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
AIM：To test the therapeutic effects of delayed treatment of mesenchymal stem cells（MSCs） in recurrent experimental autoimmune uveitis（r EAU）.METHODS： The efficacy of different regimens of MSC administration in r...AIM：To test the therapeutic effects of delayed treatment of mesenchymal stem cells（MSCs） in recurrent experimental autoimmune uveitis（r EAU）.METHODS： The efficacy of different regimens of MSC administration in r EAU were tested by evaluation of clinical and pathological intraocular inflammation,as well as retinal structural and functional integrity using optical coherence tomography（OCT） and electroretinogram（ERG）.The retinal sections were also immunostained with antibodies to glial fibrillary acidic protein（GFAP）and rhodopsin（RHO）. RESULTS： Delayed treatment of MSCs effectively alleviated the severity of intraocular inflammation with relative intact of outer retinal structure and function.Moreover,double therapies with longer interval led to an even better clinical evaluation,as well as a trend of decrease in relapse and amelioration of retinal function.MSC therapies also effectively reduced GFAP expression and increased RHO expression in the retina.CONCLUSION： MSC administration can effectively treat developed diseases of rEAU,and multiple therapies can provide additional therapeutic benefits.展开更多
Uveitis is a severe inflammatory disease that can cause visual impairment.Recently,activatedγδT cells were proved to play a central role in the development of experimental autoimmune uveitis(EAU).However,the mechani...Uveitis is a severe inflammatory disease that can cause visual impairment.Recently,activatedγδT cells were proved to play a central role in the development of experimental autoimmune uveitis(EAU).However,the mechanism underlyingγδT cell activation in EAU is incompletely known.In this study,we determined the percentage changes in and the phenotypes ofγδT cells and dendritic cells(DCs)obtained from the spleens of immunized C57BL/6(B6)mice,an animal model of EAU.We found that the number ofγδT cells and DCs obviously increased during the inflammation phase of EAU(days 16-20 of our experiment),and that during this time,γδT cells expressed high levels of CD69 and the integrin lymphocyte function-associated antigen-1(LF A-1)and secreted high levels of interleukin(IL)-17A.Moreover,DCs obtained during this phase expressed high levels of CD80,CD83,CD86,and intracellular cell adhesion molecule-1(ICAM-1).Furthermore,we studied the interaction between DCs andγδT cells by using flow cytometry and confocal microscopy in order to determine whether DCs affectedγδT-cell activation in vitro.Co-cultures of the two types of cells showed that DCs induced high levels of CD69,LFA-1,and I-17A inγδT cells.Imaging studies revealed contact between the DCs andγδT cells.This interaction was mediated by the accumulation of ICAM-1 and LFA-1 at the interface of DCs-γδT cells.Thus,the activation ofγδT cells in EAU was promoted by DCs interacting withγδT cells.展开更多
Effects of WH-1 and WH-2 eye drops on experimental allergic uveitis(FAU)in rabbits induced by bovine serum albumin were clinically and pathologically observed in comparisonwith local drops of dexamethasone used as pos...Effects of WH-1 and WH-2 eye drops on experimental allergic uveitis(FAU)in rabbits induced by bovine serum albumin were clinically and pathologically observed in comparisonwith local drops of dexamethasone used as positive control.The results showed that WH-2 obvi-ously inhibited the inflammatory reactions while WH-1 did not.Protein concenwation in the aqueoushumor of WH-2-treated group of rabbits was 9.24±2.34mg/ml,which was notably lower(P【0.01)than both that of the untreated(14.33±3.14 mg/ml)and of the WH-1-treated(12.91±3.95mg/ml),but signifificantly higher than that of the dexame dexamethasone-treated goup(4.43±1.43mg/ml,P【0.01).The alleviation of the intraocular inflammatory reaction by therapy of WH-2eye drops was confimed pathologically.This study indicates that WH-2 has a positiveantiphlogistic effect on EAU in rabbits.展开更多
AIM:To investigate the cytotoxic effect of specific T cells from mice with experimental autoimmune uveitis(EAU)as well as their secreted interferon(IFN)-γand interleukin(IL)-17A on murine photoreceptor(661 W)cells.ME...AIM:To investigate the cytotoxic effect of specific T cells from mice with experimental autoimmune uveitis(EAU)as well as their secreted interferon(IFN)-γand interleukin(IL)-17A on murine photoreceptor(661 W)cells.METHODS:An EAU model was established in female mice by injection of interphotoreceptor retinoid binding protein(IRBP)emulsion supplemented with complete Freund’s adjuvant(CFA)and Mycobacterium tuberculosis(TB).On day 12 after induction of EAU,specific T cells from spleen and lymph node tissues were isolated and cultured for 4 d and the levels of IFN-γand IL-17A in the supernatants were determined by enzyme-linked immunosorbent assays(ELISAs).T cells and their supernatants were added to 661 W cells to observe the alteration of cell morphology;IFN-γand IL-17A were separately added to 661 W cells to observe the effect of IFN-γand IL-17A on cell proliferation.RESULTS:The levels of IFN-γand IL-17A in the T cell supernatants were 1568.64±38.79 pg/m L and 1456.57±46.98 pg/mL,respectively.The supernatants apparently inhibited 661 W cell proliferation(P<0.05).T cells could also attach to the surface of 661 W cells,and IFN-γshowed a more serious cytotoxic effect on 661 W cells than IL-17A,inhibiting cell proliferation(P<0.01).CONCLUSION:IFN-γand IL-17A from T cells of EAU mice model can exert cytotoxic effects on murine photoreceptor cell proliferation,and IFN-γshows more serious cytotoxic effects on murine photoreceptor cells than IL-17A.展开更多
Objective: To characterize the cellular infiltrate of eyes in experimental autoimmune uveitis (EAU) induced in C57BL/6 and B10.RIII strains. Methods: EAU was induced by interphotoreceptor retinoid-binding protein with...Objective: To characterize the cellular infiltrate of eyes in experimental autoimmune uveitis (EAU) induced in C57BL/6 and B10.RIII strains. Methods: EAU was induced by interphotoreceptor retinoid-binding protein with complete Freund's adjuvant in C57BL/6 and B10.RIII mice. Clinical scores were evaluated by funduscopy and electroretinography. Cells were isolated from inflamed eyes and analyzed by flow cytometry. Results: Different forms of EAU disease were showed with earlier disease onset, peak and higher clinical scores in acute EAU mice than chronic EAU mice [1]. In addition to increase of CD4+ T lymphocytes, percentage of CD11b+ cells were higher in the eyes of acute EAU mice than those in chronic EAU mice, while no differences were showed in CD8+ T cells, natural killer cells or natural killer T cells. Among those infiltrated CD11b+ cells, percentages of macrophages and myeloid-derived suppressor cells were higher in acute EAU mice than those in chronic EAU mice. Conclusions: The different disease pattern in EAU between acute form and chronic form is associated with the increase of infiltrated CD4+ T lymphocytes, macrophages and myeloid-derived suppressor cells.展开更多
Anterior uveitis was induced by injection of lens protein into anterior chamber of rabbit eye.Tetrandrine (Tet) (50mg/kg ip) showed marked inhibition on this ocular inflammation, the total content of prostaglandin E i...Anterior uveitis was induced by injection of lens protein into anterior chamber of rabbit eye.Tetrandrine (Tet) (50mg/kg ip) showed marked inhibition on this ocular inflammation, the total content of prostaglandin E in irises, and leukocyte chemotaxis.The pathological examination revealed that inflammation of irises in Tet group was lighter than that in control group. The antiinflammatory mechanism of Tet may be related to reduction of intracellular free calcium and inhibition of synthesis of inflmmatory factor.展开更多
Th1-response plays a crucial role in determining pathogenesis of organ-specific autoimmune diseases. It is believed that both IL-12 and INF-alpha are initiators to regulate Th1-response. In our experimental autoimmune...Th1-response plays a crucial role in determining pathogenesis of organ-specific autoimmune diseases. It is believed that both IL-12 and INF-alpha are initiators to regulate Th1-response. In our experimental autoimmune uveitis (EAU) model, both Lewis and Fischer 344 rats share the same MHC class II molecules, while Lewis rat is EAU susceptible and Fischer 344 rat is EAU resistant. However, under the same condition of immunization, if pertussis toxin (PTX) was injected intraperitoneally as an additional adjuvant, Fischer 344 rat can develop EAU. In this study we investigate which mechanisms are involved in the induction of EAU in CFA+R16+PTX-treated (CRP-treated) Fischer 344 rats. In vivo and in vitro data demonstrated that Th1-cytokine, IFN-gamma mRNA expression was significantly increased in disease target tissue-eyes and in draining lymph node cells of CRP-treated Fischer 344 rat. When IL-12 and IFN-alpha mRNA expression were compared in the experimental groups, only IFN-alpha mRNA expression was associated with EAU development. To distinguish the sources of IFN-alpha producing cells, it was observed that IFN-alpha expression was mainly produced by macrophages. It was further confirmed that normal macrophage from Fischer 344 rat was able to produce significant IFN-alpha in the presence of PTX. The data strongly suggested that IFN-alpha might be involved in initiating Th1-cell differentiation and in turn contribute to the induction of EAU. High IFN-alpha expression induced by PTX may represent a novel pathway to initiate Th1 response in Fischer 344 rat.展开更多
Experimental allergic uveitis(EAU)in rabbits was induced by singleintraocular injection of bovine serum albumin(BSA).The average of protein con-centration in aqueous humor of untreated group of rabbits was 14.33±...Experimental allergic uveitis(EAU)in rabbits was induced by singleintraocular injection of bovine serum albumin(BSA).The average of protein con-centration in aqueous humor of untreated group of rabbits was 14.33±1.21mg/mland the count of tritiated thymidine(~3H-TdR)incorporated into lymphocyte T was3,987±1,156cpm/10~6.The specific antibody responses to BSA in the serum andthe aqueous were 0.508±0.034 and 0.369±0.019(OD)respectively.Meanwhile,the effect of Qingkailing on EAU was observed in comparison wi...展开更多
AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induc...AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induced in Wistar rats through subcutaneous injection of lipopolysaccharide(LPS,200μg)and the rats were then randomly assigned to EIU group(n=5)and the HPS intervention group(n=5).HPS(400 mg/kg,intraperitoneally)or its carrier was administered 24h and 1h prior to EIU induction.Eyes were examined and enucleated 24h post-induction,and total RNA was extracted from the iris-ciliary body.Gene expression microarrays were used to identify differentially expressed genes(DEGs),followed by bioinformatics analyses,including gene ontology(GO)and pathway analysis.Key findings were not experimentally validated at the mRNA or protein level.RESULTS:A total of 322 DEGs were identified,comprising 254 mRNA and 68 lncRNA genes.GO analysis revealed significant functional categories,including response to LPS.Pathway analysis identified key signaling pathways involved in uveitis,such as cytokine-cytokine receptor interactions.Notably,16 mRNA and 7 lncRNA DEGs emerged as central nodes in the gene correlation network.CONCLUSION:HPS exerts its anti-inflammatory effects through coordinated signaling pathways,offering insights into potential therapeutic targets for managing uveitis.展开更多
Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and com...Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and complex surgical and medico-legal challenges.These innovative treatments require that informed consent not be limited to simple acceptance of the medical procedure,but instead reflect a true relational and cognitive process grounded in understanding,free choice,and the ability to revoke consent at any time.In particular,it is essential that the patient understands the experimental nature of the therapy,its development stage,potential benefits and risks,as well as the implications for their health and personal dignity.In the case of stromal cell-based treatments,which may exert complex immunomodulatory effects or activate angiogenic pathways that are not yet fully understood,patients must be made fully aware that they are participating in a non-standardized therapy whose outcomes,whether beneficial or harmful,cannot yet be predicted with certainty.This requires particularly careful medical communication,using simple yet scientifically accurate explanations delivered in appropriate language,along with a final verification of the patient’s actual understanding.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
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
AIM: To characterize the clinical features, diagnosis, treatment and prognosis of uveitis associated with ankylosing spondylitis (AS) in Chinese patients. METHODS: Two hundred and three patients with uveitis associate...AIM: To characterize the clinical features, diagnosis, treatment and prognosis of uveitis associated with ankylosing spondylitis (AS) in Chinese patients. METHODS: Two hundred and three patients with uveitis associated with AS followed-up in the Third Military Medical University Daping Hospital between 2005 and 2010 were retrospectively evaluated in this study. Complete ophthalmological examinations were evaluated at baseline and during the follow-up period. The gender, age, follow-up time, mean frequency of uveitis onset, and accompanying eye examination findings, history, demographical parameters were reviewed. All the patients presented complete clinical and radiologic (sacroiliac, lumbar, dorsal and cervical spine, knee, ankle, shoulder, hip, elbow) evaluation. HLA-B27 typing was also searched. RESULTS: There were 203 patients diagnosed with AS associated welt's. All showed sacroiliac X-ray changes indicative of AS. There were 184 male and 19 female patients. The average age of patients was 35 +/- 12 (range 18-50). Mean follow-up period was 2.4 years (1-5 years). Acute anterior wets was the most common type of uveitis in both genders. 121 eyes presented unilateral involvement (55.2%), and 92 eyes presented bilateral involvement (45.3%) with onset alternately. 22 eyes occurred hypopyon, 16 eyes were found anterior vitreous cells, 7 eyes were noted reactive macular edema or exudation, 29 eyes presented posterior synechiae of iris, and 14 eyes presented cataract, 9 eyes presented secondary glaucoma, 2 eyes presented bend corneal degeneration and 1 eyes presented atrophy of eyeball. At the final visit, uveitis was well controlled in most patients. CONCLUSION: AS associated with uveitis in Chinese patients mainly manifests as acute anterior uveitis. A combination of corticosteroids with other mydriasis agents is effective for most AS associated with uveitis patients. In general, the prognosis is good in these cases.展开更多
Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extra...Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extracellular matrix proteins,mainly collagen in the cardiac interstitium.Many experimental studies have demonstrated that fibrotic injury in the heart is reversible;therefore,it is vital to understand differ-ent molecular mechanisms that are involved in the initiation,progression,and resolu-tion of cardiac fibrosis to enable the development of antifibrotic agents.Of the many experimental models,one of the recent models that has gained renewed interest is isoproterenol(ISP)-induced cardiac fibrosis.ISP is a synthetic catecholamine,sympa-thomimetic,and nonselectiveβ-adrenergic receptor agonist.The overstimulated and sustained activation ofβ-adrenergic receptors has been reported to induce biochemi-cal and physiological alterations and ultimately result in cardiac remodeling.ISP has been used for decades to induce acute myocardial infarction.However,the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis;this practice has increased in recent years.Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy.The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is consid-ered the initiating mechanism of myocardial fibrosis.ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals.In recent years,numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis.The present review exclusively provides a comprehensive summary of the pathological biochemical,histological,and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy.It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as syn-thetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.展开更多
Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism rem...Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.展开更多
OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and ...OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and common targets between QGC and sarcopenia were screened from databases.Then the herbs-compounds-targets network,and protein-protein interaction(PPI) network was constructed.Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed by R software.Next,we used a dexamethasone-induced sarcopenia mouse model to evaluate the anti-sarcopenic mechanism of QGC.RESULTS:A total of 57 common targets of QGC and sarcopenia were obtained.Based on the enrichment analysis of GO and KEGG,we took the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway as a key target to explore the mechanism of QGC on sarcopenia.Animal experiments showed that QGC could increase muscle strength and inhibit muscle fiber atrophy.In the model group,the expression of muscle ring finger-1 and Atrogin-1 were increased,while myosin heavy chain was decreased,QGC treatment reversed these changes.Moreover,compared with the model group,the expressions of pPI3K,p-Akt,p-mammalian target of rapamycin and pForkhead box O3 in the QGC group were all upregulated.CONCLUSION:QGC exerts an anti-sarcopenic effect by activating PI3K/Akt signaling pathway to regulate skeletal muscle protein metabolism.展开更多
Ultrahigh-performance concrete(UHPC)is a groundbreaking kind of concrete that distinguishes itself from conventional concrete through its unique material properties.Understanding and managing the time-dependent charac...Ultrahigh-performance concrete(UHPC)is a groundbreaking kind of concrete that distinguishes itself from conventional concrete through its unique material properties.Understanding and managing the time-dependent characteristics of these materials is essential for their effective use in various construction applications.This study presents an experimental evaluation of the compressive and bending properties of the UHPC incorporating polypropylene,steel,and glass fibers.Based on ACI-211 guidelines,the UHPC mix was designed by using three types of aggregates:limestone,andesite,and quartzite,along with 5%fiber content(at varying percentages of 0,5%,10%,15%,and 20%)relative to the cementitious materials,and three different water-to-cement(w/c)ratios(0.24,0.3,and 0.4)were used.In this research,the compressive and flexural strength tests were conducted.The results show that increasing the values of the fibers significantly enhances the compressive strength of the studied samples.Furthermore,the utilization of fibers markedly improves the bending strength of the samples,demonstrating a strong correlation with the yield resistance of the material.Also,findings show that using steel fibers increases the compressive and bending strength of the tested samples more than polypropylene and glass fibers.For instance,in UHPC samples with 0.4 w/c,the average compressive strength values are 82.2 MPa,70.3 MPa,and 67.1 MPa for steel,polypropylene,and glass fibers,respectively.Also,in the flexural strength test,the modulus of rupture is obtained as an average of 6.24 MPa,5.24 MPa and 4.83 MPa for UHPC samples with steel,polypropylene and glass fibers,respectively.展开更多
In the scenario of a steam generator tube rupture accident in a lead-cooled fast reactor,secondary circuit subcooled water under high pressure is injected into an ordinary-pressure primary vessel,where a molten lead-b...In the scenario of a steam generator tube rupture accident in a lead-cooled fast reactor,secondary circuit subcooled water under high pressure is injected into an ordinary-pressure primary vessel,where a molten lead-based alloy(typically pure lead or lead-bismuth eutectic(LBE))is used as the coolant.To clarify the pressure build-up characteristics under water-jet injection,this study conducted several experiments by injecting pressurized water into a molten LBE pool at Sun Yat-sen University.To obtain a further understanding,several new experimental parameters were adopted,including the melt temperature,water subcooling,injection pressure,injection duration,and nozzle diameter.Through detailed analyses,it was found that the pressure and temperature during the water-melt interaction exhibited a consistent variation trend with our previous water-droplet injection mode LBE experiment.Similarly,the existence of a steam explosion was confirmed,which typically results in a much stronger pressure build-up.For the non-explosion cases,increasing the injection pressure,melt-pool temperature,nozzle diameter,and water subcooling promoted pressure build-up in the melt pool.However,a limited enhancement effect was observed when increasing the injection duration,which may be owing to the continually rising pressure in the interaction vessel or the isolation effect of the generated steam cavity.Regardless of whether a steam explosion occurred,the calculated mechanical and kinetic energy conversion efficiencies of the melt were relatively small(not exceeding 4.1%and 0.7%,respectively).Moreover,the range of the conversion efficiency was similar to that of previous water-droplet experiments,although the upper limit of the jet mode was slightly lower.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
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Supported by the National Natural Science Foundation of China(No.81371005No.81428012)Tianjin Municipal Science and Technology Commission(No.15JCZDJC35600)
文摘AIM：To test the therapeutic effects of delayed treatment of mesenchymal stem cells（MSCs） in recurrent experimental autoimmune uveitis（r EAU）.METHODS： The efficacy of different regimens of MSC administration in r EAU were tested by evaluation of clinical and pathological intraocular inflammation,as well as retinal structural and functional integrity using optical coherence tomography（OCT） and electroretinogram（ERG）.The retinal sections were also immunostained with antibodies to glial fibrillary acidic protein（GFAP）and rhodopsin（RHO）. RESULTS： Delayed treatment of MSCs effectively alleviated the severity of intraocular inflammation with relative intact of outer retinal structure and function.Moreover,double therapies with longer interval led to an even better clinical evaluation,as well as a trend of decrease in relapse and amelioration of retinal function.MSC therapies also effectively reduced GFAP expression and increased RHO expression in the retina.CONCLUSION： MSC administration can effectively treat developed diseases of rEAU,and multiple therapies can provide additional therapeutic benefits.
基金the National Natural Science Foun-dation of China(81373826,81403438 and 81500710).
文摘Uveitis is a severe inflammatory disease that can cause visual impairment.Recently,activatedγδT cells were proved to play a central role in the development of experimental autoimmune uveitis(EAU).However,the mechanism underlyingγδT cell activation in EAU is incompletely known.In this study,we determined the percentage changes in and the phenotypes ofγδT cells and dendritic cells(DCs)obtained from the spleens of immunized C57BL/6(B6)mice,an animal model of EAU.We found that the number ofγδT cells and DCs obviously increased during the inflammation phase of EAU(days 16-20 of our experiment),and that during this time,γδT cells expressed high levels of CD69 and the integrin lymphocyte function-associated antigen-1(LF A-1)and secreted high levels of interleukin(IL)-17A.Moreover,DCs obtained during this phase expressed high levels of CD80,CD83,CD86,and intracellular cell adhesion molecule-1(ICAM-1).Furthermore,we studied the interaction between DCs andγδT cells by using flow cytometry and confocal microscopy in order to determine whether DCs affectedγδT-cell activation in vitro.Co-cultures of the two types of cells showed that DCs induced high levels of CD69,LFA-1,and I-17A inγδT cells.Imaging studies revealed contact between the DCs andγδT cells.This interaction was mediated by the accumulation of ICAM-1 and LFA-1 at the interface of DCs-γδT cells.Thus,the activation ofγδT cells in EAU was promoted by DCs interacting withγδT cells.
文摘Effects of WH-1 and WH-2 eye drops on experimental allergic uveitis(FAU)in rabbits induced by bovine serum albumin were clinically and pathologically observed in comparisonwith local drops of dexamethasone used as positive control.The results showed that WH-2 obvi-ously inhibited the inflammatory reactions while WH-1 did not.Protein concenwation in the aqueoushumor of WH-2-treated group of rabbits was 9.24±2.34mg/ml,which was notably lower(P【0.01)than both that of the untreated(14.33±3.14 mg/ml)and of the WH-1-treated(12.91±3.95mg/ml),but signifificantly higher than that of the dexame dexamethasone-treated goup(4.43±1.43mg/ml,P【0.01).The alleviation of the intraocular inflammatory reaction by therapy of WH-2eye drops was confimed pathologically.This study indicates that WH-2 has a positiveantiphlogistic effect on EAU in rabbits.
基金Supported by the National Natural Science Foundation of China(No.81873163)the Natural Science Foundation of Shandong Province(No.ZR2017LH042)+2 种基金the Development Project of Medicine and Health Science Technology of Shandong Province(No.2015BJYB28,No.2017WS073)the Development Project of Science and Technology of Traditional Chinese Medicine of Shandong Province(No.2015-145)the Excellent Youth Science Foundation of Shandong University of Traditional Chinese Medicine(No.2018zk26)。
文摘AIM:To investigate the cytotoxic effect of specific T cells from mice with experimental autoimmune uveitis(EAU)as well as their secreted interferon(IFN)-γand interleukin(IL)-17A on murine photoreceptor(661 W)cells.METHODS:An EAU model was established in female mice by injection of interphotoreceptor retinoid binding protein(IRBP)emulsion supplemented with complete Freund’s adjuvant(CFA)and Mycobacterium tuberculosis(TB).On day 12 after induction of EAU,specific T cells from spleen and lymph node tissues were isolated and cultured for 4 d and the levels of IFN-γand IL-17A in the supernatants were determined by enzyme-linked immunosorbent assays(ELISAs).T cells and their supernatants were added to 661 W cells to observe the alteration of cell morphology;IFN-γand IL-17A were separately added to 661 W cells to observe the effect of IFN-γand IL-17A on cell proliferation.RESULTS:The levels of IFN-γand IL-17A in the T cell supernatants were 1568.64±38.79 pg/m L and 1456.57±46.98 pg/mL,respectively.The supernatants apparently inhibited 661 W cell proliferation(P<0.05).T cells could also attach to the surface of 661 W cells,and IFN-γshowed a more serious cytotoxic effect on 661 W cells than IL-17A,inhibiting cell proliferation(P<0.01).CONCLUSION:IFN-γand IL-17A from T cells of EAU mice model can exert cytotoxic effects on murine photoreceptor cell proliferation,and IFN-γshows more serious cytotoxic effects on murine photoreceptor cells than IL-17A.
基金Natural Science Foundation of Guangdong Province (2017A030313836).
文摘Objective: To characterize the cellular infiltrate of eyes in experimental autoimmune uveitis (EAU) induced in C57BL/6 and B10.RIII strains. Methods: EAU was induced by interphotoreceptor retinoid-binding protein with complete Freund's adjuvant in C57BL/6 and B10.RIII mice. Clinical scores were evaluated by funduscopy and electroretinography. Cells were isolated from inflamed eyes and analyzed by flow cytometry. Results: Different forms of EAU disease were showed with earlier disease onset, peak and higher clinical scores in acute EAU mice than chronic EAU mice [1]. In addition to increase of CD4+ T lymphocytes, percentage of CD11b+ cells were higher in the eyes of acute EAU mice than those in chronic EAU mice, while no differences were showed in CD8+ T cells, natural killer cells or natural killer T cells. Among those infiltrated CD11b+ cells, percentages of macrophages and myeloid-derived suppressor cells were higher in acute EAU mice than those in chronic EAU mice. Conclusions: The different disease pattern in EAU between acute form and chronic form is associated with the increase of infiltrated CD4+ T lymphocytes, macrophages and myeloid-derived suppressor cells.
文摘Anterior uveitis was induced by injection of lens protein into anterior chamber of rabbit eye.Tetrandrine (Tet) (50mg/kg ip) showed marked inhibition on this ocular inflammation, the total content of prostaglandin E in irises, and leukocyte chemotaxis.The pathological examination revealed that inflammation of irises in Tet group was lighter than that in control group. The antiinflammatory mechanism of Tet may be related to reduction of intracellular free calcium and inhibition of synthesis of inflmmatory factor.
文摘Th1-response plays a crucial role in determining pathogenesis of organ-specific autoimmune diseases. It is believed that both IL-12 and INF-alpha are initiators to regulate Th1-response. In our experimental autoimmune uveitis (EAU) model, both Lewis and Fischer 344 rats share the same MHC class II molecules, while Lewis rat is EAU susceptible and Fischer 344 rat is EAU resistant. However, under the same condition of immunization, if pertussis toxin (PTX) was injected intraperitoneally as an additional adjuvant, Fischer 344 rat can develop EAU. In this study we investigate which mechanisms are involved in the induction of EAU in CFA+R16+PTX-treated (CRP-treated) Fischer 344 rats. In vivo and in vitro data demonstrated that Th1-cytokine, IFN-gamma mRNA expression was significantly increased in disease target tissue-eyes and in draining lymph node cells of CRP-treated Fischer 344 rat. When IL-12 and IFN-alpha mRNA expression were compared in the experimental groups, only IFN-alpha mRNA expression was associated with EAU development. To distinguish the sources of IFN-alpha producing cells, it was observed that IFN-alpha expression was mainly produced by macrophages. It was further confirmed that normal macrophage from Fischer 344 rat was able to produce significant IFN-alpha in the presence of PTX. The data strongly suggested that IFN-alpha might be involved in initiating Th1-cell differentiation and in turn contribute to the induction of EAU. High IFN-alpha expression induced by PTX may represent a novel pathway to initiate Th1 response in Fischer 344 rat.
文摘Experimental allergic uveitis(EAU)in rabbits was induced by singleintraocular injection of bovine serum albumin(BSA).The average of protein con-centration in aqueous humor of untreated group of rabbits was 14.33±1.21mg/mland the count of tritiated thymidine(~3H-TdR)incorporated into lymphocyte T was3,987±1,156cpm/10~6.The specific antibody responses to BSA in the serum andthe aqueous were 0.508±0.034 and 0.369±0.019(OD)respectively.Meanwhile,the effect of Qingkailing on EAU was observed in comparison wi...
基金Supported by the National Natural Science Fundation of China(No.82101107No.81471575).
文摘AIM:To identify key genes and inflammatory signaling pathways involved in the anti-inflammatory effects of Hedysarum polybotrys polysaccharide(HPS)in a rat model of endotoxin-induced uveitis(EIU).METHODS:EIU was induced in Wistar rats through subcutaneous injection of lipopolysaccharide(LPS,200μg)and the rats were then randomly assigned to EIU group(n=5)and the HPS intervention group(n=5).HPS(400 mg/kg,intraperitoneally)or its carrier was administered 24h and 1h prior to EIU induction.Eyes were examined and enucleated 24h post-induction,and total RNA was extracted from the iris-ciliary body.Gene expression microarrays were used to identify differentially expressed genes(DEGs),followed by bioinformatics analyses,including gene ontology(GO)and pathway analysis.Key findings were not experimentally validated at the mRNA or protein level.RESULTS:A total of 322 DEGs were identified,comprising 254 mRNA and 68 lncRNA genes.GO analysis revealed significant functional categories,including response to LPS.Pathway analysis identified key signaling pathways involved in uveitis,such as cytokine-cytokine receptor interactions.Notably,16 mRNA and 7 lncRNA DEGs emerged as central nodes in the gene correlation network.CONCLUSION:HPS exerts its anti-inflammatory effects through coordinated signaling pathways,offering insights into potential therapeutic targets for managing uveitis.
文摘Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and complex surgical and medico-legal challenges.These innovative treatments require that informed consent not be limited to simple acceptance of the medical procedure,but instead reflect a true relational and cognitive process grounded in understanding,free choice,and the ability to revoke consent at any time.In particular,it is essential that the patient understands the experimental nature of the therapy,its development stage,potential benefits and risks,as well as the implications for their health and personal dignity.In the case of stromal cell-based treatments,which may exert complex immunomodulatory effects or activate angiogenic pathways that are not yet fully understood,patients must be made fully aware that they are participating in a non-standardized therapy whose outcomes,whether beneficial or harmful,cannot yet be predicted with certainty.This requires particularly careful medical communication,using simple yet scientifically accurate explanations delivered in appropriate language,along with a final verification of the patient’s actual understanding.
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.
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Supported by National Natural Science Foundation of China (No. 30400487)International Cooperation Project of Guangdong Province, China (No. 2004B50301002)"1135" Talent Doctor Foundation of Daping Hospital, China(2008-2012)
文摘AIM: To characterize the clinical features, diagnosis, treatment and prognosis of uveitis associated with ankylosing spondylitis (AS) in Chinese patients. METHODS: Two hundred and three patients with uveitis associated with AS followed-up in the Third Military Medical University Daping Hospital between 2005 and 2010 were retrospectively evaluated in this study. Complete ophthalmological examinations were evaluated at baseline and during the follow-up period. The gender, age, follow-up time, mean frequency of uveitis onset, and accompanying eye examination findings, history, demographical parameters were reviewed. All the patients presented complete clinical and radiologic (sacroiliac, lumbar, dorsal and cervical spine, knee, ankle, shoulder, hip, elbow) evaluation. HLA-B27 typing was also searched. RESULTS: There were 203 patients diagnosed with AS associated welt's. All showed sacroiliac X-ray changes indicative of AS. There were 184 male and 19 female patients. The average age of patients was 35 +/- 12 (range 18-50). Mean follow-up period was 2.4 years (1-5 years). Acute anterior wets was the most common type of uveitis in both genders. 121 eyes presented unilateral involvement (55.2%), and 92 eyes presented bilateral involvement (45.3%) with onset alternately. 22 eyes occurred hypopyon, 16 eyes were found anterior vitreous cells, 7 eyes were noted reactive macular edema or exudation, 29 eyes presented posterior synechiae of iris, and 14 eyes presented cataract, 9 eyes presented secondary glaucoma, 2 eyes presented bend corneal degeneration and 1 eyes presented atrophy of eyeball. At the final visit, uveitis was well controlled in most patients. CONCLUSION: AS associated with uveitis in Chinese patients mainly manifests as acute anterior uveitis. A combination of corticosteroids with other mydriasis agents is effective for most AS associated with uveitis patients. In general, the prognosis is good in these cases.
基金United Arab Emirates University,Grant/Award Number:12R104 and 12R121。
文摘Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extracellular matrix proteins,mainly collagen in the cardiac interstitium.Many experimental studies have demonstrated that fibrotic injury in the heart is reversible;therefore,it is vital to understand differ-ent molecular mechanisms that are involved in the initiation,progression,and resolu-tion of cardiac fibrosis to enable the development of antifibrotic agents.Of the many experimental models,one of the recent models that has gained renewed interest is isoproterenol(ISP)-induced cardiac fibrosis.ISP is a synthetic catecholamine,sympa-thomimetic,and nonselectiveβ-adrenergic receptor agonist.The overstimulated and sustained activation ofβ-adrenergic receptors has been reported to induce biochemi-cal and physiological alterations and ultimately result in cardiac remodeling.ISP has been used for decades to induce acute myocardial infarction.However,the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis;this practice has increased in recent years.Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy.The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is consid-ered the initiating mechanism of myocardial fibrosis.ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals.In recent years,numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis.The present review exclusively provides a comprehensive summary of the pathological biochemical,histological,and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy.It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as syn-thetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.
文摘Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.
基金Shanghai Clinical Research Center for Chronic Musculoskeletal Diseases (20MC1920600)Shanghai Key Clinical Specialty "Traditional Chinese Medicine Orthopaedic Traumatology"(shslczdzk03901)+3 种基金The Second Round of Construction Project of National TCM Academic School Inheritance Studio "Shi's Trauma Department"[Letter of the People's Education of Traditional Chinese Medicine (2019) No.62]Shanghai High-level Local Universities "Chronic Muscle and Bone Damage Research and Transformation" Innovation Team [No.3 of Shanghai Education Commission (2022)]Program for Shanghai High-Level Local University Innovation Team (SZY20220315)Shanghai Shenkang Hospital Development Center Clinical Three-year Action Plan (SHDC2020CR3090B)。
文摘OBJECTIVE:To explore the potential molecular mechanism of Qigu capsule(芪骨胶囊,QGC) in the treatment of sarcopenia through network pharmacology and to verify it experimentally.METHODS:The active compounds of QGC and common targets between QGC and sarcopenia were screened from databases.Then the herbs-compounds-targets network,and protein-protein interaction(PPI) network was constructed.Gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed by R software.Next,we used a dexamethasone-induced sarcopenia mouse model to evaluate the anti-sarcopenic mechanism of QGC.RESULTS:A total of 57 common targets of QGC and sarcopenia were obtained.Based on the enrichment analysis of GO and KEGG,we took the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway as a key target to explore the mechanism of QGC on sarcopenia.Animal experiments showed that QGC could increase muscle strength and inhibit muscle fiber atrophy.In the model group,the expression of muscle ring finger-1 and Atrogin-1 were increased,while myosin heavy chain was decreased,QGC treatment reversed these changes.Moreover,compared with the model group,the expressions of pPI3K,p-Akt,p-mammalian target of rapamycin and pForkhead box O3 in the QGC group were all upregulated.CONCLUSION:QGC exerts an anti-sarcopenic effect by activating PI3K/Akt signaling pathway to regulate skeletal muscle protein metabolism.
文摘Ultrahigh-performance concrete(UHPC)is a groundbreaking kind of concrete that distinguishes itself from conventional concrete through its unique material properties.Understanding and managing the time-dependent characteristics of these materials is essential for their effective use in various construction applications.This study presents an experimental evaluation of the compressive and bending properties of the UHPC incorporating polypropylene,steel,and glass fibers.Based on ACI-211 guidelines,the UHPC mix was designed by using three types of aggregates:limestone,andesite,and quartzite,along with 5%fiber content(at varying percentages of 0,5%,10%,15%,and 20%)relative to the cementitious materials,and three different water-to-cement(w/c)ratios(0.24,0.3,and 0.4)were used.In this research,the compressive and flexural strength tests were conducted.The results show that increasing the values of the fibers significantly enhances the compressive strength of the studied samples.Furthermore,the utilization of fibers markedly improves the bending strength of the samples,demonstrating a strong correlation with the yield resistance of the material.Also,findings show that using steel fibers increases the compressive and bending strength of the tested samples more than polypropylene and glass fibers.For instance,in UHPC samples with 0.4 w/c,the average compressive strength values are 82.2 MPa,70.3 MPa,and 67.1 MPa for steel,polypropylene,and glass fibers,respectively.Also,in the flexural strength test,the modulus of rupture is obtained as an average of 6.24 MPa,5.24 MPa and 4.83 MPa for UHPC samples with steel,polypropylene and glass fibers,respectively.
基金supported by Basic and Applied Basic research foundation of Guangdong province(Nos.2021A1515010343 and 2022A1515011582)the Science and Technology Program of Guangdong Province(Nos.2021A0505030026 and 2022A0505050029).
文摘In the scenario of a steam generator tube rupture accident in a lead-cooled fast reactor,secondary circuit subcooled water under high pressure is injected into an ordinary-pressure primary vessel,where a molten lead-based alloy(typically pure lead or lead-bismuth eutectic(LBE))is used as the coolant.To clarify the pressure build-up characteristics under water-jet injection,this study conducted several experiments by injecting pressurized water into a molten LBE pool at Sun Yat-sen University.To obtain a further understanding,several new experimental parameters were adopted,including the melt temperature,water subcooling,injection pressure,injection duration,and nozzle diameter.Through detailed analyses,it was found that the pressure and temperature during the water-melt interaction exhibited a consistent variation trend with our previous water-droplet injection mode LBE experiment.Similarly,the existence of a steam explosion was confirmed,which typically results in a much stronger pressure build-up.For the non-explosion cases,increasing the injection pressure,melt-pool temperature,nozzle diameter,and water subcooling promoted pressure build-up in the melt pool.However,a limited enhancement effect was observed when increasing the injection duration,which may be owing to the continually rising pressure in the interaction vessel or the isolation effect of the generated steam cavity.Regardless of whether a steam explosion occurred,the calculated mechanical and kinetic energy conversion efficiencies of the melt were relatively small(not exceeding 4.1%and 0.7%,respectively).Moreover,the range of the conversion efficiency was similar to that of previous water-droplet experiments,although the upper limit of the jet mode was slightly lower.
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).
