We analysed histologically two Acanthamoeba keratitis(AK) eyes with anterior and posterior segment inflammation and blindness. Two enucleated eyes of 2 patients(age 45 and 51y) with AK(PCR of epithelial abrasion posit...We analysed histologically two Acanthamoeba keratitis(AK) eyes with anterior and posterior segment inflammation and blindness. Two enucleated eyes of 2 patients(age 45 and 51y) with AK(PCR of epithelial abrasion positive) were analysed. Histological analysis was performed using hematoxylin-eosin, periodic acid-Schiff and G?m?rimethenamine silver staining. We could not observe Acanthamoeba trophozoites or cysts neither in the cornea nor in other ocular tissues. Meanwhile, we found uveitis, retinal vasculitis and scleritis in these eyes, due to the long-standing, recalcitrant AK. So in this stage of AK, systemic immune suppression may be necessary for a longer time period.展开更多
BACKGROUND Chronic idiopathic uveitis(CIU)and juvenile idiopathic arthritis-associated uveitis(U-JIA)are both vision-threatening conditions that share similar autoimmune mechanisms,but treatment approaches differ sign...BACKGROUND Chronic idiopathic uveitis(CIU)and juvenile idiopathic arthritis-associated uveitis(U-JIA)are both vision-threatening conditions that share similar autoimmune mechanisms,but treatment approaches differ significantly.In managing U-JIA,various treatment options are employed,including biological and non-biological disease-modifying anti-rheumatic drugs.These drugs are effective in clinical trials.Given the lack of established diagnostic and treatment guidelines as well as the limited number of therapeutic options available,patients with CIU frequently do not receive optimal and timely immunosuppression.This study highlighted the necessity for additional research to develop novel diag-nostic techniques,targeted therapies,and enhanced treatment outcomes for young individuals with CIU.AIM To compare the characteristics and outcomes of U-JIA and CIU.METHODS A retrospective cohort study analyzed data from 110 pediatric patients(under 18 years old)with U-JIA and 40 pediatric patients with CIU.Data was collected between 2012 and 2023.The study focused on demographic,clinical,treatment,and outcome variables.RESULTS The median onset age of arthritis was 6.4 years(2.7 years;9.3 years).In 28.2%of cases uveitis preceded the onset of arthritis.In 17.3%of cases it occurred simultan-eously.In 53.6%of cases it followed arthritis.Both groups had similar onset ages,antinuclear antibodies/human leukocyte antigen positivity rates,and ESR levels,with a slight predominance of females(60.9%vs 42.5%,P=0.062),and higher C-reactive protein levels in the U-JIA group.Anterior uveitis was more prevalent in patients with U-JIA(P=0.023),although the frequency of symptomatic,unilateral,and complicated forms did not differ significantly.The use of methotrexate(83.8%vs 96.4%)and biologics(64.7%vs 82.1%)was comparable,as was the rate of remission on methotrexate treatment(70.9%vs 56.5%)and biological therapy(77.8%vs 95%),but a immunosuppressive treatment delay in CIU observed.Patients with CIU were less likely to receive methotrexate[hazard ratio(HR)=0.48,P=0.005]or biological treatment(HR=0.42,P=0.004),but they were more likely to achieve remission with methotrexate(HR=3.70,P=0.001).CONCLUSION Treatment of uveitis is often limited to topical measures,which can delay systemic therapy and affect the outcome.Methotrexate and biological agents effectively manage eye inflammation.It is essential to develop standardized protocols for the diagnosis and management of uveitis,and collaboration between rheumatologists and ophthal-mologists is needed to achieve optimal outcomes in the treatment of CIU.展开更多
In the last decade,the study of pressure in active matter has attracted growing attention due to its fundamental relevance to nonequilibrium statistical physics.Active matter systems are composed of particles that con...In the last decade,the study of pressure in active matter has attracted growing attention due to its fundamental relevance to nonequilibrium statistical physics.Active matter systems are composed of particles that consume energy to sustain persistent motion,which are inherently far from equilibrium.These particles can exhibit complex behaviors,including motility-induced phase separation,clustering,and anomalous stress distributions,motivating the introduction of active swim stress and swim pressure.Unlike in passive fluids,pressure in active systems emerges from momentum flux originating from swim force rather than equilibrium conservative interactions,offering a distinct perspective for understanding their mechanical response.Simple models of active Brownian particles(ABPs)have been employed in theoretical and simulation studies across both dilute and dense regimes,revealing that pressure is a state function and exhibits a nontrivial dependence on density.Together with nonequilibrium statistical concepts such as effective temperature and effective adhesion,pressure offers important insight for understanding behaviors in active matter such as sedimentation equilibrium and motility induced phase separation.Extensions of ABP models beyond their simplest form have underscored the fragility of the pressure-based equation of state,which can break down under factors such as density-dependent velocity,torque,complex boundary geometries and interactions.Building on these developments,this review provides a comprehensive survey of theoretical and experimental advances,with particular emphasis on the microscopic origins of active pressure and the mechanisms underlying the breakdown of the equation of state.展开更多
BACKGROUND Uveitis associated with juvenile idiopathic arthritis(U-JIA)is a vision-threatening condition.Estimates of prevalence of uveitis in patients with known juvenile idiopathic arthritis range from 11.6%to 30.0%...BACKGROUND Uveitis associated with juvenile idiopathic arthritis(U-JIA)is a vision-threatening condition.Estimates of prevalence of uveitis in patients with known juvenile idiopathic arthritis range from 11.6%to 30.0%.First-line treatment includes topical glucocorticoids;methotrexate(MTX)is used if topical corticosteroids are ineffective.In severe cases biological therapy like adalimumab may be prescribed.Complications,including vision loss,may be related to the disease and the ongoing treatment(topical corticosteroids).In severe cases surgical intervention is often necessary and is typically associated with poor vision outcomes.AIM To highlight the characteristics of operated U-JIA and to identify predictors of treatment failure.METHODS A retrospective cohort study analyzed data from 68 pediatric patients(under 18 years old)with U-JIA between 2007 and 2023.The study focused on demographic,clinical,treatment,and outcome variables.Survival analysis using Kaplan-Meier curves and the Cox proportional hazards model was performed to estimate the impact of surgical intervention on the course of uveitis and to identify predictors of treatment failure.RESULTS Eye surgery was performed on 17(25%)patients with U-JIA.It was associated with an earlier onset of uveitis(P=0.017),lower uveitis remission rate[odds ratio=5.29,95%confidence interval(CI):1.23-24.90,P=0.015],longer time to remission(P=0.036),reduced probability of achieving remission on MTX(P=0.033),and the necessity of the following treatment with biological diseasemodifying antirheumatic drugs(odds ratio=5.60;95%CI:1.11-55.19,P=0.021)with similar efficacy with biological treatments in operated and non-operated cases.Kaplan-Meier curves showed a borderline difference in time to surgical intervention based on the MTX initiation cutoff(P=0.065)although earlier MTX initiation might be associated with a higher likelihood of deferred surgery.CONCLUSION Operated patients exhibited an aggressive early-onset uveitis profile that needed early and more intensive treatment.Delayed and failed MTX treatment as well as delayed switching to biologics often required subsequent eye surgery.展开更多
Considering the uncertainty of grid connection of electric vehicle charging stations and the uncertainty of new energy and residential electricity load,a spatio-temporal decoupling strategy of dynamic reactive power o...Considering the uncertainty of grid connection of electric vehicle charging stations and the uncertainty of new energy and residential electricity load,a spatio-temporal decoupling strategy of dynamic reactive power optimization based on clustering-local relaxation-correction is proposed.Firstly,the k-medoids clustering algorithm is used to divide the reduced power scene into periods.Then,the discrete variables and continuous variables are optimized in the same period of time.Finally,the number of input groups of parallel capacitor banks(CB)in multiple periods is fixed,and then the secondary static reactive power optimization correction is carried out by using the continuous reactive power output device based on the static reactive power compensation device(SVC),the new energy grid-connected inverter,and the electric vehicle charging station.According to the characteristics of the model,a hybrid optimization algorithm with a cross-feedback mechanism is used to solve different types of variables,and an improved artificial hummingbird algorithm based on tent chaotic mapping and adaptive mutation is proposed to improve the solution efficiency.The simulation results show that the proposed decoupling strategy can obtain satisfactory optimization resultswhile strictly guaranteeing the dynamic constraints of discrete variables,and the hybrid algorithm can effectively solve the mixed integer nonlinear optimization problem.展开更多
Background:Noninfectious uveitis,a chronic ocular inflammatory disease,is char-acterized by the activation of immune cells in the eye,with most studies focusing on the role of the adaptive immune system in the disease...Background:Noninfectious uveitis,a chronic ocular inflammatory disease,is char-acterized by the activation of immune cells in the eye,with most studies focusing on the role of the adaptive immune system in the disease.However,limited data exist on the potential contribution of the innate immune system,specifically the nucleotide-binding oligomerization domain and leucine-rich repeat receptor-3(NLRP3)inflamma-some pathway.This pathway has previously been identified as a driver of inflammation in several low-grade,progressive inflammatory eye diseases such as diabetic retin-opathy.The aim of this study was to determine whether the NLRP3 inflammasome pathway plays a role in the pathogenesis and chronicity of experimental autoimmune uveitis(EAU).Methods:EAU was induced in C57BL/6J mice via intraperitoneal pertussis toxin and subcutaneous interphotoreceptor retinoid-binding protein injections.After 12 weeks,eyes were enucleated,and whole eye sections were assessed for inflammasome,macrophage,and microglial markers in the retina,ciliary body,and cornea using immunohistochemistry.Results:Our study confirmed higher NLRP3 inflammasome activation(increased ex-pression of NLRP3 and cleaved caspase 1 labeling)in EAU mouse retinas compared to controls.This correlated with increased astrogliosis and microglial activation through-out the eye.Migratory innate and adaptive peripheral immune cells(macrophages and leukocytes)were also found within the retina and ciliary body of EAU mice.Connexin43 proteins,which form hexameric hemichannels that can release adeno-sine triphosphate(ATP),an upstream inflammasome priming signal,were also found upregulated in the retina and cornea of EAU mice.Conclusion:Overall,our findings support the idea that in the EAU model there is active inflammation,even 12 weeks post induction,and that it can be correlated to inflammasome activation.This contributes to the pathogenesis and chronicity of non-infectious uveitis,and our results emphasize that targeting the inflammasome path-way could be efficacious for noninfectious uveitis treatment.展开更多
Pump valve pipeline vibration brings serious safety hazards to the operation of the equipment,for the pump valve system in the process of variable flow,variable speed,variable openings lead to excessive pipeline vibra...Pump valve pipeline vibration brings serious safety hazards to the operation of the equipment,for the pump valve system in the process of variable flow,variable speed,variable openings lead to excessive pipeline vibration.An active damping device(ADD)is used to the vibration of the pump valve pipeline system to apply the control force,to achieve the active control of the pipeline vibration.A pump-valve pipeline vibration test bench was built to compare the control effect of active damping device on pipeline vibration under different pump valve working conditions,and the results show that applying ADD control could effectively suppress the vibration of the pump valve pipeline and enhance the stability of the equipment during operation.At different pump operating rotation frequencies,the vibration amplitude of the pump valve pipeline in working frequency and its multiple frequencies are also effectively suppressed,with the maximum amplitude reduction of more than 60%.For the valve vibration caused by different operating openings,the vibration of the highest reduction of 68%,and the centrifugal pump drive shaft vi-bration reduced by up to 73%,which provides a new idea for vibration control of pump valve pipeline system.展开更多
Electrocatalytic nitrate reduction reaction(NitRR)utilizing water as a hydrogen source under ambient conditions represents a highly promising avenue for sustainable ammonia synthesis and environmental remediation.Howe...Electrocatalytic nitrate reduction reaction(NitRR)utilizing water as a hydrogen source under ambient conditions represents a highly promising avenue for sustainable ammonia synthesis and environmental remediation.However,achieving high efficiency and selectivity in NitRR is fundamentally challenged by the complex lifecycle management of active hydrogen derived from water splitting.This review provides a timely and comprehensive analysis centered on the pivotal role and meticulous regulation of active hydrogen throughout the NitRR process.We first elucidate the distinct functions and characteristics of various hydrogen species,followed by a survey of advanced characterization techniques crucial for monitoring the dynamics of active hydrogen.Critically,three core strategies were systematically dissected to modulate the active hydrogen lifecycle:accelerating water activation and dissociation,enhancing the directional transport of hydrogen species,and precisely tuning active hydrogen coupling pathways while suppressing parasitic hydrogen evolution.By consolidating current understanding from both catalyst design and reaction mechanism perspectives,this review offers a hydrogen-centric roadmap and highlights emerging opportunities for rationally engineering advanced NitRR systems.展开更多
Spider mites are significant pests in agricultural production.The increasing resistance of spider mites,along with environmental pollution and ecological imbalance caused by their control,is primarily attributed to th...Spider mites are significant pests in agricultural production.The increasing resistance of spider mites,along with environmental pollution and ecological imbalance caused by their control,is primarily attributed to the long-term use of chemical acaricides in agriculture.In contrast,bioactive substances of biological origin offer advantages such as wide availability,environmental friendliness,and low tendency to induce resistance,making them a research hotspot for spider mite control.This review summarizes recent advances in the use of plant-derived active compounds(exemplified by extracts from Veratrum rhizomes),RNA interference(RNAi)technology,and microorganism-derived active substances for controlling spider mites.These bioactive agents exert acaricidal effects by disrupting the nervous system,interfering with metabolic processes,or silencing key genes in mites,demonstrating favorable efficacy and considerable potential for development.However,challenges remain,including poor environmental stability,slow action,high production costs,and insufficient understanding of their effects on non-target organisms.Therefore,future research should focus on the screening and development of novel bioactive substances of biological origin,elucidation of their mechanisms of action,optimization of formulation technologies,and assessment of their ecological safety.These efforts will provide valuable insights for promoting the advancement of bioactive substances and supporting sustainable agricultural development.展开更多
Molecular recognition of bioreceptors and enzymes relies on orthogonal interactions with small molecules within their cavity. To date, Chinese scientists have developed three types of strategies for introducing active...Molecular recognition of bioreceptors and enzymes relies on orthogonal interactions with small molecules within their cavity. To date, Chinese scientists have developed three types of strategies for introducing active sites inside the cavity of macrocyclic arenes to better mimic molecular recognition of bioreceptors and enzymes.The editorial aims to enlighten scientists in this field when they develop novel macrocycles for molecular recognition, supramolecular assembly, and applications.展开更多
The conventional feedforward hybrid active noise control(FFHANC)system combines the advantages of the feedforward narrowband active noise control(FFNANC)system and the feedforward broadband active noise control(FFBANC...The conventional feedforward hybrid active noise control(FFHANC)system combines the advantages of the feedforward narrowband active noise control(FFNANC)system and the feedforward broadband active noise control(FFBANC)system.To enhance its adaptive adjustment capability under frequency mismatch(FM)conditions,this paper introduces a narrowband frequency adaptive estimation module into the conventional FFHANC system.This module integrates an autoregressive(AR)model and a linear cascaded adaptive notch filter(LCANF),enabling accurate reference signal frequency estimation even under significant FM.Furthermore,in order to improve the coherence between narrowband and broadband components in the system’s error signal and its corresponding control filter for the conventional FFHANC system,this paper proposes an algorithm based on autoregressive bandpass filter bank(AR-BPFB)for error separation.Simulation results demonstrate that the proposed FFHANC system maintains robust performance under high FM conditions and effectively suppresses hybrid-band noise.The AR-BPFB algorithm significantly elevates the convergence speed of the FFHANC system.展开更多
Corrosion activities and related accidents are significant issues for marine facilities,leading to considerable economic losses.Waterborne epoxy(EP)coating has been seen as one of the optimal options for corrosion pro...Corrosion activities and related accidents are significant issues for marine facilities,leading to considerable economic losses.Waterborne epoxy(EP)coating has been seen as one of the optimal options for corrosion protection due to its stable properties and eco-friendliness(0 g/L volatile organic compounds).Nevertheless,several intrinsic deficiencies require improvement,such as fragile mechanical properties and defects(macro and micro),resulting in the continuous deterioration of comprehensive coating performances.In this work,a novel nanocomposite coating with mechanical enhancement,intelligent self-reporting,and active protection is fabricated by integrating the functionalized and compatible graphene oxide/cerium based metal-organic framework multiscale structure(GO-CeMOF-P/M).Notably,the homogenous dispersion of GO-CeMOF-P/M and its chemical interaction with the polymer matrix effectively reduces the defects resulting from solution volatilizing and enhances the compactness,which boosts the tensile strength(32.1 MPa/8.5%)and dry adhesion force(5.8 MPa)of the coating.Additionally,the controllable responsiveness and release of multiscale nanocomposite within external environments endow intelligent active protection and self-reporting characteristics for the GO-CeMOF-P/M-EP coating,making it especially suitable for a variety of practical marine applications.Furthermore,following immersion of 80 d in the aggressive environment,Zf=0.01 Hz value of GO-CeMOF-P/M-EP coating is 1.2×10^(10)Ωcm^(2),which is 164.4 times larger than that of EP coating(7.3×10^(7)Ωcm^(2)),demonstrating remarkably strengthened anti-corrosion ability.Consequently,by offering an intriguing design strategy,the current work anticipates addressing the inherent deficiencies of EP coating and facilitating its practicality and feasibility in real sea environments.展开更多
In clinical practice,antibiotics have historically been utilized for the treatment of pathogenic bacteria.However,the gradual emergence of antibiotic resistance among bacterial strains has posed a significant challeng...In clinical practice,antibiotics have historically been utilized for the treatment of pathogenic bacteria.However,the gradual emergence of antibiotic resistance among bacterial strains has posed a significant challenge to this approach.In 2022,Escherichia coli,a Gram-negative bacterium renowned for its widespread pathogenicity and high virulence,emerged as the predominant pathogenic bacterium in China.The rapid emergence of antibiotic-resistant E.coli strains has rendered antibiotics insufficient to fight E.coli infections.Traditional Chinese medicine(TCM)has made remarkable contributions to the health of Chinese people for thousands of years,and its significant therapeutic effects have been proven in clinical practice.In this paper,we provide a comprehensive review of the advances and mechanisms of TCM and its active ingredients against antibiotic-resistant E.coli infections.First of all,this review introduces the classification,antibiotic resistance characteristics and mechanisms of E.coli.Then,the TCM formulas and extracts are listed along with their active ingredients against E.coli,including extraction solution,minimum inhibitory concentration(MIC),and the antibacterial mechanisms.In addition,there is growing evidence supporting the synergistic therapeutic strategy of combining TCM with antibiotics for the treatment of antibiotic-resistant E.coli infections,and we provide a summary of this evidence and its underlying mechanisms.In conclusion,we present a comprehensive review of TCM and highlight its potential and advantages in the prevention and treatment of E.coli infections.We hold the opinion that TCM will play an important role in global health,pharmaceutical development,and livestock farming in the future.展开更多
Gallium nitride(GaN)single crystal with prominent electron mobility and heat resistance have great potential in the high temperature integrate electric power systems.However,the sluggish charge storage kinetics and in...Gallium nitride(GaN)single crystal with prominent electron mobility and heat resistance have great potential in the high temperature integrate electric power systems.However,the sluggish charge storage kinetics and inadequate energy densities are bottlenecks to its practical application.Herein,the self-supported GaN/Mn_(3)O_(4) integrated electrode is developed for both energy harvesting and storage under the high temperature environment.The experimental and theoretical calculations results reveal that such integrated structures with Mn-N heterointerface bring abundant active sites and reconstruct low-energy barrier channels for efficient charge transferring,reasonably optimizing the ions adsorption ability and strengthening the structural stability.Consequently,the assembled GaN based supercapacitors deliver the power density of 34.0 mW cm^(-2) with capacitance retention of 81.3%after 10000 cycles at 130℃.This work innovatively correlates the centimeter scale GaN single crystal with ideal theoretical capacity Mn_(3)O_(4) and provides an effective avenue for the follow-up energy storage applications of the wide bandgap semiconductor.展开更多
The output feedback active disturbance rejection control of a valve-controlled cylinder electro-hydraulic servo system is investigated in this paper.First,a comprehensive nonlinear mathematical model that encompasses ...The output feedback active disturbance rejection control of a valve-controlled cylinder electro-hydraulic servo system is investigated in this paper.First,a comprehensive nonlinear mathematical model that encompasses both matched and mismatched disturbances is formulated.Due to the fact that only position information can be measured,a linear Extended State Observer(ESO)is introduced to estimate unknown states and matched disturbances,while a dedicated disturbance observer is constructed to estimate mismatched disturbances.Different from the traditional observer results,the design of the disturbance observer used in this study is carried out under the constraint of output feedback.Furthermore,an output feedback nonlinear controller is proposed leveraging the aforementioned observers to achieve accurate trajectory tracking.To mitigate the inherent differential explosion problem of the traditional backstepping framework,a finite-time stable command filter is incorporated.Simultaneously,considering transient filtering errors,a set of error compensation signals are designed to counter their negative impact effectively.Theoretical analysis affirms that the proposed control strategy ensures the boundedness of all signals within the closed-loop system.Additionally,under the specific condition of only time-invariant disturbances in the system,the conclusion of asymptotic stability is established.Finally,the algorithm’s efficacy is validated through comparative experiments.展开更多
Permanent magnet synchronous motor based electro-mechanical actuation servo drives have widespread applications in the aviation field,such as unmanned aerial vehicle electric servos,electric cabin doors,and mechanical...Permanent magnet synchronous motor based electro-mechanical actuation servo drives have widespread applications in the aviation field,such as unmanned aerial vehicle electric servos,electric cabin doors,and mechanical arms.The performance of the servo drive,which encompasses the response to the torque,efficiency,control bandwidth and the steady-state positioning accuracy,significantly influences the performance of the aviation actuation.Consequently,enhancing the control bandwidth and refining the positioning accuracy of aviation electro-mechanical actuation servo drives have emerged as a focal point of research.This paper investigates the multi-source disturbances present in aviation electro-mechanical actuation servo systems and summarizes recent research on high-performance servo control methods based on active disturbance rejection control(ADRC).We present a comprehensive overview of the research status pertaining to servo control architecture,strategies for suppressing disturbances in the current loop,and ADRC-based strategies for the position loop.We delineate the research challenges and difficulties encountered by aviation electro-mechanical actuation servo drive control technology.展开更多
Uveitis is an inflammatory disease affecting the uvea,which includes the iris,ciliary body and choroid(1).Noninfective uveitis is more prevalent in developed countries and primarily impacts individuals of working age,...Uveitis is an inflammatory disease affecting the uvea,which includes the iris,ciliary body and choroid(1).Noninfective uveitis is more prevalent in developed countries and primarily impacts individuals of working age,with a mean onset of around 40 years.It accounts for 5-10%of severe vision impairment globally(1,2).This form of uveitis is often associated with systemic diseases,such as ankylosing spondylosis,juvenile idiopathic arthritis,sarcoidosis and Behcet’s disease(2,3).展开更多
AIM:To characterize a Portuguese population of patients with juvenile idiopathic arthritis(JIA)and to evaluate possible associations between clinical factors and ocular involvement.METHODS:Patients diagnosed with JIA ...AIM:To characterize a Portuguese population of patients with juvenile idiopathic arthritis(JIA)and to evaluate possible associations between clinical factors and ocular involvement.METHODS:Patients diagnosed with JIA in the previous 20y in Hospital Garcia de Orta were included.Data were assessed from Reuma.pt database.Associations between demographic(age and sex),clinical(articular involvement,extra-articular manifestations,biological therapy),laboratory data[anti-nuclear antibodies,anti-cyclic citrullinated peptide(CCP)antibodies,rheumatoid factor,human leukocyte antigen B27(HLA-B27),C-reactive protein,erythrocyte sedimentation rate]and ocular involvement were assessed.Statistical analysis was performed using Chi-square for categorical variables and Mann-Whitney test for continuous variables.RESULTS:Totally 91 patients were included,11(12%)with previous episodes of uveitis.There was a statistically significant preponderance of early age at JIA diagnosis(mean 4.73 vs 9.58y,P=0.008),antinuclear antibodies positivity(P=0.01),and oligoarticular subtype(P=0.04)in the Juvenile idiopathic arthritis-associated uveitis(JIA-U)group.Ocular complications occurred in 36.4%of patients(n=4):cataracts(n=2),band keratopathy(n=1)and posterior synechiae(n=1).The occurrence of complications was corelated with a shorter period between JIA diagnosis and the first JIA-U episode(mean 0.67 vs 4.88y,P=0.012)but not with age at JIA diagnosis or articular involvement.There was erythrocyte sedimentation rate elevation in the 12mo preceding uveitis(mean 40.5 mm/h,range 13-83).CONCLUSION:The occurrence of JIA-U shortly after JIA diagnosis is shown to be a potential risk factor for ocular complications.展开更多
AIM:To use two-sample Mendelian randomization(MR)method to study uveitis causal association with wet age-related macular degeneration(wAMD)risk from the genetic level.METHODS:Two-sample MR analysis was used to assess ...AIM:To use two-sample Mendelian randomization(MR)method to study uveitis causal association with wet age-related macular degeneration(wAMD)risk from the genetic level.METHODS:Two-sample MR analysis was used to assess the causal role of uveitis on wAMD risk,using the 8 genetic variants associated strongly with uveitis as instrumental variables.Besides,eight MR methods[inverse variance weighted(IVW),weighted median,MR-Egger regression,weighted mode,simple mode,robust adjusted profile score(RAPS),contamination inverse-variance weighted method,and debiased inverse-variance weighted method]were used to get the whole causal estimate for multiple instrumental single nucleotide polymorphism(SNPs).The MR analysis was based on Europeans.RESULTS:Uveitis was related to a higher risk of wAMD[odds ratio(OR):1.08,95%confidence interval(CI)1.03–1.12;P=1.03×10^(-3)]with the IVW method.No heterogeneity and directional pleiotropy were detected.On the contrary,no significant results were detected in reverse MR analysis.CONCLUSION:Uveitis is related to an increased risk of wAMD.Due to the high blindness rate of wAMD,understanding and controlling the risk factors of AMD is of great significance for reducing its incidence and early diagnosis and treatment.展开更多
Non-infectious uveitis(NIU),although a highly blinding but preventable cause of blindness around the world,has few approved pharmaceuticals for its treatment.Lack of access to effective treatment is likely a major cau...Non-infectious uveitis(NIU),although a highly blinding but preventable cause of blindness around the world,has few approved pharmaceuticals for its treatment.Lack of access to effective treatment is likely a major cause of poor visual outcomes in NIU.However,despite a revolution in rheumatologic disease treatment with the advent of multiple biologic therapeutics selectively targeting the immune response,there remains a gap in the long-term management of NIU.Adalimumab remains the only systemic medication approved for the treatment of NIU by the Food and Drug Administration(FDA).All other systemic treatments,including older anti-metabolites such as methotrexate and mycophenolate,are used offlabel for NIU,posing significant treatment challenges.Given the nature and rarity of the disease,there are few well designed,large,clinical trials evaluating the efficacy of novel therapeutic agents within this field.We therefore read with great interest Srivastava et al.’s randomized clinical trial on the efficacy of filgotinib,a Janus kinase inhibitor(JAKi),in active NIU(1).The early termination of the trial due to business considerations highlights the industry difficulty in FDA medication approval for NIU.展开更多
文摘We analysed histologically two Acanthamoeba keratitis(AK) eyes with anterior and posterior segment inflammation and blindness. Two enucleated eyes of 2 patients(age 45 and 51y) with AK(PCR of epithelial abrasion positive) were analysed. Histological analysis was performed using hematoxylin-eosin, periodic acid-Schiff and G?m?rimethenamine silver staining. We could not observe Acanthamoeba trophozoites or cysts neither in the cornea nor in other ocular tissues. Meanwhile, we found uveitis, retinal vasculitis and scleritis in these eyes, due to the long-standing, recalcitrant AK. So in this stage of AK, systemic immune suppression may be necessary for a longer time period.
文摘BACKGROUND Chronic idiopathic uveitis(CIU)and juvenile idiopathic arthritis-associated uveitis(U-JIA)are both vision-threatening conditions that share similar autoimmune mechanisms,but treatment approaches differ significantly.In managing U-JIA,various treatment options are employed,including biological and non-biological disease-modifying anti-rheumatic drugs.These drugs are effective in clinical trials.Given the lack of established diagnostic and treatment guidelines as well as the limited number of therapeutic options available,patients with CIU frequently do not receive optimal and timely immunosuppression.This study highlighted the necessity for additional research to develop novel diag-nostic techniques,targeted therapies,and enhanced treatment outcomes for young individuals with CIU.AIM To compare the characteristics and outcomes of U-JIA and CIU.METHODS A retrospective cohort study analyzed data from 110 pediatric patients(under 18 years old)with U-JIA and 40 pediatric patients with CIU.Data was collected between 2012 and 2023.The study focused on demographic,clinical,treatment,and outcome variables.RESULTS The median onset age of arthritis was 6.4 years(2.7 years;9.3 years).In 28.2%of cases uveitis preceded the onset of arthritis.In 17.3%of cases it occurred simultan-eously.In 53.6%of cases it followed arthritis.Both groups had similar onset ages,antinuclear antibodies/human leukocyte antigen positivity rates,and ESR levels,with a slight predominance of females(60.9%vs 42.5%,P=0.062),and higher C-reactive protein levels in the U-JIA group.Anterior uveitis was more prevalent in patients with U-JIA(P=0.023),although the frequency of symptomatic,unilateral,and complicated forms did not differ significantly.The use of methotrexate(83.8%vs 96.4%)and biologics(64.7%vs 82.1%)was comparable,as was the rate of remission on methotrexate treatment(70.9%vs 56.5%)and biological therapy(77.8%vs 95%),but a immunosuppressive treatment delay in CIU observed.Patients with CIU were less likely to receive methotrexate[hazard ratio(HR)=0.48,P=0.005]or biological treatment(HR=0.42,P=0.004),but they were more likely to achieve remission with methotrexate(HR=3.70,P=0.001).CONCLUSION Treatment of uveitis is often limited to topical measures,which can delay systemic therapy and affect the outcome.Methotrexate and biological agents effectively manage eye inflammation.It is essential to develop standardized protocols for the diagnosis and management of uveitis,and collaboration between rheumatologists and ophthal-mologists is needed to achieve optimal outcomes in the treatment of CIU.
基金financial support from the General Program of the National Natural Science Foundation of China(Grant No.12474195)the Key Project of Guangdong Provincial Department of Education(Grant No.2023ZDZX3021)the Natural Science Foundation of Guangdong Province(Grant No.2024A1515011343)。
文摘In the last decade,the study of pressure in active matter has attracted growing attention due to its fundamental relevance to nonequilibrium statistical physics.Active matter systems are composed of particles that consume energy to sustain persistent motion,which are inherently far from equilibrium.These particles can exhibit complex behaviors,including motility-induced phase separation,clustering,and anomalous stress distributions,motivating the introduction of active swim stress and swim pressure.Unlike in passive fluids,pressure in active systems emerges from momentum flux originating from swim force rather than equilibrium conservative interactions,offering a distinct perspective for understanding their mechanical response.Simple models of active Brownian particles(ABPs)have been employed in theoretical and simulation studies across both dilute and dense regimes,revealing that pressure is a state function and exhibits a nontrivial dependence on density.Together with nonequilibrium statistical concepts such as effective temperature and effective adhesion,pressure offers important insight for understanding behaviors in active matter such as sedimentation equilibrium and motility induced phase separation.Extensions of ABP models beyond their simplest form have underscored the fragility of the pressure-based equation of state,which can break down under factors such as density-dependent velocity,torque,complex boundary geometries and interactions.Building on these developments,this review provides a comprehensive survey of theoretical and experimental advances,with particular emphasis on the microscopic origins of active pressure and the mechanisms underlying the breakdown of the equation of state.
文摘BACKGROUND Uveitis associated with juvenile idiopathic arthritis(U-JIA)is a vision-threatening condition.Estimates of prevalence of uveitis in patients with known juvenile idiopathic arthritis range from 11.6%to 30.0%.First-line treatment includes topical glucocorticoids;methotrexate(MTX)is used if topical corticosteroids are ineffective.In severe cases biological therapy like adalimumab may be prescribed.Complications,including vision loss,may be related to the disease and the ongoing treatment(topical corticosteroids).In severe cases surgical intervention is often necessary and is typically associated with poor vision outcomes.AIM To highlight the characteristics of operated U-JIA and to identify predictors of treatment failure.METHODS A retrospective cohort study analyzed data from 68 pediatric patients(under 18 years old)with U-JIA between 2007 and 2023.The study focused on demographic,clinical,treatment,and outcome variables.Survival analysis using Kaplan-Meier curves and the Cox proportional hazards model was performed to estimate the impact of surgical intervention on the course of uveitis and to identify predictors of treatment failure.RESULTS Eye surgery was performed on 17(25%)patients with U-JIA.It was associated with an earlier onset of uveitis(P=0.017),lower uveitis remission rate[odds ratio=5.29,95%confidence interval(CI):1.23-24.90,P=0.015],longer time to remission(P=0.036),reduced probability of achieving remission on MTX(P=0.033),and the necessity of the following treatment with biological diseasemodifying antirheumatic drugs(odds ratio=5.60;95%CI:1.11-55.19,P=0.021)with similar efficacy with biological treatments in operated and non-operated cases.Kaplan-Meier curves showed a borderline difference in time to surgical intervention based on the MTX initiation cutoff(P=0.065)although earlier MTX initiation might be associated with a higher likelihood of deferred surgery.CONCLUSION Operated patients exhibited an aggressive early-onset uveitis profile that needed early and more intensive treatment.Delayed and failed MTX treatment as well as delayed switching to biologics often required subsequent eye surgery.
基金funded by the“Research and Application Project of Collaborative Optimization Control Technology for Distribution Station Area for High Proportion Distributed PV Consumption(4000-202318079A-1-1-ZN)”of the Headquarters of the State Grid Corporation.
文摘Considering the uncertainty of grid connection of electric vehicle charging stations and the uncertainty of new energy and residential electricity load,a spatio-temporal decoupling strategy of dynamic reactive power optimization based on clustering-local relaxation-correction is proposed.Firstly,the k-medoids clustering algorithm is used to divide the reduced power scene into periods.Then,the discrete variables and continuous variables are optimized in the same period of time.Finally,the number of input groups of parallel capacitor banks(CB)in multiple periods is fixed,and then the secondary static reactive power optimization correction is carried out by using the continuous reactive power output device based on the static reactive power compensation device(SVC),the new energy grid-connected inverter,and the electric vehicle charging station.According to the characteristics of the model,a hybrid optimization algorithm with a cross-feedback mechanism is used to solve different types of variables,and an improved artificial hummingbird algorithm based on tent chaotic mapping and adaptive mutation is proposed to improve the solution efficiency.The simulation results show that the proposed decoupling strategy can obtain satisfactory optimization resultswhile strictly guaranteeing the dynamic constraints of discrete variables,and the hybrid algorithm can effectively solve the mixed integer nonlinear optimization problem.
基金funded by a Maurice and Phyllis Paykel Trust Grant(203134)supported by a Buchanan Ocular Therapeutics Unit Doctoral Scholarship.Odunayo O.Mugisho is supported by a Neurological Foundation First Postdoctoral Research Fellowship(2001 FFE)+2 种基金an Auckland Medical Research Foundation Grant(1121013)an Auckland Medical Research Foundation Postdoctoral Fellowship(1323001)supported by the Buchanan Charitable Foundation,with part of her salary also supported by the Health Research Council of New Zealand(20/317).
文摘Background:Noninfectious uveitis,a chronic ocular inflammatory disease,is char-acterized by the activation of immune cells in the eye,with most studies focusing on the role of the adaptive immune system in the disease.However,limited data exist on the potential contribution of the innate immune system,specifically the nucleotide-binding oligomerization domain and leucine-rich repeat receptor-3(NLRP3)inflamma-some pathway.This pathway has previously been identified as a driver of inflammation in several low-grade,progressive inflammatory eye diseases such as diabetic retin-opathy.The aim of this study was to determine whether the NLRP3 inflammasome pathway plays a role in the pathogenesis and chronicity of experimental autoimmune uveitis(EAU).Methods:EAU was induced in C57BL/6J mice via intraperitoneal pertussis toxin and subcutaneous interphotoreceptor retinoid-binding protein injections.After 12 weeks,eyes were enucleated,and whole eye sections were assessed for inflammasome,macrophage,and microglial markers in the retina,ciliary body,and cornea using immunohistochemistry.Results:Our study confirmed higher NLRP3 inflammasome activation(increased ex-pression of NLRP3 and cleaved caspase 1 labeling)in EAU mouse retinas compared to controls.This correlated with increased astrogliosis and microglial activation through-out the eye.Migratory innate and adaptive peripheral immune cells(macrophages and leukocytes)were also found within the retina and ciliary body of EAU mice.Connexin43 proteins,which form hexameric hemichannels that can release adeno-sine triphosphate(ATP),an upstream inflammasome priming signal,were also found upregulated in the retina and cornea of EAU mice.Conclusion:Overall,our findings support the idea that in the EAU model there is active inflammation,even 12 weeks post induction,and that it can be correlated to inflammasome activation.This contributes to the pathogenesis and chronicity of non-infectious uveitis,and our results emphasize that targeting the inflammasome path-way could be efficacious for noninfectious uveitis treatment.
基金The Fundamental Research Funds for the Central Universities(JD2423)。
文摘Pump valve pipeline vibration brings serious safety hazards to the operation of the equipment,for the pump valve system in the process of variable flow,variable speed,variable openings lead to excessive pipeline vibration.An active damping device(ADD)is used to the vibration of the pump valve pipeline system to apply the control force,to achieve the active control of the pipeline vibration.A pump-valve pipeline vibration test bench was built to compare the control effect of active damping device on pipeline vibration under different pump valve working conditions,and the results show that applying ADD control could effectively suppress the vibration of the pump valve pipeline and enhance the stability of the equipment during operation.At different pump operating rotation frequencies,the vibration amplitude of the pump valve pipeline in working frequency and its multiple frequencies are also effectively suppressed,with the maximum amplitude reduction of more than 60%.For the valve vibration caused by different operating openings,the vibration of the highest reduction of 68%,and the centrifugal pump drive shaft vi-bration reduced by up to 73%,which provides a new idea for vibration control of pump valve pipeline system.
基金financially supported by the National Natural Science Foundation of China(22179035)the Science Fund for Distinguished Young Scholars of Heilongjiang Province(JQ2022B001)the Fundamental Research Funds for the Universities of Heilongjiang Province of China(2023-KYYWF1440)。
文摘Electrocatalytic nitrate reduction reaction(NitRR)utilizing water as a hydrogen source under ambient conditions represents a highly promising avenue for sustainable ammonia synthesis and environmental remediation.However,achieving high efficiency and selectivity in NitRR is fundamentally challenged by the complex lifecycle management of active hydrogen derived from water splitting.This review provides a timely and comprehensive analysis centered on the pivotal role and meticulous regulation of active hydrogen throughout the NitRR process.We first elucidate the distinct functions and characteristics of various hydrogen species,followed by a survey of advanced characterization techniques crucial for monitoring the dynamics of active hydrogen.Critically,three core strategies were systematically dissected to modulate the active hydrogen lifecycle:accelerating water activation and dissociation,enhancing the directional transport of hydrogen species,and precisely tuning active hydrogen coupling pathways while suppressing parasitic hydrogen evolution.By consolidating current understanding from both catalyst design and reaction mechanism perspectives,this review offers a hydrogen-centric roadmap and highlights emerging opportunities for rationally engineering advanced NitRR systems.
文摘Spider mites are significant pests in agricultural production.The increasing resistance of spider mites,along with environmental pollution and ecological imbalance caused by their control,is primarily attributed to the long-term use of chemical acaricides in agriculture.In contrast,bioactive substances of biological origin offer advantages such as wide availability,environmental friendliness,and low tendency to induce resistance,making them a research hotspot for spider mite control.This review summarizes recent advances in the use of plant-derived active compounds(exemplified by extracts from Veratrum rhizomes),RNA interference(RNAi)technology,and microorganism-derived active substances for controlling spider mites.These bioactive agents exert acaricidal effects by disrupting the nervous system,interfering with metabolic processes,or silencing key genes in mites,demonstrating favorable efficacy and considerable potential for development.However,challenges remain,including poor environmental stability,slow action,high production costs,and insufficient understanding of their effects on non-target organisms.Therefore,future research should focus on the screening and development of novel bioactive substances of biological origin,elucidation of their mechanisms of action,optimization of formulation technologies,and assessment of their ecological safety.These efforts will provide valuable insights for promoting the advancement of bioactive substances and supporting sustainable agricultural development.
文摘Molecular recognition of bioreceptors and enzymes relies on orthogonal interactions with small molecules within their cavity. To date, Chinese scientists have developed three types of strategies for introducing active sites inside the cavity of macrocyclic arenes to better mimic molecular recognition of bioreceptors and enzymes.The editorial aims to enlighten scientists in this field when they develop novel macrocycles for molecular recognition, supramolecular assembly, and applications.
基金supported in part by the Postgraduate Research&Practice Innovation Program of Nanjing University of Aeronautics and Astronautics(No.xcxjh20240326).
文摘The conventional feedforward hybrid active noise control(FFHANC)system combines the advantages of the feedforward narrowband active noise control(FFNANC)system and the feedforward broadband active noise control(FFBANC)system.To enhance its adaptive adjustment capability under frequency mismatch(FM)conditions,this paper introduces a narrowband frequency adaptive estimation module into the conventional FFHANC system.This module integrates an autoregressive(AR)model and a linear cascaded adaptive notch filter(LCANF),enabling accurate reference signal frequency estimation even under significant FM.Furthermore,in order to improve the coherence between narrowband and broadband components in the system’s error signal and its corresponding control filter for the conventional FFHANC system,this paper proposes an algorithm based on autoregressive bandpass filter bank(AR-BPFB)for error separation.Simulation results demonstrate that the proposed FFHANC system maintains robust performance under high FM conditions and effectively suppresses hybrid-band noise.The AR-BPFB algorithm significantly elevates the convergence speed of the FFHANC system.
基金financially supported by the National Natural Science Foundation of China(Nos.52371088,52071347,and U20A20233)Guangdong Basic and Applied Basic Research Foundation(No.2023A1515240007)Shenzhen Science and Technology Program(No.KJZD20230923114819041).
文摘Corrosion activities and related accidents are significant issues for marine facilities,leading to considerable economic losses.Waterborne epoxy(EP)coating has been seen as one of the optimal options for corrosion protection due to its stable properties and eco-friendliness(0 g/L volatile organic compounds).Nevertheless,several intrinsic deficiencies require improvement,such as fragile mechanical properties and defects(macro and micro),resulting in the continuous deterioration of comprehensive coating performances.In this work,a novel nanocomposite coating with mechanical enhancement,intelligent self-reporting,and active protection is fabricated by integrating the functionalized and compatible graphene oxide/cerium based metal-organic framework multiscale structure(GO-CeMOF-P/M).Notably,the homogenous dispersion of GO-CeMOF-P/M and its chemical interaction with the polymer matrix effectively reduces the defects resulting from solution volatilizing and enhances the compactness,which boosts the tensile strength(32.1 MPa/8.5%)and dry adhesion force(5.8 MPa)of the coating.Additionally,the controllable responsiveness and release of multiscale nanocomposite within external environments endow intelligent active protection and self-reporting characteristics for the GO-CeMOF-P/M-EP coating,making it especially suitable for a variety of practical marine applications.Furthermore,following immersion of 80 d in the aggressive environment,Zf=0.01 Hz value of GO-CeMOF-P/M-EP coating is 1.2×10^(10)Ωcm^(2),which is 164.4 times larger than that of EP coating(7.3×10^(7)Ωcm^(2)),demonstrating remarkably strengthened anti-corrosion ability.Consequently,by offering an intriguing design strategy,the current work anticipates addressing the inherent deficiencies of EP coating and facilitating its practicality and feasibility in real sea environments.
基金supported by the Fundamental Research Funds for the Central Public Welfare Research Institutes,China(Grant Nos.:ZZ16-YQ-037,JIPY2023003,and JJPY2022022)China Academy of Chinese Medical Sciences(CACMS)Innovation Fund(Grant No.:CI2021A00601).
文摘In clinical practice,antibiotics have historically been utilized for the treatment of pathogenic bacteria.However,the gradual emergence of antibiotic resistance among bacterial strains has posed a significant challenge to this approach.In 2022,Escherichia coli,a Gram-negative bacterium renowned for its widespread pathogenicity and high virulence,emerged as the predominant pathogenic bacterium in China.The rapid emergence of antibiotic-resistant E.coli strains has rendered antibiotics insufficient to fight E.coli infections.Traditional Chinese medicine(TCM)has made remarkable contributions to the health of Chinese people for thousands of years,and its significant therapeutic effects have been proven in clinical practice.In this paper,we provide a comprehensive review of the advances and mechanisms of TCM and its active ingredients against antibiotic-resistant E.coli infections.First of all,this review introduces the classification,antibiotic resistance characteristics and mechanisms of E.coli.Then,the TCM formulas and extracts are listed along with their active ingredients against E.coli,including extraction solution,minimum inhibitory concentration(MIC),and the antibacterial mechanisms.In addition,there is growing evidence supporting the synergistic therapeutic strategy of combining TCM with antibiotics for the treatment of antibiotic-resistant E.coli infections,and we provide a summary of this evidence and its underlying mechanisms.In conclusion,we present a comprehensive review of TCM and highlight its potential and advantages in the prevention and treatment of E.coli infections.We hold the opinion that TCM will play an important role in global health,pharmaceutical development,and livestock farming in the future.
基金supported by NSFC(Grant No.52202265,52302004,52472010,62434010)the Taishan Scholars Program of Shandong Province(tsqn202306330)+1 种基金Shenzhen Science and Technology Program(JCYJ20230807094009018)Xiaomi Young Talents Program(2023XM06).
文摘Gallium nitride(GaN)single crystal with prominent electron mobility and heat resistance have great potential in the high temperature integrate electric power systems.However,the sluggish charge storage kinetics and inadequate energy densities are bottlenecks to its practical application.Herein,the self-supported GaN/Mn_(3)O_(4) integrated electrode is developed for both energy harvesting and storage under the high temperature environment.The experimental and theoretical calculations results reveal that such integrated structures with Mn-N heterointerface bring abundant active sites and reconstruct low-energy barrier channels for efficient charge transferring,reasonably optimizing the ions adsorption ability and strengthening the structural stability.Consequently,the assembled GaN based supercapacitors deliver the power density of 34.0 mW cm^(-2) with capacitance retention of 81.3%after 10000 cycles at 130℃.This work innovatively correlates the centimeter scale GaN single crystal with ideal theoretical capacity Mn_(3)O_(4) and provides an effective avenue for the follow-up energy storage applications of the wide bandgap semiconductor.
基金supported by the National Key R&D Program of China(No.2021YFB2011300)the Special Funds Project for the Transformation of Scientific and Technological Achievements of Jiangsu Province,China(No.BA2023039)+1 种基金the National Natural Science Foundation of China(No.52075262)the Fundamental Research Funds for the Central Universities,China(No.30922010706).
文摘The output feedback active disturbance rejection control of a valve-controlled cylinder electro-hydraulic servo system is investigated in this paper.First,a comprehensive nonlinear mathematical model that encompasses both matched and mismatched disturbances is formulated.Due to the fact that only position information can be measured,a linear Extended State Observer(ESO)is introduced to estimate unknown states and matched disturbances,while a dedicated disturbance observer is constructed to estimate mismatched disturbances.Different from the traditional observer results,the design of the disturbance observer used in this study is carried out under the constraint of output feedback.Furthermore,an output feedback nonlinear controller is proposed leveraging the aforementioned observers to achieve accurate trajectory tracking.To mitigate the inherent differential explosion problem of the traditional backstepping framework,a finite-time stable command filter is incorporated.Simultaneously,considering transient filtering errors,a set of error compensation signals are designed to counter their negative impact effectively.Theoretical analysis affirms that the proposed control strategy ensures the boundedness of all signals within the closed-loop system.Additionally,under the specific condition of only time-invariant disturbances in the system,the conclusion of asymptotic stability is established.Finally,the algorithm’s efficacy is validated through comparative experiments.
基金supported by the National Natural Science Foundation of China(Nos.52177059 and 52407064).
文摘Permanent magnet synchronous motor based electro-mechanical actuation servo drives have widespread applications in the aviation field,such as unmanned aerial vehicle electric servos,electric cabin doors,and mechanical arms.The performance of the servo drive,which encompasses the response to the torque,efficiency,control bandwidth and the steady-state positioning accuracy,significantly influences the performance of the aviation actuation.Consequently,enhancing the control bandwidth and refining the positioning accuracy of aviation electro-mechanical actuation servo drives have emerged as a focal point of research.This paper investigates the multi-source disturbances present in aviation electro-mechanical actuation servo systems and summarizes recent research on high-performance servo control methods based on active disturbance rejection control(ADRC).We present a comprehensive overview of the research status pertaining to servo control architecture,strategies for suppressing disturbances in the current loop,and ADRC-based strategies for the position loop.We delineate the research challenges and difficulties encountered by aviation electro-mechanical actuation servo drive control technology.
文摘Uveitis is an inflammatory disease affecting the uvea,which includes the iris,ciliary body and choroid(1).Noninfective uveitis is more prevalent in developed countries and primarily impacts individuals of working age,with a mean onset of around 40 years.It accounts for 5-10%of severe vision impairment globally(1,2).This form of uveitis is often associated with systemic diseases,such as ankylosing spondylosis,juvenile idiopathic arthritis,sarcoidosis and Behcet’s disease(2,3).
文摘AIM:To characterize a Portuguese population of patients with juvenile idiopathic arthritis(JIA)and to evaluate possible associations between clinical factors and ocular involvement.METHODS:Patients diagnosed with JIA in the previous 20y in Hospital Garcia de Orta were included.Data were assessed from Reuma.pt database.Associations between demographic(age and sex),clinical(articular involvement,extra-articular manifestations,biological therapy),laboratory data[anti-nuclear antibodies,anti-cyclic citrullinated peptide(CCP)antibodies,rheumatoid factor,human leukocyte antigen B27(HLA-B27),C-reactive protein,erythrocyte sedimentation rate]and ocular involvement were assessed.Statistical analysis was performed using Chi-square for categorical variables and Mann-Whitney test for continuous variables.RESULTS:Totally 91 patients were included,11(12%)with previous episodes of uveitis.There was a statistically significant preponderance of early age at JIA diagnosis(mean 4.73 vs 9.58y,P=0.008),antinuclear antibodies positivity(P=0.01),and oligoarticular subtype(P=0.04)in the Juvenile idiopathic arthritis-associated uveitis(JIA-U)group.Ocular complications occurred in 36.4%of patients(n=4):cataracts(n=2),band keratopathy(n=1)and posterior synechiae(n=1).The occurrence of complications was corelated with a shorter period between JIA diagnosis and the first JIA-U episode(mean 0.67 vs 4.88y,P=0.012)but not with age at JIA diagnosis or articular involvement.There was erythrocyte sedimentation rate elevation in the 12mo preceding uveitis(mean 40.5 mm/h,range 13-83).CONCLUSION:The occurrence of JIA-U shortly after JIA diagnosis is shown to be a potential risk factor for ocular complications.
基金Supported by the National Natural Science Foundation of China(No.82201163)Natural Science Foundation Youth Foundation of Shaanxi Province(No.2023-JC-QN-0861)Shaanxi Province Key Research and Development Program(No.2021SF-332).
文摘AIM:To use two-sample Mendelian randomization(MR)method to study uveitis causal association with wet age-related macular degeneration(wAMD)risk from the genetic level.METHODS:Two-sample MR analysis was used to assess the causal role of uveitis on wAMD risk,using the 8 genetic variants associated strongly with uveitis as instrumental variables.Besides,eight MR methods[inverse variance weighted(IVW),weighted median,MR-Egger regression,weighted mode,simple mode,robust adjusted profile score(RAPS),contamination inverse-variance weighted method,and debiased inverse-variance weighted method]were used to get the whole causal estimate for multiple instrumental single nucleotide polymorphism(SNPs).The MR analysis was based on Europeans.RESULTS:Uveitis was related to a higher risk of wAMD[odds ratio(OR):1.08,95%confidence interval(CI)1.03–1.12;P=1.03×10^(-3)]with the IVW method.No heterogeneity and directional pleiotropy were detected.On the contrary,no significant results were detected in reverse MR analysis.CONCLUSION:Uveitis is related to an increased risk of wAMD.Due to the high blindness rate of wAMD,understanding and controlling the risk factors of AMD is of great significance for reducing its incidence and early diagnosis and treatment.
基金Unrestricted departmental grant from Research to Prevent Blindness.T.M.J.receives funding from the National Institutes of Health(K12TR005104).
文摘Non-infectious uveitis(NIU),although a highly blinding but preventable cause of blindness around the world,has few approved pharmaceuticals for its treatment.Lack of access to effective treatment is likely a major cause of poor visual outcomes in NIU.However,despite a revolution in rheumatologic disease treatment with the advent of multiple biologic therapeutics selectively targeting the immune response,there remains a gap in the long-term management of NIU.Adalimumab remains the only systemic medication approved for the treatment of NIU by the Food and Drug Administration(FDA).All other systemic treatments,including older anti-metabolites such as methotrexate and mycophenolate,are used offlabel for NIU,posing significant treatment challenges.Given the nature and rarity of the disease,there are few well designed,large,clinical trials evaluating the efficacy of novel therapeutic agents within this field.We therefore read with great interest Srivastava et al.’s randomized clinical trial on the efficacy of filgotinib,a Janus kinase inhibitor(JAKi),in active NIU(1).The early termination of the trial due to business considerations highlights the industry difficulty in FDA medication approval for NIU.
