七十年代,联合国环境规划署(UNEP)建立了全球环境监测系统(GEMS),世界卫生组织(WHO)主持了与健康有关的监测活动(HEALTH RELATED MONITORING),开展了全球大气、水质、食品、生物(人血中铅、镉;人乳中有机氯)以及呼吸气个体接触量监测....七十年代,联合国环境规划署(UNEP)建立了全球环境监测系统(GEMS),世界卫生组织(WHO)主持了与健康有关的监测活动(HEALTH RELATED MONITORING),开展了全球大气、水质、食品、生物(人血中铅、镉;人乳中有机氯)以及呼吸气个体接触量监测.八十年代初,我国参加全部上述监测的合作规化,江苏省的无锡以及南京、常州等城市,分别参加了全球水质及生物监测点的工作.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 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
German violinist donates her concert fees in China to quake-hit victims The performances of German violin master Anne-Sophie Mutter in China during May 25-28 turned out to beverv poignant for the performer and audienc...German violinist donates her concert fees in China to quake-hit victims The performances of German violin master Anne-Sophie Mutter in China during May 25-28 turned out to beverv poignant for the performer and audiences, coming in the aftermath of the devastating Sichuan earthquake.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
BACKGROUND Mesenchymal stem cells,found in various tissues,possess significant healing and immunomodulatory properties,influencing macrophage polarization,which is essential for wound repair.However,chronic wounds pre...BACKGROUND Mesenchymal stem cells,found in various tissues,possess significant healing and immunomodulatory properties,influencing macrophage polarization,which is essential for wound repair.However,chronic wounds present significant therapeutic challenges,requiring novel strategies to improve healing outcomes.AIM To investigate the potential of fetal dermal mesenchymal stem cells(FDMSCs)in enhancing wound healing through modulation of macrophage polarization,specifically by promoting the M2 phenotype to address inflammatory responses in chronic wounds.METHODS FDMSCs were isolated from BalB/C mice and co-cultured with RAW264.7 macrophages to assess their effects on macrophage polarization.Flow cytometry,quantitative reverse transcriptase polymerase chain reaction,and histological analyses were employed to evaluate shifts in macrophage phenotype and wound healing in a mouse model.Statistical analysis was performed using GraphPad Prism.RESULTS FDMSCs induced macrophage polarization from the M1 to M2 phenotype,as demonstrated by a reduction in proinflammatory markers(inducible nitric oxide synthase,interleukin-6)and an increase in anti-inflammatory markers[mannose receptor(CD206),arginase-1]in co-cultured RAW264.7 macrophages.These shifts were confirmed by flow cytometry.In an acute skin wound model,FDMSC-treated mice exhibited faster wound healing,enhanced collagen deposition,and improved vascular regeneration compared to controls.Significantly higher expression of arginase-1 further indicated an enriched M2 macrophage environment.CONCLUSION FDMSCs effectively modulate macrophage polarization from M1 to M2,reduce inflammation,and enhance tissue repair,demonstrating their potential as an immunomodulatory strategy in wound healing.These findings highlight the promising therapeutic application of FDMSCs in managing chronic wounds.展开更多
Refractory wounds cause significant harm to the health of patients and the most common treatments in clinical practice are surgical debridement and wound dressings.However,certain challenges,including surgical difficu...Refractory wounds cause significant harm to the health of patients and the most common treatments in clinical practice are surgical debridement and wound dressings.However,certain challenges,including surgical difficulty,lengthy recovery times,and a high recurrence rate persist.Conductive hydrogel dressings with combined monitoring and therapeutic properties have strong advantages in promoting wound healing due to the stimulation of endogenous current on wounds and are the focus of recent advancements.Therefore,this review introduces the mechanism of conductive hydrogel used for wound monitoring and healing,the materials selection of conductive hydrogel dressings used for wound monitoring,focuses on the conductive hydrogel sensor to monitor the output categories of wound status signals,proving invaluable for non-invasive,real-time evaluation of wound condition to encourage wound healing.Notably,the research of artificial intelligence(AI)model based on sensor derived data to predict the wound healing state,AI makes use of this abundant data set to forecast and optimize the trajectory of tissue regeneration and assess the stage of wound healing.Finally,refractory wounds including pressure ulcers,diabetes ulcers and articular wounds,and the corresponding wound monitoring and healing process are discussed in detail.This manuscript supports the growth of clinically linked disciplines and offers motivation to researchers working in the multidisciplinary field of conductive hydrogel dressings.展开更多
Scar formation resulting from burns or severe trauma can significantly compromise the structural integrity of skin and lead to permanent loss of skin appendages,ultimately impairing its normal physiological function.A...Scar formation resulting from burns or severe trauma can significantly compromise the structural integrity of skin and lead to permanent loss of skin appendages,ultimately impairing its normal physiological function.Accumulating evidence underscores the potential of targeted modulation of mechanical cues to enhance skin regeneration,promoting scarless repair by influencing the extracellular microenvironment and driving the phenotypic transitions.The field of skin repair and skin appendage regeneration has witnessed remarkable advancements in the utilization of biomaterials with distinct physical properties.However,a comprehensive understanding of the underlying mechanisms remains somewhat elusive,limiting the broader application of these innovations.In this review,we present two promising biomaterial-based mechanical approaches aimed at bolstering the regenerative capacity of compromised skin.The first approach involves leveraging biomaterials with specific biophysical properties to create an optimal scarless environment that supports cellular activities essential for regeneration.The second approach centers on harnessing mechanical forces exerted by biomaterials to enhance cellular plasticity,facilitating efficient cellular reprogramming and,consequently,promoting the regeneration of skin appendages.In summary,the manipulation of mechanical cues using biomaterial-based strategies holds significant promise as a supplementary approach for achieving scarless wound healing,coupled with the restoration of multiple skin appendage functions.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)affect approximately 18.6 million people worldwide every year.Patients with DFU often present with symptoms such as lower limb infections,ulcers,and deep tissue damage.Platelet-ric...BACKGROUND Diabetic foot ulcers(DFUs)affect approximately 18.6 million people worldwide every year.Patients with DFU often present with symptoms such as lower limb infections,ulcers,and deep tissue damage.Platelet-rich plasma(PRP)is a concentrated platelet product that can trigger the release of growth factors and cytokines,which stimulate tissue healing and regeneration and thus alleviates DFU.At present,no comprehensive study has been conducted to verify the effect of PRP in both in vitro and clinical settings for treating DFUs.AIM To perform the in vitro and clinical evaluation of PRP combined with endovascular angioplasty in treating diabetic foot.METHODS This study focused on both in vitro and clinical settings.In the in vitro study,human umbilical vein endothelial cells(HUVECs),human dermal fibroblasts(HSFs),and human immortalized keratinocytes(HaCaTs)were treated with PRP.Experiments involving proliferation,migration,tubule formation,and angiogenesis signaling pathways were conducted.In this clinical study,patients who visited the Affiliated Panyu Central Hospital of Guangzhou Medical University from 2020 to 2024 and met enrollment criteria were randomly assigned to 2 groups using prospective block randomization.In the control group,the DFU was treated with endovascular angioplasty and wound debridement.In the PRP+endovascular angioplasty group,PRP was evenly used on the surface of superficial ulcers,followed by endovascular angioplasty to treat vascular occlusion.The key outcomes were measured,including the Rutherford scale,Wagner scale,foot skin temperature,and ulcer repair area before and after treatment.RESULTS In the in vitro study,6%PRP could promote the proliferation and migration of HUVECs,HSFs,and HaCaTs in a high-glucose environment.Additionally,it promoted tubule formation in HUVECs by activating signaling proteins such as Ak strain transforming and extracellular regulated protein kinases 1/2.In the clinical study,a total of 208 patients participated.After 12 months of treatment,the ulcer repair area(14.95±0.16 cm^(2))and ulcer healing rate were improved in the PRP+endovascular angioplasty group than in the control group(P<0.05).CONCLUSION The combination of 6%activated PRP and endovascular angioplasty may improve the microcirculation and tissue repair in DFUs.This study offers a novel treatment option for patients with diabetic foot.展开更多
Bone morphogenetic proteins are essential for bone regeneration/fracture healing but can also induce heterotopic ossification(HO).Understanding accessory factors modulating BMP signaling would provide both a means of ...Bone morphogenetic proteins are essential for bone regeneration/fracture healing but can also induce heterotopic ossification(HO).Understanding accessory factors modulating BMP signaling would provide both a means of enhancing BMP-dependent regeneration while preventing HO.This study focuses on the ability of the collagen receptor,discoidin domain receptor 2(DDR2),to regulate BMP activity.As will be shown,induction of bone formation by subcutaneous BMP2 implants is severely compromised in Ddr2-deficient mice.In addition,Ddr2 deficiency attenuates HO in mice expressing the ACVR1 mutation associated with human fibrodysplasia ossificans progressiva.In cells migrating into BMP2 implants,DDR2 is co-expressed with GLI1,a skeletal stem cell marker,and DDR2/GLI1-positive cells participate in BMP2-induced bone formation where they contribute to chondrogenic and osteogenic lineages.Consistent with this distribution,conditional knockout of Ddr2 in Gli1-expressing cells inhibited bone formation to the same extent seen in globally Ddr2-deficient animals.This response was explained by selective inhibition of Gli1+cell proliferation without changes in apoptosis.The basis for this DDR2 requirement was explored further using bone marrow stromal cells.Although Ddr2 deficiency inhibited BMP2-dependent chondrocyte and osteoblast differentiation and in vivo,bone formation,early BMP responses including SMAD phosphorylation remained largely intact.Instead,Ddr2 deficiency reduced the nuclear/cytoplasmic ratio of the Hippo pathway intermediates,YAP and TAZ.This suggests that DDR2 regulates Hippo pathway-mediated responses to the collagen matrix,which subsequently affect BMP responsiveness.In summary,DDR2 is an important modulator of BMP signaling and a potential therapeutic target both for enhancing regeneration and treating HO.展开更多
Intervertebral disc degeneration(IDD),osteoarthritis(OA),and osteoporosis(OP)are common musculoskeletal disorders(MSDs)with similar age-related risk factors,representing the leading causes of disability.However,succes...Intervertebral disc degeneration(IDD),osteoarthritis(OA),and osteoporosis(OP)are common musculoskeletal disorders(MSDs)with similar age-related risk factors,representing the leading causes of disability.However,successful therapeutic development and translation have been hampered by the lack of clinically-relevant animal models.In this study,we investigated the potential suitability of the tree shrew,a small mammal with a close genetic relationship to primates,as a new animal model for MSDs.Age-related spontaneous IDD in parallel with a gradual disappearance of notochordal cells were commonly observed in tree shrews upon skeletal maturity with no sex differences,while age-related osteoporotic changes including bone loss in the metaphyses were primarily presented in aged females,similar to observations in humans.Moreover,in the osteochondral defect model,tree shrew cartilage exhibited behavior similar to that of humans,characterized by a more restricted self-healing capacity compared to the rapid spontaneous healing of joint surfaces observed in rats.The induced OA model in tree shrews was highly efficient and reproducible,characterized by gradual deterioration of articular cartilage,recapitulating the human OA phenotype to some degree.Surgery-induced IDD models were successfully established in tree shrews,in which the lumbar spine instability model developed slow progressive disc degeneration with more similarity to the clinical state,whereas the needle puncture model led to the rapid development of IDD with more severe symptoms.Taken together,our findings pave the way for the development of the tree shrew as a new animal model for the study of MSDs and aging.展开更多
Abnormal wound scarring often leads to functional impairments and cosmetic deformities,primarily driven by the prolonged activation of the TGF-β/Smad signaling pathway.Addressing this challenge,we developed a biomime...Abnormal wound scarring often leads to functional impairments and cosmetic deformities,primarily driven by the prolonged activation of the TGF-β/Smad signaling pathway.Addressing this challenge,we developed a biomimetic scaffold aimed at facilitating rapid and scarless wound healing.This highly in-tegrated 3D-printed dermal scaffold comprised modified recombinant human type III collagen(rhCOLIII-MA),gelatin methacrylate(GelMA),and liposomes encapsulating SB431542 to target TGF-β1(Lip@SB).The rhCOLIII-MA/GelMA(CG)scaffold retained inherent biomaterial characteristics,exhibited tailored physicochemical properties,and demonstrated favorable biocompatibility.Moreover,the Lip@SB-loaded CG scaffold(CGL)effectively promoted in vitro wound healing,while enabling controlled release of SB431542 to inhibit pathological collagen deposition.In a full-thickness skin defect rat model,the CGL dermal scaffold combined with split-thickness skin graft(STSG)minimized scar contraction,stimulated functional neovascularization,and enhanced graft aesthetics comparable to normal skin.Remarkably,the performance of the CGL scaffold surpassed that of commercially available anti-scarring alternatives.This innovative strategy presents a straightforward approach toward scarless skin regeneration and holds promise in alleviating the prolonged,painful postoperative rehabilitation.展开更多
BACKGROUND Mucosal healing has become an important goal of Crohn’s disease(CD)treat-ments.Modulen,enriched with transforming growth factor-beta 2,and budeso-nide are commonly accepted treatments for mild-moderate CD....BACKGROUND Mucosal healing has become an important goal of Crohn’s disease(CD)treat-ments.Modulen,enriched with transforming growth factor-beta 2,and budeso-nide are commonly accepted treatments for mild-moderate CD.However,their effects on the small bowel(SB)mucosa remain underexplored.AIM To prospectively assess clinical and mucosal responses to Modulen vs budesonide in adults with CD,using SB capsule endoscopy.METHODS Thirty patients were divided into two groups:Modulen+home-based diet(21 patients)and budesonide(9 patients)for an eight-week intervention followed by four weeks of follow-up.Clinical,laboratory,and endoscopic responses were evaluated.The mucosal changes were assessed through SB capsule endoscopy.RESULTS Results indicated significant clinical improvement in the Modulen group with reduced CD activity index(P=0.041)and improved inflammatory bowel disease questionnaire score(P=0.016).Moreover,Modulen was associated with a signifi-cant SB mucosal improvement,evidenced by a decrease in Lewis score(P=0.027).No significant changes were observed in calprotectin or other laboratory parame-ters.Conversely,budesonide exhibited more modest clinical effects,but it improved calprotectin,hemoglobin,and C-reactive protein levels(P=0.051,P=0.014,and P=0.038,respectively).The capsule endoscopy did not reveal a significant mucosal response in the budesonide group.CONCLUSION Both interventions have a role in CD treatment.Yet,their effects differ and may complement each other:Modulen yields clinical and mucosal improvements,while budesonide primarily leads mainly to laboratory improvements.展开更多
Loss-of-function variants of low-density lipoprotein receptor-related protein 5(LRP5)can lead to reduced bone formation,culminating in diminished bone mass.Our previous study reported transcription factor osterix(SP7)...Loss-of-function variants of low-density lipoprotein receptor-related protein 5(LRP5)can lead to reduced bone formation,culminating in diminished bone mass.Our previous study reported transcription factor osterix(SP7)-binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration.However,the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown.In this study,we used mice with a conditional knockout(c KO)of LRP5 in mature osteoblasts,which presented decreased osteogenesis.The in vitro experimental results showed that SP7 could promote LRP5 expression,thereby upregulating the osteogenic markers such as alkaline phosphatase(ALP),Runt-related transcription factor 2(Runx2),andβ-catenin(P<0.05).For the in vivo experiment,the SP7 overexpression virus was injected into a bone defect model of LRP5 c KO mice,resulting in increased bone mineral density(BMD)(P<0.001)and volumetric density(bone volume(BV)/total volume(TV))(P<0.001),and decreased trabecular separation(Tb.Sp)(P<0.05).These data suggested that SP7 could ameliorate bone defect healing in LRP5 c KO mice.Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.展开更多
文摘七十年代,联合国环境规划署(UNEP)建立了全球环境监测系统(GEMS),世界卫生组织(WHO)主持了与健康有关的监测活动(HEALTH RELATED MONITORING),开展了全球大气、水质、食品、生物(人血中铅、镉;人乳中有机氯)以及呼吸气个体接触量监测.八十年代初,我国参加全部上述监测的合作规化,江苏省的无锡以及南京、常州等城市,分别参加了全球水质及生物监测点的工作.
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.
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.
文摘German violinist donates her concert fees in China to quake-hit victims The performances of German violin master Anne-Sophie Mutter in China during May 25-28 turned out to beverv poignant for the performer and audiences, coming in the aftermath of the devastating Sichuan earthquake.
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National Natural Science Foundation of China,No.81873934and Jinan Science and Technology Planning Project,No.202225065.
文摘BACKGROUND Mesenchymal stem cells,found in various tissues,possess significant healing and immunomodulatory properties,influencing macrophage polarization,which is essential for wound repair.However,chronic wounds present significant therapeutic challenges,requiring novel strategies to improve healing outcomes.AIM To investigate the potential of fetal dermal mesenchymal stem cells(FDMSCs)in enhancing wound healing through modulation of macrophage polarization,specifically by promoting the M2 phenotype to address inflammatory responses in chronic wounds.METHODS FDMSCs were isolated from BalB/C mice and co-cultured with RAW264.7 macrophages to assess their effects on macrophage polarization.Flow cytometry,quantitative reverse transcriptase polymerase chain reaction,and histological analyses were employed to evaluate shifts in macrophage phenotype and wound healing in a mouse model.Statistical analysis was performed using GraphPad Prism.RESULTS FDMSCs induced macrophage polarization from the M1 to M2 phenotype,as demonstrated by a reduction in proinflammatory markers(inducible nitric oxide synthase,interleukin-6)and an increase in anti-inflammatory markers[mannose receptor(CD206),arginase-1]in co-cultured RAW264.7 macrophages.These shifts were confirmed by flow cytometry.In an acute skin wound model,FDMSC-treated mice exhibited faster wound healing,enhanced collagen deposition,and improved vascular regeneration compared to controls.Significantly higher expression of arginase-1 further indicated an enriched M2 macrophage environment.CONCLUSION FDMSCs effectively modulate macrophage polarization from M1 to M2,reduce inflammation,and enhance tissue repair,demonstrating their potential as an immunomodulatory strategy in wound healing.These findings highlight the promising therapeutic application of FDMSCs in managing chronic wounds.
基金supports received from Scientific Research Fund of Liaoning Province Education Department(Grant No.JYTQN 2023025)Scientific Research Fund of Liaoning Province Education Department(Grant No.JYTQN 2023025)+3 种基金the Natural Science Foundation of Liaoning Province(Grant No.2024-MS-075)the National Natural Science Foundation of China(32201179)National Key R&D Program of China(2023YFC2508200)Liaoning Provincial Natural Science Foundation Joint Fund(General Support Program Project)(2023-MSBA-093).
文摘Refractory wounds cause significant harm to the health of patients and the most common treatments in clinical practice are surgical debridement and wound dressings.However,certain challenges,including surgical difficulty,lengthy recovery times,and a high recurrence rate persist.Conductive hydrogel dressings with combined monitoring and therapeutic properties have strong advantages in promoting wound healing due to the stimulation of endogenous current on wounds and are the focus of recent advancements.Therefore,this review introduces the mechanism of conductive hydrogel used for wound monitoring and healing,the materials selection of conductive hydrogel dressings used for wound monitoring,focuses on the conductive hydrogel sensor to monitor the output categories of wound status signals,proving invaluable for non-invasive,real-time evaluation of wound condition to encourage wound healing.Notably,the research of artificial intelligence(AI)model based on sensor derived data to predict the wound healing state,AI makes use of this abundant data set to forecast and optimize the trajectory of tissue regeneration and assess the stage of wound healing.Finally,refractory wounds including pressure ulcers,diabetes ulcers and articular wounds,and the corresponding wound monitoring and healing process are discussed in detail.This manuscript supports the growth of clinically linked disciplines and offers motivation to researchers working in the multidisciplinary field of conductive hydrogel dressings.
基金supported in part by the National Nature Science Foundation of China(92268206,81830064)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-059)+4 种基金the Military Medical Research Projects(145AKJ260015000X,2022-JCJQ-ZB-09600)the Military Key Basic Research of Foundational Strengthening Program(2020-JCJQ-ZD-256-021)the Science Foundation of National Defense Science and Technology for Excellent Young(2022-JCJQ-ZQ-017)the Military Medical Research and Development Projects(AWS17J005,2019-126)the Specific Research Fund of The Innovation Platform for Academicians of Hainan Province(YSPTZX202317).
文摘Scar formation resulting from burns or severe trauma can significantly compromise the structural integrity of skin and lead to permanent loss of skin appendages,ultimately impairing its normal physiological function.Accumulating evidence underscores the potential of targeted modulation of mechanical cues to enhance skin regeneration,promoting scarless repair by influencing the extracellular microenvironment and driving the phenotypic transitions.The field of skin repair and skin appendage regeneration has witnessed remarkable advancements in the utilization of biomaterials with distinct physical properties.However,a comprehensive understanding of the underlying mechanisms remains somewhat elusive,limiting the broader application of these innovations.In this review,we present two promising biomaterial-based mechanical approaches aimed at bolstering the regenerative capacity of compromised skin.The first approach involves leveraging biomaterials with specific biophysical properties to create an optimal scarless environment that supports cellular activities essential for regeneration.The second approach centers on harnessing mechanical forces exerted by biomaterials to enhance cellular plasticity,facilitating efficient cellular reprogramming and,consequently,promoting the regeneration of skin appendages.In summary,the manipulation of mechanical cues using biomaterial-based strategies holds significant promise as a supplementary approach for achieving scarless wound healing,coupled with the restoration of multiple skin appendage functions.
基金Supported by the Medical Science and Technology Foundation of Guangdong Province,No.A2024625the Guangzhou Municipal Science and Technology Program Key Projects,No.202103000002the Panyu Science and Technology Planning Project,No.2023-Z04-019.
文摘BACKGROUND Diabetic foot ulcers(DFUs)affect approximately 18.6 million people worldwide every year.Patients with DFU often present with symptoms such as lower limb infections,ulcers,and deep tissue damage.Platelet-rich plasma(PRP)is a concentrated platelet product that can trigger the release of growth factors and cytokines,which stimulate tissue healing and regeneration and thus alleviates DFU.At present,no comprehensive study has been conducted to verify the effect of PRP in both in vitro and clinical settings for treating DFUs.AIM To perform the in vitro and clinical evaluation of PRP combined with endovascular angioplasty in treating diabetic foot.METHODS This study focused on both in vitro and clinical settings.In the in vitro study,human umbilical vein endothelial cells(HUVECs),human dermal fibroblasts(HSFs),and human immortalized keratinocytes(HaCaTs)were treated with PRP.Experiments involving proliferation,migration,tubule formation,and angiogenesis signaling pathways were conducted.In this clinical study,patients who visited the Affiliated Panyu Central Hospital of Guangzhou Medical University from 2020 to 2024 and met enrollment criteria were randomly assigned to 2 groups using prospective block randomization.In the control group,the DFU was treated with endovascular angioplasty and wound debridement.In the PRP+endovascular angioplasty group,PRP was evenly used on the surface of superficial ulcers,followed by endovascular angioplasty to treat vascular occlusion.The key outcomes were measured,including the Rutherford scale,Wagner scale,foot skin temperature,and ulcer repair area before and after treatment.RESULTS In the in vitro study,6%PRP could promote the proliferation and migration of HUVECs,HSFs,and HaCaTs in a high-glucose environment.Additionally,it promoted tubule formation in HUVECs by activating signaling proteins such as Ak strain transforming and extracellular regulated protein kinases 1/2.In the clinical study,a total of 208 patients participated.After 12 months of treatment,the ulcer repair area(14.95±0.16 cm^(2))and ulcer healing rate were improved in the PRP+endovascular angioplasty group than in the control group(P<0.05).CONCLUSION The combination of 6%activated PRP and endovascular angioplasty may improve the microcirculation and tissue repair in DFUs.This study offers a novel treatment option for patients with diabetic foot.
基金Scientific Research Training Program for Young Talents of Union Hospital,Tongji Medical College,Huazhong University of Science and Technology(F.W.),NIH/NIDCR grants DE029012 and DE029465Department of Defense Grant PR190899(R.T.F.)Michigan Musculoskeletal Health Core Center(NIH/NIAMS P30 AR069620)。
文摘Bone morphogenetic proteins are essential for bone regeneration/fracture healing but can also induce heterotopic ossification(HO).Understanding accessory factors modulating BMP signaling would provide both a means of enhancing BMP-dependent regeneration while preventing HO.This study focuses on the ability of the collagen receptor,discoidin domain receptor 2(DDR2),to regulate BMP activity.As will be shown,induction of bone formation by subcutaneous BMP2 implants is severely compromised in Ddr2-deficient mice.In addition,Ddr2 deficiency attenuates HO in mice expressing the ACVR1 mutation associated with human fibrodysplasia ossificans progressiva.In cells migrating into BMP2 implants,DDR2 is co-expressed with GLI1,a skeletal stem cell marker,and DDR2/GLI1-positive cells participate in BMP2-induced bone formation where they contribute to chondrogenic and osteogenic lineages.Consistent with this distribution,conditional knockout of Ddr2 in Gli1-expressing cells inhibited bone formation to the same extent seen in globally Ddr2-deficient animals.This response was explained by selective inhibition of Gli1+cell proliferation without changes in apoptosis.The basis for this DDR2 requirement was explored further using bone marrow stromal cells.Although Ddr2 deficiency inhibited BMP2-dependent chondrocyte and osteoblast differentiation and in vivo,bone formation,early BMP responses including SMAD phosphorylation remained largely intact.Instead,Ddr2 deficiency reduced the nuclear/cytoplasmic ratio of the Hippo pathway intermediates,YAP and TAZ.This suggests that DDR2 regulates Hippo pathway-mediated responses to the collagen matrix,which subsequently affect BMP responsiveness.In summary,DDR2 is an important modulator of BMP signaling and a potential therapeutic target both for enhancing regeneration and treating HO.
基金National Natural Science Foundation of China(Grant Nos.92268204,32160209,82160175)Yunling Scholar Project of Yunnan Revitalization Talent Support Program,the Foundation of Expert Workstation of Bai Xiaochun(YSZJGZZ-2020040)Applied Basic Research Foundation of Yunnan Province(Grant Nos.202001AY070001-014,202201AY070001-032)。
文摘Intervertebral disc degeneration(IDD),osteoarthritis(OA),and osteoporosis(OP)are common musculoskeletal disorders(MSDs)with similar age-related risk factors,representing the leading causes of disability.However,successful therapeutic development and translation have been hampered by the lack of clinically-relevant animal models.In this study,we investigated the potential suitability of the tree shrew,a small mammal with a close genetic relationship to primates,as a new animal model for MSDs.Age-related spontaneous IDD in parallel with a gradual disappearance of notochordal cells were commonly observed in tree shrews upon skeletal maturity with no sex differences,while age-related osteoporotic changes including bone loss in the metaphyses were primarily presented in aged females,similar to observations in humans.Moreover,in the osteochondral defect model,tree shrew cartilage exhibited behavior similar to that of humans,characterized by a more restricted self-healing capacity compared to the rapid spontaneous healing of joint surfaces observed in rats.The induced OA model in tree shrews was highly efficient and reproducible,characterized by gradual deterioration of articular cartilage,recapitulating the human OA phenotype to some degree.Surgery-induced IDD models were successfully established in tree shrews,in which the lumbar spine instability model developed slow progressive disc degeneration with more similarity to the clinical state,whereas the needle puncture model led to the rapid development of IDD with more severe symptoms.Taken together,our findings pave the way for the development of the tree shrew as a new animal model for the study of MSDs and aging.
基金supported by the National Natural Science Foundation of China(No.82272297).
文摘Abnormal wound scarring often leads to functional impairments and cosmetic deformities,primarily driven by the prolonged activation of the TGF-β/Smad signaling pathway.Addressing this challenge,we developed a biomimetic scaffold aimed at facilitating rapid and scarless wound healing.This highly in-tegrated 3D-printed dermal scaffold comprised modified recombinant human type III collagen(rhCOLIII-MA),gelatin methacrylate(GelMA),and liposomes encapsulating SB431542 to target TGF-β1(Lip@SB).The rhCOLIII-MA/GelMA(CG)scaffold retained inherent biomaterial characteristics,exhibited tailored physicochemical properties,and demonstrated favorable biocompatibility.Moreover,the Lip@SB-loaded CG scaffold(CGL)effectively promoted in vitro wound healing,while enabling controlled release of SB431542 to inhibit pathological collagen deposition.In a full-thickness skin defect rat model,the CGL dermal scaffold combined with split-thickness skin graft(STSG)minimized scar contraction,stimulated functional neovascularization,and enhanced graft aesthetics comparable to normal skin.Remarkably,the performance of the CGL scaffold surpassed that of commercially available anti-scarring alternatives.This innovative strategy presents a straightforward approach toward scarless skin regeneration and holds promise in alleviating the prolonged,painful postoperative rehabilitation.
文摘BACKGROUND Mucosal healing has become an important goal of Crohn’s disease(CD)treat-ments.Modulen,enriched with transforming growth factor-beta 2,and budeso-nide are commonly accepted treatments for mild-moderate CD.However,their effects on the small bowel(SB)mucosa remain underexplored.AIM To prospectively assess clinical and mucosal responses to Modulen vs budesonide in adults with CD,using SB capsule endoscopy.METHODS Thirty patients were divided into two groups:Modulen+home-based diet(21 patients)and budesonide(9 patients)for an eight-week intervention followed by four weeks of follow-up.Clinical,laboratory,and endoscopic responses were evaluated.The mucosal changes were assessed through SB capsule endoscopy.RESULTS Results indicated significant clinical improvement in the Modulen group with reduced CD activity index(P=0.041)and improved inflammatory bowel disease questionnaire score(P=0.016).Moreover,Modulen was associated with a signifi-cant SB mucosal improvement,evidenced by a decrease in Lewis score(P=0.027).No significant changes were observed in calprotectin or other laboratory parame-ters.Conversely,budesonide exhibited more modest clinical effects,but it improved calprotectin,hemoglobin,and C-reactive protein levels(P=0.051,P=0.014,and P=0.038,respectively).The capsule endoscopy did not reveal a significant mucosal response in the budesonide group.CONCLUSION Both interventions have a role in CD treatment.Yet,their effects differ and may complement each other:Modulen yields clinical and mucosal improvements,while budesonide primarily leads mainly to laboratory improvements.
文摘Loss-of-function variants of low-density lipoprotein receptor-related protein 5(LRP5)can lead to reduced bone formation,culminating in diminished bone mass.Our previous study reported transcription factor osterix(SP7)-binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration.However,the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown.In this study,we used mice with a conditional knockout(c KO)of LRP5 in mature osteoblasts,which presented decreased osteogenesis.The in vitro experimental results showed that SP7 could promote LRP5 expression,thereby upregulating the osteogenic markers such as alkaline phosphatase(ALP),Runt-related transcription factor 2(Runx2),andβ-catenin(P<0.05).For the in vivo experiment,the SP7 overexpression virus was injected into a bone defect model of LRP5 c KO mice,resulting in increased bone mineral density(BMD)(P<0.001)and volumetric density(bone volume(BV)/total volume(TV))(P<0.001),and decreased trabecular separation(Tb.Sp)(P<0.05).These data suggested that SP7 could ameliorate bone defect healing in LRP5 c KO mice.Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.
