AIM To review and report functional outcomes, complications,and survivorship associated with total knee arthroplasty(TKA) in the treatment of post-traumatic arthritis(PTA).METHODS We conducted a systematic review acco...AIM To review and report functional outcomes, complications,and survivorship associated with total knee arthroplasty(TKA) in the treatment of post-traumatic arthritis(PTA).METHODS We conducted a systematic review according to the PRISMA guidelines. We searched PubMed, Cochrane Library, and SCOPUS in December 2015 for Englishlanguage clinical research studies, both prospective and retrospective, examining the use of TKA for the treatment of PTA. All relevant articles were accessed in full. The manual search included references of retrieved articles.We extracted data on patients' demographics and clinical outcomes, including preoperative diagnosis and pre- and post-operative functional scores. We summarized the data and reported the results in tables and text.RESULTS Sixteen studies, four prospective and ten retrospective,examined patients who underwent TKA for PTA due to fractures of the proximal tibia, patella, and/or distal femur. Eleven studies utilized the Knee Society Scores criteria to assess functional outcomes. All studies utilizing these criteria reported an improvement in functional and knee scores of patients following TKA. Further, studies reported an increased range of motion(ROM) and reduction of pain following surgery. The most commonly reported complications with TKA included infection, stiffness, wound complications, intraoperative rupture of tendons, and osteolysis/polyethylene wear. The overwhelming majority of these complications occurred within the first two years following surgery. Six studies examined the survivorship of TKA with subsequent revision for any reason as an endpoint. Compared to patients with osteoarthritis, patients with PTA required more revisions, the majority for polyethylene wear.CONCLUSION Although associated with higher complication rates,TKA is an effective treatment for PTA, as it improves ROM, pain and functional outcomes.展开更多
Background : To study the relationships among emodin, synovial fibroblasts (FLSs), and macrophages (STMs) to provide guidance for the use of emodin in rheumatoid arthritis (RA) treatment. Methods : RA clinical samples...Background : To study the relationships among emodin, synovial fibroblasts (FLSs), and macrophages (STMs) to provide guidance for the use of emodin in rheumatoid arthritis (RA) treatment. Methods : RA clinical samples from patients with different pathological processes were collected, and the correlations between the subsets of FLSs and STMs and pathological processes were analyzed via flow cytometry. In vitro experimental methods such as enzyme linked immunosorbent assay (ELISA), Western blotting, Transwell assays, CCK- 8 assays and cell coculture were used to assess cell proliferation, migration and secretion of inflammatory factors. A collagen- induced arthritis mouse model was constructed to investigate the therapeutic potential of emodin in RA by flow cytometry, micro- CT and staining. Results : Unique subsets of FLSs and STMs, namely, FAPα ^(+)THY1 − FLSs, FAPα ^(+)THY1 ^(+)FLSs, and MerTK ^(pos) TREM2 ^(high) STMs, were identified in synovial tissues from RA patients. The number of MerTK ^(pos) TREM2 ^(high) STMs was negatively correlated with the degree of damage in RA, while the number of FAPα ^(+)THY1 − FLSs was positively correlated with damage. On the one hand, emodin promoted the aggregation of MerTKposTREM2high STMs. Moreover, MerTK pos TREM2 high STM- mediated secretion of exosomes was promoted, which can inhibit the secretion of pro- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs and promote the secretion of anti- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs, thereby inhibiting FAPα ^(+)THY1 − FLS proliferation and migration, improving the local immune microenvironment, and inhibiting RA damage. Conclusion : Emodin was shown to regulate the aggregation of STM subsets and exosome secretion, affecting the secretion, proliferation and migration of inflammatory factors in FLS subsets, and ultimately achieving good therapeutic efficacy in RA patients, suggesting that it has important clinical value.展开更多
Rheumatoid arthritis(RA)is a chronic autoimmune disease that affects approxi-mately 0.46%of the global population.Conventional therapeutics for RA,including disease-modifying antirheumatic drugs(DMARDs),nonsteroidal a...Rheumatoid arthritis(RA)is a chronic autoimmune disease that affects approxi-mately 0.46%of the global population.Conventional therapeutics for RA,including disease-modifying antirheumatic drugs(DMARDs),nonsteroidal anti-inflammatory drugs(NSAIDs),and corticosteroids,frequently result in unintended adverse effects.Dexamethasone(DEX)is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive properties.Liposomal delivery of DEX,particu-larly when liposomes are surface-modified with targeting ligands like peptides or sialic acid,can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity.This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA.Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models,reduces joint inflammation and damage,and alleviates cartilage destruction compared to free DEX.The liposomal formulation also shows better hemocompatibility,fewer adverse effects on body weight and immune organ index,and a longer circulation time with higher bioavailability.The anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α(TNF-α)and B-cell-activating factor(BAFF),which are key players in the pathogenesis of RA.Additionally,liposomal DEX can induce the expres-sion of anti-inflammatory cytokines like interleukin-10(IL-10),which has significant anti-inflammatory and immunoregulatory properties.The findings suggest that lipo-somal DEX represents a promising candidate for effective and safe RA therapy,with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.展开更多
Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19...Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19 is important for its function in osteoclast differentiation,and LEL-Fc,a competitive inhibitor of Tm4sf19,effectively suppresses osteoclast multinucleation and prevent bone loss associated with osteoporosis.This study aimed to investigate the role of Tm4sf19 in RA,an inflammatory and abnormal osteoclast disease,using a mouse model of collagen-induced arthritis(CIA).Tm4sf19 expression was observed in macrophages and osteoclasts within the inflamed synovium,and Tm4sf19 expression was increased together with inflammatory genes in the joint bones of CIA-induced mice compared with the sham control group.Inhibition of Tm4sf19 by LEL-Fc demonstrated both preventive and therapeutic effects in a CIA mouse model,reducing the CIA score,swelling,inflammation,cartilage damage,and bone damage.Knockout of Tm4sf19 gene or inhibition of Tm4sf19 activity by LEL-Fc suppressed LPS/IFN-γ-induced TLR4-mediated inflammatory signaling in macrophages.LEL-Fc disrupted not only the interaction between Tm4sf19 and TLR4/MD2,but also the interaction between TLR4 and MD2.μCT analysis showed that LEL-Fc treatment significantly reduced joint bone destruction and bone loss caused by hyperactivated osteoclasts in CIA mice.Taken together,these findings suggest that LELFc may be a potential treatment for RA and RA-induced osteoporosis by simultaneously targeting joint inflammation and bone destruction caused by abnormal osteoclast activation.展开更多
Rheumatoid arthritis(RA)is a systemic autoimmune disease in which synovial fibroblasts(SFs)maintain chronic inflammation by secreting proinflammatory mediators,leading to joint destruction.While the role of proinflamm...Rheumatoid arthritis(RA)is a systemic autoimmune disease in which synovial fibroblasts(SFs)maintain chronic inflammation by secreting proinflammatory mediators,leading to joint destruction.While the role of proinflammatory mediators in this process is well-established,the contribution of non-inflammatory regulators in SFs to joint pathology remains poorly understood.In this study,we investigated the non-inflammatory role of SFs in RA using a co-culture model,and found that SFs from RA patients promote apoptosis of human chondrocytes.Mechanistic investigations reveal that SFs can secrete small extracellular vesicles(sEVs),which are taken up by chondrocytes and induce chondrocyte apoptosis in both normal chondrocytes and chondrocytes from patients with RA.sEV-derived miRNA 15-29148 are identified as key signaling molecules mediating the apoptosis effects of chondrocytes.Further studies reveal that SF-derived miRNA 15-29148 targeting CIAPIN1 results in increased chondrocyte apoptosis.We further demonstrate that SF-derived miRNA 15-29148 is transferred to chondrocytes,exacerbating cartilage damage in vivo.Moreover,chondrocyte-specific aptamer-modified polyamidoamine nanoparticles not only ameliorated RA but also prevented its onset.This study suggests that,in RA,the secretion of specific sEV-miRNAs from SFs plays a crucial role in promoting chondrocyte apoptosis,potentially through non-inflammatory regulation,and that sEV-miRNA inhibition in SFs may represent an early preventive treatment strategy for cartilage degradation in RA.展开更多
Rheumatoid arthritis(RA) is a chronic inflammatory disease with multi-system damage and autoimmune features.The main clinical manifestations of RA include joint pain,swelling,and stiffness,and RA may lead to joint def...Rheumatoid arthritis(RA) is a chronic inflammatory disease with multi-system damage and autoimmune features.The main clinical manifestations of RA include joint pain,swelling,and stiffness,and RA may lead to joint deformity and dysfunction in severe cases.The pathologic development of RA involves complex interactions of multiple biomarkers,and detecting a single biomarker may produce falsepositive results due to other confounding factors.Therefore,fluorescent probes that can detect multiple biomarkers simultaneously are crucial for precise RA diagnosis.Peroxynitrite(ONOO^(-)) and viscosity are inflammation-related factors in cells.In this study,we developed a dual responsive near-infrared fluorescent probe,YLS,for ONOO^(-) and viscosity.The probe features dual-channel turn-on fluorescence responses at 625 and 760 nm upon the presence of ONOO^(-) and viscosity,respectively.Supported by YLS,we found that during RA pathology,lymphocyte infiltration not only increases the concentration of proteins in the joint fluid resulting in elevated viscosity;at the same time,the overproduction of ONOO^(-) exacerbates oxidative stress and inflammatory responses.This multiparameter assay is expected to improve the diagnostic accuracy of the early stages of RA,thus providing a scientific basis for early intervention and personalized treatment.展开更多
Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events.Currently,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with...Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events.Currently,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress disorder.In addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate treatment.Evidence suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress disorder.We performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December 2023.These included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum exosomes.One of these studies had also used whole plasma.Two studies were excluded as they did not involve microRNA biomarkers.Most of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult subjects.In measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString panels.Only six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to controls.The miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/exosomes;and miR-18a-3p and-7-1-5p in blood plasma.Several important limitations identified in the studies need to be taken into account in future studies.Further studies are warranted with war veterans and recently traumatized children,adolescents,and adults having PTSD and use of animal models subjected to various stressors and the effects of suppressing or overexpressing specific microRNAs.展开更多
Introduction: Among the chronic and feared complications of this disease, rheumatoid vasculitis stands out as one of the most severe, albeit rare. The most frequently affected sites by rheumatoid vasculitis are the sk...Introduction: Among the chronic and feared complications of this disease, rheumatoid vasculitis stands out as one of the most severe, albeit rare. The most frequently affected sites by rheumatoid vasculitis are the skin and the peripheral nervous system. We report a case of rheumatoid vasculitis complicating a 30-year history of untreated rheumatoid arthritis. Case Report: The patient is a 75-year-old male with a 30-year history of deforming and erosive seropositive rheumatoid arthritis. He presented with polyarthritis and digital necrosis. Physical examination revealed peripheral joint syndrome with characteristic deformities of rheumatoid arthritis. Additionally, there was well-demarcated dry gangrene affecting the first and second digits of the right hand. Laboratory findings indicated an inflammatory syndrome. Tests for antinuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA) to investigate other causes of vasculitis were negative. The patient received a corticosteroid bolus. After two weeks, there was a marked reduction in pain and an improvement in the general condition. The dry gangrene remained stable. Conclusion: Rheumatoid vasculitis remains a serious and chronic complication of rheumatoid arthritis, associated with significant mortality. This case highlights the crucial importance of early diagnosis and effective management of rheumatoid arthritis.展开更多
Arthritis,encompassing osteoarthritis(OA),rheumatoid arthritis(RA),and gouty arthritis(GA),is a prevalent inflammatory disease that significantly impacts quality of life.Natural products(NPs),derived from animals,plan...Arthritis,encompassing osteoarthritis(OA),rheumatoid arthritis(RA),and gouty arthritis(GA),is a prevalent inflammatory disease that significantly impacts quality of life.Natural products(NPs),derived from animals,plants,marine organisms,and microorganisms,have demonstrated beneficial effects in arthritis treatment both domestically and internationally.These natural compounds offer advantages in drug discovery due to their skeletal diversity,structural complexity,and multi-effect,multi-target,and low-toxicity properties compared to conventional small-molecule medicines.However,unclear mechanisms have hindered the development and clinical application of NPs.This review summarizes recent experimental studies from the past decade on natural medicine for arthritis treatment,emphasizing key NPs with therapeutic effects on OA,RA,and GA.It examines the effects and molecular mechanisms of NPs acting on different cells to treat arthritis.Furthermore,this review provides insights into the future prospects of NP research in this field,which is crucial for advancing NP-based arthritis treatments.展开更多
BACKGROUND Prevalence of the main rheumatic diseases in the Republic of Sakha(Yakutia)[RS(Y)],one of the regions of the Russian Federation,differs from the other regions of the Russian Federation due to its ethnic and...BACKGROUND Prevalence of the main rheumatic diseases in the Republic of Sakha(Yakutia)[RS(Y)],one of the regions of the Russian Federation,differs from the other regions of the Russian Federation due to its ethnic and geographic features.Knowledge regarding the prevalence and structure of juvenile idiopathic arthritis(JIA)allows us to shape the work of the pediatric rheumatology service in the region correctly,and optimize the healthcare system and the need for medica-tions.AIM To describe the epidemiological,demographic,clinical,and laboratory characteristics of children with JIA in the RS(Y)and evaluate the main outcomes.METHODS This retrospective cohort study assessed all the data from the medical histories of the patients(n=225)diagnosed with JIA(2016-2023)in the Cardiorheumatology Department of the M.E.Nikolaev National Center of Medicine.Pearson'sχ²test,Fisher's exact test,Mann–Whitney and Kruskal-Wallis tests were used for statistical analyses.RESULTS The ethnic prevalence of JIA is higher in Sakha than in Russian children at 110.1 per 100000 children and 69.4 per 100000 children,respectively.The prevalence of JIA among boys and girls in Sakha was similar,unlike in Russians,where the number of girls predominated.The JIA categories were as follows:(1)Systemic arthritis:3.5%;(2)Oligoarthritis(persistent and extended):33.8%;(3)Rheumatoid factor(RF)(+)polyarthritis:0.9%;(4)RF(-)polyarthritis:14.7%;(5)Enthesitis-related arthritis(ERA):44%;and(6)Psoriatic arthritis:3.1%.Prevalence of the ERA category was 4.4 times higher in Sakha children,but the prevalence of systemic arthritis was 2.9 times lower compared to Russians(P=0.0005).The frequency of uveitis was 10.2%,and the frequency of human leukocyte antigen(HLA)B27 was 39.6%in JIA children.Biologic treatment was received by 40.4%of JIA children and 45.3%achieved remission.CONCLUSION Higher JIA prevalence,male and ERA predominance,related to a higher frequency of HLA B27 are typical in RS(Y).These data might improve the pediatric rheumatology health service.展开更多
Objective To reveal the therapeutic effects of moxibustion in collagen-induced arthritis(CIA)rat models using the combined analysis of plasma and synovial membrane lipidomic profil-ing and to enhance the understanding...Objective To reveal the therapeutic effects of moxibustion in collagen-induced arthritis(CIA)rat models using the combined analysis of plasma and synovial membrane lipidomic profil-ing and to enhance the understanding of how moxibustion affects lipid metabolism in rheumatoid arthritis(RA).Methods A total of 32 male Sprague-Dawley(SD)rats were randomly assigned to four groups:control,moxibustion control(MC),model,and moxibustion model(MM)groups,with 8 rats in each group.CIA was induced in SD rats by two immunizations.The paw volume was mea-sured before the induction of CIA.Following induction,after assessing paw volume and arthritis index(AI)scores,the MC and MM groups received treatment at bilateral Shenshu(BL23)and Zusanli(ST36)acupoints for 10 min per acupoint.The intervention included three treatment courses,each spanning 6 d and followed by a 1-d interval.Paw volume and AI scores were assessed after each treatment course.After the completion of the three treatment courses,serum,plasma,synovial tissue,and ankle joint samples were collected.Enzyme-linked immunosorbent assay(ELISA)was employed to quantify the levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-αin serum.Hematoxylin and eosin(HE)staining was per-formed for histopathological examination of the ankle joint tissues.Meanwhile,ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS)was utilized to analyze the plasma and synovial tissue sam-ples.In addition,multivariate statistical analysis was performed to identify differential lipid metabolites,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was applied to explore metabolic pathways modulated by moxibustion therapy.Results No significant difference in hind paw volume and AI scores was observed among the groups(P>0.05).After CIA induction,model group showed increased hind paw volume and AI scores compared with control group(P<0.05),which were significantly reduced after mox-ibustion treatment in MM group compared with model group(P<0.05).The levels of IL-6 and TNF-αwere significantly higher in model and MM groups compared with control group(P<0.05),but were lower in MM group than those in model group(P<0.05).Histopathologi-cal analysis showed improved cartilage and reduced inflammation in MM group.A total of 33 differential lipid metabolites in the plasma and 24 in the synovial membranes of CIA rat mod-els were identified when compared with control group.Among these lipid metabolites,31 in the plasma and all 24 in the synovial membranes were regulated by moxibustion treatment.Pathological analysis revealed upregulation of diacylglycerol(DG)and fatty acid(FA)levels,alongside downregulation of lysophosphatidylcholine(LPC),phosphatidylcholine(PC),and phosphatidylethanolamine(PE).Under physiological conditions,the treatment specifically reduced LPC and PC levels.Pathway enrichment analysis revealed that moxibustion predom-inantly affectedα-linolenic acid,glycerophospholipid,and sphingolipid metabolism under pathological conditions.Under physiological conditions,the regulation was centered aroundα-linolenic acid and glycerophospholipid metabolism.Conclusion The RA rat models exhibited significant lipid metabolic disturbances.Moxibus-tion alleviated paw swelling,reduced AI scores,modulated inflammatory cytokine levels,and partially corrected the altered levels of multiple lipid metabolites.The potential metabolic pathways implicated in the regulation of lipid metabolism under both physiological and pathological conditions includeα-linolenic acid,glycerophospholipid,and sphingolipid metabolism.展开更多
Objectives:This study examines the effectiveness of an eight-week game-based physical activity program designed to reduce post-traumatic stress levels in children affected by the Kahramanmaraş-centered earthquakes tha...Objectives:This study examines the effectiveness of an eight-week game-based physical activity program designed to reduce post-traumatic stress levels in children affected by the Kahramanmaraş-centered earthquakes that occurred in Turkey on 06 February 2023.Following the earthquake,millions of children experienced significant changes in their education and living conditions,adversely affecting their psychological health.Methods:The therapeutic effects of physical activity on post-traumatic stress disorder(PTSD)are frequently emphasized in the literature,and this study specifically focuses on the impact of game-based exercises.The research employed an experimental design,involving 80 earthquake-affected children aged 10 to 13,who were randomly assigned to either an experimental group(n=40)or a control group(n=40).The experimental group participated in game-based physical activities three times per week for eight weeks,with each session lasting 60 min.Data were collected using the Child Post-Traumatic Stress Reaction Index(CPTS-RI),and pre-test and post-test comparisons were conducted.Results:Children in the experimental group showed a marked reduction in PTSD symptoms,with mean CPTS-RI scores decreasing from 2.60 at pre-test to 1.91 at post-test.In contrast,the control group’s scores remained virtually unchanged(2.59 at pre-test vs.2.57 at post-test).Two-way ANOVA demonstrated significant main effects of group and time,as well as a significant group×time interaction(F=114.88,p<0.001,η^(2)=0.42),indicating that the reduction was attributable to participation in the game-based physical activity program.These findings highlight not only the statistical significance but also the practical relevance of structured,culturally adapted physical activity interventions for trauma-exposed children.Conclusion:These findings suggest that regular,structured game-based physical activities can support the mental health of children following traumatic events such as earthquakes and reduce their stress levels.The study recommends integrating physical activity into post-disaster psychosocial support programs and highlights it as an effective,accessible,and enjoyable method to enhance children’s trauma coping skills.Accordingly,it advocates for the wider implementation of physical activity-based interventions in similar crisis situations.展开更多
Itaconate,a macrophage-specific anti-inflammatory metabolite,has recently emerged as a critical regulator in rheumatoid arthritis pathogenesis.We found that itaconate is a TNF-αresponsive metabolite significantly ele...Itaconate,a macrophage-specific anti-inflammatory metabolite,has recently emerged as a critical regulator in rheumatoid arthritis pathogenesis.We found that itaconate is a TNF-αresponsive metabolite significantly elevated in the serum and synovial fluid of rheumatoid arthritis patients and we demonstrated that itaconate is primarily produced by inflammatory macrophages rather than osteoclasts or osteoblasts.In TNF-transgenic and Irg1−/−hybrid mice,a more severe bone destruction phenotype was observed.展开更多
Rheumatoid arthritis(RA)is a common chronic autoimmune disease characterized by joint pain,swelling and dysfunction[1].According to epidemiologic statistics,the incidence of RA is 1%–2%,and in severe cases,it can dev...Rheumatoid arthritis(RA)is a common chronic autoimmune disease characterized by joint pain,swelling and dysfunction[1].According to epidemiologic statistics,the incidence of RA is 1%–2%,and in severe cases,it can develop into joint deformity and disability,which brings a heavy burden to the family and society[2].However,the pathogenesis of RA is complex and involves multiple cellular interactions,which increases the difficulty of curing RA.Current therapeutic options,such as disease-modifying antirheumatic drugs,non-steroidal anti-inflammatory drugs,and biologics,still face the challenge of relapse after drug discontinuation[3,4].Therefore,the pathogenesis of RA needs to be analyzed in depth to break through the existing therapeutic bottlenecks and promote the iterative innovation of individualized diagnosis and treatment.展开更多
Eosinophils are multifunctional granulocytes that contribute to the initiation and modulation of inflammation.Accumulating evidence suggests that eosinophils are adaptable leukocytes that orchestrate the resolution of...Eosinophils are multifunctional granulocytes that contribute to the initiation and modulation of inflammation.Accumulating evidence suggests that eosinophils are adaptable leukocytes that orchestrate the resolution of inflammatory responses.The most prevalent chronic inflammatory illness,rheumatoid arthritis(RA),is typified by persistent synovitis thatmakes it hard for the disease to go away on its own.Interestingly,a unique subset of eosinophils known as regulatory eosinophils has been found in RA patients’synovium,especially while the disease is in remission.Pro-resolving signatures of regulatory eosinophils in the synovium are distinct from those of their lung counterparts.The most recent research on eosinophils and their function in this disease pathogenesis is compiled in this review.Based on the role of regulatory eosinophils,a new pathological model of inflammation resolution in RA is proposed,and potential therapeutic strategies aimed at enhancing the action of regulatory eosinophils in RA are proposed.展开更多
BACKGROUND Postoperative anxiety,depression,irritability,and even fear in patients with intertrochanteric femoral fractures may hinder recovery,compromise treatment efficacy,and impede rehabilitation.AIM To investigat...BACKGROUND Postoperative anxiety,depression,irritability,and even fear in patients with intertrochanteric femoral fractures may hinder recovery,compromise treatment efficacy,and impede rehabilitation.AIM To investigate the correlations among anxiety,depression,sense of coherence(SOC),and post-traumatic growth(PTG)in patients who underwent intertrochanteric femoral fracture surgery to improve clinical management strategies and outcomes.METHODS This study carefully selected 211 patients who received surgical treatment for intertrochanteric femoral fractures and were admitted to Dongying People’s Hospital from March 2022 to March 2024.Anxiety and depression in these patients were assessed with the anxiety and depression subscales of the Hospital Anxiety and Depression Scale(HADS),respectively.SOC was evaluated using the 13-item SOC scale(SOC-13),which encompasses three key dimensions:Comprehensibility,manageability,and meaningfulness.PTG was assessed with the Chinese version of PTG Inventory(CPTGI),covering five distinct dimensions:Personal strength,appreciation of life,relating to others,new possibilities,and spiritual change.The Pearson correlation coefficient was used to meticulously analyze the associations among HADS-Anxiety,HADS-Depression,SOC-13,and CPTGI.Further,univariate and multivariate analyses were conducted to identify factors that affect PTG in patients who underwent intertrochanteric femoral fracture surgery.RESULTS The collected data demonstrated that 67.30%and 60.66%of the 211 patients experienced anxiety and depression,respectively,with overall anxiety levels ranging from mild to moderate and depression levels being mild.The mean SOC-13 score was 55.73±8.81 points,indicating a generally low SOC level.The average CPTGI score was 54.93±9.92 points,demonstrating a relatively low PTG level.Notably,both HADS-Anxiety and HADS-Depression scores were significantly negatively correlated with CPTGI,whereas SOC-13 scores were significantly positively correlated with CPTGI.Univariate and multivariate analyses identified the presence of comorbidities[odds ratio(OR)=2.747,P=0.003],monthly household income(OR=3.292,P<0.001),and exercise habits(OR=4.651,P<0.001)as independent predictors of PTG in patients.CONCLUSION The results of this study indicate a significant negative correlation of anxiety and depression with PTG in patients after intertrochanteric femoral fracture surgery,whereas a significant positive association exists between SOC and PTG.This study helps more comprehensively understand the psychological status and recovery processes of such patients,thereby potentially providing valuable information for clinical practice and psychological interventions.展开更多
Rheumatoid arthritis(RA)is a prevalent and debilitating inflammatory disease that significantly impairs functional capacity and quality of life.RA accelerates musculoskeletal aging,leading to complications such as mus...Rheumatoid arthritis(RA)is a prevalent and debilitating inflammatory disease that significantly impairs functional capacity and quality of life.RA accelerates musculoskeletal aging,leading to complications such as muscle degeneration and sarcopenia.Recent research has identified myopenia as a condition of significant muscle loss associated with illness,distinct from the muscle wasting seen in other chronic diseases like cancer cachexia or heart failure.In RA,myopenia is characterized by muscle depletion without concurrent significant fat loss,and it can affect individuals of all ages.While inflammation plays a central role,it is not the sole factor contributing to the high incidence of muscle wasting in RA.In subsequent discussions,secondary sarcopenia will be considered alongside myopenia,as both involve muscle wasting decline primarily due to disease.This review summarizes recent findings on the impact of RA-related myopenia and secondary sarcopenia on functional capacity,explores its underlying mechanisms,and discusses contemporary strategies to mitigate the process of musculoskeletal aging in RA patients.展开更多
Arthritis is an inflammatory joint disorder that progressively impairs function and diminishes quality of life.Conventional therapies often prove ineffective,as oral administration lacks specificity,resulting in off-t...Arthritis is an inflammatory joint disorder that progressively impairs function and diminishes quality of life.Conventional therapies often prove ineffective,as oral administration lacks specificity,resulting in off-target side effects like hepatotoxicity and GIT-related issues.Intravenous administration causes systemic side effects.The characteristic joint-localized symptoms such as pain,stiffness,and inflammation make the localized drug delivery suitable for managing arthritis.Topical/transdermal/intraarticular routes have become viable options for drug delivery in treating arthritis.However,challenges with those localized drug delivery routes include skin barrier and cartilage impermeability.Additionally,conventional intra-articular drug delivery also leads to rapid clearance of drugs from the synovial joint tissue.To circumvent these limitations,researchers have developed nanocarriers that enhance drug permeability through skin and cartilage,influencing localized action.Gel-based nanoengineered therapy employs a gel matrix to incorporate the drug-encapsulated nanocarriers.This approach combines the benefits of gels and nanocarriers to enhance therapeutic effects and improve patient compliance.This review emphasizes deep insights into drug delivery using diverse gelbased novel nanocarriers,exploring their various applications embedded in hyaluronic acid(biopolymer)–based gels,carbopol-based gels,and others.Furthermore,this review discusses the influence of nanocarrier pharmacokinetics on the localization and therapeutic manipulation of macrophages mediated by nanocarriers.The ELVIS(extravasation through leaky vasculature and inflammatory cell-mediated sequestration)effect associated with arthritis is advantageous in drug delivery.Simply put,the ELVIS effect refers to the extravasation of nanocarriers through leaky vasculatures,which finally results in the accumulation of nanocarriers in the joint cavity.展开更多
BACKGROUND Although exposure therapy is a proven treatment for post-traumatic stress disorder(PTSD),empirical research is difficult due to ethical issues.Recently,virtual reality-based content that can provide space a...BACKGROUND Although exposure therapy is a proven treatment for post-traumatic stress disorder(PTSD),empirical research is difficult due to ethical issues.Recently,virtual reality-based content that can provide space and time similar to reality for exposure therapy techniques is increasing.AIM To examine exposure therapy using driving simulations in patients with PTSD due to traffic accidents with PTSD symptoms.METHODS The intervention was provided to two individuals who experienced PTSD symptoms after a traffic accident using a driving simulator.Among the singlesubject experimental designs,the ABA(baseline-intervention-baseline)design was used,and the PTSD checklist and brain wave frequency were used to measure the results.RESULTS In all participants,the standard category departure time of the electroencephalogram decreased from baseline,and PTSD symptoms decreased after the intervention.CONCLUSION These results suggest the potential use of a driving simulator as an exposure treatment tool for PTSD.展开更多
Dear Editor,Post-traumatic stress disorder(PTSD)is a major issue for military personnel,with prevalence rates between 1%and 35%in veterans^([1]),significantly higher than in the general population^([2]).Psychological ...Dear Editor,Post-traumatic stress disorder(PTSD)is a major issue for military personnel,with prevalence rates between 1%and 35%in veterans^([1]),significantly higher than in the general population^([2]).Psychological resources,particularly hope,can protect against PTSD and promote post-traumatic growth^([3]).Hope,conceptualized as both a trait and a state,contributes to well-being and resilience and is negatively associated with PTSD symptoms,representing a psychological factor while mitigating the impact of trauma by fostering resilience and adaptive coping mechanisms.展开更多
文摘AIM To review and report functional outcomes, complications,and survivorship associated with total knee arthroplasty(TKA) in the treatment of post-traumatic arthritis(PTA).METHODS We conducted a systematic review according to the PRISMA guidelines. We searched PubMed, Cochrane Library, and SCOPUS in December 2015 for Englishlanguage clinical research studies, both prospective and retrospective, examining the use of TKA for the treatment of PTA. All relevant articles were accessed in full. The manual search included references of retrieved articles.We extracted data on patients' demographics and clinical outcomes, including preoperative diagnosis and pre- and post-operative functional scores. We summarized the data and reported the results in tables and text.RESULTS Sixteen studies, four prospective and ten retrospective,examined patients who underwent TKA for PTA due to fractures of the proximal tibia, patella, and/or distal femur. Eleven studies utilized the Knee Society Scores criteria to assess functional outcomes. All studies utilizing these criteria reported an improvement in functional and knee scores of patients following TKA. Further, studies reported an increased range of motion(ROM) and reduction of pain following surgery. The most commonly reported complications with TKA included infection, stiffness, wound complications, intraoperative rupture of tendons, and osteolysis/polyethylene wear. The overwhelming majority of these complications occurred within the first two years following surgery. Six studies examined the survivorship of TKA with subsequent revision for any reason as an endpoint. Compared to patients with osteoarthritis, patients with PTA required more revisions, the majority for polyethylene wear.CONCLUSION Although associated with higher complication rates,TKA is an effective treatment for PTA, as it improves ROM, pain and functional outcomes.
文摘Background : To study the relationships among emodin, synovial fibroblasts (FLSs), and macrophages (STMs) to provide guidance for the use of emodin in rheumatoid arthritis (RA) treatment. Methods : RA clinical samples from patients with different pathological processes were collected, and the correlations between the subsets of FLSs and STMs and pathological processes were analyzed via flow cytometry. In vitro experimental methods such as enzyme linked immunosorbent assay (ELISA), Western blotting, Transwell assays, CCK- 8 assays and cell coculture were used to assess cell proliferation, migration and secretion of inflammatory factors. A collagen- induced arthritis mouse model was constructed to investigate the therapeutic potential of emodin in RA by flow cytometry, micro- CT and staining. Results : Unique subsets of FLSs and STMs, namely, FAPα ^(+)THY1 − FLSs, FAPα ^(+)THY1 ^(+)FLSs, and MerTK ^(pos) TREM2 ^(high) STMs, were identified in synovial tissues from RA patients. The number of MerTK ^(pos) TREM2 ^(high) STMs was negatively correlated with the degree of damage in RA, while the number of FAPα ^(+)THY1 − FLSs was positively correlated with damage. On the one hand, emodin promoted the aggregation of MerTKposTREM2high STMs. Moreover, MerTK pos TREM2 high STM- mediated secretion of exosomes was promoted, which can inhibit the secretion of pro- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs and promote the secretion of anti- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs, thereby inhibiting FAPα ^(+)THY1 − FLS proliferation and migration, improving the local immune microenvironment, and inhibiting RA damage. Conclusion : Emodin was shown to regulate the aggregation of STM subsets and exosome secretion, affecting the secretion, proliferation and migration of inflammatory factors in FLS subsets, and ultimately achieving good therapeutic efficacy in RA patients, suggesting that it has important clinical value.
文摘Rheumatoid arthritis(RA)is a chronic autoimmune disease that affects approxi-mately 0.46%of the global population.Conventional therapeutics for RA,including disease-modifying antirheumatic drugs(DMARDs),nonsteroidal anti-inflammatory drugs(NSAIDs),and corticosteroids,frequently result in unintended adverse effects.Dexamethasone(DEX)is a potent glucocorticoid used to treat RA due to its anti-inflammatory and immunosuppressive properties.Liposomal delivery of DEX,particu-larly when liposomes are surface-modified with targeting ligands like peptides or sialic acid,can improve drug efficacy by enhancing its distribution to inflamed joints and minimizing toxicity.This study investigates the potential of liposomal drug delivery systems to enhance the efficacy and targeting of DEX in the treatment of RA.Results from various studies demonstrate that liposomal DEX significantly inhibits arthritis progression in animal models,reduces joint inflammation and damage,and alleviates cartilage destruction compared to free DEX.The liposomal formulation also shows better hemocompatibility,fewer adverse effects on body weight and immune organ index,and a longer circulation time with higher bioavailability.The anti-inflammatory mechanism is associated with the downregulation of pro-inflammatory cytokines like tumor necrosis factor-α(TNF-α)and B-cell-activating factor(BAFF),which are key players in the pathogenesis of RA.Additionally,liposomal DEX can induce the expres-sion of anti-inflammatory cytokines like interleukin-10(IL-10),which has significant anti-inflammatory and immunoregulatory properties.The findings suggest that lipo-somal DEX represents a promising candidate for effective and safe RA therapy,with the potential to improve the management of this debilitating disease by providing targeted delivery and sustained release of the drug.
基金supported by GILO Foundation.This research is in part supported by Korea Drug Development Fund funded by Ministry of Science and ICT,Ministry of Trade,Industry,and Energy,and Ministry of Health and Welfare(RS-2023-00282595,Republic of Korea).
文摘Rheumatoid arthritis(RA)is an autoimmune disease characterized by inflammation and abnormal osteoclast activation,leading to bone destruction.We previously demonstrated that the large extracellular loop(LEL)of Tm4sf19 is important for its function in osteoclast differentiation,and LEL-Fc,a competitive inhibitor of Tm4sf19,effectively suppresses osteoclast multinucleation and prevent bone loss associated with osteoporosis.This study aimed to investigate the role of Tm4sf19 in RA,an inflammatory and abnormal osteoclast disease,using a mouse model of collagen-induced arthritis(CIA).Tm4sf19 expression was observed in macrophages and osteoclasts within the inflamed synovium,and Tm4sf19 expression was increased together with inflammatory genes in the joint bones of CIA-induced mice compared with the sham control group.Inhibition of Tm4sf19 by LEL-Fc demonstrated both preventive and therapeutic effects in a CIA mouse model,reducing the CIA score,swelling,inflammation,cartilage damage,and bone damage.Knockout of Tm4sf19 gene or inhibition of Tm4sf19 activity by LEL-Fc suppressed LPS/IFN-γ-induced TLR4-mediated inflammatory signaling in macrophages.LEL-Fc disrupted not only the interaction between Tm4sf19 and TLR4/MD2,but also the interaction between TLR4 and MD2.μCT analysis showed that LEL-Fc treatment significantly reduced joint bone destruction and bone loss caused by hyperactivated osteoclasts in CIA mice.Taken together,these findings suggest that LELFc may be a potential treatment for RA and RA-induced osteoporosis by simultaneously targeting joint inflammation and bone destruction caused by abnormal osteoclast activation.
基金the National Natural Science Foundation of China(82372412)the Social Development Project of Jiangsu Province(BE2022701)+4 种基金the Top Talent Support Program for Young and Middle-aged People of the Wuxi Health Committee(BJ2020044,BJ2020057,HB2020043)the Fundamental Research Funds of the Health and Family Planning Commission of Wuxi(M202024)the Special Program for Translational Medicine Research of the Wuxi Translational Medicine Center(2020DHYB07,2020DHYB03)the Key Special Project of Precision Medicine of the Wuxi Health Commission(J202101)peking union medical college hospital talent cultivation program(UHB50192).
文摘Rheumatoid arthritis(RA)is a systemic autoimmune disease in which synovial fibroblasts(SFs)maintain chronic inflammation by secreting proinflammatory mediators,leading to joint destruction.While the role of proinflammatory mediators in this process is well-established,the contribution of non-inflammatory regulators in SFs to joint pathology remains poorly understood.In this study,we investigated the non-inflammatory role of SFs in RA using a co-culture model,and found that SFs from RA patients promote apoptosis of human chondrocytes.Mechanistic investigations reveal that SFs can secrete small extracellular vesicles(sEVs),which are taken up by chondrocytes and induce chondrocyte apoptosis in both normal chondrocytes and chondrocytes from patients with RA.sEV-derived miRNA 15-29148 are identified as key signaling molecules mediating the apoptosis effects of chondrocytes.Further studies reveal that SF-derived miRNA 15-29148 targeting CIAPIN1 results in increased chondrocyte apoptosis.We further demonstrate that SF-derived miRNA 15-29148 is transferred to chondrocytes,exacerbating cartilage damage in vivo.Moreover,chondrocyte-specific aptamer-modified polyamidoamine nanoparticles not only ameliorated RA but also prevented its onset.This study suggests that,in RA,the secretion of specific sEV-miRNAs from SFs plays a crucial role in promoting chondrocyte apoptosis,potentially through non-inflammatory regulation,and that sEV-miRNA inhibition in SFs may represent an early preventive treatment strategy for cartilage degradation in RA.
基金the National Natural Science Foundation of China(Nos.22325703,22377071,U23A6009)Research Project Supported by Shanxi Scholarship Council of China(No.2022-002)+1 种基金the Shanxi Province Science Foundation(No.202203021221009)Shanxi Province Science and Technology activities for overseas people selected funding project(No.2024001)。
文摘Rheumatoid arthritis(RA) is a chronic inflammatory disease with multi-system damage and autoimmune features.The main clinical manifestations of RA include joint pain,swelling,and stiffness,and RA may lead to joint deformity and dysfunction in severe cases.The pathologic development of RA involves complex interactions of multiple biomarkers,and detecting a single biomarker may produce falsepositive results due to other confounding factors.Therefore,fluorescent probes that can detect multiple biomarkers simultaneously are crucial for precise RA diagnosis.Peroxynitrite(ONOO^(-)) and viscosity are inflammation-related factors in cells.In this study,we developed a dual responsive near-infrared fluorescent probe,YLS,for ONOO^(-) and viscosity.The probe features dual-channel turn-on fluorescence responses at 625 and 760 nm upon the presence of ONOO^(-) and viscosity,respectively.Supported by YLS,we found that during RA pathology,lymphocyte infiltration not only increases the concentration of proteins in the joint fluid resulting in elevated viscosity;at the same time,the overproduction of ONOO^(-) exacerbates oxidative stress and inflammatory responses.This multiparameter assay is expected to improve the diagnostic accuracy of the early stages of RA,thus providing a scientific basis for early intervention and personalized treatment.
文摘Post-traumatic stress disorder is a mental disorder caused by exposure to severe traumatic life events.Currently,there are no validated biomarkers or laboratory tests that can distinguish between trauma survivors with and without post-traumatic stress disorder.In addition,the heterogeneity of clinical presentations of post-traumatic stress disorder and the overlap of symptoms with other conditions can lead to misdiagnosis and inappropriate treatment.Evidence suggests that this condition is a multisystem disorder that affects many biological systems,raising the possibility that peripheral markers of disease may be used to diagnose post-traumatic stress disorder.We performed a PubMed search for microRNAs(miRNAs)in post-traumatic stress disorder(PTSD)that could serve as diagnostic biomarkers and found 18 original research articles on studies performed with human patients and published January 2012 to December 2023.These included four studies with whole blood,seven with peripheral blood mononuclear cells,four with plasma extracellular vesicles/exosomes,and one with serum exosomes.One of these studies had also used whole plasma.Two studies were excluded as they did not involve microRNA biomarkers.Most of the studies had collected samples from adult male Veterans who had returned from deployment and been exposed to combat,and only two were from recently traumatized adult subjects.In measuring miRNA expression levels,many of the studies had used microarray miRNA analysis,miRNA Seq analysis,or NanoString panels.Only six studies had used real time polymerase chain reaction assay to determine/validate miRNA expression in PTSD subjects compared to controls.The miRNAs that were found/validated in these studies may be considered as potential candidate biomarkers for PTSD and include miR-3130-5p in whole blood;miR-193a-5p,-7113-5p,-125a,-181c,and-671-5p in peripheral blood mononuclear cells;miR-10b-5p,-203a-3p,-4488,-502-3p,-874-3p,-5100,and-7641 in plasma extracellular vesicles/exosomes;and miR-18a-3p and-7-1-5p in blood plasma.Several important limitations identified in the studies need to be taken into account in future studies.Further studies are warranted with war veterans and recently traumatized children,adolescents,and adults having PTSD and use of animal models subjected to various stressors and the effects of suppressing or overexpressing specific microRNAs.
文摘Introduction: Among the chronic and feared complications of this disease, rheumatoid vasculitis stands out as one of the most severe, albeit rare. The most frequently affected sites by rheumatoid vasculitis are the skin and the peripheral nervous system. We report a case of rheumatoid vasculitis complicating a 30-year history of untreated rheumatoid arthritis. Case Report: The patient is a 75-year-old male with a 30-year history of deforming and erosive seropositive rheumatoid arthritis. He presented with polyarthritis and digital necrosis. Physical examination revealed peripheral joint syndrome with characteristic deformities of rheumatoid arthritis. Additionally, there was well-demarcated dry gangrene affecting the first and second digits of the right hand. Laboratory findings indicated an inflammatory syndrome. Tests for antinuclear antibodies (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA) to investigate other causes of vasculitis were negative. The patient received a corticosteroid bolus. After two weeks, there was a marked reduction in pain and an improvement in the general condition. The dry gangrene remained stable. Conclusion: Rheumatoid vasculitis remains a serious and chronic complication of rheumatoid arthritis, associated with significant mortality. This case highlights the crucial importance of early diagnosis and effective management of rheumatoid arthritis.
基金supported by the National Natural Science Foundation of China(No.82373887)。
文摘Arthritis,encompassing osteoarthritis(OA),rheumatoid arthritis(RA),and gouty arthritis(GA),is a prevalent inflammatory disease that significantly impacts quality of life.Natural products(NPs),derived from animals,plants,marine organisms,and microorganisms,have demonstrated beneficial effects in arthritis treatment both domestically and internationally.These natural compounds offer advantages in drug discovery due to their skeletal diversity,structural complexity,and multi-effect,multi-target,and low-toxicity properties compared to conventional small-molecule medicines.However,unclear mechanisms have hindered the development and clinical application of NPs.This review summarizes recent experimental studies from the past decade on natural medicine for arthritis treatment,emphasizing key NPs with therapeutic effects on OA,RA,and GA.It examines the effects and molecular mechanisms of NPs acting on different cells to treat arthritis.Furthermore,this review provides insights into the future prospects of NP research in this field,which is crucial for advancing NP-based arthritis treatments.
文摘BACKGROUND Prevalence of the main rheumatic diseases in the Republic of Sakha(Yakutia)[RS(Y)],one of the regions of the Russian Federation,differs from the other regions of the Russian Federation due to its ethnic and geographic features.Knowledge regarding the prevalence and structure of juvenile idiopathic arthritis(JIA)allows us to shape the work of the pediatric rheumatology service in the region correctly,and optimize the healthcare system and the need for medica-tions.AIM To describe the epidemiological,demographic,clinical,and laboratory characteristics of children with JIA in the RS(Y)and evaluate the main outcomes.METHODS This retrospective cohort study assessed all the data from the medical histories of the patients(n=225)diagnosed with JIA(2016-2023)in the Cardiorheumatology Department of the M.E.Nikolaev National Center of Medicine.Pearson'sχ²test,Fisher's exact test,Mann–Whitney and Kruskal-Wallis tests were used for statistical analyses.RESULTS The ethnic prevalence of JIA is higher in Sakha than in Russian children at 110.1 per 100000 children and 69.4 per 100000 children,respectively.The prevalence of JIA among boys and girls in Sakha was similar,unlike in Russians,where the number of girls predominated.The JIA categories were as follows:(1)Systemic arthritis:3.5%;(2)Oligoarthritis(persistent and extended):33.8%;(3)Rheumatoid factor(RF)(+)polyarthritis:0.9%;(4)RF(-)polyarthritis:14.7%;(5)Enthesitis-related arthritis(ERA):44%;and(6)Psoriatic arthritis:3.1%.Prevalence of the ERA category was 4.4 times higher in Sakha children,but the prevalence of systemic arthritis was 2.9 times lower compared to Russians(P=0.0005).The frequency of uveitis was 10.2%,and the frequency of human leukocyte antigen(HLA)B27 was 39.6%in JIA children.Biologic treatment was received by 40.4%of JIA children and 45.3%achieved remission.CONCLUSION Higher JIA prevalence,male and ERA predominance,related to a higher frequency of HLA B27 are typical in RS(Y).These data might improve the pediatric rheumatology health service.
基金National Natural Science Foundation of China(81774383)Major Project of Philosophy and Social Science Research in Colleges and Universities of Jiangsu Province (2020SJA0335)Graduate Research and Innovation Projects of Jiangsu Province (SJCX23_0735)。
文摘Objective To reveal the therapeutic effects of moxibustion in collagen-induced arthritis(CIA)rat models using the combined analysis of plasma and synovial membrane lipidomic profil-ing and to enhance the understanding of how moxibustion affects lipid metabolism in rheumatoid arthritis(RA).Methods A total of 32 male Sprague-Dawley(SD)rats were randomly assigned to four groups:control,moxibustion control(MC),model,and moxibustion model(MM)groups,with 8 rats in each group.CIA was induced in SD rats by two immunizations.The paw volume was mea-sured before the induction of CIA.Following induction,after assessing paw volume and arthritis index(AI)scores,the MC and MM groups received treatment at bilateral Shenshu(BL23)and Zusanli(ST36)acupoints for 10 min per acupoint.The intervention included three treatment courses,each spanning 6 d and followed by a 1-d interval.Paw volume and AI scores were assessed after each treatment course.After the completion of the three treatment courses,serum,plasma,synovial tissue,and ankle joint samples were collected.Enzyme-linked immunosorbent assay(ELISA)was employed to quantify the levels of interleukin(IL)-6 and tumor necrosis factor(TNF)-αin serum.Hematoxylin and eosin(HE)staining was per-formed for histopathological examination of the ankle joint tissues.Meanwhile,ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry(UHPLC-Q-Exactive Orbitrap MS)was utilized to analyze the plasma and synovial tissue sam-ples.In addition,multivariate statistical analysis was performed to identify differential lipid metabolites,and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was applied to explore metabolic pathways modulated by moxibustion therapy.Results No significant difference in hind paw volume and AI scores was observed among the groups(P>0.05).After CIA induction,model group showed increased hind paw volume and AI scores compared with control group(P<0.05),which were significantly reduced after mox-ibustion treatment in MM group compared with model group(P<0.05).The levels of IL-6 and TNF-αwere significantly higher in model and MM groups compared with control group(P<0.05),but were lower in MM group than those in model group(P<0.05).Histopathologi-cal analysis showed improved cartilage and reduced inflammation in MM group.A total of 33 differential lipid metabolites in the plasma and 24 in the synovial membranes of CIA rat mod-els were identified when compared with control group.Among these lipid metabolites,31 in the plasma and all 24 in the synovial membranes were regulated by moxibustion treatment.Pathological analysis revealed upregulation of diacylglycerol(DG)and fatty acid(FA)levels,alongside downregulation of lysophosphatidylcholine(LPC),phosphatidylcholine(PC),and phosphatidylethanolamine(PE).Under physiological conditions,the treatment specifically reduced LPC and PC levels.Pathway enrichment analysis revealed that moxibustion predom-inantly affectedα-linolenic acid,glycerophospholipid,and sphingolipid metabolism under pathological conditions.Under physiological conditions,the regulation was centered aroundα-linolenic acid and glycerophospholipid metabolism.Conclusion The RA rat models exhibited significant lipid metabolic disturbances.Moxibus-tion alleviated paw swelling,reduced AI scores,modulated inflammatory cytokine levels,and partially corrected the altered levels of multiple lipid metabolites.The potential metabolic pathways implicated in the regulation of lipid metabolism under both physiological and pathological conditions includeα-linolenic acid,glycerophospholipid,and sphingolipid metabolism.
基金funded by the Scientific Research Projects Unit(BAP)ofİnönüUniversity under project number SBA-2024-3449.
文摘Objectives:This study examines the effectiveness of an eight-week game-based physical activity program designed to reduce post-traumatic stress levels in children affected by the Kahramanmaraş-centered earthquakes that occurred in Turkey on 06 February 2023.Following the earthquake,millions of children experienced significant changes in their education and living conditions,adversely affecting their psychological health.Methods:The therapeutic effects of physical activity on post-traumatic stress disorder(PTSD)are frequently emphasized in the literature,and this study specifically focuses on the impact of game-based exercises.The research employed an experimental design,involving 80 earthquake-affected children aged 10 to 13,who were randomly assigned to either an experimental group(n=40)or a control group(n=40).The experimental group participated in game-based physical activities three times per week for eight weeks,with each session lasting 60 min.Data were collected using the Child Post-Traumatic Stress Reaction Index(CPTS-RI),and pre-test and post-test comparisons were conducted.Results:Children in the experimental group showed a marked reduction in PTSD symptoms,with mean CPTS-RI scores decreasing from 2.60 at pre-test to 1.91 at post-test.In contrast,the control group’s scores remained virtually unchanged(2.59 at pre-test vs.2.57 at post-test).Two-way ANOVA demonstrated significant main effects of group and time,as well as a significant group×time interaction(F=114.88,p<0.001,η^(2)=0.42),indicating that the reduction was attributable to participation in the game-based physical activity program.These findings highlight not only the statistical significance but also the practical relevance of structured,culturally adapted physical activity interventions for trauma-exposed children.Conclusion:These findings suggest that regular,structured game-based physical activities can support the mental health of children following traumatic events such as earthquakes and reduce their stress levels.The study recommends integrating physical activity into post-disaster psychosocial support programs and highlights it as an effective,accessible,and enjoyable method to enhance children’s trauma coping skills.Accordingly,it advocates for the wider implementation of physical activity-based interventions in similar crisis situations.
基金supported by the National Natural Science Foundation of China(NSFC)(No.82130073,No.82372430,No.31871431,No.31821002,No.32101011,No.22177073)Shanghai Frontiers Science Center of Degeneration and Regeneration in Skeletal System+3 种基金Shanghai Science and Technology Committee(No.23ZR1437600,No.24410710600,No.24141901302)Shenzhen Medical Research Fund(No.B2302005)The Open Project Funding of Shanghai Key Laboratory of Orthopedics(No.KFKT202201)Biomaterials and Regenerative Medicine Institute Cooperative,Research Project,Shanghai Jiao Tong University School of Medicine(No.2022LHA01).
文摘Itaconate,a macrophage-specific anti-inflammatory metabolite,has recently emerged as a critical regulator in rheumatoid arthritis pathogenesis.We found that itaconate is a TNF-αresponsive metabolite significantly elevated in the serum and synovial fluid of rheumatoid arthritis patients and we demonstrated that itaconate is primarily produced by inflammatory macrophages rather than osteoclasts or osteoblasts.In TNF-transgenic and Irg1−/−hybrid mice,a more severe bone destruction phenotype was observed.
文摘Rheumatoid arthritis(RA)is a common chronic autoimmune disease characterized by joint pain,swelling and dysfunction[1].According to epidemiologic statistics,the incidence of RA is 1%–2%,and in severe cases,it can develop into joint deformity and disability,which brings a heavy burden to the family and society[2].However,the pathogenesis of RA is complex and involves multiple cellular interactions,which increases the difficulty of curing RA.Current therapeutic options,such as disease-modifying antirheumatic drugs,non-steroidal anti-inflammatory drugs,and biologics,still face the challenge of relapse after drug discontinuation[3,4].Therefore,the pathogenesis of RA needs to be analyzed in depth to break through the existing therapeutic bottlenecks and promote the iterative innovation of individualized diagnosis and treatment.
基金supported by NIH grants to M Bukrinsky P30 AI117970by the“Creation of Experimental Laboratories in the Natural Sciences Program”and Basic Research Program at the Higher School of Economics University.
文摘Eosinophils are multifunctional granulocytes that contribute to the initiation and modulation of inflammation.Accumulating evidence suggests that eosinophils are adaptable leukocytes that orchestrate the resolution of inflammatory responses.The most prevalent chronic inflammatory illness,rheumatoid arthritis(RA),is typified by persistent synovitis thatmakes it hard for the disease to go away on its own.Interestingly,a unique subset of eosinophils known as regulatory eosinophils has been found in RA patients’synovium,especially while the disease is in remission.Pro-resolving signatures of regulatory eosinophils in the synovium are distinct from those of their lung counterparts.The most recent research on eosinophils and their function in this disease pathogenesis is compiled in this review.Based on the role of regulatory eosinophils,a new pathological model of inflammation resolution in RA is proposed,and potential therapeutic strategies aimed at enhancing the action of regulatory eosinophils in RA are proposed.
文摘BACKGROUND Postoperative anxiety,depression,irritability,and even fear in patients with intertrochanteric femoral fractures may hinder recovery,compromise treatment efficacy,and impede rehabilitation.AIM To investigate the correlations among anxiety,depression,sense of coherence(SOC),and post-traumatic growth(PTG)in patients who underwent intertrochanteric femoral fracture surgery to improve clinical management strategies and outcomes.METHODS This study carefully selected 211 patients who received surgical treatment for intertrochanteric femoral fractures and were admitted to Dongying People’s Hospital from March 2022 to March 2024.Anxiety and depression in these patients were assessed with the anxiety and depression subscales of the Hospital Anxiety and Depression Scale(HADS),respectively.SOC was evaluated using the 13-item SOC scale(SOC-13),which encompasses three key dimensions:Comprehensibility,manageability,and meaningfulness.PTG was assessed with the Chinese version of PTG Inventory(CPTGI),covering five distinct dimensions:Personal strength,appreciation of life,relating to others,new possibilities,and spiritual change.The Pearson correlation coefficient was used to meticulously analyze the associations among HADS-Anxiety,HADS-Depression,SOC-13,and CPTGI.Further,univariate and multivariate analyses were conducted to identify factors that affect PTG in patients who underwent intertrochanteric femoral fracture surgery.RESULTS The collected data demonstrated that 67.30%and 60.66%of the 211 patients experienced anxiety and depression,respectively,with overall anxiety levels ranging from mild to moderate and depression levels being mild.The mean SOC-13 score was 55.73±8.81 points,indicating a generally low SOC level.The average CPTGI score was 54.93±9.92 points,demonstrating a relatively low PTG level.Notably,both HADS-Anxiety and HADS-Depression scores were significantly negatively correlated with CPTGI,whereas SOC-13 scores were significantly positively correlated with CPTGI.Univariate and multivariate analyses identified the presence of comorbidities[odds ratio(OR)=2.747,P=0.003],monthly household income(OR=3.292,P<0.001),and exercise habits(OR=4.651,P<0.001)as independent predictors of PTG in patients.CONCLUSION The results of this study indicate a significant negative correlation of anxiety and depression with PTG in patients after intertrochanteric femoral fracture surgery,whereas a significant positive association exists between SOC and PTG.This study helps more comprehensively understand the psychological status and recovery processes of such patients,thereby potentially providing valuable information for clinical practice and psychological interventions.
基金supported in part by the National Natural Science Foundation of China(Grant No.82350710800,82374470,82202757)Shenzhen Medical Research Fund B2302005,and NHMRC,APP1163933.
文摘Rheumatoid arthritis(RA)is a prevalent and debilitating inflammatory disease that significantly impairs functional capacity and quality of life.RA accelerates musculoskeletal aging,leading to complications such as muscle degeneration and sarcopenia.Recent research has identified myopenia as a condition of significant muscle loss associated with illness,distinct from the muscle wasting seen in other chronic diseases like cancer cachexia or heart failure.In RA,myopenia is characterized by muscle depletion without concurrent significant fat loss,and it can affect individuals of all ages.While inflammation plays a central role,it is not the sole factor contributing to the high incidence of muscle wasting in RA.In subsequent discussions,secondary sarcopenia will be considered alongside myopenia,as both involve muscle wasting decline primarily due to disease.This review summarizes recent findings on the impact of RA-related myopenia and secondary sarcopenia on functional capacity,explores its underlying mechanisms,and discusses contemporary strategies to mitigate the process of musculoskeletal aging in RA patients.
文摘Arthritis is an inflammatory joint disorder that progressively impairs function and diminishes quality of life.Conventional therapies often prove ineffective,as oral administration lacks specificity,resulting in off-target side effects like hepatotoxicity and GIT-related issues.Intravenous administration causes systemic side effects.The characteristic joint-localized symptoms such as pain,stiffness,and inflammation make the localized drug delivery suitable for managing arthritis.Topical/transdermal/intraarticular routes have become viable options for drug delivery in treating arthritis.However,challenges with those localized drug delivery routes include skin barrier and cartilage impermeability.Additionally,conventional intra-articular drug delivery also leads to rapid clearance of drugs from the synovial joint tissue.To circumvent these limitations,researchers have developed nanocarriers that enhance drug permeability through skin and cartilage,influencing localized action.Gel-based nanoengineered therapy employs a gel matrix to incorporate the drug-encapsulated nanocarriers.This approach combines the benefits of gels and nanocarriers to enhance therapeutic effects and improve patient compliance.This review emphasizes deep insights into drug delivery using diverse gelbased novel nanocarriers,exploring their various applications embedded in hyaluronic acid(biopolymer)–based gels,carbopol-based gels,and others.Furthermore,this review discusses the influence of nanocarrier pharmacokinetics on the localization and therapeutic manipulation of macrophages mediated by nanocarriers.The ELVIS(extravasation through leaky vasculature and inflammatory cell-mediated sequestration)effect associated with arthritis is advantageous in drug delivery.Simply put,the ELVIS effect refers to the extravasation of nanocarriers through leaky vasculatures,which finally results in the accumulation of nanocarriers in the joint cavity.
文摘BACKGROUND Although exposure therapy is a proven treatment for post-traumatic stress disorder(PTSD),empirical research is difficult due to ethical issues.Recently,virtual reality-based content that can provide space and time similar to reality for exposure therapy techniques is increasing.AIM To examine exposure therapy using driving simulations in patients with PTSD due to traffic accidents with PTSD symptoms.METHODS The intervention was provided to two individuals who experienced PTSD symptoms after a traffic accident using a driving simulator.Among the singlesubject experimental designs,the ABA(baseline-intervention-baseline)design was used,and the PTSD checklist and brain wave frequency were used to measure the results.RESULTS In all participants,the standard category departure time of the electroencephalogram decreased from baseline,and PTSD symptoms decreased after the intervention.CONCLUSION These results suggest the potential use of a driving simulator as an exposure treatment tool for PTSD.
基金supported by the Institut de Recherche Biomédicale des Armées(Brétigny-sur-Orge,France).
文摘Dear Editor,Post-traumatic stress disorder(PTSD)is a major issue for military personnel,with prevalence rates between 1%and 35%in veterans^([1]),significantly higher than in the general population^([2]).Psychological resources,particularly hope,can protect against PTSD and promote post-traumatic growth^([3]).Hope,conceptualized as both a trait and a state,contributes to well-being and resilience and is negatively associated with PTSD symptoms,representing a psychological factor while mitigating the impact of trauma by fostering resilience and adaptive coping mechanisms.
