Bone resorption is a vital physiological process that enables skeletal remodeling,maintenance,and adaptation to mechanical forces throughout life.While tightly regulated under the physiological state,its dysregulation...Bone resorption is a vital physiological process that enables skeletal remodeling,maintenance,and adaptation to mechanical forces throughout life.While tightly regulated under the physiological state,its dysregulation contributes to pathological conditions such as osteoporosis,rheumatoid arthritis,and periodontitis.Periodontitis is a highly prevalent chronic inflammatory disease driven by dysbiotic biofilms that disrupt the oral microbiome,leading to the progressive breakdown of the periodontal ligament,cementum,and alveolar bone and ultimately resulting in tooth loss.This review outlines the molecular and cellular mechanisms underlying periodontitis,focusing on osteoclastogenesis,the differentiation and activation of osteoclasts,the primary mediators of bone resorption.Key transcriptional regulators,including NFATc1,c-Fos,and c-Src are discussed alongside major signaling pathways such as Mitogen Activated Protein Kinase(MAPK),Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription(JAK/STAT),Nuclear Factor Kappa B(NF-κB),and Phosphoinositide 3-kinase(PI3K)/Akt,to elucidate their roles in the initiation and progression of periodontal bone loss.These pathways orchestrate the inflammatory response and osteoclast activity,underscoring their relevance in periodontitis and other osteolytic conditions.Hallmark features of periodontitis,including chronic inflammation,immune dysregulation,and tissue destruction are highlighted,with emphasis on current and emerging therapeutic strategies targeting these molecular pathways.Special attention is given to small molecules,biologics,and natural compounds that have the potential to modulate key signaling pathways.Although advances in understanding these mechanisms have identified promising therapeutic targets,translation into effective clinical interventions remains challenging.Continued research into regulating bone-resorptive signaling pathways is essential for developing more effective treatments for periodontitis and related inflammatory bone diseases.展开更多
Acute carbon monoxide(CO) poisoning constitutes a lethal hazard globally,causing substantial mortality and morbidity worldwide.^([1-2]) Studies have shown that multiple mechanisms contribute to acute CO poisoning,incl...Acute carbon monoxide(CO) poisoning constitutes a lethal hazard globally,causing substantial mortality and morbidity worldwide.^([1-2]) Studies have shown that multiple mechanisms contribute to acute CO poisoning,including ischemic-hypoxic injury,reactive oxygen species(ROS) generation and inflammatory responses.^([2-5]) Furthermore,excessive inflammatory responses can induce adverse metabolic changes.^([6-7]) Considering these evidence,an interaction may exist between acute CO poisoning and both inflammatory factors and metabolites.However,the mechanisms through which inflammatory factors mediate CO toxicity via metabolic pathways remain largely unexplored.展开更多
Background:Neonatal-onset multisystem inflammatory disease is characterized by fever,urticarial rash,aseptic meningitis,deforming arthropathy,hearing loss,and mental retardation.Many patients have mutations in the col...Background:Neonatal-onset multisystem inflammatory disease is characterized by fever,urticarial rash,aseptic meningitis,deforming arthropathy,hearing loss,and mental retardation.Many patients have mutations in the cold-induced autoinflammatory syndrome 1(CIAS1)gene,encoding cryopyrin,a protein that regulates inflammation.展开更多
Neutrophils,macrophages,CD3^(+),CD4^(+),and CD8^(+)T lymphocytes expressμ-,δ-,andκ-opioid receptors(ORs)with varying affinities for opioids.Mast cells express the atypical OR Mas-related G-protein-coupled receptor ...Neutrophils,macrophages,CD3^(+),CD4^(+),and CD8^(+)T lymphocytes expressμ-,δ-,andκ-opioid receptors(ORs)with varying affinities for opioids.Mast cells express the atypical OR Mas-related G-protein-coupled receptor X2(MRGPRX2),which has a low affinity for morphine.Neutrophils and macrophages can synthesize and release endogenous opioid peptides.Activation of ORs enhances the synthesis of proinflammatory cytokines and the production of reactive oxygen species(ROS)in unstimulated leukocytes.Conversely,OR activation reduces proinflammatory cytokine synthesis in stimulated neutrophils and macrophages.Morphine inhibits Toll-like receptor 4(TLR4)expression in macrophages,thereby attenuating inflammation,whereas methadone induces ROS production in mast cells through TLR4 activation.Stimulation of TLR4 triggersβ-endorphin synthesis in macrophages.The production of proinflammatory cytokines and ROS contributes to cardiac reperfusion injury.Importantly,activation ofκ1-andμ-ORs suppresses proinflammatory cytokine production by leukocytes,thereby mitigating inflammatory injury to the heart and other organs.展开更多
Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrat...Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrated significant associations between CRC risk and various serum metabolites as well as inflammatory cytokines;however,due to limitations in study design and potential confounding factors,the causal relationships remain unclear.This study aims to investigate the causal relationships between inflammatory cytokines,serum metabolites,and CRC risk,providing a theoretical basis for the development of novel early diagnostic biomarkers and therapeutic targets.Methods:A two-sample Mendelian randomization(MR)design was applied using summary statistics from genome-wide association studies(GWAS).Instrumental variables(IVs)were derived from:1)metabolomics GWAS data of 1400 serum metabolites(n=8299);2)cytokine GWAS data of 91 inflammatory factors(n=14824);and 3)CRC risk data from the FinnGen consortium(6847 cases and 314193 controls).The primary analysis was conducted using the inverse-variance weighted(IVW)method,with sensitivity analyses performed using MR Egger regression and the weighted median method.Effect estimates including odds ratios(OR),95%confidence intervals(CI),and false discovery rates(FDR)were calculated.Results:MR analysis indicated that higher levels of axin-1(AXIN1)(OR=0.84195%CI 0.714 to 0.991)and Fms-related tyrosine kinase 3 ligand(Flt3L)(OR=0.916,95%CI 0.844 to 0.994)were associated with a reduced risk of CRC.In contrast,higher levels of Delta/Notchlike epidermal growth factor-related receptor(DNER)(OR=1.119,95%CI 1.009 to 1.241)and vascular endothelial growth factor A(VEGF-A)(OR=1.078,95%CI 1.011 to 1.150)were associated with an increased risk of CRC(all P<0.05).Metabolomics association analysis further identified 144 serum metabolites significantly correlated with these four key inflammatory cytokines(FDR<0.05),suggesting that they may regulate CRC risk through inflammatory pathways.Conclusion:Specific inflammatory cytokines and serum metabolites have causal relationships with the risk of CRC.These findings provide insights for further exploration of potential risk factors and the development of effective prevention strategies for CRC.展开更多
Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen...Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen et al systematically evaluated six complete blood count-derived inflammatory indices:Neutrophil-tolymphocyte ratio,monocyte-to-lymphocyte ratio,platelet-to-lymphocyte ratio,systemic immune-inflammation index,systemic inflammatory response index(SIRI),and aggregate index of systemic inflammation and demonstrated their positive associations with GU prevalence,identifying SIRI as the strongest predictor.This editorial contextualizes these findings within the broader literature,clarifies that these indices reflect systemic rather than GU-specific inflammation,highlights methodological strengths and major limitations,and proposes a conceptual clinical algorithm for integrating SIRI into GU risk assessment.Future multicenter studies incorporating Helicobacter pylori infection,non-steroidal antiinflammatory drug exposure,and prospective design are essential to validate and translate these findings into clinical practice.展开更多
Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),is a chronic inflammatory condition affecting the gastrointestinal tract.The global incidence and prevalence of IBD continu...Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),is a chronic inflammatory condition affecting the gastrointestinal tract.The global incidence and prevalence of IBD continue to increase.While multiple clinical treatments exist,conventional therapies frequently present limitations and adverse effects.Natural polysaccharides(PSs)have emerged as a significant focus of research interest due to their therapeutic potential and applications in functional foods and health products.This review synthesizes current understanding of IBD pathophysiology and the mechanisms by which natural PSs counter IBD,including their capacity to restore immune homeostasis and intestinal barrier function,modulate gut microbiota and metabolites,reduce oxidative stress,and address irregularities in autophagy and endoplasmic reticulum stress(ERS).The review examines the structure-activity relationships of PSs demonstrating anti-IBD effects and identifies promising therapeutic products.The discussion encompasses pharmacokinetics,safety evaluations,and clinical applications of these compounds.This comprehensive review establishes a theoretical foundation for developing natural PS-based therapeutic approaches for IBD management.展开更多
AIM:To investigate the potential causal associations between 41 inflammatory cytokines and myopia using a two-sample Mendelian randomization(MR)approach.METHODS:Publicly available genome-wide association study(GWAS)da...AIM:To investigate the potential causal associations between 41 inflammatory cytokines and myopia using a two-sample Mendelian randomization(MR)approach.METHODS:Publicly available genome-wide association study(GWAS)datasets were utilized for this two-sample MR analysis.Inflammatory cytokine-related GWAS data were extracted from The University of Bristol’s Research Data Repository,and myopia-related GWAS data were obtained from the FinnGen project.Single nucleotide polymorphisms(SNPs)associated with inflammatory cytokines were systematically selected as instrumental variables(IVs)based on three rigorous criteria:relevance,independence,and exclusion of pleiotropy.Five MR methods were employed for causal inference:the inverse-variance weighted(IVW)method as the primary analysis,supplemented by MREgger regression,weighted median estimator,simple mode,and weighted mode approaches.Sensitivity analyses were performed to evaluate the robustness of the causal estimates.RESULTS:A total of 773 myopia-associated SNPs were identified.MR analysis revealed that higher levels of macrophage inflammatory protein 1-α(MIP-1α)were associated with a 17%reduced risk of myopia[odds ratio(OR)=0.83;95%confidence interval(CI):0.69-0.99;P<0.05].In contrast,elevated levels of eotaxin(OR=1.26;95%CI:1.07-1.47;P<0.01),stromal cell-derived factor-1α(SDF-1α;OR=1.68;95%CI:1.08-2.62;P<0.05),and interleukin-2 receptor subunit alpha(IL-2Rα;OR=1.25;95%CI:1.01-1.53;P<0.05)were significantly associated with an increased risk of myopia.Sensitivity analyses confirmed the reliability of these results.CONCLUSION:This study provides evidence supporting a causal relationship between specific inflammatory cytokines and myopia.MIP-1αmay act as a protective factor against myopia,while eotaxin,SDF-1α,and IL-2Rαare potential risk factors for myopia.These findings emphasize the critical role of inflammatory pathways in the pathogenesis of myopia,offering novel insights for the development of preventive and therapeutic strategies for myopia.展开更多
Background:The analgesic effects of multiple electroacupuncture(EA)sessions and single EA sessions differ significantly in pain management.Area 24b(A24b)of the anterior cingulate cortex(ACC)is crucial in pain processi...Background:The analgesic effects of multiple electroacupuncture(EA)sessions and single EA sessions differ significantly in pain management.Area 24b(A24b)of the anterior cingulate cortex(ACC)is crucial in pain processing.EA relieves pain by targeting and modulating the neuronal activity within this subregion.However,whether the cumulative effect of EA antinociception is connected to A24b mechanisms has remained unclear.Methods:In our study,we used the Complete Freund's Adjuvant(CFA)model to induce inflammatory pain and the Spared Nerve Injury(SNI)model to induce neuropathic pain,and adult male C57BL/6,FosTRAP,and FosTRAP:Ai9 mice were used as experimental subjects to investigate the cumulative effect of EA antinociception and whether multiple EA sessions and a single EA session regulate different neuronal populations in the A24b.Results:We observed that EA effectively alleviated pain in mice,with three EA sessions yielding superior analgesic effects compared to a single session.Using chemical genetics combined with FosCreER technology to activate EA-TRAPed cells in the A24b,we found that pain relief was more pronounced with three EA sessions.Moreover,chemogenetic inhibition of EA-TRAPed cells in the A24b reversed the analgesic effects of a single EA session but not those of three EA sessions.Fluorescent in situ hybridization results indicated that three EA sessions significantly increased the number of GABAergic neurons in the A24b compared with a single session.Additionally,retrograde tracing revealed that the A24b circuit that monosynaptically innervates EA-TRAPed cells included projections from the central lateral nucleus(CL),lateral mediodorsal thalamic nucleus(MDL),lateral habenula(LHb),dorsal raphe nucleus(DR),caudal linear nucleus of the raphe(CLi),dorsal tuberomamillary nucleus(DTM),periventricular hypothalamic nucleus(Pe)and hippocampal fields CA1,CA2,and CA3.These findings suggest that multiple EA sessions and single EA sessions activated different neuronal populations in the A24b.The enhanced analgesic effect of multiple EA sessions may be attributed to an increase in the proportion of GABAergic neurons within the A24b.Conclusions:Multiple and single EA sessions recruit distinct neuronal populations in A24b,with the stronger analgesic effect of repeated EA linked to a higher proportion of GABAergic neurons in this region.展开更多
Fluctuating chronic conditions(FCC)in young adults aged 18-30 years,such as type 1 diabetes(T1D),sickle cell disease(SCD),and inflammatory bowel disease(IBD),present unique self-management challenges due to unpredicta...Fluctuating chronic conditions(FCC)in young adults aged 18-30 years,such as type 1 diabetes(T1D),sickle cell disease(SCD),and inflammatory bowel disease(IBD),present unique self-management challenges due to unpredictable symptom patterns that disrupt daily life.Tailored self-management interventions are essential for improving quality of life and health outcomes in this population.This scoping review synthesizes the literature on self-management interventions for young adults with T1D,SCD,and IBD,focusing on key concepts,intervention components,barriers,facilitators,and underlying theoretical frameworks.A systematic search was conducted across seven databases(PubMed,Embase,Cochrane Library,PsycINFO,Medline,CINAHL,and Web of Science)for studies in English published between January 2003 and January 2025.Studies were included if they examined self-management interventions for T1D,SCD,or IBD in young adults aged 18-30 years.Thirty-three studies met the inclusion criteria.Key interventions identified included structured educational programs,digital health tools,and peer support networks.Across different conditions,common themes emerged emphasizing patient education,empowerment,self-regulation,and psychosocial support.Interventions that integrated technology with peer support demonstrated improved engagement and health outcomes.Despite the diversity of approaches,there remains a need for more developmentally appropriate,inclusive interventions that address both condition-specific and shared challenges faced by young adults with FCC.This review highlights gaps in the current evidence base and underscores the importance of personalized,technology-enabled strategies to optimize self-management and health outcomes for this population.展开更多
Background:Immune-mediated inflammatory disease(IMID)and cancer share underlying mechanisms.We aimed to comprehensively evaluate the associations between IMIDs and cancers from global,population and genetic perspectiv...Background:Immune-mediated inflammatory disease(IMID)and cancer share underlying mechanisms.We aimed to comprehensively evaluate the associations between IMIDs and cancers from global,population and genetic perspectives.Methods:A triangulation framework was employed to assess the association between IMIDs and cancers,using the Global Burden of Disease Study(2012-2021)to analyse six IMIDs and 33 cancers.The UK Biobank(UKBB)prospective cohort was subsequently used to validate these associations,with hazard ratios(HRs)and 95%confidence intervals(CIs)estimated by Cox proportional hazards models.Causal inference based on genetic instruments was performed in the FinnGen and UKBB to assess the potential causal effects between IMIDs and cancers.Results:IMIDs were positively associated with the occurrence of cancers from a global perspective.Moreover,170 specific IMID-cancer pairs revealed statistically significant associations.A total of 20 pairs of specific IMID-cancer associations were further confirmed in the UKBB cohort.Among these,the five most pronounced associations included atopic dermatitis with Hodgkin lymphoma(HR=12.56,95%CI:1.76-89.59),with ovarian cancer(HR=5.65,95%CI:1.41-22.65)and with non-Hodgkin lymphoma(HR=5.11,95%CI:1.91-13.63);rheumatoid arthritis with Hodgkin lymphoma(HR=3.85,95%CI:1.11-13.32);and psoriasis with Hodgkin lymphoma(HR=3.43,95%CI:1.69-6.96).Additionally,a positive causal association between rheumatoid arthritis and Hodgkin lymphoma(inverse variance weighted OR=1.31,95%CI:1.10-1.57)was observed.Conclusions:This study provides comprehensive evidence of the relationships between IMIDs and cancers from global,population and genetic perspectives and identifies 20 pairs of specific IMID-cancer associations,thereby contributing to advancements in cancer prevention and control.展开更多
AIM:To investigate the clinical features and prognosis of patients with orbital inflammatory myofibroblastic tumor(IMT).METHODS:This retrospective study collected clinical data from 22 patients diagnosed with orbital ...AIM:To investigate the clinical features and prognosis of patients with orbital inflammatory myofibroblastic tumor(IMT).METHODS:This retrospective study collected clinical data from 22 patients diagnosed with orbital IMT based on histopathological examination.The patients were followed up to assess their prognosis.Clinical data from patients,including age,gender,course of disease,past medical history,primary symptoms,ophthalmologic examination findings,general condition,as well as imaging,laboratory,histopathological,and immunohistochemical results from digital records were collected.Orbital magnetic resonance imaging(MRI)and(or)computed tomography(CT)scans were performed to assess bone destruction of the mass,invasion of surrounding tissues,and any inflammatory changes in periorbital areas.RESULTS:The mean age of patients with orbital IMT was 28.24±3.30y,with a male-to-female ratio of 1.2:1.Main clinical manifestations were proptosis,blurred vision,palpable mass,and pain.Bone destruction and surrounding tissue invasion occurred in 72.73%and 54.55%of cases,respectively.Inflammatory changes in the periorbital site were observed in 77.27%of the patients.Hematoxylin and eosin staining showed proliferation of fibroblasts and myofibroblasts,accompanied by infiltration of lymphocytes and plasma cells.Immunohistochemical staining revealed that smooth muscle actin(SMA)and vimentin were positive in 100%of cases,while anaplastic lymphoma kinase(ALK)showed positivity in 47.37%.The recurrence rate of orbital IMT was 27.27%,and sarcomatous degeneration could occur.There were no significant correlations between recurrence and factors such as age,gender,laterality,duration of the disease,periorbital tissue invasion,bone destruction,periorbital inflammation,tumor size,fever,leukocytosis,or treatment(P>0.05).However,lymphadenopathy and a Ki-67 index of 10%or higher may be risk factors for recurrence(P=0.046;P=0.023).CONCLUSION:Orbital IMT is a locally invasive disease that may recur or lead to sarcomatoid degeneration,primarily affecting young and middle-aged patients.The presence of lymphadenopathy and a Ki-67 index of 10%or higher may signify a poor prognosis.展开更多
Therapy discontinuation in inflammatory bowel disease,particularly involving immunomodulators,biologics,and small molecules,remains a controversial and evolving topic.This letter reflects on developments following the...Therapy discontinuation in inflammatory bowel disease,particularly involving immunomodulators,biologics,and small molecules,remains a controversial and evolving topic.This letter reflects on developments following the publication by Meštrovićet al,emphasizing the complex balance between risks of relapse,antidrug antibody formation,and potential complications of long-term immunosuppression.Recent evidence underscores high relapse rates following withdrawal-especially of anti-tumor necrosis factor agents-and highlights the lack of robust data for newer biologics.Updated guidelines from European Crohn’s and Colitis Organization,British Society of Gastroenterology,and American College of Gastroenterology all support cautious and individualized approaches,with strict criteria and close follow-up,particularly in Crohn’s disease.For ulcerative colitis,therapeutic cycling remains insufficiently addressed.We proposed a flowchart to support clinical decision-making and stress the importance of shared decisionmaking in the era of personalized medicine since,despite new drug classes and evolving strategies,the therapeutic ceiling in inflammatory bowel disease has yet to be fully overcome.展开更多
Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim...Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim to control the spread of neuroinflammation during the acute phase but later hinder axon regeneration in later stages.Recent studies have enhanced our understanding of immunomodulation,revealing that injury-associated inflammation involves various cell types and molecules with positive and negative effects.This review employs bibliometric analysis to examine the literature on inflammatory mediators in spinal cord injury,highlighting recent research and providing a comprehensive overview of the current state of research and the latest advances in studies on neuroinflammation related to spinal cord injury.We summarize the immune and inflammatory responses at different stages of spinal cord injury,offering crucial insights for future research.Additionally,we review repair strategies based on inflammatory mediators for the injured spinal cord.Finally,this review discusses the current status and future directions of translational research focused on immune-targeting strategies,including pharmaceuticals,biomedical engineering,and gene therapy.The development of a combined,precise,and multitemporal strategy for the repair of injured spinal cords represents a promising direction for future research.展开更多
Objective:Based on the theory of“Taiyang governs tendons”,to explore the effect of acupuncture at points of the Bladder Meridian of Foot-Taiyang on the expression of serum inflammatory factors in rabbit models of ce...Objective:Based on the theory of“Taiyang governs tendons”,to explore the effect of acupuncture at points of the Bladder Meridian of Foot-Taiyang on the expression of serum inflammatory factors in rabbit models of cervical spondylosis.Methods:Thirty New Zealand white rabbits were randomly divided into a blank group,a model group,and a treatment group,with 10 rabbits in each group.The models of cervical spondylosis in the model group and treatment group were established by long-term head-down flexion combined with cold-damp stimulation.After modeling,the treatment group received acupuncture at three points(Kunlun,Weizhong,and Feishu)on the Bladder Meridian of Foot-Taiyang,once a day for 20 minutes each time,for 14 consecutive days;the model group and blank group received no therapeutic intervention.After the intervention,cardiac blood was collected from all rabbits to detect the expression levels of serum inflammatory factors IL-6,TNF-α,and IL-1β.Meanwhile,cervical muscle tissue was collected,stained with HE,and the morphological changes of the posterior cervical muscle tissue in each group were observed under an optical microscope.Results:After modeling,the levels of inflammatory factors in the serum of rabbits in the model group and treatment group were significantly increased compared with those before modeling,with a statistically significant difference(p<0.01).After intervention,the serum inflammatory factors in the treatment group decreased significantly compared with those in the model group,and the difference was statistically significant(p<0.01).Conclusion:Acupuncture at points of the Bladder Meridian of Foot-Taiyang in rabbit models of cervical spondylosis can reduce the serum levels of inflammatory factors TNF-α,IL-1β,and IL-6.展开更多
Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues...Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues,their role in spinal cord injury has yet to be determined.In this study,we investigated the role and mechanisms of spinal cord tissue exosomes in the inflammatory response following spinal cord injury.We found morphological,concentration,and functional differences between exosomes extracted from injured and normal spinal cord tissues,and identified proinflammatory effects associated with spinal cord injury-generated tissue exosomes but not with exosomes derived from normal spinal cord tissue.Our in vivo and in vitro analyses showed that spinal cord injury-generated tissue exosomes promoted microglial M1 polarization and inflammatory cytokine expression,thereby exacerbating tissue and neuronal injury in the spinal cord.In addition,the combination of exosomal miRNA sequencing and experimental verification showed that the miR-155-5p level was higher in spinal cord injury-generated tissue exosomes than in spinal cord tissue.We further found that spinal cord injury-generated tissue exosomes-derived miR-155-5p induced a significant inhibition of forkhead box O3a phosphorylation and activated the nuclear factor-kappa B pathway,thereby promoting microglial M1 polarization and inflammatory cytokine expression.These findings suggest that injury-induced miR-155-5p-containing exosomes exacerbate spinal cord injury via the promotion of microglial M1 polarization and inflammatory responses.Thus,targeting miR-155-5p expression or exosome secretion could be a novel strategy for attenuating inflammation and reducing secondary injury post-spinal cord injury.展开更多
Inflammatory bowel disease(IBD)is increasing globally,with risk factors still poorly understood and influenced by both genetic and environmental factors.The role of atmospheric pollutants,particularly precursor organi...Inflammatory bowel disease(IBD)is increasing globally,with risk factors still poorly understood and influenced by both genetic and environmental factors.The role of atmospheric pollutants,particularly precursor organic pollutants contributing to<2.5μm size particulate matter(PM_(2.5)),remains unclear.In this multi-decadal global study,we investigated their contribution to IBD prevalence using data from the Global Burden of Disease(GBD,1990–2019),NASA’s MERRA-2,and AERONET datasets.A graph neural network(GNN)modeled spatio-temporal dependencies and incorporated immune dysfunction and socio-economic disparities.The dataset was split into 75%training and 25%testing,achieving mean squared errors of 4.3%and 4.6%respectively,with strong predictive validity(R2=0.87).A 10%global increase in organics was associated with a rise in odds ratio(OR)by 0.21(95%CI:0.12–0.29,p<0.001),compared to a smaller OR increase of 0.04(95%CI:0.01–0.09,p<0.001)for PM_(2.5).Regional disparities were evident,with Sub-Saharan Africa exhibiting higher odds ratios(OR=1.25;95%CI:1.09–1.43,p<0.01)than North America(OR=1.08;95%CI:1.03–1.24,p<0.05)at an organic burden of 5μg/m^(3).However,this trend reversed at higher exposure(25μg/m^(3)),where the OR for North America approaches 2,while Sub-Saharan Africa plateaued near 1.5.Notably,particles under 100 nm posed the greatest risk.Concluding,organic pollutants play a disproportionate and size-dependent role in IBD prevalence,with significant regional variability.This underscores the need to consider organics as a distinct environmental risk factor in IBD epidemiology.展开更多
Heat shock protein beta-1 may be involved in regulating ferroptosis in cells.The expression of heat shock protein beta-1 is upregulated after stroke;however,the underlying mechanism of action of heat shock protein bet...Heat shock protein beta-1 may be involved in regulating ferroptosis in cells.The expression of heat shock protein beta-1 is upregulated after stroke;however,the underlying mechanism of action of heat shock protein beta-1 in cerebral ischemia/reperfusion injury remains unclear.Here,using both in vivo and in vitro models of ischemic injury-middle cerebral artery occlusion/reperfusion in C57BL/6J mice and oxygen-glucose deprivation/reoxygenation in BV-2 microglial cells-we observed that heat shock protein beta-1 overexpression significantly reduced infarct volume,mitigated neuronal loss,and improved neurological outcomes.Mechanistically,heat shock protein beta-1 attenuated lipid peroxidation,intracellular iron accumulation,and reactive oxygen species generation in microglia;this was accompanied by enhanced glutathione peroxidase 4 expression and suppressed nuclear factor-κB pathway activation.Notably,the pharmacological activation of nuclear factor-κB with phorbol 12-myristate 13-acetate reversed the protective effects of heat shock protein beta-1,confirming the functional relevance of this pathway.Together,our findings indicate that heat shock protein beta-1 exerts neuroprotective effects against cerebral ischemia/reperfusion injury by suppressing microglial ferroptosis and pro-inflammatory activation via modulation of the nuclear factor-κB/glutathione peroxidase 4 signaling axis.These findings establish heat shock protein beta-1 as a critical regulator of the nuclear factor-κB/glutathione peroxidase 4 axis in microglia,thereby offering a dual-targeted strategy to inhibit ferroptosis and inflammation in ischemic stroke.Importantly,our study highlights heat shock protein beta-1 as a promising therapeutic candidate for preserving neurological function following cerebral ischemic injury.展开更多
Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical ...Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical assessments,endoscopic evaluations,imaging studies,and biomarker testing,where early diagnosis is essential for effective management and prevention of long-term complications,highlighting the need for continual advancements in diagnostic methods.The intricate interplay between genetic factors and the outcomes of biological therapy is of critical importance.Unraveling the genetic determinants that influence responses and failures to biological therapy holds significant promise for optimizing treatment strategies for patients with IBD on biologics.Through an indepth examination of current literature,this review article synthesizes critical genetic markers associated with therapeutic efficacy and resistance in IBD.Understanding these genetic actors paves the way for personalized approaches,informing clinicians on predicting,tailoring,and enhancing the effectiveness of biological therapies for improved outcomes in patients with IBD.展开更多
Pediatric inflammatory bowel disease(IBD),encompassing Crohn’s disease,ulcerative colitis,and IBD-unclassified,has become increasingly prevalent worldwide,including in previously low-incidence regions.Children often ...Pediatric inflammatory bowel disease(IBD),encompassing Crohn’s disease,ulcerative colitis,and IBD-unclassified,has become increasingly prevalent worldwide,including in previously low-incidence regions.Children often present with more extensive and aggressive disease,creating unique diagnostic and management challenges that differ significantly from adult-onset IBD.This review aims to synthesize current knowledge on pediatric IBD,highlighting historical challenges while exploring emerging frontiers in diagnosis,treatment,and long-term care strategies.A narrative synthesis of global and regional epidemiological data,clinical classifications,diagnostic advancements,management approaches,and psychosocial considerations was conducted,with a particular emphasis on innovations in precision medicine,microbiome-targeted therapy,and multidisciplinary care models.Pediatric IBD continues to rise globally,driven by environmental and genetic interactions,especially in rapidly industrializing regions.Novel diagnostic tools,age-specific treatment protocols,biologics,nutritional strategies,and psychosocial support are reshaping care.Emphasis on very early-onset IBD,transition care,and regional policy adaptations underscores the evolving complexity of managing pediatric IBD.The landscape of pediatric IBD care is rapidly evolving.Addressing the distinct pathophysiology,developmental impact,and healthcare challenges of pediatric patients requires an integrated,child-centered approach.Ongoing research into genetics,immune pathways,and the microbiome will be essential in tailoring precision therapies and improving outcomes globally.展开更多
基金supported by grant provided by the Sao Paulo Research Foundation-FAPESP.Grant#2023/15750-7。
文摘Bone resorption is a vital physiological process that enables skeletal remodeling,maintenance,and adaptation to mechanical forces throughout life.While tightly regulated under the physiological state,its dysregulation contributes to pathological conditions such as osteoporosis,rheumatoid arthritis,and periodontitis.Periodontitis is a highly prevalent chronic inflammatory disease driven by dysbiotic biofilms that disrupt the oral microbiome,leading to the progressive breakdown of the periodontal ligament,cementum,and alveolar bone and ultimately resulting in tooth loss.This review outlines the molecular and cellular mechanisms underlying periodontitis,focusing on osteoclastogenesis,the differentiation and activation of osteoclasts,the primary mediators of bone resorption.Key transcriptional regulators,including NFATc1,c-Fos,and c-Src are discussed alongside major signaling pathways such as Mitogen Activated Protein Kinase(MAPK),Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription(JAK/STAT),Nuclear Factor Kappa B(NF-κB),and Phosphoinositide 3-kinase(PI3K)/Akt,to elucidate their roles in the initiation and progression of periodontal bone loss.These pathways orchestrate the inflammatory response and osteoclast activity,underscoring their relevance in periodontitis and other osteolytic conditions.Hallmark features of periodontitis,including chronic inflammation,immune dysregulation,and tissue destruction are highlighted,with emphasis on current and emerging therapeutic strategies targeting these molecular pathways.Special attention is given to small molecules,biologics,and natural compounds that have the potential to modulate key signaling pathways.Although advances in understanding these mechanisms have identified promising therapeutic targets,translation into effective clinical interventions remains challenging.Continued research into regulating bone-resorptive signaling pathways is essential for developing more effective treatments for periodontitis and related inflammatory bone diseases.
基金supported by the National Natural Science Foundation of China (82372211)。
文摘Acute carbon monoxide(CO) poisoning constitutes a lethal hazard globally,causing substantial mortality and morbidity worldwide.^([1-2]) Studies have shown that multiple mechanisms contribute to acute CO poisoning,including ischemic-hypoxic injury,reactive oxygen species(ROS) generation and inflammatory responses.^([2-5]) Furthermore,excessive inflammatory responses can induce adverse metabolic changes.^([6-7]) Considering these evidence,an interaction may exist between acute CO poisoning and both inflammatory factors and metabolites.However,the mechanisms through which inflammatory factors mediate CO toxicity via metabolic pathways remain largely unexplored.
文摘Background:Neonatal-onset multisystem inflammatory disease is characterized by fever,urticarial rash,aseptic meningitis,deforming arthropathy,hearing loss,and mental retardation.Many patients have mutations in the cold-induced autoinflammatory syndrome 1(CIAS1)gene,encoding cryopyrin,a protein that regulates inflammation.
基金supported by the Russian Science Foundation(Grant No.23-65-10017 to B.K.K.and M.K.)The Ministry of Science and Higher Education of the Russian Federation(Grant No.122020300042-4 to L.N.M.)supported the preparation of the minichapter titled"Opioids reduce inflammatory injury of the heart".
文摘Neutrophils,macrophages,CD3^(+),CD4^(+),and CD8^(+)T lymphocytes expressμ-,δ-,andκ-opioid receptors(ORs)with varying affinities for opioids.Mast cells express the atypical OR Mas-related G-protein-coupled receptor X2(MRGPRX2),which has a low affinity for morphine.Neutrophils and macrophages can synthesize and release endogenous opioid peptides.Activation of ORs enhances the synthesis of proinflammatory cytokines and the production of reactive oxygen species(ROS)in unstimulated leukocytes.Conversely,OR activation reduces proinflammatory cytokine synthesis in stimulated neutrophils and macrophages.Morphine inhibits Toll-like receptor 4(TLR4)expression in macrophages,thereby attenuating inflammation,whereas methadone induces ROS production in mast cells through TLR4 activation.Stimulation of TLR4 triggersβ-endorphin synthesis in macrophages.The production of proinflammatory cytokines and ROS contributes to cardiac reperfusion injury.Importantly,activation ofκ1-andμ-ORs suppresses proinflammatory cytokine production by leukocytes,thereby mitigating inflammatory injury to the heart and other organs.
基金supported by the Natural Science Foundation of Hunan Province (2022JJ30987)the Key Research and Development Project of Hunan Province (2024JK2107),China。
文摘Objective:The incidence and mortality of colorectal carcinoma(CRC)continue to rise globally,highlighting the need to identify modifiable risk factors for early detection and prevention.Previous studies have demonstrated significant associations between CRC risk and various serum metabolites as well as inflammatory cytokines;however,due to limitations in study design and potential confounding factors,the causal relationships remain unclear.This study aims to investigate the causal relationships between inflammatory cytokines,serum metabolites,and CRC risk,providing a theoretical basis for the development of novel early diagnostic biomarkers and therapeutic targets.Methods:A two-sample Mendelian randomization(MR)design was applied using summary statistics from genome-wide association studies(GWAS).Instrumental variables(IVs)were derived from:1)metabolomics GWAS data of 1400 serum metabolites(n=8299);2)cytokine GWAS data of 91 inflammatory factors(n=14824);and 3)CRC risk data from the FinnGen consortium(6847 cases and 314193 controls).The primary analysis was conducted using the inverse-variance weighted(IVW)method,with sensitivity analyses performed using MR Egger regression and the weighted median method.Effect estimates including odds ratios(OR),95%confidence intervals(CI),and false discovery rates(FDR)were calculated.Results:MR analysis indicated that higher levels of axin-1(AXIN1)(OR=0.84195%CI 0.714 to 0.991)and Fms-related tyrosine kinase 3 ligand(Flt3L)(OR=0.916,95%CI 0.844 to 0.994)were associated with a reduced risk of CRC.In contrast,higher levels of Delta/Notchlike epidermal growth factor-related receptor(DNER)(OR=1.119,95%CI 1.009 to 1.241)and vascular endothelial growth factor A(VEGF-A)(OR=1.078,95%CI 1.011 to 1.150)were associated with an increased risk of CRC(all P<0.05).Metabolomics association analysis further identified 144 serum metabolites significantly correlated with these four key inflammatory cytokines(FDR<0.05),suggesting that they may regulate CRC risk through inflammatory pathways.Conclusion:Specific inflammatory cytokines and serum metabolites have causal relationships with the risk of CRC.These findings provide insights for further exploration of potential risk factors and the development of effective prevention strategies for CRC.
基金Supported by the National Natural Science Foundation of China,No.82170406 and No.81970238.
文摘Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen et al systematically evaluated six complete blood count-derived inflammatory indices:Neutrophil-tolymphocyte ratio,monocyte-to-lymphocyte ratio,platelet-to-lymphocyte ratio,systemic immune-inflammation index,systemic inflammatory response index(SIRI),and aggregate index of systemic inflammation and demonstrated their positive associations with GU prevalence,identifying SIRI as the strongest predictor.This editorial contextualizes these findings within the broader literature,clarifies that these indices reflect systemic rather than GU-specific inflammation,highlights methodological strengths and major limitations,and proposes a conceptual clinical algorithm for integrating SIRI into GU risk assessment.Future multicenter studies incorporating Helicobacter pylori infection,non-steroidal antiinflammatory drug exposure,and prospective design are essential to validate and translate these findings into clinical practice.
基金supported by the National Natural Science Foundation of China(Nos.82003977,82274134 and 82274139)the National Key Research and Development Plan(No.2017YFC1702200)+1 种基金the Key Research and Development Program of Zhejiang Province(No.2020C04020)the Science and Technology Program of Zhejiang Province(No.2025C02183).
文摘Inflammatory bowel disease(IBD),which includes Crohn’s disease(CD)and ulcerative colitis(UC),is a chronic inflammatory condition affecting the gastrointestinal tract.The global incidence and prevalence of IBD continue to increase.While multiple clinical treatments exist,conventional therapies frequently present limitations and adverse effects.Natural polysaccharides(PSs)have emerged as a significant focus of research interest due to their therapeutic potential and applications in functional foods and health products.This review synthesizes current understanding of IBD pathophysiology and the mechanisms by which natural PSs counter IBD,including their capacity to restore immune homeostasis and intestinal barrier function,modulate gut microbiota and metabolites,reduce oxidative stress,and address irregularities in autophagy and endoplasmic reticulum stress(ERS).The review examines the structure-activity relationships of PSs demonstrating anti-IBD effects and identifies promising therapeutic products.The discussion encompasses pharmacokinetics,safety evaluations,and clinical applications of these compounds.This comprehensive review establishes a theoretical foundation for developing natural PS-based therapeutic approaches for IBD management.
文摘AIM:To investigate the potential causal associations between 41 inflammatory cytokines and myopia using a two-sample Mendelian randomization(MR)approach.METHODS:Publicly available genome-wide association study(GWAS)datasets were utilized for this two-sample MR analysis.Inflammatory cytokine-related GWAS data were extracted from The University of Bristol’s Research Data Repository,and myopia-related GWAS data were obtained from the FinnGen project.Single nucleotide polymorphisms(SNPs)associated with inflammatory cytokines were systematically selected as instrumental variables(IVs)based on three rigorous criteria:relevance,independence,and exclusion of pleiotropy.Five MR methods were employed for causal inference:the inverse-variance weighted(IVW)method as the primary analysis,supplemented by MREgger regression,weighted median estimator,simple mode,and weighted mode approaches.Sensitivity analyses were performed to evaluate the robustness of the causal estimates.RESULTS:A total of 773 myopia-associated SNPs were identified.MR analysis revealed that higher levels of macrophage inflammatory protein 1-α(MIP-1α)were associated with a 17%reduced risk of myopia[odds ratio(OR)=0.83;95%confidence interval(CI):0.69-0.99;P<0.05].In contrast,elevated levels of eotaxin(OR=1.26;95%CI:1.07-1.47;P<0.01),stromal cell-derived factor-1α(SDF-1α;OR=1.68;95%CI:1.08-2.62;P<0.05),and interleukin-2 receptor subunit alpha(IL-2Rα;OR=1.25;95%CI:1.01-1.53;P<0.05)were significantly associated with an increased risk of myopia.Sensitivity analyses confirmed the reliability of these results.CONCLUSION:This study provides evidence supporting a causal relationship between specific inflammatory cytokines and myopia.MIP-1αmay act as a protective factor against myopia,while eotaxin,SDF-1α,and IL-2Rαare potential risk factors for myopia.These findings emphasize the critical role of inflammatory pathways in the pathogenesis of myopia,offering novel insights for the development of preventive and therapeutic strategies for myopia.
基金The National Natural Science Fund of China(82374561,82174490,81873360)the Research Project of Zhejiang Chinese Medical University(2022JKZKTS44,2022FSYYZZ07)the Zhejiang Medical and Health Science and Technology Program(2021RC098)。
文摘Background:The analgesic effects of multiple electroacupuncture(EA)sessions and single EA sessions differ significantly in pain management.Area 24b(A24b)of the anterior cingulate cortex(ACC)is crucial in pain processing.EA relieves pain by targeting and modulating the neuronal activity within this subregion.However,whether the cumulative effect of EA antinociception is connected to A24b mechanisms has remained unclear.Methods:In our study,we used the Complete Freund's Adjuvant(CFA)model to induce inflammatory pain and the Spared Nerve Injury(SNI)model to induce neuropathic pain,and adult male C57BL/6,FosTRAP,and FosTRAP:Ai9 mice were used as experimental subjects to investigate the cumulative effect of EA antinociception and whether multiple EA sessions and a single EA session regulate different neuronal populations in the A24b.Results:We observed that EA effectively alleviated pain in mice,with three EA sessions yielding superior analgesic effects compared to a single session.Using chemical genetics combined with FosCreER technology to activate EA-TRAPed cells in the A24b,we found that pain relief was more pronounced with three EA sessions.Moreover,chemogenetic inhibition of EA-TRAPed cells in the A24b reversed the analgesic effects of a single EA session but not those of three EA sessions.Fluorescent in situ hybridization results indicated that three EA sessions significantly increased the number of GABAergic neurons in the A24b compared with a single session.Additionally,retrograde tracing revealed that the A24b circuit that monosynaptically innervates EA-TRAPed cells included projections from the central lateral nucleus(CL),lateral mediodorsal thalamic nucleus(MDL),lateral habenula(LHb),dorsal raphe nucleus(DR),caudal linear nucleus of the raphe(CLi),dorsal tuberomamillary nucleus(DTM),periventricular hypothalamic nucleus(Pe)and hippocampal fields CA1,CA2,and CA3.These findings suggest that multiple EA sessions and single EA sessions activated different neuronal populations in the A24b.The enhanced analgesic effect of multiple EA sessions may be attributed to an increase in the proportion of GABAergic neurons within the A24b.Conclusions:Multiple and single EA sessions recruit distinct neuronal populations in A24b,with the stronger analgesic effect of repeated EA linked to a higher proportion of GABAergic neurons in this region.
文摘Fluctuating chronic conditions(FCC)in young adults aged 18-30 years,such as type 1 diabetes(T1D),sickle cell disease(SCD),and inflammatory bowel disease(IBD),present unique self-management challenges due to unpredictable symptom patterns that disrupt daily life.Tailored self-management interventions are essential for improving quality of life and health outcomes in this population.This scoping review synthesizes the literature on self-management interventions for young adults with T1D,SCD,and IBD,focusing on key concepts,intervention components,barriers,facilitators,and underlying theoretical frameworks.A systematic search was conducted across seven databases(PubMed,Embase,Cochrane Library,PsycINFO,Medline,CINAHL,and Web of Science)for studies in English published between January 2003 and January 2025.Studies were included if they examined self-management interventions for T1D,SCD,or IBD in young adults aged 18-30 years.Thirty-three studies met the inclusion criteria.Key interventions identified included structured educational programs,digital health tools,and peer support networks.Across different conditions,common themes emerged emphasizing patient education,empowerment,self-regulation,and psychosocial support.Interventions that integrated technology with peer support demonstrated improved engagement and health outcomes.Despite the diversity of approaches,there remains a need for more developmentally appropriate,inclusive interventions that address both condition-specific and shared challenges faced by young adults with FCC.This review highlights gaps in the current evidence base and underscores the importance of personalized,technology-enabled strategies to optimize self-management and health outcomes for this population.
基金National Natural Science Foundation of China,Grant/Award Numbers:82404340,82273722,82373685,82204143CAMS Innovation Fund for Medical Science,Grant/Award Number:2021-I2M-1-067Open Research Fund Programme of Changzhou Institute for Advanced Study of Public Health,Nanjing Medical University,Grant/Award Number:CPHM202301。
文摘Background:Immune-mediated inflammatory disease(IMID)and cancer share underlying mechanisms.We aimed to comprehensively evaluate the associations between IMIDs and cancers from global,population and genetic perspectives.Methods:A triangulation framework was employed to assess the association between IMIDs and cancers,using the Global Burden of Disease Study(2012-2021)to analyse six IMIDs and 33 cancers.The UK Biobank(UKBB)prospective cohort was subsequently used to validate these associations,with hazard ratios(HRs)and 95%confidence intervals(CIs)estimated by Cox proportional hazards models.Causal inference based on genetic instruments was performed in the FinnGen and UKBB to assess the potential causal effects between IMIDs and cancers.Results:IMIDs were positively associated with the occurrence of cancers from a global perspective.Moreover,170 specific IMID-cancer pairs revealed statistically significant associations.A total of 20 pairs of specific IMID-cancer associations were further confirmed in the UKBB cohort.Among these,the five most pronounced associations included atopic dermatitis with Hodgkin lymphoma(HR=12.56,95%CI:1.76-89.59),with ovarian cancer(HR=5.65,95%CI:1.41-22.65)and with non-Hodgkin lymphoma(HR=5.11,95%CI:1.91-13.63);rheumatoid arthritis with Hodgkin lymphoma(HR=3.85,95%CI:1.11-13.32);and psoriasis with Hodgkin lymphoma(HR=3.43,95%CI:1.69-6.96).Additionally,a positive causal association between rheumatoid arthritis and Hodgkin lymphoma(inverse variance weighted OR=1.31,95%CI:1.10-1.57)was observed.Conclusions:This study provides comprehensive evidence of the relationships between IMIDs and cancers from global,population and genetic perspectives and identifies 20 pairs of specific IMID-cancer associations,thereby contributing to advancements in cancer prevention and control.
基金Supported by the National Key R&D Program of China(No.2023YFC2410203)Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(No.ZLRK202503).
文摘AIM:To investigate the clinical features and prognosis of patients with orbital inflammatory myofibroblastic tumor(IMT).METHODS:This retrospective study collected clinical data from 22 patients diagnosed with orbital IMT based on histopathological examination.The patients were followed up to assess their prognosis.Clinical data from patients,including age,gender,course of disease,past medical history,primary symptoms,ophthalmologic examination findings,general condition,as well as imaging,laboratory,histopathological,and immunohistochemical results from digital records were collected.Orbital magnetic resonance imaging(MRI)and(or)computed tomography(CT)scans were performed to assess bone destruction of the mass,invasion of surrounding tissues,and any inflammatory changes in periorbital areas.RESULTS:The mean age of patients with orbital IMT was 28.24±3.30y,with a male-to-female ratio of 1.2:1.Main clinical manifestations were proptosis,blurred vision,palpable mass,and pain.Bone destruction and surrounding tissue invasion occurred in 72.73%and 54.55%of cases,respectively.Inflammatory changes in the periorbital site were observed in 77.27%of the patients.Hematoxylin and eosin staining showed proliferation of fibroblasts and myofibroblasts,accompanied by infiltration of lymphocytes and plasma cells.Immunohistochemical staining revealed that smooth muscle actin(SMA)and vimentin were positive in 100%of cases,while anaplastic lymphoma kinase(ALK)showed positivity in 47.37%.The recurrence rate of orbital IMT was 27.27%,and sarcomatous degeneration could occur.There were no significant correlations between recurrence and factors such as age,gender,laterality,duration of the disease,periorbital tissue invasion,bone destruction,periorbital inflammation,tumor size,fever,leukocytosis,or treatment(P>0.05).However,lymphadenopathy and a Ki-67 index of 10%or higher may be risk factors for recurrence(P=0.046;P=0.023).CONCLUSION:Orbital IMT is a locally invasive disease that may recur or lead to sarcomatoid degeneration,primarily affecting young and middle-aged patients.The presence of lymphadenopathy and a Ki-67 index of 10%or higher may signify a poor prognosis.
文摘Therapy discontinuation in inflammatory bowel disease,particularly involving immunomodulators,biologics,and small molecules,remains a controversial and evolving topic.This letter reflects on developments following the publication by Meštrovićet al,emphasizing the complex balance between risks of relapse,antidrug antibody formation,and potential complications of long-term immunosuppression.Recent evidence underscores high relapse rates following withdrawal-especially of anti-tumor necrosis factor agents-and highlights the lack of robust data for newer biologics.Updated guidelines from European Crohn’s and Colitis Organization,British Society of Gastroenterology,and American College of Gastroenterology all support cautious and individualized approaches,with strict criteria and close follow-up,particularly in Crohn’s disease.For ulcerative colitis,therapeutic cycling remains insufficiently addressed.We proposed a flowchart to support clinical decision-making and stress the importance of shared decisionmaking in the era of personalized medicine since,despite new drug classes and evolving strategies,the therapeutic ceiling in inflammatory bowel disease has yet to be fully overcome.
基金supported by the National Natural Science Foundation of China,Nos.82272470 (to GN),82072439 (to GN),81930070 (to SF)the Tianjin Health Key Discipline Special Project,No.TJWJ2022XK011 (to GN)+2 种基金the Outstanding Youth Foundation of Tianjin Medical University General Hospital,No.22ZYYJQ01 (to GN)Tianjin Key Medical Disciplines,No.TJYXZDXK-027A (to SF)National Key Research and Development Program-Stem Cells and Transformation Research,No.2019YFA0112100 (to SF)
文摘Traumatic spinal cord injury result in considerable and lasting functional impairments,triggering complex inflammatory and pathological events.Spinal cord scars,often metaphorically referred to as“fire barriers,”aim to control the spread of neuroinflammation during the acute phase but later hinder axon regeneration in later stages.Recent studies have enhanced our understanding of immunomodulation,revealing that injury-associated inflammation involves various cell types and molecules with positive and negative effects.This review employs bibliometric analysis to examine the literature on inflammatory mediators in spinal cord injury,highlighting recent research and providing a comprehensive overview of the current state of research and the latest advances in studies on neuroinflammation related to spinal cord injury.We summarize the immune and inflammatory responses at different stages of spinal cord injury,offering crucial insights for future research.Additionally,we review repair strategies based on inflammatory mediators for the injured spinal cord.Finally,this review discusses the current status and future directions of translational research focused on immune-targeting strategies,including pharmaceuticals,biomedical engineering,and gene therapy.The development of a combined,precise,and multitemporal strategy for the repair of injured spinal cords represents a promising direction for future research.
基金Yunnan Provincial High-Level Traditional Chinese Medicine Talent Training ProjectYunnan Provincial Department of Science and Technology Traditional Chinese Medicine Basic Research Joint Special Project(Project No.:202101AZ070001-138)。
文摘Objective:Based on the theory of“Taiyang governs tendons”,to explore the effect of acupuncture at points of the Bladder Meridian of Foot-Taiyang on the expression of serum inflammatory factors in rabbit models of cervical spondylosis.Methods:Thirty New Zealand white rabbits were randomly divided into a blank group,a model group,and a treatment group,with 10 rabbits in each group.The models of cervical spondylosis in the model group and treatment group were established by long-term head-down flexion combined with cold-damp stimulation.After modeling,the treatment group received acupuncture at three points(Kunlun,Weizhong,and Feishu)on the Bladder Meridian of Foot-Taiyang,once a day for 20 minutes each time,for 14 consecutive days;the model group and blank group received no therapeutic intervention.After the intervention,cardiac blood was collected from all rabbits to detect the expression levels of serum inflammatory factors IL-6,TNF-α,and IL-1β.Meanwhile,cervical muscle tissue was collected,stained with HE,and the morphological changes of the posterior cervical muscle tissue in each group were observed under an optical microscope.Results:After modeling,the levels of inflammatory factors in the serum of rabbits in the model group and treatment group were significantly increased compared with those before modeling,with a statistically significant difference(p<0.01).After intervention,the serum inflammatory factors in the treatment group decreased significantly compared with those in the model group,and the difference was statistically significant(p<0.01).Conclusion:Acupuncture at points of the Bladder Meridian of Foot-Taiyang in rabbit models of cervical spondylosis can reduce the serum levels of inflammatory factors TNF-α,IL-1β,and IL-6.
基金supported by the Joint Funds for the Innovation of Science and Technology,Fujian Province,No.2023Y9233(to HH)the QuanzhouScience and Technology Project,No.2022C036R(to HH)+1 种基金the Science and Technology Bureau of Quanzhou,No.2020CT003(to SL)the Quanzhou MunicipalMedical and Health Guiding Science and Technology Project,No.2023N066S(to YZhou).
文摘Spinal cord injury is a critical event characterized by intricate pathogenic mechanisms.Although recent studies have highlighted tissue exosomes as key mediators of inflammatory responses in diverse organs and tissues,their role in spinal cord injury has yet to be determined.In this study,we investigated the role and mechanisms of spinal cord tissue exosomes in the inflammatory response following spinal cord injury.We found morphological,concentration,and functional differences between exosomes extracted from injured and normal spinal cord tissues,and identified proinflammatory effects associated with spinal cord injury-generated tissue exosomes but not with exosomes derived from normal spinal cord tissue.Our in vivo and in vitro analyses showed that spinal cord injury-generated tissue exosomes promoted microglial M1 polarization and inflammatory cytokine expression,thereby exacerbating tissue and neuronal injury in the spinal cord.In addition,the combination of exosomal miRNA sequencing and experimental verification showed that the miR-155-5p level was higher in spinal cord injury-generated tissue exosomes than in spinal cord tissue.We further found that spinal cord injury-generated tissue exosomes-derived miR-155-5p induced a significant inhibition of forkhead box O3a phosphorylation and activated the nuclear factor-kappa B pathway,thereby promoting microglial M1 polarization and inflammatory cytokine expression.These findings suggest that injury-induced miR-155-5p-containing exosomes exacerbate spinal cord injury via the promotion of microglial M1 polarization and inflammatory responses.Thus,targeting miR-155-5p expression or exosome secretion could be a novel strategy for attenuating inflammation and reducing secondary injury post-spinal cord injury.
文摘Inflammatory bowel disease(IBD)is increasing globally,with risk factors still poorly understood and influenced by both genetic and environmental factors.The role of atmospheric pollutants,particularly precursor organic pollutants contributing to<2.5μm size particulate matter(PM_(2.5)),remains unclear.In this multi-decadal global study,we investigated their contribution to IBD prevalence using data from the Global Burden of Disease(GBD,1990–2019),NASA’s MERRA-2,and AERONET datasets.A graph neural network(GNN)modeled spatio-temporal dependencies and incorporated immune dysfunction and socio-economic disparities.The dataset was split into 75%training and 25%testing,achieving mean squared errors of 4.3%and 4.6%respectively,with strong predictive validity(R2=0.87).A 10%global increase in organics was associated with a rise in odds ratio(OR)by 0.21(95%CI:0.12–0.29,p<0.001),compared to a smaller OR increase of 0.04(95%CI:0.01–0.09,p<0.001)for PM_(2.5).Regional disparities were evident,with Sub-Saharan Africa exhibiting higher odds ratios(OR=1.25;95%CI:1.09–1.43,p<0.01)than North America(OR=1.08;95%CI:1.03–1.24,p<0.05)at an organic burden of 5μg/m^(3).However,this trend reversed at higher exposure(25μg/m^(3)),where the OR for North America approaches 2,while Sub-Saharan Africa plateaued near 1.5.Notably,particles under 100 nm posed the greatest risk.Concluding,organic pollutants play a disproportionate and size-dependent role in IBD prevalence,with significant regional variability.This underscores the need to consider organics as a distinct environmental risk factor in IBD epidemiology.
基金“Dawn”Program of Shanghai Education Commission,No.22SG37(to PY)the National Natural Science Foundation of China,Nos.82371313(to PY),82401536(to YongxinZ).
文摘Heat shock protein beta-1 may be involved in regulating ferroptosis in cells.The expression of heat shock protein beta-1 is upregulated after stroke;however,the underlying mechanism of action of heat shock protein beta-1 in cerebral ischemia/reperfusion injury remains unclear.Here,using both in vivo and in vitro models of ischemic injury-middle cerebral artery occlusion/reperfusion in C57BL/6J mice and oxygen-glucose deprivation/reoxygenation in BV-2 microglial cells-we observed that heat shock protein beta-1 overexpression significantly reduced infarct volume,mitigated neuronal loss,and improved neurological outcomes.Mechanistically,heat shock protein beta-1 attenuated lipid peroxidation,intracellular iron accumulation,and reactive oxygen species generation in microglia;this was accompanied by enhanced glutathione peroxidase 4 expression and suppressed nuclear factor-κB pathway activation.Notably,the pharmacological activation of nuclear factor-κB with phorbol 12-myristate 13-acetate reversed the protective effects of heat shock protein beta-1,confirming the functional relevance of this pathway.Together,our findings indicate that heat shock protein beta-1 exerts neuroprotective effects against cerebral ischemia/reperfusion injury by suppressing microglial ferroptosis and pro-inflammatory activation via modulation of the nuclear factor-κB/glutathione peroxidase 4 signaling axis.These findings establish heat shock protein beta-1 as a critical regulator of the nuclear factor-κB/glutathione peroxidase 4 axis in microglia,thereby offering a dual-targeted strategy to inhibit ferroptosis and inflammation in ischemic stroke.Importantly,our study highlights heat shock protein beta-1 as a promising therapeutic candidate for preserving neurological function following cerebral ischemic injury.
基金Supported by The European Union-Next Generation EU,through the National Recovery and Resilience Plan of the Republic of Bulgaria,No.BG-RRP-2.004-0008。
文摘Inflammatory bowel disease(IBD)represents a significant disease burden marked by chronic inflammation and complications that adversely affect patients’quality of life.Effective diagnostic strategies involve clinical assessments,endoscopic evaluations,imaging studies,and biomarker testing,where early diagnosis is essential for effective management and prevention of long-term complications,highlighting the need for continual advancements in diagnostic methods.The intricate interplay between genetic factors and the outcomes of biological therapy is of critical importance.Unraveling the genetic determinants that influence responses and failures to biological therapy holds significant promise for optimizing treatment strategies for patients with IBD on biologics.Through an indepth examination of current literature,this review article synthesizes critical genetic markers associated with therapeutic efficacy and resistance in IBD.Understanding these genetic actors paves the way for personalized approaches,informing clinicians on predicting,tailoring,and enhancing the effectiveness of biological therapies for improved outcomes in patients with IBD.
文摘Pediatric inflammatory bowel disease(IBD),encompassing Crohn’s disease,ulcerative colitis,and IBD-unclassified,has become increasingly prevalent worldwide,including in previously low-incidence regions.Children often present with more extensive and aggressive disease,creating unique diagnostic and management challenges that differ significantly from adult-onset IBD.This review aims to synthesize current knowledge on pediatric IBD,highlighting historical challenges while exploring emerging frontiers in diagnosis,treatment,and long-term care strategies.A narrative synthesis of global and regional epidemiological data,clinical classifications,diagnostic advancements,management approaches,and psychosocial considerations was conducted,with a particular emphasis on innovations in precision medicine,microbiome-targeted therapy,and multidisciplinary care models.Pediatric IBD continues to rise globally,driven by environmental and genetic interactions,especially in rapidly industrializing regions.Novel diagnostic tools,age-specific treatment protocols,biologics,nutritional strategies,and psychosocial support are reshaping care.Emphasis on very early-onset IBD,transition care,and regional policy adaptations underscores the evolving complexity of managing pediatric IBD.The landscape of pediatric IBD care is rapidly evolving.Addressing the distinct pathophysiology,developmental impact,and healthcare challenges of pediatric patients requires an integrated,child-centered approach.Ongoing research into genetics,immune pathways,and the microbiome will be essential in tailoring precision therapies and improving outcomes globally.
