In-office interventions are becoming increasingly desired by patients,secondary to the decreased cost and downtime when compared to procedures performed in the operating theater.This is particularly evident in Facial ...In-office interventions are becoming increasingly desired by patients,secondary to the decreased cost and downtime when compared to procedures performed in the operating theater.This is particularly evident in Facial Plastic&Reconstructive Surgery(FPRS),where facility and anesthesia fees can make nonfunctional procedures costprohibitive.This special issue aims to inform readers on how to best equip their office to safely and effectively offer these services,while providing an overview of the types of procedures that can be wellsuited for the office-based setting.展开更多
Diabetic wounds(DWs)are a major complication of diabetes mellitus,characterized by a complex patho-physiological microenvironment that is associated with elevated morbidity and mortality.Conventional management strate...Diabetic wounds(DWs)are a major complication of diabetes mellitus,characterized by a complex patho-physiological microenvironment that is associated with elevated morbidity and mortality.Conventional management strategies often fail to address the multifaceted nature of these wounds effectively.Recent advancements in understanding the mechanisms of DW healing have spurred the development of a plethora of bioactive dressings designed to interact with and modulate the DW microenvironment.These innovations have culminated in the introduction of the“microenvironment-sensitive with on-demand management”paradigm aimed at delivering precision therapy responsive to dynamic changes within DW.Despite these advancements,the current literature lacks a comprehensive review that cate-gorizes and evaluates active,passive,and on-demand approaches that address the DW microenviron-ment.Herein,we describe the unique pathogenic mechanisms and microenvironmental characteristics that distinguish DW from normal acute wounds.This review provides an extensive overview of contem-porary active and passive management strategies incorporating on-demand management principles designed for DW microenvironments.Furthermore,it addresses the principal challenges faced in this therapeutic domain and outlines the potential innovations that can enhance the efficacy and specificity of bioactive dressings.The insights presented here aim to guide further research and development in the on-demand management of DW to improve patient outcomes by aligning personalized therapy modali-ties with the pathophysiological realities of DW.展开更多
BACKGROUND In recent years,the number of studies on spondylolisthesis has been increasing,and there are many publications on this disorder.To our knowledge,there is no bibliometric analysis of spondylolisthesis to dat...BACKGROUND In recent years,the number of studies on spondylolisthesis has been increasing,and there are many publications on this disorder.To our knowledge,there is no bibliometric analysis of spondylolisthesis to date.AIM To investigate emerging directions in Spondylolisthesis research and systematically evaluate the academic literature with the highest citation impact within this field.METHODS All data were collected from the Web of Science Core Collection database.Years of publications,countries,journals,institutions and total number of citations were extracted and analyzed by VOSviewer software.In addition,we analyzed the top 100 most-cited articles on spondylolisthesis.RESULTS A total of 1831 articles related to spondylolisthesis were identified.The frequency of publications on spondylolisthesis has increased dramatically over time.Among all countries,United States has contributed the most publications on spondylolisthesis(n=574).The institution with the most articles was the University of California,San Francisco(n=52).Spine topped the list of journals and has published 291 spondylolisthesis-related reports.The hotspot of research changed from posterolateral fusion to interbody fusion.CONCLUSION In recent years,academic investigations on spondylolisthesis have exhibited significant growth.As the inaugural bibliometric evaluation in this domain,our research establishes a methodological framework for synthesizing the historical progression and current advancements of spondylolisthesis studies.展开更多
Nerve regeneration conditioned fluid is secreted by nerve stumps inside a nerve regeneration chamber.A better understanding of the proteinogram of nerve regeneration conditioned fluid can provide evidence for studying...Nerve regeneration conditioned fluid is secreted by nerve stumps inside a nerve regeneration chamber.A better understanding of the proteinogram of nerve regeneration conditioned fluid can provide evidence for studying the role of the microenvironment in peripheral nerve regeneration.In this study,we used cylindrical silicone tubes as the nerve regeneration chamber model for the repair of injured rat sciatic nerve.Isobaric tags for relative and absolute quantitation proteomics technology and western blot analysis confirmed that there were more than 10 complement components（complement factor I,C1q-A,C1q-B,C2,C3,C4,C5,C7,C8β and complement factor D） in the nerve regeneration conditioned fluid and each varied at different time points.These findings suggest that all these complement components have a functional role in nerve regeneration.展开更多
Oral squamous cell carcinoma(OSCC)is a prevalent malignant tumor affecting the head and neck region(Leemans et al.,2018).It is often diagnosed at a later stage,leading to a poor prognosis(Muzaffar et al.,2021;Li et al...Oral squamous cell carcinoma(OSCC)is a prevalent malignant tumor affecting the head and neck region(Leemans et al.,2018).It is often diagnosed at a later stage,leading to a poor prognosis(Muzaffar et al.,2021;Li et al.,2023).Despite advances in OSCC treatment,the overall 5-year survival rate of OSCC patients remains alarmingly low,falling below 50%(Jehn et al.,2019;Johnson et al.,2020).According to statistics,only 50%of patients with oral cancer can be treated with surgery.Once discovered,it is more frequently at an advanced stage.In addition,owing to the aggressively invasive and metastatic characteristics of OSCC,most patients die within one year of diagnosis.Hence,the pursuit of novel therapeutic drugs and treatments to improve the response of oral cancer to medication,along with a deeper understanding of their effects.展开更多
Objective To evaluate the therapeutic efficacy of complex decongestive therapy in the treatment of elephantiasis of the lower extremities.Methods Seventeen patients with unilateral lower limb elephantiasis were includ...Objective To evaluate the therapeutic efficacy of complex decongestive therapy in the treatment of elephantiasis of the lower extremities.Methods Seventeen patients with unilateral lower limb elephantiasis were included in the study(5 with primary lymphedema and 12 with secondary lymphedema).All patients were treated with one course(4 weeks)of complex decongestive therapy.Changes inextracellular fluid(ECF),BMI,circumferences,and skin properties including skin stiffness(SF),percent water content(PWC),and trans-epidermal water loss(TEWL)were measured before and after treatment.Results The“elephantiasis-like”appearance of the affected limb was greatly improved after treatment.The ECF,BMI,and circumferences were significantly decreased after treatment(P<0.001)with an average ECF of 2.97±1.82 L,BMI of 1.638±2.647 kg/m^2,and circumference of 6.58±2.79 cm.The values of PWC,TEWL,and SFwere 50.5%±10.6%,18.55±10.2 g/m^2 h,and 0.161±0.176 N,respectively,before treatment and 36.05%±7%,8.3±2.07 g/m^2h,and 0.086±0.038 N,respectively,after treatment,there by showing significant decreases(P<0.05).Conclusion Complex decongestive therapy is effective in the treatment of advanced stages of chronic lymphedema.展开更多
Background: Dressing of split-thickness skin graft donor sites can be traumatic for the patient. The most advanced and expensive dressings have been compared to the most basic of dressings, with little or no consensus...Background: Dressing of split-thickness skin graft donor sites can be traumatic for the patient. The most advanced and expensive dressings have been compared to the most basic of dressings, with little or no consensus and an unpersuasive level of evidence. We aimed to determine the efficacy of the locally manufactured non-adherent, hydroconductive Drawtex? dressing and compare it to our current standard-of-care dressing, a thin transparent polyurethane film, in the healing of split-thickness donor sites. Methods: This prospective, within-patient controlled study included 27 adult participants, each with two split-thickness skin donor sites. The 54 donor site wounds were compared with regard to time to re-epithelialisation, perceived pain and healed wound quality. Results: By day 5, complete healing of donor site wounds, defined as >90% of epithelialized surface, was significantly higher in the hydroconductive dressing group compared to the polyurethane film group (22.2% and 3.7%, respectively;p < 0.0001). The hydroconductive dressing-treated donor site wounds were significantly less painful at 24-hours, 48-hours and 7-days post-operatively, and had fewer complications and superior wound healing quality. Conclusion: We have demonstrated that the relatively cheap and readily available dressing made locally in South Africa, Drawtex? is at least as safe, and potentially superior in wound healing, when compared to our current standard-of-care dressing.展开更多
Myelosuppression is a common and severe side effect of cancer chemotherapy,with current treatments hindered by limitations such as depletion of hematopoietic reserves,poor patient compliance,delayed therapeutic onset,...Myelosuppression is a common and severe side effect of cancer chemotherapy,with current treatments hindered by limitations such as depletion of hematopoietic reserves,poor patient compliance,delayed therapeutic onset,and high cost.To overcome these challenges,we developed Epimedium-derived nanovesicles(ENVs)from the traditional Chinese medicinal herb Epimedium,addressing the solubility and bioavailability issues associated with conventional extracts.ENVs encapsulate bioactive constituents,including icariin and hematopoiesis-promoting ceramides.In a cyclophosphamide(CTX)-induced myelosuppression mouse model,prophylactic and therapeutic oral administration of ENVs effectively alleviated hematopoietic suppression,significantly outperforming the Epimedium-based herbal extract“Joungal”(Shengbai Formula)despite equivalent icariin content.Notably,ENVs promoted hematopoietic stem cell(HSC)proliferation—an outcome rarely achieved with existing therapies.Mechanistically,ENVs modulated the gut microbiota,enriching lactobacillus species and enhancing lactate production.This microbiota-driven lactate signaling stimulated LepR+mesenchymal stem cells(MSCs)in the bone marrow niche to secrete stromal cellderived factor-1(SDF-1)and stem cell factor(SCF),thereby supporting HSC expansion and restoring hematopoietic function.In vivo safety evaluations confirmed the excellent biocompatibility of ENVs.Our findings uncover a gut-lactate-bone marrow axis through which ENVs enhance hematopoiesis and promote HSC regeneration.This work introduces a cost-effective,scalable,and orally administrable biomaterial platform with strong translational potential for the prevention and treatment of chemotherapy-induced myelosuppression.展开更多
The pathological microenvironment of osteoporosis poses a substantial clinical challenge for bone defect regeneration.Through single-cell RNA-sequencing(scRNA-seq)analysis,we identified a reactive oxygen species(ROS)-...The pathological microenvironment of osteoporosis poses a substantial clinical challenge for bone defect regeneration.Through single-cell RNA-sequencing(scRNA-seq)analysis,we identified a reactive oxygen species(ROS)-overloading osteoblast subpopulation as a critical pathological feature of osteoporotic niches.Guided by scRNA-seq analysis,we engineered a microenvironment-adaptive hydrogel system through precise integration of antioxidant curcumin-encapsulated zeolitic imidazolate framework-8 nanoparticles(CCM@ZIF-8 NPs)within photo-crosslinkable alginate methacrylate(AlgMA)hydrogel(AlgMA/CCM@ZIF-8).This engineered design exhibited dual functions:effectively scavenging ROS in bone marrow-derived mesenchymal stem cells(BMSCs)while simultaneously suppressing osteoclast differentiation.The osteo-regenerative superiority of the AlgMA/CCM@ZIF-8 nanocomposite hydrogel was conclusively demonstrated in bone defect models of osteoporotic mice.This scRNA-seq-informed engineering strategy offers a promising approach for developing pathophysiology-adapted biomaterials to promote regenerative repair in osteoporotic bone defects.展开更多
Phosphatase and tensin homolog(PTEN)is a tumor sup-pressor gene located at 10q23.3 and serves as a crucial negative regulator of the PI3K-AKT signaling cascade by dephosphorylating phosphatidylinositol(3,4,5)-triphos-...Phosphatase and tensin homolog(PTEN)is a tumor sup-pressor gene located at 10q23.3 and serves as a crucial negative regulator of the PI3K-AKT signaling cascade by dephosphorylating phosphatidylinositol(3,4,5)-triphos-phate and inhibiting AKT activation.PTEN hamartoma tumor syndrome(PHTS)is an umbrella term employed to describe a spectrum of disorders caused by germline PTEN variants,including Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome.While distinct entitles included in PHTS have their unique diagnostic criteria,they also share common phenotypic features such as benign hamartomas of the three germ layers.展开更多
Facial infiltrating lipomatosis(FIL)is a congenital disorder caused by the hyperproliferation of adipose and skeletal tissue within the facial region.Infiltration of mature adipose tissue into adjacent structures is a...Facial infiltrating lipomatosis(FIL)is a congenital disorder caused by the hyperproliferation of adipose and skeletal tissue within the facial region.Infiltration of mature adipose tissue into adjacent structures is a hallmark pathologic finding.In addition to the aesthetic implications,patients may suffer from impaired facial function,including difficulty in swallowing and breathing,sleep disturbances,and visual field displacement.展开更多
The complex lower extremity wound is frequently encountered by orthopedic and plastic surgeons.Innovations in wound care,soft tissue coverage and surgical fixation techniques allow for improved functional outcomes in ...The complex lower extremity wound is frequently encountered by orthopedic and plastic surgeons.Innovations in wound care,soft tissue coverage and surgical fixation techniques allow for improved functional outcomes in this patient population with highly morbid injuries.In this review,the principles of reconstruction of complex lower extremity traumatic wounds are outlined.These principles include appropriate initial evaluation of the patient and mangled extremity,as well as appropriate patient selection for limb salvage.The authors emphasize proper planning for reconstruction,timing of reconstruction and the importance of an understanding of the most appropriate reconstructive option.The role of different reconstructive and wound care modalities is discussed,notably negative pressure wound therapy and dermal substitutes.The role of pedicled flaps and microvascular free-tissue transfer are discussed,as are innovations in understanding of perforator anatomy and perforator flap surgery that have broadened the reconstruction surgeon’s armamentarium.Finally,the importance of a multidisciplinary team is highlighted via the principle of the orthoplastic approach to management of complex lower extremity wounds.Upon completion of this review,the reader should have a thorough understanding of the principles of contemporary lower extremity reconstruction.展开更多
Fibroblast growth factors(FGF)and their receptors serve many functions in both the developing and adult organism.Humans contain 18 FGF ligands and four FGF receptors(FGFR).FGF ligands are polypeptide growth factors th...Fibroblast growth factors(FGF)and their receptors serve many functions in both the developing and adult organism.Humans contain 18 FGF ligands and four FGF receptors(FGFR).FGF ligands are polypeptide growth factors that regulate several developmental processes including cellular proliferation,differentiation,and migration,morphogenesis,and patterning.FGF-FGFR signaling is also critical to the developing axial and craniofacial skeleton.In particular,the signaling cascade has been implicated in intramembranous ossification of cranial bones as well as cranial suture homeostasis.In the adult,FGFs and FGFRs are crucial for tissue repair.FGF signaling generally follows one of three transduction pathways:RAS/MAP kinase,PI3/AKT,or PLCg.Each pathway likely regulates specific cellular behaviors.Inappropriate expression of FGF and improper activation of FGFRs are associated with various pathologic conditions,unregulated cell growth,and tumorigenesis.Additionally,aberrant signaling has been implicated in many skeletal abnormalities including achondroplasia and craniosynostosis.The biology and mechanisms of the FGF family have been the subject of significant research over the past 30 years.Recently,work has focused on the therapeutic targeting and potential of FGF ligands and their associated receptors.The majority of FGF-related therapy is aimed at age-related disorders.Increased understanding of FGF signaling and biology may reveal additional therapeutic roles,both in utero and postnatally.This review discusses the role of FGF signaling in general physiologic and pathologic embryogenesis and further explores it within the context of skeletal development.展开更多
The author reviews his pioneering work in aesthetic restoration of the severely disfigured burn face first introduced in 1995 and refined over the past two decades. The reader will be exposed to the step by step appro...The author reviews his pioneering work in aesthetic restoration of the severely disfigured burn face first introduced in 1995 and refined over the past two decades. The reader will be exposed to the step by step approach to achieving cosmetic enhancement and functional rehabilitation of advanced facial burns. The"keystone"of the autogenous reconstruction is the pre-patterned, sculpted microvascular free flap designed to fit like the"piece of a puzzle"into the aesthetic units of the face to replace disfiguring burn scars. Aggressive intraoperative"sculpting"is employed both"in situ"at the donor site and during the flap transfer to simulate the normal facial contours and planes. Comparisons of the author's approach are made to the whole spectrum of reconstructive modalities ranging from conventional grafting to expanded pre-fabricated flaps and even to CTA face transplants;advantages/disadvantages of each are discussed. The pre-patterned, sculpted microvascular (MV) free flap offers the benefit of a single-stage transfer of composite skin/soft tissue hiding the seams at the junction of facial planes. When harvested from distant donor sites, the donor deformities can easily be concealed. The MV free tissue transfer offers the substrate that can be sculpted into nuanced facial components as well as the"palette"upon which the face can be painted with creative camouflage makeup. The soft contour and texture of the autogenous patterned transfers translates into a"natural"facial appearance while preserving fluid motions of facial expression.展开更多
Background:Zinc-based biomaterials,including biodegradable metal,nanoparticles,and coatings used in medical implants release zinc ions that may increase the whole-body and serum zinc concentrations.The impact of serum...Background:Zinc-based biomaterials,including biodegradable metal,nanoparticles,and coatings used in medical implants release zinc ions that may increase the whole-body and serum zinc concentrations.The impact of serum zinc concentrations on major health outcomes can provide insights for device design and clinical transformation of zinc-based biomaterials.Methods:This nationally representative cross-sectional study enrolled participants from the National Health and Nutrition Examination Survey(NHANES,2011-2014)including 3607 participants.Using unadjusted and multivariate-adjusted logistic regression analyses,two-piecewise linear regression model with a smoothing function and threshold level analysis,we evaluated the associations between elevated serum zinc levels and major health outcomes.Results:Elevated serum zinc levels were significantly associated with an increase in total spine and total femur bone mineral density(BMD).Every 10μg/dL increase was associated with a 1.12-fold increase in diabetes mellitus(DM)and 1.23-fold and 1.29-fold increase in cardiovascular diseases(CVD)and coronary heart disease(CHD),in participants with serum zinc levels≥100μg/dL.It had no significant linear or nonlinear associations with risk of fractures,congestive heart failure,heart attack,thyroid disease,arthritis,osteoarthritis,rheumatoid arthritis,dyslipidemia and cancer.Conclusion:Serum zinc levels are significantly associated with increased BMD in the total spine and total femur,and risk of DM,and CVD/CHD among participants with serum zinc levels≥100μg/dL.展开更多
Sustained,high level transgene expression in mammalian cells is desired in many cases for studying gene functions.Traditionally,stable transgene expression has been accomplished by using retroviral or lentiviral vecto...Sustained,high level transgene expression in mammalian cells is desired in many cases for studying gene functions.Traditionally,stable transgene expression has been accomplished by using retroviral or lentiviral vectors.However,such viral vector-mediated transgene expression is often at low levels and can be reduced over time due to low copy numbers and/or chromatin remodeling repression.The piggyBac transposon has emerged as a promising nonviral vector system for efficient gene transfer into mammalian cells.Despite its inherent advantages over lentiviral and retroviral systems,piggyBac system has not been widely used,at least in part due to their limited manipulation flexibilities.Here,we seek to optimize piggyBac-mediated transgene expression and generate a more efficient,user-friendly piggyBac system.By engineering a panel of versatile piggyBac vectors and constructing recombinant adenoviruses expressing piggyBac transposase(PBase),we demonstrate that adenovirusmediated PBase expression significantly enhances the integration efficiency and expression level of transgenes in mesenchymal stem cells and osteosarcoma cells,compared to that obtained from co-transfection of the CMV-PBase plasmid.We further determine the drug selection timeline to achieve optimal stable transgene expression.Moreover,we demonstrate that the transgene copy number of piggyBac-mediated integration is approximately 10 times higher than that mediated by retroviral vectors.Using the engineered tandem expression vector,we show that three transgenes can be simultaneously expressed in a single vector with high efficiency.Thus,these results strongly suggest that the optimized piggyBac system is a valuable tool for making stable cell lines with sustained,high transgene expression.展开更多
Objective:As the population ages,facial plastic providers must remain aware of the treatments to prevent and reverse the external signs of aging.In the mandibular region,skin laxity and soft tissue sagging in the jawl...Objective:As the population ages,facial plastic providers must remain aware of the treatments to prevent and reverse the external signs of aging.In the mandibular region,skin laxity and soft tissue sagging in the jawline may lead to jowling and chin ptosis along with reduced chin projection.While surgical procedures,including chin implantation,may be performed,nonsurgical procedures are becoming increasingly popular due to their temporary,noninvasive,yet effective methods.This review covers the use of hyaluronic acid,calcium hydroxylapatite,poly-L-lactic acid,and polymethyl methacrylate in the jawline.Methods:PubMed was searched for data on the mechanism of action,pertinent anatomy,indications,contraindications,technique,and evidence supporting the safety and efficacy of the fillers.Results:There are a wide variety of fillers available for use in the lower face with unique characteristics and application methods.While the advantages of injectable fillers include relatively affordable cost,minimal patient discomfort,and limited recovery times,taking measures to prevent short-and long-term complications is necessary for optimal results.Conclusions:Understanding the benefits and limitations of injectable fillers in the jawline can help providers appropriately counsel and treat patients.展开更多
The normal growth and development of the skull is a tightly regulated process that occurs along the osteogenic interfaces of the cranial sutures.Here,the borders of the calvarial bones and neighboring tissues above an...The normal growth and development of the skull is a tightly regulated process that occurs along the osteogenic interfaces of the cranial sutures.Here,the borders of the calvarial bones and neighboring tissues above and below,function as a complex.Through coordinated remodeling efforts of bone deposition and resorption,the cranial sutures maintain a state of patency from infancy through early adulthood as the skull continues to grow and accommodate the developing brain’s demands for expansion.However,when this delicate balance is disturbed,a number of pathologic conditions ensue;and if left uncorrected,may result in visual and neurocognitive impairments.A prime example includes craniosynostosis,or premature fusion of one or more cranial and/or facial suture(s).At the present time,the only therapeutic measure for craniosynostosis is surgical correction by cranial vault reconstruction.However,elegant studies performed over the past decade have identified several genes critical for the maintenance of suture patency and induction of suture fusion.Such deeper understandings of the pathogenesis and molecular mechanisms that regulate suture biology may provide necessary insights toward the development of non-surgical therapeutic alternatives for patients with cranial suture defects.In this review,we discuss the intricate cellular and molecular interplay that exists within the suture among its three major components:dura mater,osteoblastic related molecular pathways and osteoclastic related molecular pathways.展开更多
Purpose:Defects aro und the distal one third of the leg and ankle are difficult to man age by con servative measures or simple split thickness skin graft.Distally based peroneus brevis muscle flap is a well described ...Purpose:Defects aro und the distal one third of the leg and ankle are difficult to man age by con servative measures or simple split thickness skin graft.Distally based peroneus brevis muscle flap is a well described flap for such defects.Methods:This is a retrospective analysis conducted on 25 patients with soft tissue and bony defects of distal third of lower leg and an kle,which were treated using distally based per on eus brevis muscle flap from January 2013 to January 2018.Information regarding patient demographics,etiology,size and location of defects and complications were collected.All patients were followed up for at least 3 months after surgery.Results:There were 21 males and 4 females with the mean age of 39(5-76)years.The most comm on cause of injuries was road traffic accident,followed by complicated open injury.The average size of defects was 20(4—50)cm^2.The mean operating time was 75(60-90)min for flap harvest and inset.We had no patient with complete loss of the flap.Five patients(20%)had marginal necrosis of the flap and two patie nts have graft loss due to un derlyi ng hematoma and required sec on dary split thickness skin grafting.Conclusion:The distally based peroneus brevis muscle flap is a safe optio n w让h reliable an atomy for small to moderate sized defects following low velocity injury around the ankle.The commonest complication encountered is skin graft loss which can be reduced by primary delayed grafting.展开更多
Background:Atopic dermatitis(AD)affects approximately 10%of adults worldwide.CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling.This ...Background:Atopic dermatitis(AD)affects approximately 10%of adults worldwide.CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling.This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods:This multicenter,randomized,double-blind,placebo-controlled,phase 2b trial was conducted in 21 medical institutions in China from February to November 2021.Totally 120 eligible patients were enrolled and randomized(1:1:1)to receive subcutaneous injections of 300 mg CM310,150 mg CM310,or placebo every 2 weeks for 16 weeks,followed by an 8-week follow-up period.The primary endpoint was the proportion of patients achieving≥75%improvement in the Eczema Area and Severity Index(EASI-75)score from baseline at week 16.Safety and pharmacodynamics were also studied.Results:At week 16,the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups(70%[28/40]for high-dose and 65%[26/40]for low-dose)than that in the placebo group(20%[8/40]).The differences in EASI-75 response rate were 50%(high vs.placebo,95%CI 31%-69%)and 45%(low vs.placebo,95%CI 26%-64%),with both P values<0.0001.CM310 at both doses also significantly improved the EASI score,Investigator’s Global Assessment score,daily peak pruritus Numerical Rating Scale,AD-affected body surface area,and Dermatology Life Quality Index compared with placebo.CM310 treatment reduced levels of thymus and activation-regulated chemokine,total immunoglobulin E,lactate dehydrogenase,and blood eosinophils.The incidence of treatment-emergent adverse events(TEAEs)was similar among all three groups,with the most common TEAEs reported being upper respiratory tract infection,atopic dermatitis,hyperlipidemia,and hyperuricemia.No severe adverse events were deemed to be attributed to CM310.Conclusion:CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration:ClinicalTrials.gov,NCT04805411.展开更多
文摘In-office interventions are becoming increasingly desired by patients,secondary to the decreased cost and downtime when compared to procedures performed in the operating theater.This is particularly evident in Facial Plastic&Reconstructive Surgery(FPRS),where facility and anesthesia fees can make nonfunctional procedures costprohibitive.This special issue aims to inform readers on how to best equip their office to safely and effectively offer these services,while providing an overview of the types of procedures that can be wellsuited for the office-based setting.
基金supported by the National Natural Science Foundation of China(22408078,82401057,32101170)the Zhejiang Province Postdoctoral Excellence Funding Program-Special Support(ZJ2024004).
文摘Diabetic wounds(DWs)are a major complication of diabetes mellitus,characterized by a complex patho-physiological microenvironment that is associated with elevated morbidity and mortality.Conventional management strategies often fail to address the multifaceted nature of these wounds effectively.Recent advancements in understanding the mechanisms of DW healing have spurred the development of a plethora of bioactive dressings designed to interact with and modulate the DW microenvironment.These innovations have culminated in the introduction of the“microenvironment-sensitive with on-demand management”paradigm aimed at delivering precision therapy responsive to dynamic changes within DW.Despite these advancements,the current literature lacks a comprehensive review that cate-gorizes and evaluates active,passive,and on-demand approaches that address the DW microenviron-ment.Herein,we describe the unique pathogenic mechanisms and microenvironmental characteristics that distinguish DW from normal acute wounds.This review provides an extensive overview of contem-porary active and passive management strategies incorporating on-demand management principles designed for DW microenvironments.Furthermore,it addresses the principal challenges faced in this therapeutic domain and outlines the potential innovations that can enhance the efficacy and specificity of bioactive dressings.The insights presented here aim to guide further research and development in the on-demand management of DW to improve patient outcomes by aligning personalized therapy modali-ties with the pathophysiological realities of DW.
基金Supported by Science and Technology Department of the State Administration of Traditional Chinese Medicine-Zhejiang Provincial Administration of Traditional Chinese Medicine Joint Science and Technology Program,No.GZY-ZJ-KJ-23057Bijie City Science and Technology Program 2023(Second Batch),No.BKH(2023)552024 Guizhou Province Chinese Medicine,Ethnic Medicine Science and Technology Research Special Project,No.QZYY-2024-109.
文摘BACKGROUND In recent years,the number of studies on spondylolisthesis has been increasing,and there are many publications on this disorder.To our knowledge,there is no bibliometric analysis of spondylolisthesis to date.AIM To investigate emerging directions in Spondylolisthesis research and systematically evaluate the academic literature with the highest citation impact within this field.METHODS All data were collected from the Web of Science Core Collection database.Years of publications,countries,journals,institutions and total number of citations were extracted and analyzed by VOSviewer software.In addition,we analyzed the top 100 most-cited articles on spondylolisthesis.RESULTS A total of 1831 articles related to spondylolisthesis were identified.The frequency of publications on spondylolisthesis has increased dramatically over time.Among all countries,United States has contributed the most publications on spondylolisthesis(n=574).The institution with the most articles was the University of California,San Francisco(n=52).Spine topped the list of journals and has published 291 spondylolisthesis-related reports.The hotspot of research changed from posterolateral fusion to interbody fusion.CONCLUSION In recent years,academic investigations on spondylolisthesis have exhibited significant growth.As the inaugural bibliometric evaluation in this domain,our research establishes a methodological framework for synthesizing the historical progression and current advancements of spondylolisthesis studies.
基金supported by grants from the National Natural Science Foundation of China,No.30925034,81101437
文摘Nerve regeneration conditioned fluid is secreted by nerve stumps inside a nerve regeneration chamber.A better understanding of the proteinogram of nerve regeneration conditioned fluid can provide evidence for studying the role of the microenvironment in peripheral nerve regeneration.In this study,we used cylindrical silicone tubes as the nerve regeneration chamber model for the repair of injured rat sciatic nerve.Isobaric tags for relative and absolute quantitation proteomics technology and western blot analysis confirmed that there were more than 10 complement components（complement factor I,C1q-A,C1q-B,C2,C3,C4,C5,C7,C8β and complement factor D） in the nerve regeneration conditioned fluid and each varied at different time points.These findings suggest that all these complement components have a functional role in nerve regeneration.
基金supported by the Zhejiang Provincial Traditional Chinese Medicine Science and Technology Project(Nos.2019ZB015 and 2019ZA014),China.
文摘Oral squamous cell carcinoma(OSCC)is a prevalent malignant tumor affecting the head and neck region(Leemans et al.,2018).It is often diagnosed at a later stage,leading to a poor prognosis(Muzaffar et al.,2021;Li et al.,2023).Despite advances in OSCC treatment,the overall 5-year survival rate of OSCC patients remains alarmingly low,falling below 50%(Jehn et al.,2019;Johnson et al.,2020).According to statistics,only 50%of patients with oral cancer can be treated with surgery.Once discovered,it is more frequently at an advanced stage.In addition,owing to the aggressively invasive and metastatic characteristics of OSCC,most patients die within one year of diagnosis.Hence,the pursuit of novel therapeutic drugs and treatments to improve the response of oral cancer to medication,along with a deeper understanding of their effects.
文摘Objective To evaluate the therapeutic efficacy of complex decongestive therapy in the treatment of elephantiasis of the lower extremities.Methods Seventeen patients with unilateral lower limb elephantiasis were included in the study(5 with primary lymphedema and 12 with secondary lymphedema).All patients were treated with one course(4 weeks)of complex decongestive therapy.Changes inextracellular fluid(ECF),BMI,circumferences,and skin properties including skin stiffness(SF),percent water content(PWC),and trans-epidermal water loss(TEWL)were measured before and after treatment.Results The“elephantiasis-like”appearance of the affected limb was greatly improved after treatment.The ECF,BMI,and circumferences were significantly decreased after treatment(P<0.001)with an average ECF of 2.97±1.82 L,BMI of 1.638±2.647 kg/m^2,and circumference of 6.58±2.79 cm.The values of PWC,TEWL,and SFwere 50.5%±10.6%,18.55±10.2 g/m^2 h,and 0.161±0.176 N,respectively,before treatment and 36.05%±7%,8.3±2.07 g/m^2h,and 0.086±0.038 N,respectively,after treatment,there by showing significant decreases(P<0.05).Conclusion Complex decongestive therapy is effective in the treatment of advanced stages of chronic lymphedema.
文摘Background: Dressing of split-thickness skin graft donor sites can be traumatic for the patient. The most advanced and expensive dressings have been compared to the most basic of dressings, with little or no consensus and an unpersuasive level of evidence. We aimed to determine the efficacy of the locally manufactured non-adherent, hydroconductive Drawtex? dressing and compare it to our current standard-of-care dressing, a thin transparent polyurethane film, in the healing of split-thickness donor sites. Methods: This prospective, within-patient controlled study included 27 adult participants, each with two split-thickness skin donor sites. The 54 donor site wounds were compared with regard to time to re-epithelialisation, perceived pain and healed wound quality. Results: By day 5, complete healing of donor site wounds, defined as >90% of epithelialized surface, was significantly higher in the hydroconductive dressing group compared to the polyurethane film group (22.2% and 3.7%, respectively;p < 0.0001). The hydroconductive dressing-treated donor site wounds were significantly less painful at 24-hours, 48-hours and 7-days post-operatively, and had fewer complications and superior wound healing quality. Conclusion: We have demonstrated that the relatively cheap and readily available dressing made locally in South Africa, Drawtex? is at least as safe, and potentially superior in wound healing, when compared to our current standard-of-care dressing.
基金supported by National Natural Science Foundation of China(Nos.82104445 and 82470182]Basic Scientific Research Funds of Department of Education of Zhejiang Province(No.KYZD2024013)+2 种基金The Startup Foundation of Zhejiang Provincial People’s Hospital(Nos.C-2023-QDJJ12 and C-2024-ZZJJ05)Science and Technology Plan Project of Traditional Chinese Medicine in Zhejiang Province(No.2025ZR007)The National Administration of Traditional Chinese Medicine(No.GZY-ZJ-KJ-24044).
文摘Myelosuppression is a common and severe side effect of cancer chemotherapy,with current treatments hindered by limitations such as depletion of hematopoietic reserves,poor patient compliance,delayed therapeutic onset,and high cost.To overcome these challenges,we developed Epimedium-derived nanovesicles(ENVs)from the traditional Chinese medicinal herb Epimedium,addressing the solubility and bioavailability issues associated with conventional extracts.ENVs encapsulate bioactive constituents,including icariin and hematopoiesis-promoting ceramides.In a cyclophosphamide(CTX)-induced myelosuppression mouse model,prophylactic and therapeutic oral administration of ENVs effectively alleviated hematopoietic suppression,significantly outperforming the Epimedium-based herbal extract“Joungal”(Shengbai Formula)despite equivalent icariin content.Notably,ENVs promoted hematopoietic stem cell(HSC)proliferation—an outcome rarely achieved with existing therapies.Mechanistically,ENVs modulated the gut microbiota,enriching lactobacillus species and enhancing lactate production.This microbiota-driven lactate signaling stimulated LepR+mesenchymal stem cells(MSCs)in the bone marrow niche to secrete stromal cellderived factor-1(SDF-1)and stem cell factor(SCF),thereby supporting HSC expansion and restoring hematopoietic function.In vivo safety evaluations confirmed the excellent biocompatibility of ENVs.Our findings uncover a gut-lactate-bone marrow axis through which ENVs enhance hematopoiesis and promote HSC regeneration.This work introduces a cost-effective,scalable,and orally administrable biomaterial platform with strong translational potential for the prevention and treatment of chemotherapy-induced myelosuppression.
基金supported by the Zhejiang Traditional Chinese Medicine Administration Program(No.2023ZL242)the Zhejiang Provincial Medical and Health Science and Technology Program(No.2023KY035),China.
文摘The pathological microenvironment of osteoporosis poses a substantial clinical challenge for bone defect regeneration.Through single-cell RNA-sequencing(scRNA-seq)analysis,we identified a reactive oxygen species(ROS)-overloading osteoblast subpopulation as a critical pathological feature of osteoporotic niches.Guided by scRNA-seq analysis,we engineered a microenvironment-adaptive hydrogel system through precise integration of antioxidant curcumin-encapsulated zeolitic imidazolate framework-8 nanoparticles(CCM@ZIF-8 NPs)within photo-crosslinkable alginate methacrylate(AlgMA)hydrogel(AlgMA/CCM@ZIF-8).This engineered design exhibited dual functions:effectively scavenging ROS in bone marrow-derived mesenchymal stem cells(BMSCs)while simultaneously suppressing osteoclast differentiation.The osteo-regenerative superiority of the AlgMA/CCM@ZIF-8 nanocomposite hydrogel was conclusively demonstrated in bone defect models of osteoporotic mice.This scRNA-seq-informed engineering strategy offers a promising approach for developing pathophysiology-adapted biomaterials to promote regenerative repair in osteoporotic bone defects.
基金supported by the Major and Key Cultivation Projects of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine(No.JYZP005)the Top Priority Research Center of Shanghai-Plastic Surgery Research Center,China(No.2023ZZ02023)+1 种基金the Fundamental Research Funds for the Central Universities of China(No.YG2023ZD13)the Treatment and Mechanism of PI3K/mTOR Dual-Target Inhibitor(WX390)on PIK3CA-Related Overgrowth Spectrum(PROS)(China)(No.JYHX2022004).
文摘Phosphatase and tensin homolog(PTEN)is a tumor sup-pressor gene located at 10q23.3 and serves as a crucial negative regulator of the PI3K-AKT signaling cascade by dephosphorylating phosphatidylinositol(3,4,5)-triphos-phate and inhibiting AKT activation.PTEN hamartoma tumor syndrome(PHTS)is an umbrella term employed to describe a spectrum of disorders caused by germline PTEN variants,including Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome.While distinct entitles included in PHTS have their unique diagnostic criteria,they also share common phenotypic features such as benign hamartomas of the three germ layers.
基金supported by the Major and Key Cultivation Projects of Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine (China) (No.JYZP005)the Treatment and Mechanism of PI3K/mTOR Dual-target Inhibitor (WX390)on PIK3CA-related Overgrowth Spectrum (PROS) (China) (No.JYWO22075)Fundamental Research Funds for the Central Universities (China) (No.YG2023ZD13).
文摘Facial infiltrating lipomatosis(FIL)is a congenital disorder caused by the hyperproliferation of adipose and skeletal tissue within the facial region.Infiltration of mature adipose tissue into adjacent structures is a hallmark pathologic finding.In addition to the aesthetic implications,patients may suffer from impaired facial function,including difficulty in swallowing and breathing,sleep disturbances,and visual field displacement.
文摘The complex lower extremity wound is frequently encountered by orthopedic and plastic surgeons.Innovations in wound care,soft tissue coverage and surgical fixation techniques allow for improved functional outcomes in this patient population with highly morbid injuries.In this review,the principles of reconstruction of complex lower extremity traumatic wounds are outlined.These principles include appropriate initial evaluation of the patient and mangled extremity,as well as appropriate patient selection for limb salvage.The authors emphasize proper planning for reconstruction,timing of reconstruction and the importance of an understanding of the most appropriate reconstructive option.The role of different reconstructive and wound care modalities is discussed,notably negative pressure wound therapy and dermal substitutes.The role of pedicled flaps and microvascular free-tissue transfer are discussed,as are innovations in understanding of perforator anatomy and perforator flap surgery that have broadened the reconstruction surgeon’s armamentarium.Finally,the importance of a multidisciplinary team is highlighted via the principle of the orthoplastic approach to management of complex lower extremity wounds.Upon completion of this review,the reader should have a thorough understanding of the principles of contemporary lower extremity reconstruction.
基金supported in part by research grants from the NIH K08 Career Development Award(RRR,NIH 5K08DE20140-5)the American Society of Plastic Surgeons/Plastic Surgery Foundation’s(PSF)Pilot Research Grant Program(RRR).EMF and JR were recipients of the Pritzker Research Fellowship funded through a NIH T-35 training grant(NIDDK).
文摘Fibroblast growth factors(FGF)and their receptors serve many functions in both the developing and adult organism.Humans contain 18 FGF ligands and four FGF receptors(FGFR).FGF ligands are polypeptide growth factors that regulate several developmental processes including cellular proliferation,differentiation,and migration,morphogenesis,and patterning.FGF-FGFR signaling is also critical to the developing axial and craniofacial skeleton.In particular,the signaling cascade has been implicated in intramembranous ossification of cranial bones as well as cranial suture homeostasis.In the adult,FGFs and FGFRs are crucial for tissue repair.FGF signaling generally follows one of three transduction pathways:RAS/MAP kinase,PI3/AKT,or PLCg.Each pathway likely regulates specific cellular behaviors.Inappropriate expression of FGF and improper activation of FGFRs are associated with various pathologic conditions,unregulated cell growth,and tumorigenesis.Additionally,aberrant signaling has been implicated in many skeletal abnormalities including achondroplasia and craniosynostosis.The biology and mechanisms of the FGF family have been the subject of significant research over the past 30 years.Recently,work has focused on the therapeutic targeting and potential of FGF ligands and their associated receptors.The majority of FGF-related therapy is aimed at age-related disorders.Increased understanding of FGF signaling and biology may reveal additional therapeutic roles,both in utero and postnatally.This review discusses the role of FGF signaling in general physiologic and pathologic embryogenesis and further explores it within the context of skeletal development.
文摘The author reviews his pioneering work in aesthetic restoration of the severely disfigured burn face first introduced in 1995 and refined over the past two decades. The reader will be exposed to the step by step approach to achieving cosmetic enhancement and functional rehabilitation of advanced facial burns. The"keystone"of the autogenous reconstruction is the pre-patterned, sculpted microvascular free flap designed to fit like the"piece of a puzzle"into the aesthetic units of the face to replace disfiguring burn scars. Aggressive intraoperative"sculpting"is employed both"in situ"at the donor site and during the flap transfer to simulate the normal facial contours and planes. Comparisons of the author's approach are made to the whole spectrum of reconstructive modalities ranging from conventional grafting to expanded pre-fabricated flaps and even to CTA face transplants;advantages/disadvantages of each are discussed. The pre-patterned, sculpted microvascular (MV) free flap offers the benefit of a single-stage transfer of composite skin/soft tissue hiding the seams at the junction of facial planes. When harvested from distant donor sites, the donor deformities can easily be concealed. The MV free tissue transfer offers the substrate that can be sculpted into nuanced facial components as well as the"palette"upon which the face can be painted with creative camouflage makeup. The soft contour and texture of the autogenous patterned transfers translates into a"natural"facial appearance while preserving fluid motions of facial expression.
基金supported by National Natural Science Foundation of China[grant numbers 51931001,51631009,51431002,51871004]NSFC/RGC Joint Research Scheme[grant number 51661165014]Shanghai"Rising Stars of Medical Talent"Youth Development Program(Youth Medical Talents-Specialist Program).
文摘Background:Zinc-based biomaterials,including biodegradable metal,nanoparticles,and coatings used in medical implants release zinc ions that may increase the whole-body and serum zinc concentrations.The impact of serum zinc concentrations on major health outcomes can provide insights for device design and clinical transformation of zinc-based biomaterials.Methods:This nationally representative cross-sectional study enrolled participants from the National Health and Nutrition Examination Survey(NHANES,2011-2014)including 3607 participants.Using unadjusted and multivariate-adjusted logistic regression analyses,two-piecewise linear regression model with a smoothing function and threshold level analysis,we evaluated the associations between elevated serum zinc levels and major health outcomes.Results:Elevated serum zinc levels were significantly associated with an increase in total spine and total femur bone mineral density(BMD).Every 10μg/dL increase was associated with a 1.12-fold increase in diabetes mellitus(DM)and 1.23-fold and 1.29-fold increase in cardiovascular diseases(CVD)and coronary heart disease(CHD),in participants with serum zinc levels≥100μg/dL.It had no significant linear or nonlinear associations with risk of fractures,congestive heart failure,heart attack,thyroid disease,arthritis,osteoarthritis,rheumatoid arthritis,dyslipidemia and cancer.Conclusion:Serum zinc levels are significantly associated with increased BMD in the total spine and total femur,and risk of DM,and CVD/CHD among participants with serum zinc levels≥100μg/dL.
基金supported in part by research grants from the National Institutes of Health(AT004418,AR50142,and AR054381 to TCH,RCH and HHL)the National Natural Science Foundation(Grant#81202119 to XC)+1 种基金the Chicago Biomedical Consortium Catalyst Award(RRR and TCH)supported in part by The University of Chicago Core Facility Subsidy grant from the National Center for Advancing Translational Sciences(NCATS)of the National Institutes of Health through Grant Number UL1 TR000430.
文摘Sustained,high level transgene expression in mammalian cells is desired in many cases for studying gene functions.Traditionally,stable transgene expression has been accomplished by using retroviral or lentiviral vectors.However,such viral vector-mediated transgene expression is often at low levels and can be reduced over time due to low copy numbers and/or chromatin remodeling repression.The piggyBac transposon has emerged as a promising nonviral vector system for efficient gene transfer into mammalian cells.Despite its inherent advantages over lentiviral and retroviral systems,piggyBac system has not been widely used,at least in part due to their limited manipulation flexibilities.Here,we seek to optimize piggyBac-mediated transgene expression and generate a more efficient,user-friendly piggyBac system.By engineering a panel of versatile piggyBac vectors and constructing recombinant adenoviruses expressing piggyBac transposase(PBase),we demonstrate that adenovirusmediated PBase expression significantly enhances the integration efficiency and expression level of transgenes in mesenchymal stem cells and osteosarcoma cells,compared to that obtained from co-transfection of the CMV-PBase plasmid.We further determine the drug selection timeline to achieve optimal stable transgene expression.Moreover,we demonstrate that the transgene copy number of piggyBac-mediated integration is approximately 10 times higher than that mediated by retroviral vectors.Using the engineered tandem expression vector,we show that three transgenes can be simultaneously expressed in a single vector with high efficiency.Thus,these results strongly suggest that the optimized piggyBac system is a valuable tool for making stable cell lines with sustained,high transgene expression.
文摘Objective:As the population ages,facial plastic providers must remain aware of the treatments to prevent and reverse the external signs of aging.In the mandibular region,skin laxity and soft tissue sagging in the jawline may lead to jowling and chin ptosis along with reduced chin projection.While surgical procedures,including chin implantation,may be performed,nonsurgical procedures are becoming increasingly popular due to their temporary,noninvasive,yet effective methods.This review covers the use of hyaluronic acid,calcium hydroxylapatite,poly-L-lactic acid,and polymethyl methacrylate in the jawline.Methods:PubMed was searched for data on the mechanism of action,pertinent anatomy,indications,contraindications,technique,and evidence supporting the safety and efficacy of the fillers.Results:There are a wide variety of fillers available for use in the lower face with unique characteristics and application methods.While the advantages of injectable fillers include relatively affordable cost,minimal patient discomfort,and limited recovery times,taking measures to prevent short-and long-term complications is necessary for optimal results.Conclusions:Understanding the benefits and limitations of injectable fillers in the jawline can help providers appropriately counsel and treat patients.
基金The authors thank Justine C.Lee,MD,PhD of UCLA for providing the artwork for the figures.The reported work was supported in part by research grants from The American Society of Plastic Surgeons/Plastic Surgery Foundation’s(PSF)Pilot Research Grant Program,and the American Society of Craniofacial Surgeons/Komedyplast Foundation Award.MB and EMF were recipients of the Pritzker Research Fellowship funded through a NIH T-35 training grant(NIDDK).MB was a recipient of the Alpha Omega Alpha Carolyn L.Kuckein Research Fellowship.RRR was a recipient of the Clinical Investigator Award/Mentored Research Award DE020140-01(NIDCR)from the National Institutes of Health.
文摘The normal growth and development of the skull is a tightly regulated process that occurs along the osteogenic interfaces of the cranial sutures.Here,the borders of the calvarial bones and neighboring tissues above and below,function as a complex.Through coordinated remodeling efforts of bone deposition and resorption,the cranial sutures maintain a state of patency from infancy through early adulthood as the skull continues to grow and accommodate the developing brain’s demands for expansion.However,when this delicate balance is disturbed,a number of pathologic conditions ensue;and if left uncorrected,may result in visual and neurocognitive impairments.A prime example includes craniosynostosis,or premature fusion of one or more cranial and/or facial suture(s).At the present time,the only therapeutic measure for craniosynostosis is surgical correction by cranial vault reconstruction.However,elegant studies performed over the past decade have identified several genes critical for the maintenance of suture patency and induction of suture fusion.Such deeper understandings of the pathogenesis and molecular mechanisms that regulate suture biology may provide necessary insights toward the development of non-surgical therapeutic alternatives for patients with cranial suture defects.In this review,we discuss the intricate cellular and molecular interplay that exists within the suture among its three major components:dura mater,osteoblastic related molecular pathways and osteoclastic related molecular pathways.
文摘Purpose:Defects aro und the distal one third of the leg and ankle are difficult to man age by con servative measures or simple split thickness skin graft.Distally based peroneus brevis muscle flap is a well described flap for such defects.Methods:This is a retrospective analysis conducted on 25 patients with soft tissue and bony defects of distal third of lower leg and an kle,which were treated using distally based per on eus brevis muscle flap from January 2013 to January 2018.Information regarding patient demographics,etiology,size and location of defects and complications were collected.All patients were followed up for at least 3 months after surgery.Results:There were 21 males and 4 females with the mean age of 39(5-76)years.The most comm on cause of injuries was road traffic accident,followed by complicated open injury.The average size of defects was 20(4—50)cm^2.The mean operating time was 75(60-90)min for flap harvest and inset.We had no patient with complete loss of the flap.Five patients(20%)had marginal necrosis of the flap and two patie nts have graft loss due to un derlyi ng hematoma and required sec on dary split thickness skin grafting.Conclusion:The distally based peroneus brevis muscle flap is a safe optio n w让h reliable an atomy for small to moderate sized defects following low velocity injury around the ankle.The commonest complication encountered is skin graft loss which can be reduced by primary delayed grafting.
基金funded by the National 13th Five-Year Plan for Major New Drug Development of China(No.2017ZX09302010)
文摘Background:Atopic dermatitis(AD)affects approximately 10%of adults worldwide.CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling.This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods:This multicenter,randomized,double-blind,placebo-controlled,phase 2b trial was conducted in 21 medical institutions in China from February to November 2021.Totally 120 eligible patients were enrolled and randomized(1:1:1)to receive subcutaneous injections of 300 mg CM310,150 mg CM310,or placebo every 2 weeks for 16 weeks,followed by an 8-week follow-up period.The primary endpoint was the proportion of patients achieving≥75%improvement in the Eczema Area and Severity Index(EASI-75)score from baseline at week 16.Safety and pharmacodynamics were also studied.Results:At week 16,the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups(70%[28/40]for high-dose and 65%[26/40]for low-dose)than that in the placebo group(20%[8/40]).The differences in EASI-75 response rate were 50%(high vs.placebo,95%CI 31%-69%)and 45%(low vs.placebo,95%CI 26%-64%),with both P values<0.0001.CM310 at both doses also significantly improved the EASI score,Investigator’s Global Assessment score,daily peak pruritus Numerical Rating Scale,AD-affected body surface area,and Dermatology Life Quality Index compared with placebo.CM310 treatment reduced levels of thymus and activation-regulated chemokine,total immunoglobulin E,lactate dehydrogenase,and blood eosinophils.The incidence of treatment-emergent adverse events(TEAEs)was similar among all three groups,with the most common TEAEs reported being upper respiratory tract infection,atopic dermatitis,hyperlipidemia,and hyperuricemia.No severe adverse events were deemed to be attributed to CM310.Conclusion:CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration:ClinicalTrials.gov,NCT04805411.
