Tendon-bone healing remains a significant clinical challenge due to the high risk of re-rupture following injury.While mesenchymal stem cells(MSCs)show great potential in enhancing tendon-bone healing,their clinical a...Tendon-bone healing remains a significant clinical challenge due to the high risk of re-rupture following injury.While mesenchymal stem cells(MSCs)show great potential in enhancing tendon-bone healing,their clinical application is limited by issues such as low delivery efficiency,restricted differentiation potential,and potential immunogenicity.Recently,various strategies combining MSCs with other approaches,such as preconditioning,biomaterial integration,gene modification,and exosome application,have been developed,resulting in improved therapeutic outcomes.This review explored the current methods used to optimize MSC therapy for tendon-bone healing,examining the advantages,disadvantages,and underlying mechanisms of each approach,providing a foundation for future research and clinical applications.展开更多
BACKGROUND Anterior cruciate ligament reconstruction(ACLR)is the dominant clinical modality for the treatment of anterior cruciate ligament injuries.The success of ACLR is largely dependent on tendon-bone healing,and ...BACKGROUND Anterior cruciate ligament reconstruction(ACLR)is the dominant clinical modality for the treatment of anterior cruciate ligament injuries.The success of ACLR is largely dependent on tendon-bone healing,and stem cell biotherapies are often used to facilitate this process.Histone lactylation modifications are involved in the regulation of various diseases.Lactate dehydrogenase A(LDHA)has been shown to play an important role in exosomes.AIM To explore the regulation of tendon-bone healing after ACLR by LDHA in exosomes derived from bone marrow mesenchymal stem cells(BMSC-Exos).METHODS BMSC-Exos and LDHA were characterized and analyzed by transmission electron microscopy,qNano,immunofluorescence and western blotting assay.The corresponding low expression cell lines were obtained using RNA interference transfection;LDHA expression in rat bone tissues after ACLR was analyzed by western blotting.The volume of newborn bone tissues was monitored by micro-computed tomography imaging.Tendon and fibrocartilage regeneration were further analyzed and calculated by histological analysis,including hematoxylin and eosin and Safranin O-Fast green staining,respectively;LDHA levels of chondrocyte stem cells(CSPCs)after co-incubation with BMSC-Exos were analyzed by western blotting.Extracellularly secreted lactic acid content was determined by lactate assay kit.Cell viability was assessed by cell counting kit 8 assay,and the proliferation and differentiation ability of cells was further examined by the expression of collagen II,SOX9 and aggrecan.Histone H3K18 lactylation modification was analyzed by western blotting.H3K18 La binding on bone morphogenetic protein 7(BMP7)promoter was analyzed by chromatin immunoprecipitation-quantitative polymerase chain reaction;BMP7 promoter activity was analyzed by dual luciferase reporter gene;BMP7 protein expression was analyzed using quantitative polymerase chain reaction and western blotting.Then,the proliferation of CSPCs promoted by BMSC-Exos LDHA was analyzed by protein expression levels of LDHA,BMP7,collagen II,SOX9,aggrecan,extracellular lactate content,and cell counting kit 8 assay.RESULTS The spherical nanosized BMSC-Exos could be uptaken by CSPCs.LDHA was highly expressed in BMSC-Exos,which could infiltrate into the bone tissue of ACLR rats and promoted the generation of new bone tissue,as well as significantly increased the regeneration of tendon and fibrocartilage.Co-incubation of CSPCs with high-expressing LDHA BMSC-Exos increased the secretion of lactate content from CSPCs,cell viability,and the expression of markers related to cell proliferation and differentiation,including collagen II,SOX9,and aggrecan;LDHA in BMSC-Exos upregulated BMP7 through histone H3K18 lactate modification;high LDHA expression reversed the knockdown of BMP7,further increasing the proliferation and differentiation of CSPCs,thereby inducing cartilage formation.CONCLUSION LDHA in BMSC-Exos promotes BMP7 expression via H3K18 lactylation modification,which further promotes tendon-bone healing after ACLR.展开更多
Tendon-bone healing is essential for an effective rotator cuff tendon repair surgery,however,this remains a significant challenge due to the lack of biomaterials with high strength and bioactivity.Inspired by the high...Tendon-bone healing is essential for an effective rotator cuff tendon repair surgery,however,this remains a significant challenge due to the lack of biomaterials with high strength and bioactivity.Inspired by the high-performance exoskeleton of natural organisms,we set out to apply natural fish scale(FS)modified by calcium silicate nanoparticles(CS NPs)as a new biomaterial(CS-FS)to overcome the challenge.Benefit from its“Bouligand”microstructure,such FS-based scaffold maintained excellent tensile strength(125.05 MPa)and toughness(14.16 MJ/m^(3)),which are 1.93 and 2.72 times that of natural tendon respectively,allowing it to well meet the requirements for rotator cuff tendon repair.Additionally,CS-FS showed diverse bioactivities by stimulating the differentiation and phenotypic maintenance of multiple types of cells participated into the composition of tendon-bone junction,(e.g.bone marrow mesenchymal stem cells(BMSCs),chondrocyte,and tendon stem/progenitor cells(TSPCs)).In both rat and rabbit rotator cuff tear(RCT)models,CS-FS played a key role in the tendon-bone interface regeneration and biomechanical function,which may be achieved by activating BMP-2/Smad/Runx2 pathway in BMSCs.Therefore,natural fish scale-based biomaterials are the promising candidate for clinical tendon repair due to their outstanding strength and bioactivity.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
Incorporation of a tendon graft within the bone tunnel represents a challenging clinical problem. Successfulanterior cruciate ligament (ACL) reconstruction requires solid healing of the tendon graft in the bone tunnel...Incorporation of a tendon graft within the bone tunnel represents a challenging clinical problem. Successfulanterior cruciate ligament (ACL) reconstruction requires solid healing of the tendon graft in the bone tunnel. En-hancement of graft healing to bone is important to facilitate early aggressive rehabilitation and a rapid return topre-injury activity levels. No convenient, effective or inexpensive procedures exist to enhance tendon-bone (T-B)healing after surgery. Low-intensity pulsed ultrasound (LIPUS) improves local blood perfusion and angiogenesis,stimulates cartilage maturation, enhances differentiation and proliferation of osteoblasts, and motivates osteogenic differentiation of mesenchymal stem cells (MSCs), and therefore, appears to be a potential non-invasive tool for T-Bhealing in early stage of rehabilitation of ACL reconstruction. It is conceivable that LIPUS could be used to stimulateT-B tunnel healing in the home, with the aim of accelerating rehabilitation and an earlier return to normal activities inthe near future. The purpose of this review is to demonstrate how LIPUS stimulates T-B healing at the cellular andmolecular levels, describe studies in animal models, and provide a future direction for research.展开更多
The treatment of rotator cuff tear is one of the major challenges for orthopedic surgeons.The key to treatment is the reconstruction of the tendon-bone interface(TBI).Autologous platelet-rich plasma(PRP)is used as a t...The treatment of rotator cuff tear is one of the major challenges for orthopedic surgeons.The key to treatment is the reconstruction of the tendon-bone interface(TBI).Autologous platelet-rich plasma(PRP)is used as a therapeutic agent to accelerate the healing of tendons,as it contains a variety of growth factors and is easy to prepare.Graphene oxide(GO)is known to improve the physical properties of biomaterials and promote tissue repair.In this study,PRP gels containing various concentrations of GO were prepared to promote TBI healing and supraspinatus tendon reconstruction in a rabbit model.The incorporation of GO improved the ultrastructure and mechanical properties of the PRP gels.The gels containing 0.5 mg/ml GO(0.5 GO/PRP)continuously released transforming growth factor-b1(TGF-b1)and platelet-derived growth factor(PDGF)-AB,and the released TGF-b1 and PDGF-AB were still at high concentrations,1063.451 pg/ml and814.217 pg/ml,respectively,on the 14th day.In vitro assays showed that the 0.5 GO/PRP gels had good biocompatibility and promoted bone marrow mesenchymal stem cells proliferation and osteogenic and chondrogenic differentiation.After 12 weeks of implantation,the magnetic resonance imaging,microcomputed tomography and histological results indicated that the newly regenerated tendons in the 0.5 GO/PRP group had a similar structure to natural tendons.Moreover,the biomechanical results showed that the newly formed tendons in the 0.5 GO/PRP group had better biomechanical properties compared to those in the other groups,and had more stable TBI tissue.Therefore,the combination of PRP and GO has the potential to be a powerful advancement in the treatment of rotator cuff injuries.展开更多
Tendon-bone interface injuries pose a significant challenge in tissue regeneration,necessitating innovative approaches.Hydrogels with integrated supportive features and controlled release of therapeutic agents have em...Tendon-bone interface injuries pose a significant challenge in tissue regeneration,necessitating innovative approaches.Hydrogels with integrated supportive features and controlled release of therapeutic agents have emerged as promising candidates for the treatment of such injuries.In this study,we aimed to develop a temperature-sensitive composite hydrogel capable of providing sustained release of magnesium ions(Mg^(2+)).We synthesized magnesium-Procyanidin coordinated metal polyphenol nanoparticles(Mg-PC)through a self-assembly process and integrated them into a two-component hydrogel.The hydrogel was composed of dopamine-modified hyaluronic acid(Dop-HA)and F127.To ensure controlled release and mitigate the“burst release”effect of Mg^(2+),we covalently crosslinked the Mg-PC nanoparticles through coordination bonds with the catechol moiety within the hydrogel.This crosslinking strategy extended the release window of Mg^(2+)concentrations for up to 56 days.The resulting hydrogel(Mg-PC@Dop-HA/F127)exhibited favorable properties,including injectability,thermosensitivity and shape adaptability,making it suitable for injection and adaptation to irregularly shaped supraspinatus implantation sites.Furthermore,the hydrogel sustained the release of Mg^(2+)and Procyanidins,which attracted mesenchymal stem and progenitor cells,alleviated inflammation,and promoted macrophage polarization towards the M2 phenotype.Additionally,it enhanced collagen synthesis and mineralization,facilitating the repair of the tendon-bone interface.By incorporating multilevel metal phenolic networks(MPN)to control ion release,these hybridized hydrogels can be customized for various biomedical applications.展开更多
This is a correction to:Dingsu Bao,Jiacheng Sun,Min Gong,Jie Shi,Bo Qin,Kai Deng,Gang Liu,Shengqiang Zeng,Zhou Xiang,Shijie Fu,Combination of graphene oxide and platelet-rich plasma improves tendon-bone healing in a r...This is a correction to:Dingsu Bao,Jiacheng Sun,Min Gong,Jie Shi,Bo Qin,Kai Deng,Gang Liu,Shengqiang Zeng,Zhou Xiang,Shijie Fu,Combination of graphene oxide and platelet-rich plasma improves tendon-bone healing in a rabbit model of supraspinatus tendon reconstruction,Regenerative Biomaterials,Volume 8,Issue 6,December 2021,rbab045,https://doi.org/10.1093/rb/rbab045.展开更多
Rotator cuff tears are highly prevalent,and there is an urgent need to understand their healing mechanisms to improve treatment outcomes for patients.This editorial aims to summarize the roles and limitations of commo...Rotator cuff tears are highly prevalent,and there is an urgent need to understand their healing mechanisms to improve treatment outcomes for patients.This editorial aims to summarize the roles and limitations of common animal models(including rodents,rabbits,sheep,dogs,and primates)and second-look arthroscopy in rotator cuff healing research.Different animal models offer distinct advantages and disadvantages.For example,rodent models are cost-effective and suitable for genetic studies but have anatomical differences from humans.Rabbit models are favored for their relatively large tendon size and ease of surgical manipulation,yet they still deviate from human shoulder anatomy in some aspects.Larger animals like sheep and dogs have more similar shoulder structures to humans but come with high costs and challenges in maintaining consistent experimental conditions.Second-look arthroscopic studies have provided evidence for the effectiveness of current surgical techniques.Animal models will continue to play a crucial role in further exploring the local microenvironment of the rotator cuff,which is expected to help develop more effective strategies to promote healing.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
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(MH)is the major therapeutic target for Crohn's disease(CD).As the most commonly involved intestinal segment,small bowel(SB)assessment is crucial for CD patients.Yet,it poses a significan...BACKGROUND Mucosal healing(MH)is the major therapeutic target for Crohn's disease(CD).As the most commonly involved intestinal segment,small bowel(SB)assessment is crucial for CD patients.Yet,it poses a significant challenge due to its limited accessibility through conventional endoscopic methods.AIM To establish a noninvasive radiomic model based on computed tomography enterography(CTE)for MH assessment in SBCD patients.METHODS Seventy-three patients diagnosed with SBCD were included and divided into a training cohort(n=55)and a test cohort(n=18).Radiomic features were obtained from CTE images to establish a radiomic model.Patient demographics were analysed to establish a clinical model.A radiomic-clinical nomogram was constructed by combining significant clinical and radiomic features.The diagnostic efficacy and clinical benefit were evaluated via receiver operating characteristic(ROC)curve analysis and decision curve analysis(DCA),respectively.RESULTS Of the 73 patients enrolled,25 patients achieved MH.The radiomic-clinical nomogram had an area under the ROC curve of 0.961(95%confidence interval:0.886-1.000)in the training cohort and 0.958(0.877-1.000)in the test cohort and provided superior clinical benefit to either the clinical or radiomic models alone,as demonstrated by DCA.CONCLUSION These results indicate that the CTE-based radiomic-clinical nomogram is a promising imaging biomarker for MH and serves as a potential noninvasive alternative to enteroscopy for MH assessment in SBCD patients.展开更多
BACKGROUND Diabetic foot ulcers(DFUs)are a significant contributor to disability and mortality in diabetic patients.Macrophage polarization and functional regulation are promising areas of research and show therapeuti...BACKGROUND Diabetic foot ulcers(DFUs)are a significant contributor to disability and mortality in diabetic patients.Macrophage polarization and functional regulation are promising areas of research and show therapeutic potential in the field of DFU healing.However,the complex mechanism,the difficulty in clinical translation,and the large heterogeneity present significant challenges.Hence,this study was to comprehensively analyze the publication status and trends of studies on macrophage polarization and DFU healing.AIM To examine the relevant literature on macrophage polarization in DFU healing.METHODS A bibliometric analysis was conducted using the Web of Science database.Relevant literature was retrieved from the Web of Science Core Collection database between 2013 to 2023 using literature visualization and analysis software(VOSviewer and CiteSpace)and bibliometric online platforms.The obtained literature was then subjected to visualization and analysis of different countries/regions,institutions,journals,authors,and keywords to reveal the research’s major trends and focus.RESULTS The number of publications on the role of macrophage polarization in DFU healing increased rapidly from 2013 to 2023,especially in the latter period.Chinese researchers were the most prolific in this field,with 217 publications,while American researchers had been engaged in this field for a longer period.Qian Tan of Nanjing Drum Tower Hospital and Qian Ding of Nanjing University were the first to publish in this field.Shanghai Jiao Tong University was the institution with the most publications(27).The keywords“bone marrow”,“adjustment,replacement,response,tissue repair”,and“activation,repair,differentiation”appeared more frequently.The study of macrophage polarization in DFU healing focused on the regulatory mechanism,gene expression,and other aspects.CONCLUSION This study through the bibliometric method reveals the research trends and development trends in this field of macrophage polarization in DFU healing from 2013 to 2023 in the Web of Science Core Collection database.The key hotspots in this field mainly include the regulation of macrophage activation,gene expression,wound tissue repair,and new wound materials.This study provides references for future research directions.展开更多
Objective:To evaluate the effectiveness of surgical combination with traditional Chinese medicine dialectical therapy in three phases for the treatment of intertrochanteric fracture of the femur(IFF).Methods:84 patien...Objective:To evaluate the effectiveness of surgical combination with traditional Chinese medicine dialectical therapy in three phases for the treatment of intertrochanteric fracture of the femur(IFF).Methods:84 patients with IFF admitted to the hospital from December 2022 to December 2024 were selected and randomly divided into two groups using a random number table.The combined group received surgery and traditional Chinese medicine dialectical therapy in three phases,while the control group received surgery alone.The total effective rate,fracture healing time,hip function score,and lower extremity function score were compared between the two groups.Results:The total effective rate was higher in the combined group than in the control group(P<0.05).After treatment,the fracture healing time was shorter in the combined group than in the control group,and the hip function and lower extremity function scores were higher in the combined group than in the control group(P<0.05).Conclusion:Surgical combination with traditional Chinese medicine dialectical therapy in three phases can shorten the fracture healing time of IFF patients and restore their hip and lower extremity function,demonstrating significant efficacy.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
BACKGROUND Complicated crown–root fracture (CRF) involves severe injury to the crown, root,and pulp, and may be accompanied by multiple root fractures. The loss of a toothhas lifelong consequences for children and te...BACKGROUND Complicated crown–root fracture (CRF) involves severe injury to the crown, root,and pulp, and may be accompanied by multiple root fractures. The loss of a toothhas lifelong consequences for children and teenagers, but the maintenance of pulphealth and the calcific healing of multiple root fractures are rarely reported in theliterature.CASE SUMMARY This case reports healing of a permanent tooth with complicated crown–root andadditional root fractures, in which pulp health was maintained. A 10-year-old girlfell and fractured the root of her maxillary left central incisor at the cervical level.After the coronal fragment was repositioned, the tooth was splinted until thetooth was no longer mobile, 2 years later. Eight years after treatment, the toothhas remained asymptomatic with vital pulp and localized gingival overgrowth.Cone-beam computed tomography revealed not only calcified healing of the CRFbut also spontaneous healing in an additional undiagnosed root fracture. Thefracture line on the enamel could not be healed by hard tissue and formed agroove in the cervical crown. It was speculated that the groove was related to thelocalized gingival overgrowth.CONCLUSION This case provides a clinical perspective of the treatment of a tooth with acomplicated CRF and an additional root fracture.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
Chronic,non-healing wounds represent a significant challenge for healthcare systems worldwide,often requiring significant human and financial resources.Chronic wounds arise from the complex interplay of underlying com...Chronic,non-healing wounds represent a significant challenge for healthcare systems worldwide,often requiring significant human and financial resources.Chronic wounds arise from the complex interplay of underlying comorbidities,such as diabetes or vascular diseases,lifestyle factors,and genetic risk profiles which may predispose extremities to local ischemia.Injuries are further exacerbated by bacterial colonization and the formation of biofilms.Infection,consequently,perpetuates a chronic inflammatory microenvironment,preventing the progression and completion of normal wound healing.The current standard of care(SOC)for chronic wounds involves surgical debridement along with localized wound irrigation,which requires inpatient care under general anesthesia.This could be followed by,if necessary,defect coverage via a reconstructive ladder utilizing wound debridement along with skin graft,local,or free flap techniques once the wound conditions are stabilized and adequate blood supply is restored.To promote physiological wound healing,a variety of approaches have been subjected to translational research.Beyond conventional wound healing drugs and devices that currently supplement treatments,cellular and immunotherapies have emerged as promising therapeutics that can behave as tailored therapies with cell-or molecule-specific wound healing properties.However,in contrast to the clinical omnipresence of chronic wound healing disorders,there remains a shortage of studies condensing the current body of evidence on cellular therapies and immunotherapies for chronic wounds.This review provides a comprehensive exploration of current therapies,experimental approaches,and translational studies,offering insights into their efficacy and limitations.Ultimately,we hope this line of research may serve as an evidence-based foundation to guide further experimental and translational approaches and optimize patient care long-term.展开更多
基金Jinhua Public Welfare Technology Application Research Project,No.2025-4-229Zhejiang Province Medical and Health Science and Technology Plan,No.2022KY1343.
文摘Tendon-bone healing remains a significant clinical challenge due to the high risk of re-rupture following injury.While mesenchymal stem cells(MSCs)show great potential in enhancing tendon-bone healing,their clinical application is limited by issues such as low delivery efficiency,restricted differentiation potential,and potential immunogenicity.Recently,various strategies combining MSCs with other approaches,such as preconditioning,biomaterial integration,gene modification,and exosome application,have been developed,resulting in improved therapeutic outcomes.This review explored the current methods used to optimize MSC therapy for tendon-bone healing,examining the advantages,disadvantages,and underlying mechanisms of each approach,providing a foundation for future research and clinical applications.
文摘BACKGROUND Anterior cruciate ligament reconstruction(ACLR)is the dominant clinical modality for the treatment of anterior cruciate ligament injuries.The success of ACLR is largely dependent on tendon-bone healing,and stem cell biotherapies are often used to facilitate this process.Histone lactylation modifications are involved in the regulation of various diseases.Lactate dehydrogenase A(LDHA)has been shown to play an important role in exosomes.AIM To explore the regulation of tendon-bone healing after ACLR by LDHA in exosomes derived from bone marrow mesenchymal stem cells(BMSC-Exos).METHODS BMSC-Exos and LDHA were characterized and analyzed by transmission electron microscopy,qNano,immunofluorescence and western blotting assay.The corresponding low expression cell lines were obtained using RNA interference transfection;LDHA expression in rat bone tissues after ACLR was analyzed by western blotting.The volume of newborn bone tissues was monitored by micro-computed tomography imaging.Tendon and fibrocartilage regeneration were further analyzed and calculated by histological analysis,including hematoxylin and eosin and Safranin O-Fast green staining,respectively;LDHA levels of chondrocyte stem cells(CSPCs)after co-incubation with BMSC-Exos were analyzed by western blotting.Extracellularly secreted lactic acid content was determined by lactate assay kit.Cell viability was assessed by cell counting kit 8 assay,and the proliferation and differentiation ability of cells was further examined by the expression of collagen II,SOX9 and aggrecan.Histone H3K18 lactylation modification was analyzed by western blotting.H3K18 La binding on bone morphogenetic protein 7(BMP7)promoter was analyzed by chromatin immunoprecipitation-quantitative polymerase chain reaction;BMP7 promoter activity was analyzed by dual luciferase reporter gene;BMP7 protein expression was analyzed using quantitative polymerase chain reaction and western blotting.Then,the proliferation of CSPCs promoted by BMSC-Exos LDHA was analyzed by protein expression levels of LDHA,BMP7,collagen II,SOX9,aggrecan,extracellular lactate content,and cell counting kit 8 assay.RESULTS The spherical nanosized BMSC-Exos could be uptaken by CSPCs.LDHA was highly expressed in BMSC-Exos,which could infiltrate into the bone tissue of ACLR rats and promoted the generation of new bone tissue,as well as significantly increased the regeneration of tendon and fibrocartilage.Co-incubation of CSPCs with high-expressing LDHA BMSC-Exos increased the secretion of lactate content from CSPCs,cell viability,and the expression of markers related to cell proliferation and differentiation,including collagen II,SOX9,and aggrecan;LDHA in BMSC-Exos upregulated BMP7 through histone H3K18 lactate modification;high LDHA expression reversed the knockdown of BMP7,further increasing the proliferation and differentiation of CSPCs,thereby inducing cartilage formation.CONCLUSION LDHA in BMSC-Exos promotes BMP7 expression via H3K18 lactylation modification,which further promotes tendon-bone healing after ACLR.
基金supported by the National Basic Research Program of China(grant No.2021YFA0715700)the Natural Science Foundation of China(32130062)+1 种基金Innovation Cross Team of Chinese Academy of Sciences(JCTD-2018-13)Science and Technology Commission of Shanghai Municipality(20442420300,21DZ1205600).
文摘Tendon-bone healing is essential for an effective rotator cuff tendon repair surgery,however,this remains a significant challenge due to the lack of biomaterials with high strength and bioactivity.Inspired by the high-performance exoskeleton of natural organisms,we set out to apply natural fish scale(FS)modified by calcium silicate nanoparticles(CS NPs)as a new biomaterial(CS-FS)to overcome the challenge.Benefit from its“Bouligand”microstructure,such FS-based scaffold maintained excellent tensile strength(125.05 MPa)and toughness(14.16 MJ/m^(3)),which are 1.93 and 2.72 times that of natural tendon respectively,allowing it to well meet the requirements for rotator cuff tendon repair.Additionally,CS-FS showed diverse bioactivities by stimulating the differentiation and phenotypic maintenance of multiple types of cells participated into the composition of tendon-bone junction,(e.g.bone marrow mesenchymal stem cells(BMSCs),chondrocyte,and tendon stem/progenitor cells(TSPCs)).In both rat and rabbit rotator cuff tear(RCT)models,CS-FS played a key role in the tendon-bone interface regeneration and biomechanical function,which may be achieved by activating BMP-2/Smad/Runx2 pathway in BMSCs.Therefore,natural fish scale-based biomaterials are the promising candidate for clinical tendon repair due to their outstanding strength and bioactivity.
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.
基金Project (No. 81171687/H0604) supported by the National Natural Science Foundation of China
文摘Incorporation of a tendon graft within the bone tunnel represents a challenging clinical problem. Successfulanterior cruciate ligament (ACL) reconstruction requires solid healing of the tendon graft in the bone tunnel. En-hancement of graft healing to bone is important to facilitate early aggressive rehabilitation and a rapid return topre-injury activity levels. No convenient, effective or inexpensive procedures exist to enhance tendon-bone (T-B)healing after surgery. Low-intensity pulsed ultrasound (LIPUS) improves local blood perfusion and angiogenesis,stimulates cartilage maturation, enhances differentiation and proliferation of osteoblasts, and motivates osteogenic differentiation of mesenchymal stem cells (MSCs), and therefore, appears to be a potential non-invasive tool for T-Bhealing in early stage of rehabilitation of ACL reconstruction. It is conceivable that LIPUS could be used to stimulateT-B tunnel healing in the home, with the aim of accelerating rehabilitation and an earlier return to normal activities inthe near future. The purpose of this review is to demonstrate how LIPUS stimulates T-B healing at the cellular andmolecular levels, describe studies in animal models, and provide a future direction for research.
基金supported by the Luzhou Municipal People’s Government-SouthwestMedical University Science and Technology Cooperation Achievements Transformation Project(2019LZXNYDJ20C01).
文摘The treatment of rotator cuff tear is one of the major challenges for orthopedic surgeons.The key to treatment is the reconstruction of the tendon-bone interface(TBI).Autologous platelet-rich plasma(PRP)is used as a therapeutic agent to accelerate the healing of tendons,as it contains a variety of growth factors and is easy to prepare.Graphene oxide(GO)is known to improve the physical properties of biomaterials and promote tissue repair.In this study,PRP gels containing various concentrations of GO were prepared to promote TBI healing and supraspinatus tendon reconstruction in a rabbit model.The incorporation of GO improved the ultrastructure and mechanical properties of the PRP gels.The gels containing 0.5 mg/ml GO(0.5 GO/PRP)continuously released transforming growth factor-b1(TGF-b1)and platelet-derived growth factor(PDGF)-AB,and the released TGF-b1 and PDGF-AB were still at high concentrations,1063.451 pg/ml and814.217 pg/ml,respectively,on the 14th day.In vitro assays showed that the 0.5 GO/PRP gels had good biocompatibility and promoted bone marrow mesenchymal stem cells proliferation and osteogenic and chondrogenic differentiation.After 12 weeks of implantation,the magnetic resonance imaging,microcomputed tomography and histological results indicated that the newly regenerated tendons in the 0.5 GO/PRP group had a similar structure to natural tendons.Moreover,the biomechanical results showed that the newly formed tendons in the 0.5 GO/PRP group had better biomechanical properties compared to those in the other groups,and had more stable TBI tissue.Therefore,the combination of PRP and GO has the potential to be a powerful advancement in the treatment of rotator cuff injuries.
基金supported by the National Natural Science Foundation of China[grant numbers:82302639,81974327,81974328 and 82372358]National Students’Platform for Innovation and Entrepreneurship Training Program of China[grant number:No.202212121004]+1 种基金Natural Science Funds for Distinguished Young Scholar of Guangdong province[grant number:2022B1515020044]the Natural Science Foundation of Guangdong Province[grant number:2022A1515011101].
文摘Tendon-bone interface injuries pose a significant challenge in tissue regeneration,necessitating innovative approaches.Hydrogels with integrated supportive features and controlled release of therapeutic agents have emerged as promising candidates for the treatment of such injuries.In this study,we aimed to develop a temperature-sensitive composite hydrogel capable of providing sustained release of magnesium ions(Mg^(2+)).We synthesized magnesium-Procyanidin coordinated metal polyphenol nanoparticles(Mg-PC)through a self-assembly process and integrated them into a two-component hydrogel.The hydrogel was composed of dopamine-modified hyaluronic acid(Dop-HA)and F127.To ensure controlled release and mitigate the“burst release”effect of Mg^(2+),we covalently crosslinked the Mg-PC nanoparticles through coordination bonds with the catechol moiety within the hydrogel.This crosslinking strategy extended the release window of Mg^(2+)concentrations for up to 56 days.The resulting hydrogel(Mg-PC@Dop-HA/F127)exhibited favorable properties,including injectability,thermosensitivity and shape adaptability,making it suitable for injection and adaptation to irregularly shaped supraspinatus implantation sites.Furthermore,the hydrogel sustained the release of Mg^(2+)and Procyanidins,which attracted mesenchymal stem and progenitor cells,alleviated inflammation,and promoted macrophage polarization towards the M2 phenotype.Additionally,it enhanced collagen synthesis and mineralization,facilitating the repair of the tendon-bone interface.By incorporating multilevel metal phenolic networks(MPN)to control ion release,these hybridized hydrogels can be customized for various biomedical applications.
文摘This is a correction to:Dingsu Bao,Jiacheng Sun,Min Gong,Jie Shi,Bo Qin,Kai Deng,Gang Liu,Shengqiang Zeng,Zhou Xiang,Shijie Fu,Combination of graphene oxide and platelet-rich plasma improves tendon-bone healing in a rabbit model of supraspinatus tendon reconstruction,Regenerative Biomaterials,Volume 8,Issue 6,December 2021,rbab045,https://doi.org/10.1093/rb/rbab045.
文摘Rotator cuff tears are highly prevalent,and there is an urgent need to understand their healing mechanisms to improve treatment outcomes for patients.This editorial aims to summarize the roles and limitations of common animal models(including rodents,rabbits,sheep,dogs,and primates)and second-look arthroscopy in rotator cuff healing research.Different animal models offer distinct advantages and disadvantages.For example,rodent models are cost-effective and suitable for genetic studies but have anatomical differences from humans.Rabbit models are favored for their relatively large tendon size and ease of surgical manipulation,yet they still deviate from human shoulder anatomy in some aspects.Larger animals like sheep and dogs have more similar shoulder structures to humans but come with high costs and challenges in maintaining consistent experimental conditions.Second-look arthroscopic studies have provided evidence for the effectiveness of current surgical techniques.Animal models will continue to play a crucial role in further exploring the local microenvironment of the rotator cuff,which is expected to help develop more effective strategies to promote healing.
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 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.
基金Supported by Natural Science Foundation of Anhui Medical University,No.2023xkj130.
文摘BACKGROUND Mucosal healing(MH)is the major therapeutic target for Crohn's disease(CD).As the most commonly involved intestinal segment,small bowel(SB)assessment is crucial for CD patients.Yet,it poses a significant challenge due to its limited accessibility through conventional endoscopic methods.AIM To establish a noninvasive radiomic model based on computed tomography enterography(CTE)for MH assessment in SBCD patients.METHODS Seventy-three patients diagnosed with SBCD were included and divided into a training cohort(n=55)and a test cohort(n=18).Radiomic features were obtained from CTE images to establish a radiomic model.Patient demographics were analysed to establish a clinical model.A radiomic-clinical nomogram was constructed by combining significant clinical and radiomic features.The diagnostic efficacy and clinical benefit were evaluated via receiver operating characteristic(ROC)curve analysis and decision curve analysis(DCA),respectively.RESULTS Of the 73 patients enrolled,25 patients achieved MH.The radiomic-clinical nomogram had an area under the ROC curve of 0.961(95%confidence interval:0.886-1.000)in the training cohort and 0.958(0.877-1.000)in the test cohort and provided superior clinical benefit to either the clinical or radiomic models alone,as demonstrated by DCA.CONCLUSION These results indicate that the CTE-based radiomic-clinical nomogram is a promising imaging biomarker for MH and serves as a potential noninvasive alternative to enteroscopy for MH assessment in SBCD patients.
基金Supported by the Qilu Medical School Traditional Chinese Medicine Academic School Inheritance Project,No.93 LW[2022]Construction Project of the Inheritance Studio of National Famous Traditional Chinese Medicine Experts,Traditional Chinese Medicine Teaching Letter No.75[2022]Qilu Health and Fitness Talents in 2019,No.3 LWRZ[2020].
文摘BACKGROUND Diabetic foot ulcers(DFUs)are a significant contributor to disability and mortality in diabetic patients.Macrophage polarization and functional regulation are promising areas of research and show therapeutic potential in the field of DFU healing.However,the complex mechanism,the difficulty in clinical translation,and the large heterogeneity present significant challenges.Hence,this study was to comprehensively analyze the publication status and trends of studies on macrophage polarization and DFU healing.AIM To examine the relevant literature on macrophage polarization in DFU healing.METHODS A bibliometric analysis was conducted using the Web of Science database.Relevant literature was retrieved from the Web of Science Core Collection database between 2013 to 2023 using literature visualization and analysis software(VOSviewer and CiteSpace)and bibliometric online platforms.The obtained literature was then subjected to visualization and analysis of different countries/regions,institutions,journals,authors,and keywords to reveal the research’s major trends and focus.RESULTS The number of publications on the role of macrophage polarization in DFU healing increased rapidly from 2013 to 2023,especially in the latter period.Chinese researchers were the most prolific in this field,with 217 publications,while American researchers had been engaged in this field for a longer period.Qian Tan of Nanjing Drum Tower Hospital and Qian Ding of Nanjing University were the first to publish in this field.Shanghai Jiao Tong University was the institution with the most publications(27).The keywords“bone marrow”,“adjustment,replacement,response,tissue repair”,and“activation,repair,differentiation”appeared more frequently.The study of macrophage polarization in DFU healing focused on the regulatory mechanism,gene expression,and other aspects.CONCLUSION This study through the bibliometric method reveals the research trends and development trends in this field of macrophage polarization in DFU healing from 2013 to 2023 in the Web of Science Core Collection database.The key hotspots in this field mainly include the regulation of macrophage activation,gene expression,wound tissue repair,and new wound materials.This study provides references for future research directions.
文摘Objective:To evaluate the effectiveness of surgical combination with traditional Chinese medicine dialectical therapy in three phases for the treatment of intertrochanteric fracture of the femur(IFF).Methods:84 patients with IFF admitted to the hospital from December 2022 to December 2024 were selected and randomly divided into two groups using a random number table.The combined group received surgery and traditional Chinese medicine dialectical therapy in three phases,while the control group received surgery alone.The total effective rate,fracture healing time,hip function score,and lower extremity function score were compared between the two groups.Results:The total effective rate was higher in the combined group than in the control group(P<0.05).After treatment,the fracture healing time was shorter in the combined group than in the control group,and the hip function and lower extremity function scores were higher in the combined group than in the control group(P<0.05).Conclusion:Surgical combination with traditional Chinese medicine dialectical therapy in three phases can shorten the fracture healing time of IFF patients and restore their hip and lower extremity function,demonstrating significant efficacy.
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.
基金Supported by 2021 Disciplinary Construction Project in School of Dentistry,Anhui Medical University,No.2021kqxkFY05.
文摘BACKGROUND Complicated crown–root fracture (CRF) involves severe injury to the crown, root,and pulp, and may be accompanied by multiple root fractures. The loss of a toothhas lifelong consequences for children and teenagers, but the maintenance of pulphealth and the calcific healing of multiple root fractures are rarely reported in theliterature.CASE SUMMARY This case reports healing of a permanent tooth with complicated crown–root andadditional root fractures, in which pulp health was maintained. A 10-year-old girlfell and fractured the root of her maxillary left central incisor at the cervical level.After the coronal fragment was repositioned, the tooth was splinted until thetooth was no longer mobile, 2 years later. Eight years after treatment, the toothhas remained asymptomatic with vital pulp and localized gingival overgrowth.Cone-beam computed tomography revealed not only calcified healing of the CRFbut also spontaneous healing in an additional undiagnosed root fracture. Thefracture line on the enamel could not be healed by hard tissue and formed agroove in the cervical crown. It was speculated that the groove was related to thelocalized gingival overgrowth.CONCLUSION This case provides a clinical perspective of the treatment of a tooth with acomplicated CRF and an additional root fracture.
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.
基金supported by grants from the German Research Foundation (DFG)
文摘Chronic,non-healing wounds represent a significant challenge for healthcare systems worldwide,often requiring significant human and financial resources.Chronic wounds arise from the complex interplay of underlying comorbidities,such as diabetes or vascular diseases,lifestyle factors,and genetic risk profiles which may predispose extremities to local ischemia.Injuries are further exacerbated by bacterial colonization and the formation of biofilms.Infection,consequently,perpetuates a chronic inflammatory microenvironment,preventing the progression and completion of normal wound healing.The current standard of care(SOC)for chronic wounds involves surgical debridement along with localized wound irrigation,which requires inpatient care under general anesthesia.This could be followed by,if necessary,defect coverage via a reconstructive ladder utilizing wound debridement along with skin graft,local,or free flap techniques once the wound conditions are stabilized and adequate blood supply is restored.To promote physiological wound healing,a variety of approaches have been subjected to translational research.Beyond conventional wound healing drugs and devices that currently supplement treatments,cellular and immunotherapies have emerged as promising therapeutics that can behave as tailored therapies with cell-or molecule-specific wound healing properties.However,in contrast to the clinical omnipresence of chronic wound healing disorders,there remains a shortage of studies condensing the current body of evidence on cellular therapies and immunotherapies for chronic wounds.This review provides a comprehensive exploration of current therapies,experimental approaches,and translational studies,offering insights into their efficacy and limitations.Ultimately,we hope this line of research may serve as an evidence-based foundation to guide further experimental and translational approaches and optimize patient care long-term.
