Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain ...Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.展开更多
Few studies have investigated alterations in the immune cell microenvironment of the dorsal root ganglia following spinal cord injury and whether these modifications facilitate axonal regeneration.In this study,we use...Few studies have investigated alterations in the immune cell microenvironment of the dorsal root ganglia following spinal cord injury and whether these modifications facilitate axonal regeneration.In this study,we used a single-cell RNA sequencing dataset to create a comprehensive profile of the diverse cell types in the dorsal root ganglia and spinal cord of a mid-thoracic contusion injury model in cynomolgus monkeys.Cell communication analysis indicated that specific signaling events among various dorsal root ganglia cell types occur in response to spinal cord injury.Single-cell analysis using dimensionality reduction clustering identified distinct molecular signatures for nine cell types,including macrophage subpopulations,and differential gene expression profiles between dorsal root ganglia cells and spinal cord cells following spinal cord injury.The macrophage subpopulations were categorized into 11 clusters(MC0-MC10)based on differentially expressed genes,with the top 10 genes being ABCA6,RBMS3,EBF1,LAMA4,ANTXR2,LAMA2,SOX5,FOXP2,GHR,and APOD.MC0,MC1,and MC2 constituted the predominant macrophage populations.MC4,MC6,and MC9 were nearly absent in the spinal cord,but exhibited significant increases in the dorsal root ganglia post-spinal cord injury.Notably,these subpopulations possess a strong capacity for regulating axonal regeneration.The developmental progression of dorsal root ganglia macrophages after spinal cord injury was elucidated using cell trajectory and pseudo-time analyses.Genes such as EBF1(MC6 and MC9 marker),RBMS3(MC6 and MC9 marker),and ABCA6(MC6 marker)showed high expression levels in the critical pathways of macrophage function.Through ligand-receptor pair analysis,we determined that the effects of macrophages on microglia are predominantly mediated through interaction pairs(e.g.,SPP1-CD44,LAMC1-CD44,and FN1-CD44),potentially facilitating specific cellular communications within the immune microenvironment.The single-cell RNA sequencing dataset used in this study represents the first comprehensive transcriptional analysis of the dorsal root ganglia after spinal cord injury in cynomolgus monkeys,encompassing nearly all cell types within the dorsal root ganglia region.Using this dataset,we evaluated diverse subtypes of macrophages in the post-spinal cord injury dorsal root ganglia area and examined the signaling pathways that facilitate interactions among immune response-related macrophages in the dorsal root ganglia.Findings from this study provide a theoretical basis for understanding how the immune microenvironment influences the regenerative capacity of dorsal root ganglia neurons after spinal cord injury and offer novel insights into the complex processes underlying the pathobiology of spinal cord injury.展开更多
Cases of widespread bone hydatid infection are relatively rare in clinical practice.In this study,we reported for the first time a validated integrated repair therapy for multiple bone tissues,including the hip,femur,...Cases of widespread bone hydatid infection are relatively rare in clinical practice.In this study,we reported for the first time a validated integrated repair therapy for multiple bone tissues,including the hip,femur,and knee,caused by echinococ cosis.Artificial intelligence(AI)was used to develop a targeted surgical plan and to design a personalized prosthesis.Finite element analysis(FEA)was used to optimize the mechanical effectiveness of a customized integrated replacement prosthesis and to model stress distribution in the surrounding bone.Three-dimensional(3 D)printing was used to fabricate a customized prosthesis.With the assistance of AI,FEA,and 3 D printing technology,a personalized surgical plan and customized prosthesis were successfully constructed based on the patient’s disease.This approach achieved a successful therapeutic effect,demonstrating that AI-assisted personalized medicine holds great promise for the future.展开更多
Background:Despite the promise shown by large language models(LLMs)for standardized tasks,their multidimensional performance in real-world oncology decision-making remains unevaluated.This study aims to introduce a fr...Background:Despite the promise shown by large language models(LLMs)for standardized tasks,their multidimensional performance in real-world oncology decision-making remains unevaluated.This study aims to introduce a framework for evaluating LLMs and physician decisions in challenging lung cancer cases.Methods:We curated 50 challenging lung cancer cases(25 local and 25 published)classified as complex,rare,or refractory.Blinded three-dimensional,five-point Likert evaluations(1–5 for comprehensiveness,specificity,and readability)compared standalone LLMs(DeepSeek R1,Claude 3.5,Gemini 1.5,and GPT-4o),physicians by experience level(junior,intermediate,and senior),and AI-assisted juniors;intergroup differences and augmentation effects were analyzed statistically.Results:Of 50 challenging cases(18 complex,17 rare,and 15 refractory)rated by three experts,DeepSeek R1 achieved scores of 3.95±0.33,3.71±0.53,and 4.26±0.18 for comprehensiveness,specificity,and readability,respectively,positioning it between intermediate(3.68,3.68,3.75)and senior(4.50,4.64,4.53)physicians.GPT-4o and Claude 3.5 reached intermediate physician–level comprehensiveness(3.76±0.39,3.60±0.39)but junior-to-intermediate physician–level specificity(3.39±0.39,3.39±0.49).All LLMs scored higher on rare cases than intermediate physicians but fell below junior physicians in refractory-case specificity.AIassisted junior physicians showed marked gains in rare cases,with comprehensiveness rising from 2.32 to 4.29(84.8%),specificity from 2.24 to 4.26(90.8%),and readability from 2.76 to 4.59(66.0%),while specificity declined by 3.2%(3.17 to 3.07)in refractory cases.Error analysis showed complementary strengths,with physicians demonstrating reasoning stability and LLMs excelling in knowledge updating and risk management.Conclusions:LLMs performed variably in clinical decision-making tasks depending on case type,performing better in rare cases and worse in refractory cases requiring longitudinal reasoning.Complementary strengths between LLMs and physicians support case-and task-tailored human–AI collaboration.展开更多
BACKGROUND Periprosthetic joint infection(PJI)is a catastrophic complication that can occur following total knee arthroplasty(TKA).Currently,the treatment for PJI mainly includes the use of antibiotics alone,prostheti...BACKGROUND Periprosthetic joint infection(PJI)is a catastrophic complication that can occur following total knee arthroplasty(TKA).Currently,the treatment for PJI mainly includes the use of antibiotics alone,prosthetic debridement lavage,primary revision,secondary revision,joint fusion,amputation,etc.AIM To explore the clinical effect of two-stage revision surgery for the treatment of PJI after TKA.METHODS The clinical data of 27 patients(3 males and 24 females;age range,47–80 years;mean age,66.7±8.0 years;27 knees)with PJI treated with two-stage revision surgery in our hospital between January 1,2010 and December 31,2020 were analyzed retrospectively.The following outcomes were compared for changes between preoperative and last follow-up results:Erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),visual analogue scale(VAS)scores,Hospital for Special Surgery(HSS)scores,knee range of motion(ROM),and infection cure rates.RESULTS All 27 patients were followed up(range,13–112 mo).The ESR(14.5±6.3 mm/h)and CRP(0.6±0.4 mg/dL)of the patients at the last follow-up were significantly lower than those at admission;the difference was statistically significant(P<0.001).The postoperative VAS score(1.1±0.7),HSS score(82.3±7.1),and knee ROM(108.0°±19.7°)were significantly improved compared with those before the surgery;the difference was statistically significant(P<0.001).Of the 27 patients,26 were cured of the infection,whereas 1 case had an infection recurrence;the infection control rate was 96.3%.CONCLUSION Two-stage revision surgery can effectively relieve pain,control infection,and retain good joint function in the treatment of PJI after TKA.展开更多
Multicomponent core-shell microspheres have garnered significant attention as microwave absorption(MA)materials,owing to their distinctive synergistic effects arising from interfacial polarization and magnetic/dielect...Multicomponent core-shell microspheres have garnered significant attention as microwave absorption(MA)materials,owing to their distinctive synergistic effects arising from interfacial polarization and magnetic/dielectric loss.An effective method for optimizing the MA properties of materials is to construct heterogeneous interfacial engineering through component tuning and structural design.Here,a hollow flower-like CoNi@NC@SnS_(2) composite was successfully synthesized through high-temperature pyrolysis and vertical growth of SnS_(2).The surface of the CoNi@NC microsphere was uniformly coated with SnS_(2) nanosheets,resulting in the formation of a core-shell structure.The construction of Schottky barriers through the contact between semiconductors and conductors optimizes polarization relaxation processes and enhances impedance-matching properties.The Schottky interfaces generate a built-in electric field(BIEF)that enhances charge separation and inversion of charge distribution,thereby improving interfacial polarization.Additionally,the Schottky heterogeneous interfaces of composites can be activated through the controllable introduction of defects,resulting in a more robust interfacial polarization.Consequently,the core-shell CoNi@NC@SnS_(2) composite demonstrates outstanding MA performance,achieving a minimum reflection loss(RLmin)of−72.6 dB at 1.9 mm and an effective absorption bandwidth(EAB)of 13.2 GHz(ranging from 4.8 to 18.0 GHz)across a thickness range of 1.5–4.0 mm.This research offers novel insights into the mechanisms that underlie polarization loss and facilitates the development of high-performance MA materials.展开更多
Objective:Total knee arthroplasty(TKA)has become an effective treatment modality for end-stage osteoarthritis and rheumatoid arthritis.Postoperative problems such as anterior knee pain affect postoperative patient sat...Objective:Total knee arthroplasty(TKA)has become an effective treatment modality for end-stage osteoarthritis and rheumatoid arthritis.Postoperative problems such as anterior knee pain affect postoperative patient satisfaction.Patellar denervation has been proposed as a technique to relieve pain,but its efficacy remains controversial.This study evaluated the mid-and long-term effects of patellar denervation on postoperative knee joint functions,hoping to provide better guidance for clinical practice.Methods:This study is a prospective randomized controlled double-blind study.58 patients undergoing bilateral non-resurfaced total knee arthroplasty were included and randomized into two groups.Both groups underwent total knee arthroplasty while patellar denervation was performed only on the experimental group.Information regarding whether if patellar denervation was performed were withheld from all patients and outcome assessors.All surgeries were performed by the same high-level professional physician,and the post-stable knee prosthesis system(PS Scorpio NRG PS,Stryker)was used during the surgeries.The knee joint functions were evaluated by professional assessors before and after surgery.The evaluation indicators mainly include KSS scoring,Western Ontario and McMaster Universities(WOMAC)scoring and Visual Analogue Scale(VAS),FJS scoring,etc.The follow-up period was 3 years and 5 years after surgery.Results:The experimental group had better KSS and FJS scores than the control group,the difference was statistically significant.There was no significant inter-group difference in WOMAC and VAS scores.Conclusion:The patellar denervation in TKA patients has positive effects on the mid-and long-term recovery of knee joint functions,and the postoperative satisfaction is better.展开更多
Frozen shoulder(FS),also known as adhesive capsulitis,is a condition that causes contraction and stiffness of the shoulder joint capsule.The main symptoms are per-sistent shoulder pain and a limited range of motion in...Frozen shoulder(FS),also known as adhesive capsulitis,is a condition that causes contraction and stiffness of the shoulder joint capsule.The main symptoms are per-sistent shoulder pain and a limited range of motion in all directions.These symp-toms and poor prognosis affect people's physical health and quality of life.Currently,the specific mechanisms of FS remain unclear,and there is variability in treatment methods and their efficacy.Additionally,the early symptoms of FS are difficult to distinguish from those of other shoulder diseases,complicating early diagnosis and treatment.Therefore,it is necessary to develop and utilize animal models to under-stand the pathogenesis of FS and to explore treatment strategies,providing insights into the prevention and treatment of human FS.This paper reviews the rat models available for FS research,including external immobilization models,surgical internal immobilization models,injection modeling models,and endocrine modeling models.It introduces the basic procedures for these models and compares and analyzes the advantages,disadvantages,and applicability of each modeling method.Finally,our paper summarizes the common methods for evaluating FS rat models.展开更多
BACKGROUND Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spi...BACKGROUND Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spinal cord damage which in turn cause complications such as paraplegia and quadriplegia.In this study,we established a model using three concentrations of bacteria and carried out a comprehensive evaluation of the model by imaging,general observations,and histopathological and bacteriological studies.AIM To establish a rabbit model of spinal tuberculosis and examine the effect on the model’s efficacy using different concentrations of Mycobacterium tuberculosis(M.tuberculosis)inoculum.METHODS New Zealand rabbits were randomly divided into experimental,control and blank groups.The experimental and control animals were sensitized with complete Freund′s adjuvant,a hole was drilled beneath the upper endplate of the L6 vertebral body and filled with gelfoam sponge.The experimental group was divided into three subgroups(experimental 1,experimental 2,experimental 3)and infused with M.tuberculosis suspension at various concentrations.The control group was inoculated with saline and the blank group received no treatment.The 12-week post-operative survival rates were 100%,80%and 30%in the experimental groups inoculated with concentrations of 106,107 and 108 CFU/mL bacteria,respectively.RESULTS The survival rate of the control and blank groups was 100%.Vertebral body destruction at 8 weeks in the three experimental groups as determined by X-ray analysis was 33.3%,62.5%and 66.7%,and by computed tomography(CT)and 3-dimensional CT 44.4%,75%and 100%,respectively.At 12 weeks,the figures were 44.4%,75%and 100%by X-ray analysis and 44.4%,100%and 100%by CT and 3-dimensional CT,respectively.All surviving rabbits of the experimental groups had vertebral destruction.The positive bacterial culture rates were 22.2%,75%and 66.7%,respectively,in the experimental groups.After being sensitized with complete Freund's adjuvant,large differences were observed in the extent of spinal tuberculosis after inoculation of the rabbits with different concentrations of H37RV standard M.tuberculosis.CONCLUSION The experimental 1 had a low success rate at establishing an infection.The experimental 3 resulted in high mortality and complication rates.The experimental 2 was optimum for establishing a spinal tuberculosis model based on the high level of symptoms observed and the low rabbit mortality.展开更多
Neutrophil extracellular traps(NETs)have been the subject of research in the field of innate immunity since they were first described two decades ago.NETs are fibrous network structures released by neutrophils under s...Neutrophil extracellular traps(NETs)have been the subject of research in the field of innate immunity since they were first described two decades ago.NETs are fibrous network structures released by neutrophils under specific stimuli,including DNA,histones,and a variety of granular proteins.NETs have been widely studied in the fields of infectious and immune diseases,and new break-throughs have been made in the understanding of disease pathogenesis and treatment.In recent years,studies have found that NETs play an important role in the occurrence and development of osteoarticular diseases.This article reviews the progress in the research of NETs in common osteoarticular diseases such as rheumatoid arthritis,ankylosing spondylitis,gouty arthritis,osteonecrosis of the femoral head,osteoarthritis,and joint fibrosis,including the formation mecha-nism of NETs and its role in inflammation,joint destruction,pain and other pa-thological processes.The problems existing in current research are discussed,along with future research directions,to provide a reference for the in-depth study of osteoarticular diseases and the development of new treatment strategies.展开更多
BACKGROUND Intraosseous lipoma of bone is one of the rarest benign bone tumors,which often involves the metaphysis of long tubular bones,especially the femur,tibia,fibula,and calcaneus.Bone lipoma can be characterized...BACKGROUND Intraosseous lipoma of bone is one of the rarest benign bone tumors,which often involves the metaphysis of long tubular bones,especially the femur,tibia,fibula,and calcaneus.Bone lipoma can be characterized by chronic dull pain but can also be asymptomatic most of the time.As a result,it is less likely to attract people’s attention and is occasionally diagnosed through imaging examination during routine physical health check-up.CASE SUMMARY We describe a clinical case of intraosseous lipoma in a 21-year-old patient with chronic pain in the left lower limb for four years without any significant physical findings apart from the minimal swelling and local tenderness over the median ankle.Computerized tomography suggested the possibility of a lipoma on the left distal tibia,but the pathological examination could make a definite diagnosis.The intraosseous lipoma of the left distal tibia was treated by surgical curettage,bone graft,and internal fixation with steel plate,since the conservative treatment is often ineffective.Postoperatively,the patient made an uneventful recovery and was able to do daily activities without any restrictions.In addition,local recur-rence of the intraosseous lipoma was not reported in subsequent reexamination.CONCLUSION Bone lipoma is very rare and often exhibits no characteristic clinical manifestation.The confirmative diagnosis of lipoma largely relies on a combination of imageo-logy and biopsy.Surgical intervention is often recommended as a conventional therapy for bone lipoma.Postoperatively,the patient makes an uneventful reco-very with a good prognosis,and the local recurrence of the tumor is also a low probability event.展开更多
Osteoarthritis(OA) and intervertebral disc degeneration(IVDD) are degenerative musculoskeletal disorders characterized by degeneration of cartilaginous tissues and inflammation. While inflammation is implicated in the...Osteoarthritis(OA) and intervertebral disc degeneration(IVDD) are degenerative musculoskeletal disorders characterized by degeneration of cartilaginous tissues and inflammation. While inflammation is implicated in the pathogenesis of OA and IVDD, and cytosolic phospholipase A2(cPLA2) is a key mediator of inflammation, direct evidence linking cPLA2 to chondrocyte homeostasis and cartilage degeneration is lacking. This study aims to investigate the role of cPLA2 in chondrocytes and its contribution to the development of cartilage degenerative conditions such as OA and IVDD. Here, single-cell RNA sequencing was used to examine cPLA2 expression in chondrocytes. To explore its importance in chondrocytes and OA/IVDD, various cell-based assays and genetically modified mouse models with age-related and surgically induced OA/IVDD were employed. Furthermore, the therapeutic potential of fexofenadine, an over-the-counter drug recently identified as a cPLA2 inhibitor, was explored in these models. cPLA2 is predominantly expressed in prehypertrophic chondrocytes, characterized by elevated levels of cartilage degeneration markers and senescence-related genes. Genetic deletion and pharmacological inhibition of cPLA2 reduced inflammation induced catabolic activity and senescence in chondrocytes, as well as cartilage degeneration in various OA and IVDD models. This study identifies cPLA2 as a pivotal driver of cartilage degeneration and senescence in OA and IVDD, highlighting its potential as a dual-action therapeutic target that suppresses both inflammation and senescence to preserve cartilage integrity. These findings position cPLA2as a promising candidate for developing disease-modifying therapies for cartilage degenerative conditions such as OA and IVDD.展开更多
Hypochlorous acid(HClO)is a critical biomolecule in living organisms,playing an essential role in numerous physiological or pathological processes.Abnormal levels of HClO in the body may lead to a series of diseases,f...Hypochlorous acid(HClO)is a critical biomolecule in living organisms,playing an essential role in numerous physiological or pathological processes.Abnormal levels of HClO in the body may lead to a series of diseases,for instance,inflammation and cancer.Thus,accurate measurement of HClO levels should be more beneficial for understanding its role in diseases and gaining a deeper insight into the pathogenesis of diseases.In this work,we designed a near-infrared two-photon fluorescent probe(HDM-Cl-HClO)for detecting fluctuations in HClO levels in inflammatory and tumor-bearing mice.Notably,the probe can respond to HClO within 5 s and trigger a brilliant red fluorescence at 660 nm.It exhibits high specificity and sensitivity for HClO.The superior spectral capability of the probe has enabled the detection of HClO levels in cells and zebrafish,as well as achieved the detection of HClO in inflammatory and tumor mice.This work not only provides a novel strategy and tool for HClO imaging in living systems,but also holds great potential for the diagnosis of inflammation and cancer.展开更多
Fibroblast growth factor(FGF)signaling encompasses a multitude of functions,including regulation of cell proliferation,differentiation,morphogenesis,and patterning.FGFs and their receptors(FGFR)are crucial for adult t...Fibroblast growth factor(FGF)signaling encompasses a multitude of functions,including regulation of cell proliferation,differentiation,morphogenesis,and patterning.FGFs and their receptors(FGFR)are crucial for adult tissue repair processes.Aberrant FGF signal transduction is associated with various pathological conditions such as cartilage damage,bone loss,muscle reduction,and other core pathological changes observed in orthopedic degenerative diseases like osteoarthritis(OA),intervertebral disc degeneration(IVDD),osteoporosis(OP),and sarcopenia.In OA and IVDD pathologies specifically,FGF1,FGF2,FGF8,FGF9,FGF18,FGF21,and FGF23 regulate the synthesis,catabolism,and ossification of cartilage tissue.Additionally,the dysregulation of FGFR expression(FGFR1 and FGFR3)promotes the pathological process of cartilage degradation.In OP and sarcopenia,endocrine-derived FGFs(FGF19,FGF21,and FGF23)modulate bone mineral synthesis and decomposition as well as muscle tissues.FGF2 and other FGFs also exert regulatory roles.A growing body of research has focused on understanding the implications of FGF signaling in orthopedic degeneration.Moreover,an increasing number of potential targets within the FGF signaling have been identified,such as FGF9,FGF18,and FGF23.However,it should be noted that most of these discoveries are still in the experimental stage,and further studies are needed before clinical application can be considered.Presently,this review aims to document the association between the FGF signaling pathway and the development and progression of orthopedic diseases.Besides,current therapeutic strategies targeting the FGF signaling pathway to prevent and treat orthopedic degeneration will be evaluated.展开更多
Objective:To observe the effect of recombinant human bone morphogenetic protein 2/polylactide-co-glycolic acid(rhBMP-2/PLGA) with core decompression on repair of rabbit femoral head necrosis.Methods:Bilateral femoral ...Objective:To observe the effect of recombinant human bone morphogenetic protein 2/polylactide-co-glycolic acid(rhBMP-2/PLGA) with core decompression on repair of rabbit femoral head necrosis.Methods:Bilateral femoral head necrosis models of rabbit were established by steroid injection.A total of 48 rabbits(96 femoral head necrosis) were randomly divided into 4groups:Group A,control group with12 rabbits,24 femoral head necrosis;Group B,treated with rhBMP-2/PLCA implantation after core depression,with 12 rabbits,24 femoral head necrosis;Group C,treated with rhBMP-2 implantation after core depression,with 12 rabbits,24 femoral head necrosis;Croup D treated with core depression group without implantation,with 12 rabbits,24 femoral head necrosis.All animals were sacrificed after 12 weeks.The ability of repairing bone defect was evaluated by X-ray radiograph.Bone mineral density analysis of the defect regions were used to evaluate the level of ossification.The morphologic change and bone formation was assessed by HE staining.The angiogenesis was evaluated by VEGF immunohistochemistry.Results:The osteogenetic ability and quality of femoral head necrosis in group B were better than those of other groups after 12 weeks by X-ray radiograph and morphologic investigation.And the angiogenesis in group B was better than other groups.Group C had similar osteogenetic quality of femoral head necrosis and angiogenesis with group D.Conclusions:The treatment of rhBMP-2/PLCA implantation after core depression can promote the repair of rabbit femoral head necrosis.It is a promising and efficient synthetic bone material to treat the femoral head necrosis.展开更多
OBJECTIVE:To evaluate the clinical efficacy and safety of external application of Traditional Chinese Medicine (EATCM) on acute gouty arthritis (AGA).METHODS:Six electronic data bases were retrieved from their incepti...OBJECTIVE:To evaluate the clinical efficacy and safety of external application of Traditional Chinese Medicine (EATCM) on acute gouty arthritis (AGA).METHODS:Six electronic data bases were retrieved from their inception to march 2017.15 randomized controlled clinical trials (RCTs) were included.The quality of the literatures was assessed according to Cochrane review criteria by using RevMan5.3 software;and related data was counted using Stata14.0 software.RESULTS:There was no significant difference in C-reactiveprotein (CRP) between experimental intervention group and control group [(WMD =1.093,95% C/(-2.514,4.701);P =0.553)].In terms of overall efficacy,the EATCM's treatment group was significantly superior to control group [(OR =3.692;95% CI (2.408,5.661);P <0.001)].The EATCM was better than western medicine treatments or other interventions in reducing the adverse reactions [(OR =0.135;95% CI (0.067,0.274);P < 0.001)].All these funnel plots showed unlikelihood of publishing bias.But due to excessive heterogeneity,the statistical results of serum uric acid and visual analogue scale and CRP between the two groups became uncertain.CONCLUSION:The results indicate that EATCM may have greater overall efficacy with fewer adverse drug reactions,although the evidence is weak owing to the low methodological quality and the small number of the included trials.展开更多
After spinal cord injury,the number of glial cells and motor neurons expressing bone morphogenetic protein 7（BMP7）increases,indicating that upregulation of BMP7 can promote nerve repair.We,therefore,tested whether d...After spinal cord injury,the number of glial cells and motor neurons expressing bone morphogenetic protein 7（BMP7）increases,indicating that upregulation of BMP7 can promote nerve repair.We,therefore,tested whether direct injection of BMP7 into acutely injured ratalalo createrywith 50 ng BMP7（BMP7 group）or physiological saline（control group）for 7 consecutive days.Electrophysiological examination showed that the amplitude of N1 in motor evoked potentials（MEP）decreased after spinal cord injury.At 8 weeks post-operation,the amplitude of N1 in the BMP7 group was remarkably higher than that at 1 week post-operation and was higher than that of the control group.Basso,Beattie,Bresnahan scale（BBB）scores,hematoxylin-eosin staining,and western blot assay showed that at 1,2,4 and 8 weeks post-operation,BBB scores were increased;Nissl body staining was stronger;the number of Nissl-stained bodies was increased;the number of vacuoles gradually decreased;the number of synapses was increased;and the expression of neuronal marker,neurofilament protein 200,was increased in the hind limbs of the BMP7 group compared with the control group.Western blot assay showed that the expression of GFAP protein in BMP7 group and control group did not change significantly and there was no significant difference between the BMP7 and control groups.These data confirmed that local injection of BMP7 can promote neuronal regeneration after spinal cord injury and promote recovery of motor function in rats.展开更多
We hypothesized that RNA interference to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells before transplantation might further improve neurological function in rats with spinal cord trans...We hypothesized that RNA interference to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells before transplantation might further improve neurological function in rats with spinal cord transection injury. After 2 weeks, the number of neurons and BrdU-positive cells in the Nogo-66 receptor gene silencing group was higher than in the bone marrow mesenchymal stem cell group, and significantly greater compared with the model group. After 4 weeks, behavioral performance was signiifcantly enhanced in the model group. Af-ter 8 weeks, the number of horseradish peroxidase-labeled nerve ifbers was higher in the Nogo-66 receptor gene silencing group than in the bone marrow mesenchymal stem cell group, and signiifcantly higher than in the model group. The newly formed nerve ifbers and myelinated ner ve ifbers were detectable in the central transverse plane section in the bone marrow mesenchymal stem cell group and in the Nogo-66 receptor gene silencing group.展开更多
With advances in the fields of regenerative medicine,cell-free therapy has received increased attention.Exosomes have a variety of endogenous properties that provide stability for molecular transport across biological...With advances in the fields of regenerative medicine,cell-free therapy has received increased attention.Exosomes have a variety of endogenous properties that provide stability for molecular transport across biological barriers to cells,as a form of cell-to-cell communication that regulates function and phenotype.In addition,exosomes are an important component of paracrine signaling in stemcell-based therapy and can be used as a stand-alone therapy or as a drug delivery system.The remarkable potential of exosomes has paved the pathway for cell-free treatment in bone regeneration.Exosomes are enriched in distinct noncoding RNAs(ncRNAs),including microRNAs,long ncRNAs and circular RNAs.Different ncRNAs have multiple functions.Altered expression of ncRNA in exosomes is associated with the regenerative potential and development of various diseases,such as femoral head osteonecrosis,myocardial infarction,and cancer.Although there is increasing evidence that exosome-derived ncRNAs(exoncRNAs)have the potential for bone regeneration,the detailed mechanisms are not fully understood.Here,we review the biogenesis of exo-ncRNA and the effects of ncRNAs on angiogenesis and osteoblast-and osteoclast-related pathways in different diseases.However,there are still many unsolved problems and challenges in the clinical application of ncRNA;for instance,production,storage,targeted delivery and therapeutic potency assessment.Advancements in exo-ncRNA methods and design will promote the development of therapeutics,revolutionizing the present landscape.展开更多
The three-dimensional（3D） visualization of the functional bundles in the peripheral nerve provides direct and detailed intraneural spatial information. It is useful for selecting suitable surgical methods to repair ...The three-dimensional（3D） visualization of the functional bundles in the peripheral nerve provides direct and detailed intraneural spatial information. It is useful for selecting suitable surgical methods to repair nerve defects and in optimizing the construction of tissue-engineered nerve grafts. However, there remain major technical hurdles in obtaining, registering and interpreting 2D images, as well as in establishing 3D models. Moreover, the 3D models are plagued by poor accuracy and lack of detail and cannot completely reflect the stereoscopic microstructure inside the nerve. To explore and help resolve these key technical problems of 3D reconstruction, in the present study, we designed a novel method based on re-imaging techniques and computer image layer processing technology. A 20-cm ulnar nerve segment from the upper arm of a fresh adult cadaver was used for acetylcholinesterase（ACh E） staining. Then, 2D panoramic images were obtained before and after ACh E staining under the stereomicroscope. Using layer processing techniques in Photoshop, a space transformation method was used to fulfill automatic registration. The contours were outlined, and the 3D rendering of functional fascicular groups in the long-segment ulnar nerve was performed with Amira 4.1 software. The re-imaging technique based on layer processing in Photoshop produced an image that was detailed and accurate. The merging of images was accurate, and the whole procedure was simple and fast. The least square support vector machine was accurate, with an error rate of only 8.25%. The 3D reconstruction directly revealed changes in the fusion of different nerve functional fascicular groups. In conclusion. The technique is fast with satisfactory visual reconstruction.展开更多
文摘Objectives Dysregulated osteoclast function contributes to skeletal diseases.However,the specific ubiquitination regulators of the osteoclastogenesis repressor MafB,particularly at the post-translational level,remain undefined.This study aims to identify ubiquitin-specific proteases(USPs)that deubiquitinate MafB and enhance its stability.Methods We constructed a MafB-conjugated luciferase and overexpressed 40 individual USPs,measuring changes in luciferase activity.The identified USP was overexpressed in human CD14^(+) peripheral blood mononuclear cells(PBMCs)to evaluate its effect.Osteoclast differentiation was assessed through osteoclast marker Integrin alpha-V(CD51)staining and Western blot analysis.Co-immunoprecipitation(co-IP)was performed to assess the interplay.The influence on MafB ubiquitination and degradation was evaluated via immunoprecipitation and Western blot.Finally,MafB was knocked down in the USP-overexpressing PBMCs to analyze its effect on osteoclast differentiation.Results Overexpression of ubiquitin-specific protease 29(USP29)significantly increased MafB expression by approximately 75%(p<0.0001).Elevated USP29 levels strongly inhibited osteoclastic differentiation in CD14^(+) PBMCs(p<0.0001).USP29 was found to interact with MafB,markedly reducing its ubiquitination and subsequent degradation in PBMCs(p<0.001).Knocking down MafB in USP29-overexpressing PBMCs alleviated the inhibitory effect of USP29 on osteoclastogenesis.Conclusion USP29 acts as a potent stabilizer of MafB,inhibiting osteoclastogenesis in human CD14^(+) PBMCs,at least in part,by enhancing MafB stability.These findings expand our understanding of USP29’s role and the post-translational regulation of MafB.Furthermore,USP29 serves as a vital factor that controls osteoclast differentiation,and its regulatory function is at least partially mediated by deubiquitinating and stabilizing MafB.
基金supported by the Tianjin Key Medical Discipline(Specialty)Construct Project,No.TJYXZDXK-027A(to SF)the National Key Research andDevelopment Project of Stem Cell and Transformation Research,No.2019YFA0112100(to SF)+2 种基金Tianjin Natural Science Foundation’s Youth Project for DiverseInvestments,No.21JCQNJC01300(to BF)the National Natural Science Foundation of China(Youth Program),No.82102563(to BF)Tianjin Major Science andTechnology Special Projects and Engineering Projects,No.21ZXJBSY00080(to YR).
文摘Few studies have investigated alterations in the immune cell microenvironment of the dorsal root ganglia following spinal cord injury and whether these modifications facilitate axonal regeneration.In this study,we used a single-cell RNA sequencing dataset to create a comprehensive profile of the diverse cell types in the dorsal root ganglia and spinal cord of a mid-thoracic contusion injury model in cynomolgus monkeys.Cell communication analysis indicated that specific signaling events among various dorsal root ganglia cell types occur in response to spinal cord injury.Single-cell analysis using dimensionality reduction clustering identified distinct molecular signatures for nine cell types,including macrophage subpopulations,and differential gene expression profiles between dorsal root ganglia cells and spinal cord cells following spinal cord injury.The macrophage subpopulations were categorized into 11 clusters(MC0-MC10)based on differentially expressed genes,with the top 10 genes being ABCA6,RBMS3,EBF1,LAMA4,ANTXR2,LAMA2,SOX5,FOXP2,GHR,and APOD.MC0,MC1,and MC2 constituted the predominant macrophage populations.MC4,MC6,and MC9 were nearly absent in the spinal cord,but exhibited significant increases in the dorsal root ganglia post-spinal cord injury.Notably,these subpopulations possess a strong capacity for regulating axonal regeneration.The developmental progression of dorsal root ganglia macrophages after spinal cord injury was elucidated using cell trajectory and pseudo-time analyses.Genes such as EBF1(MC6 and MC9 marker),RBMS3(MC6 and MC9 marker),and ABCA6(MC6 marker)showed high expression levels in the critical pathways of macrophage function.Through ligand-receptor pair analysis,we determined that the effects of macrophages on microglia are predominantly mediated through interaction pairs(e.g.,SPP1-CD44,LAMC1-CD44,and FN1-CD44),potentially facilitating specific cellular communications within the immune microenvironment.The single-cell RNA sequencing dataset used in this study represents the first comprehensive transcriptional analysis of the dorsal root ganglia after spinal cord injury in cynomolgus monkeys,encompassing nearly all cell types within the dorsal root ganglia region.Using this dataset,we evaluated diverse subtypes of macrophages in the post-spinal cord injury dorsal root ganglia area and examined the signaling pathways that facilitate interactions among immune response-related macrophages in the dorsal root ganglia.Findings from this study provide a theoretical basis for understanding how the immune microenvironment influences the regenerative capacity of dorsal root ganglia neurons after spinal cord injury and offer novel insights into the complex processes underlying the pathobiology of spinal cord injury.
基金partially supported by the National Natural Science Foundation of China(Nos.32471474 and 82102574)the Precision Medicine Project of People’s Hospital of Xinjiang Uygur Autonomous Region(No.20220305)+4 种基金Chengdu Advanced Metal Materials Industry Technology Research Institute Co.,Ltd.Support Project(No.24H0802)Sichuan Science and Technology Program(Nos.2025YFHZ0086,2023YFS0053,2024YFHZ0125,and 2025ZNSFSC0381)Project of Tianfu Jincheng Laboratory(No.2025ZH009)Guangdong Basic and Applied Basic Research Foundation(No.2023A1515220102)Xinjiang Autonomous Region Science and Technology Support Project Plan(Directive)Project(No.2024E02049)。
文摘Cases of widespread bone hydatid infection are relatively rare in clinical practice.In this study,we reported for the first time a validated integrated repair therapy for multiple bone tissues,including the hip,femur,and knee,caused by echinococ cosis.Artificial intelligence(AI)was used to develop a targeted surgical plan and to design a personalized prosthesis.Finite element analysis(FEA)was used to optimize the mechanical effectiveness of a customized integrated replacement prosthesis and to model stress distribution in the surrounding bone.Three-dimensional(3 D)printing was used to fabricate a customized prosthesis.With the assistance of AI,FEA,and 3 D printing technology,a personalized surgical plan and customized prosthesis were successfully constructed based on the patient’s disease.This approach achieved a successful therapeutic effect,demonstrating that AI-assisted personalized medicine holds great promise for the future.
文摘Background:Despite the promise shown by large language models(LLMs)for standardized tasks,their multidimensional performance in real-world oncology decision-making remains unevaluated.This study aims to introduce a framework for evaluating LLMs and physician decisions in challenging lung cancer cases.Methods:We curated 50 challenging lung cancer cases(25 local and 25 published)classified as complex,rare,or refractory.Blinded three-dimensional,five-point Likert evaluations(1–5 for comprehensiveness,specificity,and readability)compared standalone LLMs(DeepSeek R1,Claude 3.5,Gemini 1.5,and GPT-4o),physicians by experience level(junior,intermediate,and senior),and AI-assisted juniors;intergroup differences and augmentation effects were analyzed statistically.Results:Of 50 challenging cases(18 complex,17 rare,and 15 refractory)rated by three experts,DeepSeek R1 achieved scores of 3.95±0.33,3.71±0.53,and 4.26±0.18 for comprehensiveness,specificity,and readability,respectively,positioning it between intermediate(3.68,3.68,3.75)and senior(4.50,4.64,4.53)physicians.GPT-4o and Claude 3.5 reached intermediate physician–level comprehensiveness(3.76±0.39,3.60±0.39)but junior-to-intermediate physician–level specificity(3.39±0.39,3.39±0.49).All LLMs scored higher on rare cases than intermediate physicians but fell below junior physicians in refractory-case specificity.AIassisted junior physicians showed marked gains in rare cases,with comprehensiveness rising from 2.32 to 4.29(84.8%),specificity from 2.24 to 4.26(90.8%),and readability from 2.76 to 4.59(66.0%),while specificity declined by 3.2%(3.17 to 3.07)in refractory cases.Error analysis showed complementary strengths,with physicians demonstrating reasoning stability and LLMs excelling in knowledge updating and risk management.Conclusions:LLMs performed variably in clinical decision-making tasks depending on case type,performing better in rare cases and worse in refractory cases requiring longitudinal reasoning.Complementary strengths between LLMs and physicians support case-and task-tailored human–AI collaboration.
文摘BACKGROUND Periprosthetic joint infection(PJI)is a catastrophic complication that can occur following total knee arthroplasty(TKA).Currently,the treatment for PJI mainly includes the use of antibiotics alone,prosthetic debridement lavage,primary revision,secondary revision,joint fusion,amputation,etc.AIM To explore the clinical effect of two-stage revision surgery for the treatment of PJI after TKA.METHODS The clinical data of 27 patients(3 males and 24 females;age range,47–80 years;mean age,66.7±8.0 years;27 knees)with PJI treated with two-stage revision surgery in our hospital between January 1,2010 and December 31,2020 were analyzed retrospectively.The following outcomes were compared for changes between preoperative and last follow-up results:Erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),visual analogue scale(VAS)scores,Hospital for Special Surgery(HSS)scores,knee range of motion(ROM),and infection cure rates.RESULTS All 27 patients were followed up(range,13–112 mo).The ESR(14.5±6.3 mm/h)and CRP(0.6±0.4 mg/dL)of the patients at the last follow-up were significantly lower than those at admission;the difference was statistically significant(P<0.001).The postoperative VAS score(1.1±0.7),HSS score(82.3±7.1),and knee ROM(108.0°±19.7°)were significantly improved compared with those before the surgery;the difference was statistically significant(P<0.001).Of the 27 patients,26 were cured of the infection,whereas 1 case had an infection recurrence;the infection control rate was 96.3%.CONCLUSION Two-stage revision surgery can effectively relieve pain,control infection,and retain good joint function in the treatment of PJI after TKA.
基金financial support from the National Natural Science Foundation of China(Nos.61701386,21975196,and 51771140)the Young Star Project of Science and Technology of Shaanxi Province(No.2019KJXX-033)+1 种基金Natural Sci-ence Basic Research Plan in Shaanxi Province of China(Nos.2022JM-358 and 2024JC-YBQN-0896)the Project of Xi’an Mu-nicipal Health Commission(No.2024qn11).
文摘Multicomponent core-shell microspheres have garnered significant attention as microwave absorption(MA)materials,owing to their distinctive synergistic effects arising from interfacial polarization and magnetic/dielectric loss.An effective method for optimizing the MA properties of materials is to construct heterogeneous interfacial engineering through component tuning and structural design.Here,a hollow flower-like CoNi@NC@SnS_(2) composite was successfully synthesized through high-temperature pyrolysis and vertical growth of SnS_(2).The surface of the CoNi@NC microsphere was uniformly coated with SnS_(2) nanosheets,resulting in the formation of a core-shell structure.The construction of Schottky barriers through the contact between semiconductors and conductors optimizes polarization relaxation processes and enhances impedance-matching properties.The Schottky interfaces generate a built-in electric field(BIEF)that enhances charge separation and inversion of charge distribution,thereby improving interfacial polarization.Additionally,the Schottky heterogeneous interfaces of composites can be activated through the controllable introduction of defects,resulting in a more robust interfacial polarization.Consequently,the core-shell CoNi@NC@SnS_(2) composite demonstrates outstanding MA performance,achieving a minimum reflection loss(RLmin)of−72.6 dB at 1.9 mm and an effective absorption bandwidth(EAB)of 13.2 GHz(ranging from 4.8 to 18.0 GHz)across a thickness range of 1.5–4.0 mm.This research offers novel insights into the mechanisms that underlie polarization loss and facilitates the development of high-performance MA materials.
文摘Objective:Total knee arthroplasty(TKA)has become an effective treatment modality for end-stage osteoarthritis and rheumatoid arthritis.Postoperative problems such as anterior knee pain affect postoperative patient satisfaction.Patellar denervation has been proposed as a technique to relieve pain,but its efficacy remains controversial.This study evaluated the mid-and long-term effects of patellar denervation on postoperative knee joint functions,hoping to provide better guidance for clinical practice.Methods:This study is a prospective randomized controlled double-blind study.58 patients undergoing bilateral non-resurfaced total knee arthroplasty were included and randomized into two groups.Both groups underwent total knee arthroplasty while patellar denervation was performed only on the experimental group.Information regarding whether if patellar denervation was performed were withheld from all patients and outcome assessors.All surgeries were performed by the same high-level professional physician,and the post-stable knee prosthesis system(PS Scorpio NRG PS,Stryker)was used during the surgeries.The knee joint functions were evaluated by professional assessors before and after surgery.The evaluation indicators mainly include KSS scoring,Western Ontario and McMaster Universities(WOMAC)scoring and Visual Analogue Scale(VAS),FJS scoring,etc.The follow-up period was 3 years and 5 years after surgery.Results:The experimental group had better KSS and FJS scores than the control group,the difference was statistically significant.There was no significant inter-group difference in WOMAC and VAS scores.Conclusion:The patellar denervation in TKA patients has positive effects on the mid-and long-term recovery of knee joint functions,and the postoperative satisfaction is better.
基金National Key R&D Program of China,Grant/Award Number:2021YFC2502100,2023YFC3603404 and 2019YFA0111900The National Natural Science Foundation of China,Grant/Award Number:82072506,82272611 and 92268115+7 种基金The Hunan Provincial Science Fund for Distinguished Young Scholars,Grant/Award Number:2024JJ2089The Hunan Young Talents of Science and Technology,Grant/Award Number:2021RC3025The Provincial Clinical Medical Technology Innovation Project of Hunan,Grant/Award Number:2023SK2024 and 2020SK53709The Provincial Natural Science Foundation of Hunan,Grant/Award Number:2020JJ3060The National Natural Science Foundation of Hunan Province,Grant/Award Number:2023JJ30949The National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Grant/Award Number:2021KFJJ02 and 2021LNJJ05The Hunan Provincial Innovation Foundation for Postgraduate,Grant/Award Number:CX20230308 and CX20230312The Independent Exploration and Innovation Project for Postgraduate Students of Central South University,Grant/Award Number:2024ZZTS0163。
文摘Frozen shoulder(FS),also known as adhesive capsulitis,is a condition that causes contraction and stiffness of the shoulder joint capsule.The main symptoms are per-sistent shoulder pain and a limited range of motion in all directions.These symp-toms and poor prognosis affect people's physical health and quality of life.Currently,the specific mechanisms of FS remain unclear,and there is variability in treatment methods and their efficacy.Additionally,the early symptoms of FS are difficult to distinguish from those of other shoulder diseases,complicating early diagnosis and treatment.Therefore,it is necessary to develop and utilize animal models to under-stand the pathogenesis of FS and to explore treatment strategies,providing insights into the prevention and treatment of human FS.This paper reviews the rat models available for FS research,including external immobilization models,surgical internal immobilization models,injection modeling models,and endocrine modeling models.It introduces the basic procedures for these models and compares and analyzes the advantages,disadvantages,and applicability of each modeling method.Finally,our paper summarizes the common methods for evaluating FS rat models.
基金Supported by Lanzhou City Science and Technology Development Guiding Plan Project,No.2023-ZD-170Lanzhou Science and Technology Plan Project,No.2023-2-11High-Level Talent Training Project At the 940th Hospital of the Joint Logistics Force,No.2024-G3-5.
文摘BACKGROUND Tuberculosis is among the most devastating infectious diseases worldwide.Spinal tuberculosis is not easy to detect at an early stage,which without effective treatment often leads to spinal deformity and spinal cord damage which in turn cause complications such as paraplegia and quadriplegia.In this study,we established a model using three concentrations of bacteria and carried out a comprehensive evaluation of the model by imaging,general observations,and histopathological and bacteriological studies.AIM To establish a rabbit model of spinal tuberculosis and examine the effect on the model’s efficacy using different concentrations of Mycobacterium tuberculosis(M.tuberculosis)inoculum.METHODS New Zealand rabbits were randomly divided into experimental,control and blank groups.The experimental and control animals were sensitized with complete Freund′s adjuvant,a hole was drilled beneath the upper endplate of the L6 vertebral body and filled with gelfoam sponge.The experimental group was divided into three subgroups(experimental 1,experimental 2,experimental 3)and infused with M.tuberculosis suspension at various concentrations.The control group was inoculated with saline and the blank group received no treatment.The 12-week post-operative survival rates were 100%,80%and 30%in the experimental groups inoculated with concentrations of 106,107 and 108 CFU/mL bacteria,respectively.RESULTS The survival rate of the control and blank groups was 100%.Vertebral body destruction at 8 weeks in the three experimental groups as determined by X-ray analysis was 33.3%,62.5%and 66.7%,and by computed tomography(CT)and 3-dimensional CT 44.4%,75%and 100%,respectively.At 12 weeks,the figures were 44.4%,75%and 100%by X-ray analysis and 44.4%,100%and 100%by CT and 3-dimensional CT,respectively.All surviving rabbits of the experimental groups had vertebral destruction.The positive bacterial culture rates were 22.2%,75%and 66.7%,respectively,in the experimental groups.After being sensitized with complete Freund's adjuvant,large differences were observed in the extent of spinal tuberculosis after inoculation of the rabbits with different concentrations of H37RV standard M.tuberculosis.CONCLUSION The experimental 1 had a low success rate at establishing an infection.The experimental 3 resulted in high mortality and complication rates.The experimental 2 was optimum for establishing a spinal tuberculosis model based on the high level of symptoms observed and the low rabbit mortality.
基金Supported by 2024 Suining Health Science and Technology Plan Project,No.24ZDJB03.
文摘Neutrophil extracellular traps(NETs)have been the subject of research in the field of innate immunity since they were first described two decades ago.NETs are fibrous network structures released by neutrophils under specific stimuli,including DNA,histones,and a variety of granular proteins.NETs have been widely studied in the fields of infectious and immune diseases,and new break-throughs have been made in the understanding of disease pathogenesis and treatment.In recent years,studies have found that NETs play an important role in the occurrence and development of osteoarticular diseases.This article reviews the progress in the research of NETs in common osteoarticular diseases such as rheumatoid arthritis,ankylosing spondylitis,gouty arthritis,osteonecrosis of the femoral head,osteoarthritis,and joint fibrosis,including the formation mecha-nism of NETs and its role in inflammation,joint destruction,pain and other pa-thological processes.The problems existing in current research are discussed,along with future research directions,to provide a reference for the in-depth study of osteoarticular diseases and the development of new treatment strategies.
基金Supported by the Lanzhou Science and Technology Plan,No.2023-2-11Lanzhou Talent Innovation and Entrepreneurship Project,No.2023-2-28+1 种基金Gansu University of Chinese Medicine Tutor Special Project,No.2023YXKY015Research Fund Project of 940th Hospital,No.2023YXKY014 and No.2023YXKY036.
文摘BACKGROUND Intraosseous lipoma of bone is one of the rarest benign bone tumors,which often involves the metaphysis of long tubular bones,especially the femur,tibia,fibula,and calcaneus.Bone lipoma can be characterized by chronic dull pain but can also be asymptomatic most of the time.As a result,it is less likely to attract people’s attention and is occasionally diagnosed through imaging examination during routine physical health check-up.CASE SUMMARY We describe a clinical case of intraosseous lipoma in a 21-year-old patient with chronic pain in the left lower limb for four years without any significant physical findings apart from the minimal swelling and local tenderness over the median ankle.Computerized tomography suggested the possibility of a lipoma on the left distal tibia,but the pathological examination could make a definite diagnosis.The intraosseous lipoma of the left distal tibia was treated by surgical curettage,bone graft,and internal fixation with steel plate,since the conservative treatment is often ineffective.Postoperatively,the patient made an uneventful recovery and was able to do daily activities without any restrictions.In addition,local recur-rence of the intraosseous lipoma was not reported in subsequent reexamination.CONCLUSION Bone lipoma is very rare and often exhibits no characteristic clinical manifestation.The confirmative diagnosis of lipoma largely relies on a combination of imageo-logy and biopsy.Surgical intervention is often recommended as a conventional therapy for bone lipoma.Postoperatively,the patient makes an uneventful reco-very with a good prognosis,and the local recurrence of the tumor is also a low probability event.
基金supported partly by NIH research grants R01AR078035, R01AR062207,R01AR076900 and R01NS070328。
文摘Osteoarthritis(OA) and intervertebral disc degeneration(IVDD) are degenerative musculoskeletal disorders characterized by degeneration of cartilaginous tissues and inflammation. While inflammation is implicated in the pathogenesis of OA and IVDD, and cytosolic phospholipase A2(cPLA2) is a key mediator of inflammation, direct evidence linking cPLA2 to chondrocyte homeostasis and cartilage degeneration is lacking. This study aims to investigate the role of cPLA2 in chondrocytes and its contribution to the development of cartilage degenerative conditions such as OA and IVDD. Here, single-cell RNA sequencing was used to examine cPLA2 expression in chondrocytes. To explore its importance in chondrocytes and OA/IVDD, various cell-based assays and genetically modified mouse models with age-related and surgically induced OA/IVDD were employed. Furthermore, the therapeutic potential of fexofenadine, an over-the-counter drug recently identified as a cPLA2 inhibitor, was explored in these models. cPLA2 is predominantly expressed in prehypertrophic chondrocytes, characterized by elevated levels of cartilage degeneration markers and senescence-related genes. Genetic deletion and pharmacological inhibition of cPLA2 reduced inflammation induced catabolic activity and senescence in chondrocytes, as well as cartilage degeneration in various OA and IVDD models. This study identifies cPLA2 as a pivotal driver of cartilage degeneration and senescence in OA and IVDD, highlighting its potential as a dual-action therapeutic target that suppresses both inflammation and senescence to preserve cartilage integrity. These findings position cPLA2as a promising candidate for developing disease-modifying therapies for cartilage degenerative conditions such as OA and IVDD.
基金National Natural Science Foundation of China(No.22264013)Hainan Province Clinical Medical Center(No.2021)Hainan Province Science and Technology Special Fund(No.ZDYF2024SHFZ104).
文摘Hypochlorous acid(HClO)is a critical biomolecule in living organisms,playing an essential role in numerous physiological or pathological processes.Abnormal levels of HClO in the body may lead to a series of diseases,for instance,inflammation and cancer.Thus,accurate measurement of HClO levels should be more beneficial for understanding its role in diseases and gaining a deeper insight into the pathogenesis of diseases.In this work,we designed a near-infrared two-photon fluorescent probe(HDM-Cl-HClO)for detecting fluctuations in HClO levels in inflammatory and tumor-bearing mice.Notably,the probe can respond to HClO within 5 s and trigger a brilliant red fluorescence at 660 nm.It exhibits high specificity and sensitivity for HClO.The superior spectral capability of the probe has enabled the detection of HClO levels in cells and zebrafish,as well as achieved the detection of HClO in inflammatory and tumor mice.This work not only provides a novel strategy and tool for HClO imaging in living systems,but also holds great potential for the diagnosis of inflammation and cancer.
基金supported by the National Key R&D Program of China(2023YFC3603400)the National Natural Science Foundation of China(82072506,92268115)+2 种基金the Hunan Provincial Science Fund for Distinguished Young Scholars(2024JJ2089)the Science and Technology Innovation Program of Hunan Province(2021RC3025)the National Clinical Research Center for Geriatric Disorders(Xiangya Hospital,2021KF02).
文摘Fibroblast growth factor(FGF)signaling encompasses a multitude of functions,including regulation of cell proliferation,differentiation,morphogenesis,and patterning.FGFs and their receptors(FGFR)are crucial for adult tissue repair processes.Aberrant FGF signal transduction is associated with various pathological conditions such as cartilage damage,bone loss,muscle reduction,and other core pathological changes observed in orthopedic degenerative diseases like osteoarthritis(OA),intervertebral disc degeneration(IVDD),osteoporosis(OP),and sarcopenia.In OA and IVDD pathologies specifically,FGF1,FGF2,FGF8,FGF9,FGF18,FGF21,and FGF23 regulate the synthesis,catabolism,and ossification of cartilage tissue.Additionally,the dysregulation of FGFR expression(FGFR1 and FGFR3)promotes the pathological process of cartilage degradation.In OP and sarcopenia,endocrine-derived FGFs(FGF19,FGF21,and FGF23)modulate bone mineral synthesis and decomposition as well as muscle tissues.FGF2 and other FGFs also exert regulatory roles.A growing body of research has focused on understanding the implications of FGF signaling in orthopedic degeneration.Moreover,an increasing number of potential targets within the FGF signaling have been identified,such as FGF9,FGF18,and FGF23.However,it should be noted that most of these discoveries are still in the experimental stage,and further studies are needed before clinical application can be considered.Presently,this review aims to document the association between the FGF signaling pathway and the development and progression of orthopedic diseases.Besides,current therapeutic strategies targeting the FGF signaling pathway to prevent and treat orthopedic degeneration will be evaluated.
基金supported by Shandong Province Natural Science Foundation of China:sd2018762872
文摘Objective:To observe the effect of recombinant human bone morphogenetic protein 2/polylactide-co-glycolic acid(rhBMP-2/PLGA) with core decompression on repair of rabbit femoral head necrosis.Methods:Bilateral femoral head necrosis models of rabbit were established by steroid injection.A total of 48 rabbits(96 femoral head necrosis) were randomly divided into 4groups:Group A,control group with12 rabbits,24 femoral head necrosis;Group B,treated with rhBMP-2/PLCA implantation after core depression,with 12 rabbits,24 femoral head necrosis;Group C,treated with rhBMP-2 implantation after core depression,with 12 rabbits,24 femoral head necrosis;Croup D treated with core depression group without implantation,with 12 rabbits,24 femoral head necrosis.All animals were sacrificed after 12 weeks.The ability of repairing bone defect was evaluated by X-ray radiograph.Bone mineral density analysis of the defect regions were used to evaluate the level of ossification.The morphologic change and bone formation was assessed by HE staining.The angiogenesis was evaluated by VEGF immunohistochemistry.Results:The osteogenetic ability and quality of femoral head necrosis in group B were better than those of other groups after 12 weeks by X-ray radiograph and morphologic investigation.And the angiogenesis in group B was better than other groups.Group C had similar osteogenetic quality of femoral head necrosis and angiogenesis with group D.Conclusions:The treatment of rhBMP-2/PLCA implantation after core depression can promote the repair of rabbit femoral head necrosis.It is a promising and efficient synthetic bone material to treat the femoral head necrosis.
基金Supported by National Natural Science Foundation of China Youth Science Foundation(No.81503598)
文摘OBJECTIVE:To evaluate the clinical efficacy and safety of external application of Traditional Chinese Medicine (EATCM) on acute gouty arthritis (AGA).METHODS:Six electronic data bases were retrieved from their inception to march 2017.15 randomized controlled clinical trials (RCTs) were included.The quality of the literatures was assessed according to Cochrane review criteria by using RevMan5.3 software;and related data was counted using Stata14.0 software.RESULTS:There was no significant difference in C-reactiveprotein (CRP) between experimental intervention group and control group [(WMD =1.093,95% C/(-2.514,4.701);P =0.553)].In terms of overall efficacy,the EATCM's treatment group was significantly superior to control group [(OR =3.692;95% CI (2.408,5.661);P <0.001)].The EATCM was better than western medicine treatments or other interventions in reducing the adverse reactions [(OR =0.135;95% CI (0.067,0.274);P < 0.001)].All these funnel plots showed unlikelihood of publishing bias.But due to excessive heterogeneity,the statistical results of serum uric acid and visual analogue scale and CRP between the two groups became uncertain.CONCLUSION:The results indicate that EATCM may have greater overall efficacy with fewer adverse drug reactions,although the evidence is weak owing to the low methodological quality and the small number of the included trials.
基金supported by the Xinjiang Production and Construction Corps Doctoral Fund of China,No.2014BB020
文摘After spinal cord injury,the number of glial cells and motor neurons expressing bone morphogenetic protein 7（BMP7）increases,indicating that upregulation of BMP7 can promote nerve repair.We,therefore,tested whether direct injection of BMP7 into acutely injured ratalalo createrywith 50 ng BMP7（BMP7 group）or physiological saline（control group）for 7 consecutive days.Electrophysiological examination showed that the amplitude of N1 in motor evoked potentials（MEP）decreased after spinal cord injury.At 8 weeks post-operation,the amplitude of N1 in the BMP7 group was remarkably higher than that at 1 week post-operation and was higher than that of the control group.Basso,Beattie,Bresnahan scale（BBB）scores,hematoxylin-eosin staining,and western blot assay showed that at 1,2,4 and 8 weeks post-operation,BBB scores were increased;Nissl body staining was stronger;the number of Nissl-stained bodies was increased;the number of vacuoles gradually decreased;the number of synapses was increased;and the expression of neuronal marker,neurofilament protein 200,was increased in the hind limbs of the BMP7 group compared with the control group.Western blot assay showed that the expression of GFAP protein in BMP7 group and control group did not change significantly and there was no significant difference between the BMP7 and control groups.These data confirmed that local injection of BMP7 can promote neuronal regeneration after spinal cord injury and promote recovery of motor function in rats.
文摘We hypothesized that RNA interference to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells before transplantation might further improve neurological function in rats with spinal cord transection injury. After 2 weeks, the number of neurons and BrdU-positive cells in the Nogo-66 receptor gene silencing group was higher than in the bone marrow mesenchymal stem cell group, and significantly greater compared with the model group. After 4 weeks, behavioral performance was signiifcantly enhanced in the model group. Af-ter 8 weeks, the number of horseradish peroxidase-labeled nerve ifbers was higher in the Nogo-66 receptor gene silencing group than in the bone marrow mesenchymal stem cell group, and signiifcantly higher than in the model group. The newly formed nerve ifbers and myelinated ner ve ifbers were detectable in the central transverse plane section in the bone marrow mesenchymal stem cell group and in the Nogo-66 receptor gene silencing group.
基金Supported by Qingdao Traditional Chinese Medicine Science and Technology Project,No. 2021-zyym28Science and technology Development Project of Shandong Geriatric Society,No. LKJGG2021W082
文摘With advances in the fields of regenerative medicine,cell-free therapy has received increased attention.Exosomes have a variety of endogenous properties that provide stability for molecular transport across biological barriers to cells,as a form of cell-to-cell communication that regulates function and phenotype.In addition,exosomes are an important component of paracrine signaling in stemcell-based therapy and can be used as a stand-alone therapy or as a drug delivery system.The remarkable potential of exosomes has paved the pathway for cell-free treatment in bone regeneration.Exosomes are enriched in distinct noncoding RNAs(ncRNAs),including microRNAs,long ncRNAs and circular RNAs.Different ncRNAs have multiple functions.Altered expression of ncRNA in exosomes is associated with the regenerative potential and development of various diseases,such as femoral head osteonecrosis,myocardial infarction,and cancer.Although there is increasing evidence that exosome-derived ncRNAs(exoncRNAs)have the potential for bone regeneration,the detailed mechanisms are not fully understood.Here,we review the biogenesis of exo-ncRNA and the effects of ncRNAs on angiogenesis and osteoblast-and osteoclast-related pathways in different diseases.However,there are still many unsolved problems and challenges in the clinical application of ncRNA;for instance,production,storage,targeted delivery and therapeutic potency assessment.Advancements in exo-ncRNA methods and design will promote the development of therapeutics,revolutionizing the present landscape.
基金supported by the National Natural Science Foundation of China,No.30571913a grant from the Science and Technology Project of Guangdong Province of China,No.2013B010404019+1 种基金the Natural Science Foundation of Guangdong Province of China,No.9151008901000006the Medical Scientific Research Foundation of Guangdong Province of China,No.A2009173
文摘The three-dimensional（3D） visualization of the functional bundles in the peripheral nerve provides direct and detailed intraneural spatial information. It is useful for selecting suitable surgical methods to repair nerve defects and in optimizing the construction of tissue-engineered nerve grafts. However, there remain major technical hurdles in obtaining, registering and interpreting 2D images, as well as in establishing 3D models. Moreover, the 3D models are plagued by poor accuracy and lack of detail and cannot completely reflect the stereoscopic microstructure inside the nerve. To explore and help resolve these key technical problems of 3D reconstruction, in the present study, we designed a novel method based on re-imaging techniques and computer image layer processing technology. A 20-cm ulnar nerve segment from the upper arm of a fresh adult cadaver was used for acetylcholinesterase（ACh E） staining. Then, 2D panoramic images were obtained before and after ACh E staining under the stereomicroscope. Using layer processing techniques in Photoshop, a space transformation method was used to fulfill automatic registration. The contours were outlined, and the 3D rendering of functional fascicular groups in the long-segment ulnar nerve was performed with Amira 4.1 software. The re-imaging technique based on layer processing in Photoshop produced an image that was detailed and accurate. The merging of images was accurate, and the whole procedure was simple and fast. The least square support vector machine was accurate, with an error rate of only 8.25%. The 3D reconstruction directly revealed changes in the fusion of different nerve functional fascicular groups. In conclusion. The technique is fast with satisfactory visual reconstruction.
