory,and regenerative properties.However,studies on the molecular mechanisms and regulatory pathways of ADSCs in DFUs are limited.AIM To investigate the dose-response relationship,the optimal administration route,persistence,and molecular mechanisms of ADSCs in DFU healing.METHODS In this study,human ADSCs were isolated and cultured,and their differentiation potential was characterized.A DFU mouse model was established to evaluate the dose-dependent effects and persistence of ADSCs administered subcutaneously or intramuscularly.Wound closure rate,angiogenesis,inflammation,and collagen deposition were assessed in the ADSC-treated and model groups.Additionally,in vitro experiments using human dermal fibroblasts and endothelial cells were conducted to elucidate the molecular mechanisms underlying ADSC-mediated wound healing.RESULTS ADSC treatment significantly enhanced wound closure,promoted angiogenesis,modulated inflammatory responses,and accelerated tissue regeneration in the DFU model.Notably,the therapeutic efficacy and retention of ADSCs were influenced by both dosage and administration route,with subcutaneous injection of 5×105 ADSCs yielding the most favorable outcomes,particularly when injected into the feet,which resulted in prolonged retention.In vitro experiments further revealed that ADSCs exert their therapeutic effects via multiple mechanisms,including phosphatidylinositol 3-kinase signaling pathway activation to enhance vascular endothelial growth factor secretion,thereby promoting angiogenesis and modulating the Notch signaling pathway in DFUs to suppress inflammation and facilitate tissue regeneration.CONCLUSION ADSCs effectively promote DFU healing and have clinical potential as a treatment for chronic non-healing diabetic wounds.These findings provide a foundation for optimizing ADSC-based therapies for treating DFUs.展开更多
BACKGROUND Diabetic foot ulcer(DFU)is a serious and destructive complication of diabetes,which has a high amputation rate and carries a huge social burden.Early detection of risk factors and intervention are essential...BACKGROUND Diabetic foot ulcer(DFU)is a serious and destructive complication of diabetes,which has a high amputation rate and carries a huge social burden.Early detection of risk factors and intervention are essential to reduce amputation rates.With the development of artificial intelligence technology,efficient interpretable predictive models can be generated in clinical practice to improve DFU care.AIM To develop and validate an interpretable model for predicting amputation risk in DFU patients.METHODS This retrospective study collected basic data from 599 patients with DFU in Beijing Shijitan Hospital between January 2015 and June 2024.The data set was randomly divided into a training set and test set with fivefold cross-validation.Three binary variable models were built with the eXtreme Gradient Boosting(XGBoost)algorithm to input risk factors that predict amputation probability.The model performance was optimized by adjusting the super parameters.The pre-dictive performance of the three models was expressed by sensitivity,specificity,positive predictive value,negative predictive value and area under the curve(AUC).Visualization of the prediction results was realized through SHapley Additive exPlanation(SHAP).RESULTS A total of 157(26.2%)patients underwent minor amputation during hospitalization and 50(8.3%)had major amputation.All three XGBoost models demonstrated good discriminative ability,with AUC values>0.7.The model for predicting major amputation achieved the highest performance[AUC=0.977,95%confidence interval(CI):0.956-0.998],followed by the minor amputation model(AUC=0.800,95%CI:0.762-0.838)and the non-amputation model(AUC=0.772,95%CI:0.730-0.814).Feature importance ranking of the three models revealed the risk factors for minor and major amputation.Wagner grade 4/5,osteomyelitis,and high C-reactive protein were all considered important predictive variables.CONCLUSION XGBoost effectively predicts diabetic foot amputation risk and provides interpretable insights to support person-alized treatment decisions.展开更多
Microneedle(MN)patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide.While reducing skin resistance or increasing driving force can accelerate the efficiency of tran...Microneedle(MN)patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide.While reducing skin resistance or increasing driving force can accelerate the efficiency of transdermal drug delivery with conventional MN patches,it can create toxic chemical residues or require the help of additional devices.Herein,a thermo-responsive microneedles patch(TMN)with high biocompatibility without additional equipment is proposed.The TMN consisted of a bilayer microneedles composed of sodium alginate(SA)-g-poly(N-isopropylacrylamide)layer(SA-g-PNIPAM)loaded with sucrose octasulfate sodium salt(SOS)and hyaluronic acid layer and a polycaprolactone/chitosan nanofiber membrane loading with tetracycline hydrochloride(TH)and SOS.PNIPAM accelerates drug release by extruding the drug through a volumetric phase transition in response to temperature changes,and TH and SOS promote wound healing by inhibiting bacterial growth and promoting vascular regeneration and epithelial formation.The results showed that the drug release of TMN was significantly faster,with the drug release rate of more than 80% in the 10th h,and the antibacterial rate of TMN could reach 800%.In addition,TMN had good biocompatibility and good healing effects in vivo,which may be helpful for the design of multifunctional dressings in the future.展开更多
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 the King Salman Center for Disability Research,No.KSRG-2023-407.
文摘Diabetic foot(DF)is a major public health concern.As evident from numerous previous studies,supervision of DF ulcer(DFU)is crucial,and a specific quality check-up is needed.Patients should be educated about glycaemic management,DFUs,foot lesions,proper care for injuries,diet,and surgery.Certain reasonably priced treatments,such as hyperbaric oxygen and vacuum-assisted closure therapy,are also available for DFUs,along with modern wound care products and techniques.Nonetheless,DF care(cleaning,applying antimicrobial cream when wounded,and foot reflexology),blood glucose monitoring to control diabetes,and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs.Between 50%and 80%of DF infections are preventable.Regardless of the intensity of the lesion,it needs to be treated carefully and checked daily during infection.Tissue regeneration can be aided by cleaning,dressing,and application of topical medicines.The choice of shoes is also important because it affects blood circulation and nerve impulses.In general,regular check-ups,monitoring of the patient’s condition,measuring blood glucose levels,and providing frequent guidance regarding DFU care are crucial.Finally,this important clinical problem requires involvement of multiple professionals to properly manage it.
文摘BACKGROUND Pain often predisposes patients with diabetic foot ulcers(DFUs)to negative emotional states,such as anxiety and depression,which can significantly impair treatment outcomes and recovery.However,very few studies have explored the relationship between anxiety,depression,and pain in DFUs,as well as the associated risk factors.AIM To analyze the correlation between anxiety,depression,and pain in patients with DFUs and to identify the associated risk factors.METHODS This study included 106 patients diagnosed with DFUs who were admitted to Tiantai County People’s Hospital between March 2022 and March 2024.The patients’anxiety levels were evaluated using Zung’s self-rating anxiety scale(SAS),depression status was assessed using Zung’s self-rating depression scale(SDS),and pain intensity was assessed using the visual analog scale(VAS).Subsequently,correlations between SAS,SDS,and VAS scores were analyzed.Univariate and multivariate analyses were conducted to explore the risk factors that contributed to anxiety and depression in patients with DFUs.RESULTS Among the 106 patients,39.62%exhibited anxiety and 43.40%presented with depression.Most patients experiencing anxiety or depression exhibited mild symptoms,with no severe cases observed.Compared with asymptomatic patients,those with anxiety or depression had significantly higher VAS scores.Correlation analysis indicated a significant positive relationship between both SAS and SDS scores and the VAS score.Univariate analysis identified sex,age,Wagner’s grade,presence of other complications,and smoking history as factors significantly associated with anxiety and depression.Multivariate analysis further confirmed that younger age,higher Wagner’s grade,and higher VAS scores were independent predictors of anxiety and depression.CONCLUSION This study reveals a significant positive correlation between anxiety,depression,and pain in patients with DFUs.This finding suggests that timely and effective pain intervention may be beneficial in alleviating negative emotions such as anxiety and depression.In addition,younger age(<50 years),higher Wagner’s grade,and higher VAS scores increase the risk of developing anxiety and depression in this patient population.
基金Supported by the National Natural Science Foundation of China,No.82202454 and No.81873934the Wang Zhengguo Trauma Medicine Fund(Growth Factor Revival Plan)No.SZYZ-TR-09+1 种基金the Shandong Provincial Natural Science Foundation Youth Fund,No.ZR2020QH168the Jinan Science and Technology Plan Project,No.202225065。
文摘BACKGROUND Diabetic foot ulcers(DFUs)are a significant challenge in diabetic care,and the efficacy of negative pressure wound therapy(NPWT)in treating them remains a subject of continuous investigation.AIM To provide a comprehensive meta-analysis of the role of NPWT in the manage-ment of DFUs.METHODS A systematic review was performed based on Preferred Reporting Items for Sys-tematic Reviews and Meta-Analyses guidelines,searching databases like PubMed,Embase,Web of Science,and the Cochrane Library.Randomized clinical trials(RCTs)were included to compare NPWT to other dressings for DFUs.Outcomes measured were wound healing time and rate,granulation tissue formation time,amputation rate,and adverse events.Study quality was evaluated using Coch-rane's risk of bias tool.Analyses utilizedχ2,I2,fixed or random-effects models via Stata v17.RESULTS Of the 1101 identified articles,9 RCTs were selected for meta-analysis.Studies spanned from 2005 to 2020 and originated from countries including the United States,Chile,Pakistan,Italy,India,and Germany.Meta-analysis demonstrated a significant improvement in wound healing rate[risk ratio(RR)=1.46,95%CI:1.22-1.76,P<0.01]and a reduction in amputation rate(RR=0.69,95%CI:0.50-0.96,P=0.006)with NPWT.Furthermore,the time for granulation tissue formation was significantly reduced by an average of 19.54 days.However,the incidence of adverse events did not significantly differ between NPWT and control treatments.CONCLUSION NPWT significantly improves wound healing rates and reduces amputation rates in DFUs.It also hastens the formation of granulation tissue.However,the therapy does not significantly alter the risk of adverse events compared to alternate treatments.
基金Supported by the Zhejiang Medical Technology Project,No.2022RC009 and No.2024KY645.
文摘Diabetic foot ulcers(DFUs)represents a significant public health issue,with a rising global prevalence and severe potential complications including amputation.Traditional treatments often fall short due to various limitations such as high recurrence rates and extensive resource utilization.This editorial explores the innovative use of acellular fish skin grafts as a transformative approach in DFU management.Recent studies and a detailed case report highlight the efficacy of acellular fish skin grafts in accelerating wound closure,reducing dressing changes,and enhancing patient outcomes with a lower socio-economic burden.Despite their promise,challenges such as limited availability,patient acceptance,and the need for further research persist.Addressing these through more extensive randomized controlled trials and fostering a multidisciplinary treatment approach may optimize DFU care and reduce the global health burden associated with these complex wounds.
文摘Diabetic foot ulcers are among the most severe complications of the lower limb in patients with diabetes.As the immune resistance decreases due to the long-term exposure to hyperglycemic microenvironment,the wound often fails to heal,leading to a poor prognosis.Foot ulcers have a high risk of amputation and mortality rates making it a growing health concern.Recently,exosomes derived from adipose mesenchymal stem cells have been shown to promote tissue healing,making them a popular topic in cell-free therapies.This article focuses on the risk factors leading to the development of diabetic foot ulcers and the mechanisms of non-healing with the hope to provide new directions or targets for future diabetic foot ulcer treatment.Additionally,this article clarifies the potential mechanisms of action of exosomes from adipose-derived stem cells in promoting the healing of diabetic foot ulcers and discusses its clinical application and limitations.This review aims to provide effective scientific evidence for research on the mechanism and clinical application of exosomes from adipose-derived stem cells for the treatment of diabetic foot ulcers.
基金Supported by Natural Science Foundation of Henan Province,No.202300410396the Young Talents Promotion Project of Henan Province,No.2021HYTP043.
文摘BACKGROUND Diabetic foot ulcers(DFUs)represent a common and serious complication of diabetes,characterized by impaired wound healing and an increased risk of infection.These infections severely impact patient health,necessitating extensive medical intervention,and increasing the risk of amputation.Vitamin D(VD)plays a critical role in immune regulation and tissue repair.AIM To investigate the effects of VD supplementation on infection rates,wound healing,and immune function in patients with DFUs.METHODS A randomized controlled trial was conducted involving 120 patients with DFUs.Participants were randomly assigned to either a control group(n=60),which received standard care without VD supplementation,or an intervention group(n=60),which received 2000 IU of oral VD3(cholecalciferol)daily for 12 weeks.The primary outcomes included the incidence and severity of infections,whereas the secondary outcomes included wound healing rate,serum 25-hydroxyvitamin D level,levels of immune markers(cathelicidin,interleukin-6 and tumor necrosis factor-α),and adverse events,such as hypercalcemia.RESULTS The incidence of infection was significantly lower in the VD supplementation group(25%)compared with the control group(45%)(P=0.01).Severe infections requiring systemic antibiotics or hospitalization were also less frequent in the VD supplementation group.Wound healing was notably enhanced in the VD supplementation group,with a 60%reduction in ulcer size compared with a 35%reduction in the control group(P<0.01).Serum 25(OH)D level significantly increased in the VD supplementation group(from 16.5 ng/mL to 35.2 ng/mL),confirming the efficacy of VD supplementation.Immune function improved,as demonstrated by a 30%rise in cathelicidin level and a 20%decline in levels of pro-inflammatory cytokines.No adverse effects,including hypercalcemia,were reported.CONCLUSION The VD supplementation effectively reduced infection rate,promoted wound healing,and strengthened immune responses in patients with DFUs.These findings support the incorporation of VD as a safe and effective adjunctive therapy in the clinical management of DFUs.
基金Supported by General Program of Hainan Natural Science Foundation,No.824MS143.
文摘BACKGROUND Diabetic foot ulcers(DFUs)are a major complication of diabetes mellitus,and anemia is commonly observed in diabetic patients.However,the relationship between anemia and the risk of developing DFUs remains unclear.AIM To investigate the relationship between anemia and the risk of DFUs in diabetic patients through a meta-analysis.METHODS A systematic search was conducted across PubMed,Embase,and Web of Science databases to identify studies that reported the co-occurrence of anemia and DFUs in diabetic patients.The primary outcome was an association between anemia and DFU risk,expressed as odds ratios(ORs).Secondary outcomes included the risk of DFU per 1-g/dL decrease in hemoglobin and the difference in hemoglobin le-vels between patients with and without DFU.Statistical analyses were performed using random-effects models to account for heterogeneity.RESULTS Sixteen studies involving 170,949 diabetic patients were included in the analysis.The results indicated a significant association between anemia and an increased risk of DFUs(eight studies,n=166173,OR:2.72,95%CI:1.73–4.25,P<0.001;I2=93%).Subgroup analyses sup-ported consistent findings across various patient characteristics,analytic models,and study quality scores(P for subgroup differences,all>0.05).Additionally,each 1-g/dL decrease in hemoglobin was associated with an excess risk of DFUs(four studies,n=2543,OR:1.65,95%CI:1.21–2.27,P=0.002;I2=68%).Furthermore,diabetic patients with DFUs exhibited significantly lower hemoglobin levels compared to those without DFUs(nine studies,n=3986,mean difference:-2.13 g/dL,95%CI:-2.58 to-1.68,P<0.001;I2=90%).CONCLUSION Anemia can be associated with an increased risk of DFUs in diabetic patients.Monitoring and managing anemia in diabetic population may help mitigate the risk of DFUs,emphasizing the need for early interventions.Further research is required to investigate the underlying mechanisms and potential therapeutic strategies.
文摘Diabetic foot ulcers(DFUs)are a serious complication of diabetes mellitus and are associated with high morbidity,risk of amputation,and increasedmortality.AlthoughDFUs typically remain a chronic,non-healing wound,a small portion of DFUsmay undergomalignant transformation.The subsequentmalignancies are skin cancers such as squamous cell carcinoma(SCC),basal cell carcinoma,or melanoma.Understanding the pathophysiology of DFUs and themolecular and clinical determinants that contribute to theirpotentialmalignant transformationif crucial for clinical management.Chronic inflammation,dysregulation of cytokine signaling,faulty immune surveillance,and impaired wound healing all play a role in creating a tumor-permissive environment for the diabetic foot.This review highlights molecularmechanisms driving this transformation,including,vascular endothelial growth factor(VEGF)and plateletderived growth factor(PDGF)pathway dysregulation,hypoxia-inducible factor 1-alpha(HIF-1α)mediated angiogenic signaling,chronic osteomyelitis,and oxidative stress,which can collectively promote progression to malignancies,most notably cutaneous squamous cell carcinoma.Classic examples like Marjolin’s ulcer demonstrate how chronic injury can drive carcinogenesis,reinforcing the importance of vigilant DFU management.Connecting findings across clinical reports and mechanistic studies reveals that understandingDFUcarcinogenesis is essential for earlier detection,informed targeted treatment,and improved patient outcomes.
基金Supported by General Project of Xuzhou Science and Technology Bureau,No.KC22070.
文摘BACKGROUND Diabetic foot ulcers(DFU)are estimated to affect about 18.6 million people worldwide annually.The pathogenesis of DFU is complex,and the available drugs are not effective.Dl-3-n-butylphthalide(NBP)is a synthetic mixture of racemates used in China for the treatment of ischemic stroke.It was initially isolated from the seeds of Apium graveolens Linn,with studies showing its potential role in treating diabetes and its complications.AIM To predict and validate the mechanism by which NBP treats DFU.METHODS Network pharmacological analysis was performed to identify pharmacological targets and signaling pathways mediating the treatment effect of NBP on DFU.In vivo and in vitro experiments were conducted to validate the therapeutic effects and mechanisms of NBP on DFU.RESULTS Network pharmacology analysis identified 26 pharmacological targets of NBP and predicted that NBP could treat DFU partially by modulating apoptosis and vascular signaling pathways.Results from animal experiments showed that NBP significantly improved DFU by increasing neovascularization and fibroblast proliferation.In vitro tests demonstrated that NBP treatment promoted the migration and proliferation of human umbilical vein endothelial cells and human dermal fibroblasts,while inhibiting the apoptosis of human umbilical vein endothelial cells,human dermal fibroblasts,and human keratinocytes cells.CONCLUSION This study found that NBP could treat DFU by decreasing the rate of apoptosis and increasing angiogenesis via the advanced glycation end products-receptor of advanced glycation end products signaling pathway and binding to the heme oxygenase 1,caspase 3,B cell leukemia/lymphoma 2,brain derived neurotrophic factor,and nuclear factor erythroid 2 L2 genes.
文摘BACKGROUND Aloe vera has been used as a traditional herbal therapy for wound management and dermatological conditions worldwide for thousands of years.Scientific evidence has confirmed that acemannan,the bioactive compound in aloe vera gel,exhibits significant anti-inflammatory and immunomodulatory properties that enhance tissue regeneration.This case report describes the successful application of an innovative acemannan-enriched glycolipid sphere dressing derived from aloe vera gel in diabetic foot ulcer(DFU)treatment,which achieved a clinically remarkable outcome.CASE SUMMARY An 80-year-old female patient with a 20-year history of type 2 diabetes mellitus experienced recurrent diabetic foot pain for 15 years.She had multiple hospitalizations due to acute infections and poorly controlled hyperglycemia.Long-term treatments included metformin and gliclazide.Upon presentation,she had a nonhealing wound on her left dorsal foot,diagnosed as a severe DFU(Texas classification:Grade II,stage D).She declined amputation and opted for conservative treatment.The medical team applied an acemannan-enriched glycolipid sphere dressing five times daily to the left calf and foot,avoiding the wound area.Frequency was reduced to three times daily after scab formation.Weight-bearing on the injured foot was avoided.Through in-person and online consultations,the team managed her lifestyle and diet,emphasizing natural foods.After 5 months,the DFU healed without significant scarring or functional loss.No recurrence was observed during the 2-year follow-up.Acemannan-enriched glycolipid sphere dressings promote DFU healing.This suggests the potential of these dressings for treating other refractory wounds.
基金Supported by the 1.3.5 Project for Excellence,West China Hospital of Sichuan University,No.ZYGD240051.3.5 Project of Center for High Altitude Medicine,West China Hospital,Sichuan University,No.GYYX24002+2 种基金Sichuan Science and Technology Program,No.2024YFFK0290Health Commission of Sichuan Province,No.23 LCYJ042Science and Technology Department of Sichuan Province,No.2025ZNSFSC1621.
文摘BACKGROUND Diabetic foot ulcer(DFU)is a common and serious complication among individuals with diabetes.However,the co-occurrence of DFU with overlap syndrome,particularly involving anti-synthetase syndrome(ASS)and systemic sclerosis(SSc),is exceptionally rare.CASE SUMMARY We report a case of overlap syndrome(ASS and SSc)with diabetes manifesting as biped gangrene.The patient,a 60-year-old female,presented with painful ulcers on both heels that had persisted for nine months.She was diagnosed with DFU,which was likely attributable to SSc,suboptimal long-term glycemic control,and glucocorticoid therapy.Following four months of treatment,the patient demonstrated significant improvement and was subsequently discharged.At the oneyear follow-up,the patient developed new cyanotic ulcers on the right 4^(th) and 5^(th) toes ten months post-discharge that resolved completely within 3 months following conservative management.The four-year follow-up revealed persistent intermittent cyanosis without ulcer recurrence,although progressive interstitial lung disease necessitated prolonged bed rest.CONCLUSION SSc-related foot ulcers demonstrate favorable outcomes when managed with conventional wound care combined with vasoactive agents.
基金supported by the National Natural Science Foundation of China(Grant Nos.82270613 and 82170844)the open fund of Metabolic Vascular Diseases Key Laboratory of Sichuan Province,China(Grant Nos.:2022MVDKL-G3 and 2022MVDKL-G4).
文摘Diabetic foot ulcer(DFU)is an increasing global burden due to the rising prevalence of diabetes,and no specific pharmacological targets or satisfactory drugs are currently available for this devastating ailment.In this study,naringenin(NAR)was found to accelerate diabetic wound healing in diabetic C57BL/6J wild-type(WT)mice by reducing oxidative stress,as assessed through histological assay.NAR also alleviated the inhibition of proliferation,inflammation,cell senescence,and apoptosis in HaCaT cells induced by high glucose(HG).Mechanistically,the beneficial effects of NAR on wound healing are dependent on the E3 ubiquitin-protein ligase parkin(Parkin/PRKN/Prkn).NAR upregulated the expression level of Parkin and promoted its mitochondrial translocation,thereby activating Parkin-mediated mitophagy and maintaining mitochondrial quality control(MQC).Moreover,the wound healingpromoting effects of NAR were significantly diminished in Parkin knockdown HaCaT cells and Prkn knockout(Prkn^(-/-))DFU mice.Inhibition of NAR binding to estrogen receptors(ERs)using tamoxifen(TAM)abolished the protective effects of NAR in HG-induced HaCaT cells.The luciferase reporter assay confirmed that NAR enhanced ERs binding to the estrogen response element(ERE),thereby upregulating Parkin transcription.Additionally,the cellular thermal shift assay(CETSA)revealed that NAR specifically bound to ERa.In conclusion,NAR promoted DFU wound healing by enhancing Parkin-mediated mitophagy via binding to ERa,highlighting its potential as a promising therapeutic candidate.
基金Supported by the National Natural Science Foundation of China,No.82274528.
文摘BACKGROUND Shifting from the inflammatory to the proliferative phase represents a pivotal step during managing diabetic foot ulcers(DFUs);however,existing medical interventions remain insufficient.MicroRNAs(miRs)highlight notable capacity for accelerating the repair process of DFUs.Previous research has demonstrated which miR-122-5p regulates matrix metalloproteinases under diabetic conditions,thereby influencing extracellular matrix dynamics.AIM To investigate the impact of miR-122-5p on the transition from the inflammatory to the proliferative stage in DFU.METHODS Analysis for miR-122-5p expression in skin tissues from diabetic ulcer patients and mice was analyzed using quantitative real-time polymerase chain reaction(qRT-PCR).A diabetic wound healing model induced by streptozotocin was used,with mice receiving intradermal injections of adeno-associated virus-DJ encoding empty vector or miR-122.Skin tissues were retrieved at 3,7,and 14 days after injury for gene expression analysis,histology,immunohistochemistry,and network studies.The study explored miR-122-5p’s role in macrophage-fibroblast interactions and its effect on transitioning from inflammation to proliferation in DFU healing.RESULTS High-throughput sequencing revealed miR-122-5p as crucial for DFU healing.qRT-PCR showed significant upregulation of miR-122-5p within diabetic skin among DFU individuals and mice.Western blot,along with immunohistochemical and enzyme-linked immunosorbent assay,demonstrating the upregulation of inflammatory mediators(hypoxia inducible factor-1α,matrix metalloproteinase 9,tumor necrosis factor-α)and reduced fibrosis markers(fibronectin 1,α-smooth muscle actin)by targeting vascular endothelial growth factor.Fluorescence in situ hybridization indicated its expression localized to epidermal keratinocytes and fibroblasts in diabetic mice.Immunofluorescence revealed enhanced increased presence of M1 macrophages and reduced M2 polarization,highlighting its role in inflammation.MiR-122-5p elevated inflammatory cytokine levels while suppressing fibrotic activity from fibroblasts exposed to macrophage-derived media,highlighting its pivotal role in regulating DFU healing.CONCLUSION MiR-122-5p impedes cutaneous healing of diabetic mice via enhancing inflammation and inhibiting fibrosis,offering insights into miR roles in human skin wound repair.
文摘BACKGROUND Diabetic foot ulcers(DFUs)in patients with type 2 diabetes(T2D)are associated with heightened risks of infection and amputation and thus require effective surgical interventions to enhance outcomes.Free anterolateral thigh(ALT)perforator flap is a promising reconstructive method;however,diabetic vasculopathy challenges optimal perfusion.This study analyzes factors influencing intraoperative blood perfusion in ALT flap repair for DFUs.AIM To identify key factors affecting intraoperative blood perfusion during free ALT perforator flap repair in patients with T2D and DFUs,thereby providing insights to improve surgical outcomes.METHODS This retrospective case-control study included 100 patients with T2D who underwent ALT flap repair at our institution between June 2016 and June 2024.Patients were categorized into normal(n=50)and abnormal(n=50)blood perfusion groups based on intraoperative perfusion assessments.Data on demographics,clinical characteristics,vascular status,metabolic control,and preoperative laboratory parameters were collected.Statistical analyses,including univariate and multivariate logistic regression,were conducted to identify significant predictive factors for perfusion outcomes.RESULTS Old age,high body mass index,long diabetes duration,and presence of diabetic peripheral neuropathy were associated with impaired perfusion.Abnormal perfusion was correlated with poor ankle-brachial index and elevated glycated hemoglobin(HbA1c),creatinine,triglycerides,and partial pressure of carbon dioxide.Conversely,high hemoglobin,albumin,and prealbumin levels and partial pressure of oxygen(PaO_(2))were protective.Multivariate analysis identified diabetes duration,HbA1c,PaCO_(2),PaO_(2),and albumin as independent predictors of perfusion,underscoring the roles of metabolic control and vascular health.CONCLUSION Optimizing metabolic control,vascular health,and nutritional status was crucial to enhance intraoperative blood perfusion in diabetic patients undergoing ALT perforator flap repair for DFUs.
基金Supported by the Zhejiang Provincial Science and Technology Plan for Traditional Chinese Medicine,No.2025ZL594Municipal-Level Science and Technology Plan Project of Zhejiang Province,No.2023ZD039.
文摘BACKGROUND Diabetic foot ulcers(DFUs)present a significant healthcare challenge attributable to their high rates of disability and the limitations of applied traditional nursing approaches.Effective management is critical for uneventful health outcomes.AIM To investigate the effects of multidisciplinary team(MDT)nursing interventions and blood glucose control on the negative emotions and satisfaction of DFUhealing patients.METHODS This retrospective cohort study included 115 patients with DFUs,divided into MDT and blood glucose control intervention group(n=60)and standard care control group(n=55).The comparison factors were wound area,new granulation tissue coverage area,wound healing rate,2-hour postprandial blood glucose level,fasting plasma glucose level,Hamilton Anxiety Scale score,Hamilton Depression Scale score,and nursing satisfaction.RESULTS After 4 weeks,the average wound area reduced from 22.04±6.48 cm^(2)to 11.96±3.63 cm^(2)(P<0.05).New granulation tissue coverage area reached 52.85±18.39 cm^(2) for the intervention group and 28.39±9.94 cm^(2)(P<0.05)in the control group,respectively.The healing rate was significantly higher in the intervention group than in the control group(91.7%vs 76.4%,P<0.05).Fasting plasma glucose decreased more sharply in the intervention group(from 8.36±0.98 mmol/L to 6.91±1.23 mmol/L)than in the control group(8.41±1.05 mmol/L to 7.81±1.27 mmol/L),with the intervention group maintaining significantly lower levels(P<0.05).The intervention group demonstrated a significantly greater reduction in 2-hour postprandial blood glucose levels(11.35±2.67 mmol/L to 7.52±1.38 mmol/L)compared to the control group(11.61±3.01 mmol/L to 8.72±1.63 mmol/L;P<0.05).Hamilton Anxiety Scale and Hamilton Depression Scale scores were significantly lower in the intervention group(P<0.05).Patient satisfaction with nursing was 93.33%and 74.55%in the intervention and control groups,respectively(P<0.05).CONCLUSION MDT combined with blood glucose control enhanced healing rates and positively influenced emotional well-being and satisfaction among patients.This strategy holds potential for application in clinical practice.
基金Supported by National Natural Science Foundation of China,No.82370903Noncommunicable Chronic Diseases-National Science and Technology Major Project,No.2023ZD0509400 and No.2023ZD0509402+1 种基金2023 Key Disciplines on Public Health Construction of Chongqing,the Natural Science Foundation of Chongqing Municipal Science and Technology Bureau,No.cstc2024ycjh-bgzxm0014Major Project of Science and Technology Research Program of Chongqing Education Commission of China,No.KJZD-M202400102.
文摘BACKGROUND Chronic nonhealing wounds,such as diabetic foot ulcer(DFU),suffer from delayed healing.Identifying effective biomarkers or targets is crucial for managing these refractory wounds.While N7-methylguanosine(m7G)methylation is important in RNA modification,its connection to chronic nonhealing wounds is poorly understood.AIM To assess the potential m7G biomarkers in DFU and their underlying molecular mechanisms.METHODS Differential expression analysis and weighted gene coexpression network analysis identified key genes in DFU.Hub genes were determined through m7G-DFU intersection,and gene set enrichment analysis was conducted.Diagnostic potential of hub genes was assessed using receiver operating characteristic curves.The hub gene’s expression(decapping scavenger enzyme,DCPS)was confirmed using quantitative reverse transcription polymerase chain reaction and immunofluorescence.In vitro,normal human epidermal keratinocyte models were knocked down for DCPS,and the function was assessed through flow cytometry,western blotting,immunofluorescence,Transwell assays,and scratch assays.RESULTS Weighted gene coexpression network analysis and differential expression analysis revealed links between DFU datasets and methylation processes,identifying hub gene DCPS as a candidate biomarker.Notably,its diagnostic value was confirmed with a test set and receiver operating characteristic curve,achieving an area under the curve of 0.98 and 0.99.Quantitative reverse transcription polymerase chain reaction and immunofluorescence analyses showed significantly reduced expression of DCPS in the wound skin of DFU patients and streptozotocin-induced diabetic mice,indicating its role as a regulatory factor of m7G in diabetic wounds.Mechanistically,in vitro studies showed that DCPS knockdown significantly reduced cyclin-dependent kinase 6 and cyclin D1 expression,disrupted the epithelial cell cycle,inhibited cell proliferation and migration,and increased apoptosis rates.CONCLUSION DCPS was identified as a promising DFU biomarker and therapeutic target,regulating m7G to affect cell cycle,proliferation,and epithelial cell migration during DFU wound healing.
基金Supported by The Zhongguancun National Independent Innovation Demonstration Zone Industrial Ecosystem Cultivation Project,No.20220468089.
文摘BACKGROUND Diabetic foot ulcers(DFUs)are a severe complication of diabetes and a leading cause of lower limb amputation due to impaired wound healing.Adipose-derived mesenchymal stem cells(ADSCs)have emerged as a promising therapeutic option for DFUs because of their angiogenic,immunomodulatory,and regenerative properties.However,studies on the molecular mechanisms and regulatory pathways of ADSCs in DFUs are limited.AIM To investigate the dose-response relationship,the optimal administration route,persistence,and molecular mechanisms of ADSCs in DFU healing.METHODS In this study,human ADSCs were isolated and cultured,and their differentiation potential was characterized.A DFU mouse model was established to evaluate the dose-dependent effects and persistence of ADSCs administered subcutaneously or intramuscularly.Wound closure rate,angiogenesis,inflammation,and collagen deposition were assessed in the ADSC-treated and model groups.Additionally,in vitro experiments using human dermal fibroblasts and endothelial cells were conducted to elucidate the molecular mechanisms underlying ADSC-mediated wound healing.RESULTS ADSC treatment significantly enhanced wound closure,promoted angiogenesis,modulated inflammatory responses,and accelerated tissue regeneration in the DFU model.Notably,the therapeutic efficacy and retention of ADSCs were influenced by both dosage and administration route,with subcutaneous injection of 5×105 ADSCs yielding the most favorable outcomes,particularly when injected into the feet,which resulted in prolonged retention.In vitro experiments further revealed that ADSCs exert their therapeutic effects via multiple mechanisms,including phosphatidylinositol 3-kinase signaling pathway activation to enhance vascular endothelial growth factor secretion,thereby promoting angiogenesis and modulating the Notch signaling pathway in DFUs to suppress inflammation and facilitate tissue regeneration.CONCLUSION ADSCs effectively promote DFU healing and have clinical potential as a treatment for chronic non-healing diabetic wounds.These findings provide a foundation for optimizing ADSC-based therapies for treating DFUs.
文摘BACKGROUND Diabetic foot ulcer(DFU)is a serious and destructive complication of diabetes,which has a high amputation rate and carries a huge social burden.Early detection of risk factors and intervention are essential to reduce amputation rates.With the development of artificial intelligence technology,efficient interpretable predictive models can be generated in clinical practice to improve DFU care.AIM To develop and validate an interpretable model for predicting amputation risk in DFU patients.METHODS This retrospective study collected basic data from 599 patients with DFU in Beijing Shijitan Hospital between January 2015 and June 2024.The data set was randomly divided into a training set and test set with fivefold cross-validation.Three binary variable models were built with the eXtreme Gradient Boosting(XGBoost)algorithm to input risk factors that predict amputation probability.The model performance was optimized by adjusting the super parameters.The pre-dictive performance of the three models was expressed by sensitivity,specificity,positive predictive value,negative predictive value and area under the curve(AUC).Visualization of the prediction results was realized through SHapley Additive exPlanation(SHAP).RESULTS A total of 157(26.2%)patients underwent minor amputation during hospitalization and 50(8.3%)had major amputation.All three XGBoost models demonstrated good discriminative ability,with AUC values>0.7.The model for predicting major amputation achieved the highest performance[AUC=0.977,95%confidence interval(CI):0.956-0.998],followed by the minor amputation model(AUC=0.800,95%CI:0.762-0.838)and the non-amputation model(AUC=0.772,95%CI:0.730-0.814).Feature importance ranking of the three models revealed the risk factors for minor and major amputation.Wagner grade 4/5,osteomyelitis,and high C-reactive protein were all considered important predictive variables.CONCLUSION XGBoost effectively predicts diabetic foot amputation risk and provides interpretable insights to support person-alized treatment decisions.
基金supported by the Joint Funds of National Natural Science Foundation of China(No.U22A20162)the Natural Science Foundation of Hebei Province of China(No.C2021202002)+1 种基金the National Natural Science Foundation of China(No.52271245),the Natural Science Foundation of Tianjin(No.21JCQNJC01280)the financial support from the Danish Council for Independent Research(9040-00219B),European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement ENSIGN(Project ID:101086226),L4DNANO(Project ID:101086227).
文摘Microneedle(MN)patches could be a promising treatment for diabetic foot ulcers that plague thousands of people worldwide.While reducing skin resistance or increasing driving force can accelerate the efficiency of transdermal drug delivery with conventional MN patches,it can create toxic chemical residues or require the help of additional devices.Herein,a thermo-responsive microneedles patch(TMN)with high biocompatibility without additional equipment is proposed.The TMN consisted of a bilayer microneedles composed of sodium alginate(SA)-g-poly(N-isopropylacrylamide)layer(SA-g-PNIPAM)loaded with sucrose octasulfate sodium salt(SOS)and hyaluronic acid layer and a polycaprolactone/chitosan nanofiber membrane loading with tetracycline hydrochloride(TH)and SOS.PNIPAM accelerates drug release by extruding the drug through a volumetric phase transition in response to temperature changes,and TH and SOS promote wound healing by inhibiting bacterial growth and promoting vascular regeneration and epithelial formation.The results showed that the drug release of TMN was significantly faster,with the drug release rate of more than 80% in the 10th h,and the antibacterial rate of TMN could reach 800%.In addition,TMN had good biocompatibility and good healing effects in vivo,which may be helpful for the design of multifunctional dressings in the future.
