Diabetes mellitus is an escalating global health issue,with 463 million adults affected in 2019.Without intervention,this number is projected to increase to 578 million by 2030 and 700 million by 2045[1].Diabetic woun...Diabetes mellitus is an escalating global health issue,with 463 million adults affected in 2019.Without intervention,this number is projected to increase to 578 million by 2030 and 700 million by 2045[1].Diabetic wound,a significant complication,is characterized by delayed healing,high disability rates,and elevated mortality[2].The challenges of wound healing in diabetic patients,compounded by their high morbidity and mortality rates,have drawn growing attention in biomedical research.展开更多
The development of highly efficient and multifunctional nanozymes holds promise for addressing the challenges posed by drugresistant bacteria.Here,copper single-atom-loaded MoS_(2) nanozymes(CuSAs/MoS_(2))were develop...The development of highly efficient and multifunctional nanozymes holds promise for addressing the challenges posed by drugresistant bacteria.Here,copper single-atom-loaded MoS_(2) nanozymes(CuSAs/MoS_(2))were developed to effectively combat drug-resistant bacteria by synergistically integrating the triple strategies of oxidative damage,cuproptosis-like death and disruption of cell wall synthesis.Density functional theory revealed that each Cu center coordinated with three sulfur ligands,enhancing the adsorption of H_(2)O_(2),which reduced the activation energy of the key step by 17%,thereby improving peroxidase-like(PODlike)activity.The generation of reactive oxygen species in combination with CuSAs/MoS_(2) glutathione peroxidase-like(GSH-Px-like)for glutathione scavenging resulted in an imbalance in redox homeostasis within bacteria.CuSAs/MoS_(2),which act as nanopioneers,drive oxidative stress to initiate the process of cuproptosis-like death,leading to abnormal aggregation of lipoylated proteins and inactivation of iron-sulfur cluster proteins.Moreover,CuSAs/MoS_(2) inhibited the biosynthesis of the peptidoglycan synthesis precursors D-glutamate and m-diaminopimelic acid and disrupted the peptidoglycan cross-linking process mediated by penicillin-binding proteins,effectively blocking the compensatory cell wall remodeling pathway ofβ-lactam-resistant bacteria.Overall,CuSAs/MoS_(2) with multiple functions can not only efficiently kill bacteria but also decelerate the development of bacterial resistance to combat drug-resistant bacterial infections.展开更多
Burn infection is one of the most common and severe complications in burn patients and a major factor contributing to high mortality rates.The loss of skin barrier function and the immunosuppressive state following bu...Burn infection is one of the most common and severe complications in burn patients and a major factor contributing to high mortality rates.The loss of skin barrier function and the immunosuppressive state following burns make patients highly susceptible to wound infections,which can progress to systemic sepsis.Although burn wounds are initially sterile,they are rapidly colonized by Gram-positive bacteria(e.g.,Staphylococcus aureus)within a short period,followed by colonization with Gram-negative bacteria(e.g.,Pseudomonas aeruginosa),thereby increasing therapeutic challenges.Current clinical management relies on a multidisciplinary collaborative approach,combining conventional antibiotics,emerging therapies,and comprehensive care strategies.Among these methods,early intervention,precise treatment administration,and prevention and control are critical to improving patient survival and prognosis.In recent years,drug-loaded hydrogels,as a class of wound repair materials characterized by biocompatibility,controlled drug release,and multifunctional integration,have demonstrated significant advantages in the treatment of burn infections.They can effectively inhibit pathogenic microorganisms,alleviate inflammation,and promote tissue regeneration.This review systematically summarizes recent research advances in the application of drug-loaded hydrogels for the treatment of infected burn wounds,aiming to provide a reference for their further development and clinical translation.展开更多
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
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
International patients are flocking to Hainan for healing through the ancient technique of traditional Chinese medicine.SAREN,a traditional Chinese medicine(TCM)doctor,keeps vipbooks filled with warm messages in var...International patients are flocking to Hainan for healing through the ancient technique of traditional Chinese medicine.SAREN,a traditional Chinese medicine(TCM)doctor,keeps vipbooks filled with warm messages in various languages in her consulting room at Sanya International Friendship Sanatorium of TCM.These expressions of gratitude not only document a long medical career,but also vividly testify to how a Chinese doctor has used acupuncture to cure patients from around the world.展开更多
Objective:To analyze the clinical application value of autologous periosteum graft combined with platelet-rich plasma(PRP)in the treatment of long bone fractures in the extremities.Methods:A total of 40 patients with ...Objective:To analyze the clinical application value of autologous periosteum graft combined with platelet-rich plasma(PRP)in the treatment of long bone fractures in the extremities.Methods:A total of 40 patients with long bone fractures in the extremities admitted to Santai Hospital Affiliated to North Sichuan Medical College from January 2023 to January 2025 were included,including cases of upper extremity forearm fractures and lower extremity femoral and tibial fractures.The patients were evenly divided using a random number table,with the control group undergoing open reduction and internal fixation(ORIF)combined with autologous periosteum graft,and the observation group undergoing ORIF,autologous periosteum graft,and PRP injection.Surgical indicators,complication rates,excellent fracture healing rates,functional satisfaction,and joint range of motion were compared between the two groups.Results:The surgical indicators in the observation group were similar to those in the control group(p>0.05).The complication rate in the observation group was lower than that in the control group,while the excellent fracture healing rate and functional satisfaction were higher in the observation group(p<0.05).Conclusion:Autologous periosteum graft combined with PRP technology is safe and reliable for the treatment of long bone fractures in the extremities,with satisfactory clinical outcomes.展开更多
This study presents a physics-informed modelling framework that combines finite element method(FEM)simulations and supervised machine learning(ML)to predict the self-healing performance of microbial concrete.A FEniCS-...This study presents a physics-informed modelling framework that combines finite element method(FEM)simulations and supervised machine learning(ML)to predict the self-healing performance of microbial concrete.A FEniCS-based FEM platform resolves multiphysics phenomena including nutrient diffusion,microbial CaCO_(3) precipitation,and stiffness recovery.These simulations,together with experimental data,are used to train ML models(Random Forest yielding normalized RMSE≈0.10)capable of predicting performance over a wide range of design parameters.Feature importance analysis identifies curing temperature,calcium carbonate precipitation rate,crack width,bacterial strain,and encapsulation method as the most influential parameters.The coupled FEM-ML approach enables sensitivity analysis,design optimization,and prediction beyond the training dataset(consistently exceeding 90%healing efficiency).Experimental validation confirms model robustness in both crack closure and strength recovery.This FEM–ML pipeline thus offers a generalizable,interpretable,and scalable strategy for the design of intelligent,self-adaptive construction materials.展开更多
One of the key challenges for underground rock reservoirs is ensuring prevention of the unwanted fluid leakage through rock fracture networks during their service life.Microbial-induced calcium carbonate precipitation...One of the key challenges for underground rock reservoirs is ensuring prevention of the unwanted fluid leakage through rock fracture networks during their service life.Microbial-induced calcium carbonate precipitation(MICP)technology has emerged as a promising bio-healing method for rock fractures with small apertures.In this study,a new“three-stage”injection strategy-based MICP(TS-MICP)bio-healing method was proposed,aiming to achieve a“three-high”performance that includes high bridging rate,high mechanical strength,and high homogeneity.A series of meter-scale rock fracture models were prepared to conduct TS-MICP grouting tests.Compared with the traditional injection strategy-based biohealing methods,the TS-MICP method significantly improved the bridging rate(32.1%e89.5%),mechanical properties(0.138e1.023 MPa),and homogeneity of CaCO_(3)precipitation(334.4%).Additionally,it achieved a higher material utilization rate(1.72 times higher),reducing the consumption of cementation solution(CS)by 258.8%,thereby demonstrating greater potential for field applications.The underlying mechanism for achieving high bridging rate and high homogeneity in CaCO_(3)precipitation can be attributed to the synergistic effects of the coupling injection strategy,which optimizes the advantages at each stage.In stage I,under the influence of gravity,the rapid flocculation and hydrogen bonding interactions of organic matter lead to formation of the dense and high-strength CaCO_(3)precipitation at the bottom using a low-concentration bacterial suspension(BS).This process establishes bridging steps along the wall sides for subsequent uniform CaCO_(3)precipitation.In stage II,concentrated BS is utilized to produce looser CaCO_(3)flocculation,which precipitates uniformly on the pre-existing bridging steps.In stage III,a two-step injection strategy was employed to reinforce the loose CaCO_(3)crystals formed in stages I and II,and finally forms a strong bridging effect with“three-high”performance.展开更多
In the northeastern and southwestern areas of the Ogcheon folded belt where Mesozoic granites are distributed,healed microcracks and fluid inclusions in the granite bodies were measured to elucidate the paleostress fi...In the northeastern and southwestern areas of the Ogcheon folded belt where Mesozoic granites are distributed,healed microcracks and fluid inclusions in the granite bodies were measured to elucidate the paleostress field that acted on these areas.The predominant orientations of healed microcracks in the northeastern and southwestern areas of the Ogcheon folded belt are the N50°W for the Inje granite,N30°W for the Jecheon granite,N55°W for the Wolaksan granite,N5°W for the Sokrisan granite,N30°W for the Daebo granite,and N70°W for the foliated granite.The homogenization and trapping temperatures of fluid inclusions in the Jecheon granite are 170–290°C and 260–390°C,respectively,and the formation period of healed microcracks is estimated to be 209–149 Ma.In the Inje granite,the homogenization and trapping temperatures of fluid inclusions are 165–290°C and 250–400°C,respectively,and the formation period of healed microcracks is estimated to be 176–160 Ma.In the Wolaksan granite,the homogenization and trapping temperatures of fluid inclusions are 165–375°C and 230–570°C,respectively,and the formation period of healed microcracks is estimated to be 116–88 Ma.In the Sokrisan granite,the homogenization and trapping temperatures of fluid inclusions are 155–280°C and 210–410°C,respectively,and the formation period of healed microcracks is estimated to be 92–84 Ma.In the foliated granite,the homogenization and trapping temperatures of fluid inclusions are 150–310°C and 380–550°C,respectively,and the formation period of healed microcracks is estimated to be 120–166 Ma.In the Daebo granite,the homogenization and trapping temperatures of fluid inclusions are 150–320°C and 380–440°C,respectively,and the formation period of healed microcracks is estimated to be 183–166 Ma.Consequently,during the Mesozoic,the predominant maximum horizontal stress direction in the Korean Peninsula was NW-SE,with secondary influences from N-S and E-W directions.Moreover,the direction of these maximum horizontal stresses is thought to have rotated from NW–SE to N–S around the mid Cretaceous period.The directions and formation periods of healed microcracks in the study area coincide well with the Mesozoic orogenies of the Korean Peninsula.The Daebo orogeny of the Jurassic to early Cretaceous mainly influenced the Jecheon granite,Inje granite,Wolaksan granite,foliated granite,and Daebo granite in the NW-SE direction,while the Bulguksa orogeny of the mid to late Cretaceous mainly influenced the Sokrisan granite in the N-S direction.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
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
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
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
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
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
BACKGROUND Fracture nonunion represents a challenging complication during fracture repair,often necessitating surgical intervention.Teriparatide,a recombinant human parathyroid hormone,has demonstrated promise in enha...BACKGROUND Fracture nonunion represents a challenging complication during fracture repair,often necessitating surgical intervention.Teriparatide,a recombinant human parathyroid hormone,has demonstrated promise in enhancing fracture healing,although its efficacy in treating established nonunion remains under investigation.CASE SUMMARY We report a case of a 27-year-old male who presented with a right humerus fracture following a traffic accident.Despite undergoing open reduction and internal fixation,the fracture resulted in a delayed union and subsequent nonunion.After 4 years of conservative management,teriparatide treatment was initiated due to persistent nonunion.Teriparatide injections were administered daily for 6 months,resulting in complete fracture healing and resolution of pain.CONCLUSION Our case demonstrates the successful use of teriparatide in treating a prolonged nonunion of a humerus fracture.Teriparatide may provide a valuable therapeutic option for established bone nonunion,even in cases that have not responded to conservative treatments.展开更多
Osteogenesis is the process of bone formation mediated by the osteoblasts,participating in various bone-related physiological processes including bone development,bone homeostasis and fracture healing.It exhibits temp...Osteogenesis is the process of bone formation mediated by the osteoblasts,participating in various bone-related physiological processes including bone development,bone homeostasis and fracture healing.It exhibits temporal and spatial interconnectivity with angiogenesis,constructed by multiple forms of cell communication occurring between bone and vascular endothelial cells.Molecular regulation among different cell types is crucial for coordinating osteogenesis and angiogenesis to facilitate bone remodeling,fracture healing,and other bone-related processes.The transmission of signaling molecules and the activation of their corresponding signal pathways are indispensable for various forms of cell communication.This communication acts as a“bridge”in coupling osteogenesis to angiogenesis.This article reviews the modes and processes of cell communication in osteogenesisangiogenesis coupling over the past decade,mainly focusing on interactions among bone-related cells and vascular endothelial cells to provide insights into the mechanism of cell communication of osteogenesis-angiogenesis coupling in different bone-related contexts.Moreover,clinical relevance and applications are also introduced in this review.展开更多
基金supported by a grant from General Scientific Research Project of Zhejiang Provincial Department of Education(No.Y202455614).
文摘Diabetes mellitus is an escalating global health issue,with 463 million adults affected in 2019.Without intervention,this number is projected to increase to 578 million by 2030 and 700 million by 2045[1].Diabetic wound,a significant complication,is characterized by delayed healing,high disability rates,and elevated mortality[2].The challenges of wound healing in diabetic patients,compounded by their high morbidity and mortality rates,have drawn growing attention in biomedical research.
基金supported by the National Natural Science Foundation of China(82372552)the Excellent Youth of Natural Science Research Projects in Anhui Province Universities(2023AH030060)+1 种基金Anhui Provincial Natural Science Foundation(2408085Y016)Anhui Province Excellent Research and Innovation Team Project(2024AH010013)。
文摘The development of highly efficient and multifunctional nanozymes holds promise for addressing the challenges posed by drugresistant bacteria.Here,copper single-atom-loaded MoS_(2) nanozymes(CuSAs/MoS_(2))were developed to effectively combat drug-resistant bacteria by synergistically integrating the triple strategies of oxidative damage,cuproptosis-like death and disruption of cell wall synthesis.Density functional theory revealed that each Cu center coordinated with three sulfur ligands,enhancing the adsorption of H_(2)O_(2),which reduced the activation energy of the key step by 17%,thereby improving peroxidase-like(PODlike)activity.The generation of reactive oxygen species in combination with CuSAs/MoS_(2) glutathione peroxidase-like(GSH-Px-like)for glutathione scavenging resulted in an imbalance in redox homeostasis within bacteria.CuSAs/MoS_(2),which act as nanopioneers,drive oxidative stress to initiate the process of cuproptosis-like death,leading to abnormal aggregation of lipoylated proteins and inactivation of iron-sulfur cluster proteins.Moreover,CuSAs/MoS_(2) inhibited the biosynthesis of the peptidoglycan synthesis precursors D-glutamate and m-diaminopimelic acid and disrupted the peptidoglycan cross-linking process mediated by penicillin-binding proteins,effectively blocking the compensatory cell wall remodeling pathway ofβ-lactam-resistant bacteria.Overall,CuSAs/MoS_(2) with multiple functions can not only efficiently kill bacteria but also decelerate the development of bacterial resistance to combat drug-resistant bacterial infections.
基金Supported by Natural Science Foundation of Guangxi(2025GXNSFHA069111,2020GXNSFAA159033,2019GXNSFAA245078)National Undergraduate Innovation and Entrepreneurship Training Program(202410601054).
文摘Burn infection is one of the most common and severe complications in burn patients and a major factor contributing to high mortality rates.The loss of skin barrier function and the immunosuppressive state following burns make patients highly susceptible to wound infections,which can progress to systemic sepsis.Although burn wounds are initially sterile,they are rapidly colonized by Gram-positive bacteria(e.g.,Staphylococcus aureus)within a short period,followed by colonization with Gram-negative bacteria(e.g.,Pseudomonas aeruginosa),thereby increasing therapeutic challenges.Current clinical management relies on a multidisciplinary collaborative approach,combining conventional antibiotics,emerging therapies,and comprehensive care strategies.Among these methods,early intervention,precise treatment administration,and prevention and control are critical to improving patient survival and prognosis.In recent years,drug-loaded hydrogels,as a class of wound repair materials characterized by biocompatibility,controlled drug release,and multifunctional integration,have demonstrated significant advantages in the treatment of burn infections.They can effectively inhibit pathogenic microorganisms,alleviate inflammation,and promote tissue regeneration.This review systematically summarizes recent research advances in the application of drug-loaded hydrogels for the treatment of infected burn wounds,aiming to provide a reference for their further development and clinical translation.
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Delayed wound healing following radical gastrectomy remains an important yet underappreciated complication that prolongs hospitalization,increases costs,and undermines patient recovery.In An et al’s recent study,the authors present a machine learning-based risk prediction approach using routinely available clinical and laboratory parameters.Among the evaluated algorithms,a decision tree model demonstrated excellent discrimination,achieving an area under the curve of 0.951 in the validation set and notably identifying all true cases of delayed wound healing at the Youden index threshold.The inclusion of variables such as drainage duration,preoperative white blood cell and neutrophil counts,alongside age and sex,highlights the pragmatic appeal of the model for early postoperative monitoring.Nevertheless,several aspects warrant critical reflection,including the reliance on a postoperative variable(drainage duration),internal validation only,and certain reporting inconsistencies.This letter underscores both the promise and the limitations of adopting interpretable machine learning models in perioperative care.We advocate for transparent reporting,external validation,and careful consideration of clinically actionable timepoints before integration into practice.Ultimately,this work represents a valuable step toward precision risk stratification in gastric cancer surgery,and sets the stage for multicenter,prospective evaluations.
文摘International patients are flocking to Hainan for healing through the ancient technique of traditional Chinese medicine.SAREN,a traditional Chinese medicine(TCM)doctor,keeps vipbooks filled with warm messages in various languages in her consulting room at Sanya International Friendship Sanatorium of TCM.These expressions of gratitude not only document a long medical career,but also vividly testify to how a Chinese doctor has used acupuncture to cure patients from around the world.
文摘Objective:To analyze the clinical application value of autologous periosteum graft combined with platelet-rich plasma(PRP)in the treatment of long bone fractures in the extremities.Methods:A total of 40 patients with long bone fractures in the extremities admitted to Santai Hospital Affiliated to North Sichuan Medical College from January 2023 to January 2025 were included,including cases of upper extremity forearm fractures and lower extremity femoral and tibial fractures.The patients were evenly divided using a random number table,with the control group undergoing open reduction and internal fixation(ORIF)combined with autologous periosteum graft,and the observation group undergoing ORIF,autologous periosteum graft,and PRP injection.Surgical indicators,complication rates,excellent fracture healing rates,functional satisfaction,and joint range of motion were compared between the two groups.Results:The surgical indicators in the observation group were similar to those in the control group(p>0.05).The complication rate in the observation group was lower than that in the control group,while the excellent fracture healing rate and functional satisfaction were higher in the observation group(p<0.05).Conclusion:Autologous periosteum graft combined with PRP technology is safe and reliable for the treatment of long bone fractures in the extremities,with satisfactory clinical outcomes.
基金funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie Grant Agreement No.945478(SASPRO2)supported by the ReBuilt project:Circular and Digital Renewal of Central Europe Construction and Building Sector CE0100390 ReBuiltthe Slovak Research and Development Agency under APVV-23-0383 and the Slovak Grant Agency VEGA No.2/0080/24.
文摘This study presents a physics-informed modelling framework that combines finite element method(FEM)simulations and supervised machine learning(ML)to predict the self-healing performance of microbial concrete.A FEniCS-based FEM platform resolves multiphysics phenomena including nutrient diffusion,microbial CaCO_(3) precipitation,and stiffness recovery.These simulations,together with experimental data,are used to train ML models(Random Forest yielding normalized RMSE≈0.10)capable of predicting performance over a wide range of design parameters.Feature importance analysis identifies curing temperature,calcium carbonate precipitation rate,crack width,bacterial strain,and encapsulation method as the most influential parameters.The coupled FEM-ML approach enables sensitivity analysis,design optimization,and prediction beyond the training dataset(consistently exceeding 90%healing efficiency).Experimental validation confirms model robustness in both crack closure and strength recovery.This FEM–ML pipeline thus offers a generalizable,interpretable,and scalable strategy for the design of intelligent,self-adaptive construction materials.
基金supported by the National Key Research and Development Program of China(Grant No.2023YFC3007102)the National Natural Science Foundation of China(Grant Nos.42477188 and 41925012).
文摘One of the key challenges for underground rock reservoirs is ensuring prevention of the unwanted fluid leakage through rock fracture networks during their service life.Microbial-induced calcium carbonate precipitation(MICP)technology has emerged as a promising bio-healing method for rock fractures with small apertures.In this study,a new“three-stage”injection strategy-based MICP(TS-MICP)bio-healing method was proposed,aiming to achieve a“three-high”performance that includes high bridging rate,high mechanical strength,and high homogeneity.A series of meter-scale rock fracture models were prepared to conduct TS-MICP grouting tests.Compared with the traditional injection strategy-based biohealing methods,the TS-MICP method significantly improved the bridging rate(32.1%e89.5%),mechanical properties(0.138e1.023 MPa),and homogeneity of CaCO_(3)precipitation(334.4%).Additionally,it achieved a higher material utilization rate(1.72 times higher),reducing the consumption of cementation solution(CS)by 258.8%,thereby demonstrating greater potential for field applications.The underlying mechanism for achieving high bridging rate and high homogeneity in CaCO_(3)precipitation can be attributed to the synergistic effects of the coupling injection strategy,which optimizes the advantages at each stage.In stage I,under the influence of gravity,the rapid flocculation and hydrogen bonding interactions of organic matter lead to formation of the dense and high-strength CaCO_(3)precipitation at the bottom using a low-concentration bacterial suspension(BS).This process establishes bridging steps along the wall sides for subsequent uniform CaCO_(3)precipitation.In stage II,concentrated BS is utilized to produce looser CaCO_(3)flocculation,which precipitates uniformly on the pre-existing bridging steps.In stage III,a two-step injection strategy was employed to reinforce the loose CaCO_(3)crystals formed in stages I and II,and finally forms a strong bridging effect with“three-high”performance.
文摘In the northeastern and southwestern areas of the Ogcheon folded belt where Mesozoic granites are distributed,healed microcracks and fluid inclusions in the granite bodies were measured to elucidate the paleostress field that acted on these areas.The predominant orientations of healed microcracks in the northeastern and southwestern areas of the Ogcheon folded belt are the N50°W for the Inje granite,N30°W for the Jecheon granite,N55°W for the Wolaksan granite,N5°W for the Sokrisan granite,N30°W for the Daebo granite,and N70°W for the foliated granite.The homogenization and trapping temperatures of fluid inclusions in the Jecheon granite are 170–290°C and 260–390°C,respectively,and the formation period of healed microcracks is estimated to be 209–149 Ma.In the Inje granite,the homogenization and trapping temperatures of fluid inclusions are 165–290°C and 250–400°C,respectively,and the formation period of healed microcracks is estimated to be 176–160 Ma.In the Wolaksan granite,the homogenization and trapping temperatures of fluid inclusions are 165–375°C and 230–570°C,respectively,and the formation period of healed microcracks is estimated to be 116–88 Ma.In the Sokrisan granite,the homogenization and trapping temperatures of fluid inclusions are 155–280°C and 210–410°C,respectively,and the formation period of healed microcracks is estimated to be 92–84 Ma.In the foliated granite,the homogenization and trapping temperatures of fluid inclusions are 150–310°C and 380–550°C,respectively,and the formation period of healed microcracks is estimated to be 120–166 Ma.In the Daebo granite,the homogenization and trapping temperatures of fluid inclusions are 150–320°C and 380–440°C,respectively,and the formation period of healed microcracks is estimated to be 183–166 Ma.Consequently,during the Mesozoic,the predominant maximum horizontal stress direction in the Korean Peninsula was NW-SE,with secondary influences from N-S and E-W directions.Moreover,the direction of these maximum horizontal stresses is thought to have rotated from NW–SE to N–S around the mid Cretaceous period.The directions and formation periods of healed microcracks in the study area coincide well with the Mesozoic orogenies of the Korean Peninsula.The Daebo orogeny of the Jurassic to early Cretaceous mainly influenced the Jecheon granite,Inje granite,Wolaksan granite,foliated granite,and Daebo granite in the NW-SE direction,while the Bulguksa orogeny of the mid to late Cretaceous mainly influenced the Sokrisan granite in the N-S direction.
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Supported by National Natural Science Foundation of China,No.82172441Suzhou City Major Disease Multicenter Clinical Research Project,No.DZXYJ202312+2 种基金Special Funding for Jiangsu Province Science and Technology Plan(Key Research and Development Program for Social Development),No.BE2023737Gusu Health Talent Plan Scientific Research Project,No.GSWS2022109Postgraduate Research and Practice Innovation Program of Jiangsu Province,No.SJCX24_2446.
文摘BACKGROUND Fracture nonunion represents a challenging complication during fracture repair,often necessitating surgical intervention.Teriparatide,a recombinant human parathyroid hormone,has demonstrated promise in enhancing fracture healing,although its efficacy in treating established nonunion remains under investigation.CASE SUMMARY We report a case of a 27-year-old male who presented with a right humerus fracture following a traffic accident.Despite undergoing open reduction and internal fixation,the fracture resulted in a delayed union and subsequent nonunion.After 4 years of conservative management,teriparatide treatment was initiated due to persistent nonunion.Teriparatide injections were administered daily for 6 months,resulting in complete fracture healing and resolution of pain.CONCLUSION Our case demonstrates the successful use of teriparatide in treating a prolonged nonunion of a humerus fracture.Teriparatide may provide a valuable therapeutic option for established bone nonunion,even in cases that have not responded to conservative treatments.
基金supported by central government-guided major science and technology project of Hebei province 236Z7709G(M.C.Q.)Tangshan science and technology project 23130216E(M.C.Q.)+8 种基金key research projects of North China University of Science and Technology ZD-YG-202309(M.C.Q.)National Natural Science Foundations of China 82230030 and 81871492(Y.L.)Beijing International Science and Technology Cooperation Project Z221100002722003(Y.L.)Beijing Natural Science Foundation L234017(Y.L.)Peking University Medicine plus X Pilot Program-Key Technologies R&D Project 2024YXXLHGG004(Y.L.)Key R&D Plan of Ningxia Hui Autonomous Region 2020BCG01001(Y.L.)First-Class Discipline Team of Kunming Medical University 2024XKTDTS08(Y.L.)Innovative Research Team of High-level Local Universities in Shanghai SHSMU-ZLCX20212402(Y.L.)Postdoctoral Fellowship Program of CPSF under Grant Number GZB20240038(X.J.C.).
文摘Osteogenesis is the process of bone formation mediated by the osteoblasts,participating in various bone-related physiological processes including bone development,bone homeostasis and fracture healing.It exhibits temporal and spatial interconnectivity with angiogenesis,constructed by multiple forms of cell communication occurring between bone and vascular endothelial cells.Molecular regulation among different cell types is crucial for coordinating osteogenesis and angiogenesis to facilitate bone remodeling,fracture healing,and other bone-related processes.The transmission of signaling molecules and the activation of their corresponding signal pathways are indispensable for various forms of cell communication.This communication acts as a“bridge”in coupling osteogenesis to angiogenesis.This article reviews the modes and processes of cell communication in osteogenesisangiogenesis coupling over the past decade,mainly focusing on interactions among bone-related cells and vascular endothelial cells to provide insights into the mechanism of cell communication of osteogenesis-angiogenesis coupling in different bone-related contexts.Moreover,clinical relevance and applications are also introduced in this review.
