ObjectiveBased on the clinical characteristics of chronic gouty arthritis （CGA） in both traditional Chinese and western medicine， this study aims to systematically evaluate the clinical concordance of existing CGA animal models， providing recommendations for establishing animal models that align with the pathological characteristics of CGA and the manifestations of traditional Chinese medicine syndromes. MethodsBy comprehensively retrieving Chinese and international databases such as China National Knowledge Infrastructure， Wanfang， VIP Chinese Science and Technology Periodical Database （VIP）， and PubMed， all relevant literature on CGA animal models was collected. Based on the guidelines， the diagnostic criteria of both traditional Chinese and western medicine were summarized and organized. The evaluation indicators for the CGA model were constructed with reference to existing evaluation modes， and the CGA animal models were analyzed to systematically evaluate the clinical concordance of existing models. ResultsThe current methods used to construct CGA animal models mainly include monosodium urate crystal induction， high-protein diet induction （poultry lack urate oxidase）， and high-fat diet combined with urate oxidase inhibitors and joint injection. Based on 11 pieces of included literature， the traditional Chinese and western medicine scoring data of each model were extracted， and the average scoring values of all models were ultimately calculated. The results show that the average clinical concordances of existing CGA animal models in both traditional Chinese and western medicine are 43.33% and 64.44%， respectively. Among them， the model with the highest clinical concordance rate is the one with a high-fat diet combined with potassium oxonate to induce hyperuricemia plus joint injection， achieving 83.33% clinical concordance in western medicine and 60% in traditional Chinese medicine. This model aligns well with the pathogenic characteristics and pathological changes of clinical CGA. ConclusionAlthough current CGA animal models can simulate some pathological characteristics of CGA， they struggle to comprehensively reflect the complex pathological processes of CGA and the characteristics of traditional Chinese medicine syndromes. Therefore， in the future， it is necessary to establish the CGA animal models that incorporate the clinical disease and syndrome characteristics of traditional Chinese and western medicine and formulate the uniform model evaluation criteria， providing more precise tools for CGA mechanism research and the development of traditional Chinese medicine.

ObjectiveThis paper aims to investigate the effects of Xixintang on aquaporin-4 （AQP4） polarity distribution， blood-brain barrier （BBB） function， and neuroinflammationin rats with Alzheimer's disease （AD）， thereby revealing the potential mechanism through which this formula protects the BBB by regulating AQP4 polarization. The aim is to provide a scientific basis for clinical treatment. MethodsSixty Sprague-Dawley （SD） rats were randomly divided into a normal group， a model group， a probiotic group， a donepezil group， and an Xixintang group. The model was established by intraperitoneal injection of D-galactose （D-Gal） combined with bilateral intracerebroventricular injection of amyloid-β_25-35 （Aβ_25-35）. The probiotic group （30.85 mg·kg^-1）， donepezil group （0.88 mg·kg^-1）， and Xixintang group （1.174 g·kg^-1） received daily gavage administration， while the normal and model groups received intragastric administration with an equal volume of normal saline for one month. Cognitive ability was assessed by using the Morris water maze. BBB permeability was detected via Evans blue extravasation. The contents of interleukin-6 （IL-6）， amyloid-β_1-42 （Aβ_1-42）， and tumor necrosis factor-α （TNF-α） in the hippocampal tissues were measured by enzyme-linked immunosorbent assay （ELISA）. The protein expressions of zonula occludens-1 （ZO-1）， occludin， tissue inhibitor of metalloproteinase-1 （TIMP-1）， matrix metalloproteinase-9 （MMP-9）， and AQP4 in the hippocampal tissues were detected by western blot. The expression and co-localization levels of Aβ_1-42， ionized calcium-binding adapter molecule 1 （IBA1）， and AQP4/platelet endothelial cell adhesion molecule 31 （CD31） in the hippocampal region were examined by immunofluorescence. ResultsCompared with the normal group， the model group exhibited a significant decline in cognitive ability （P<0.01） and a marked increase in Evans blue extravasation in the brain （P<0.01）. The expressions of ZO-1， occludin， and TIMP-1 were significantly decreased （P<0.01）， while the expressions of AQP4 and MMP-9 were significantly increased （P<0.01）. The co-localization level of AQP4/CD31 was significantly reduced （P<0.01）， and the expressions of Aβ_1-42， IL-6， TNF-α， and IBA1 were significantly elevated （P<0.01）. Compared with the model group， the Xixintang group showed significant improvement in cognitive ability （P<0.01） and a significant reduction in Evans blue extravasation in the brain （P<0.01）. The expressions of occludin， TIMP-1， and ZO-1 were significantly increased （P<0.05， P<0.01）， while the expressions of AQP4 and MMP-9 were significantly decreased （P<0.05）. The co-localization level of AQP4/CD31 was significantly enhanced （P<0.01）， and the expressions of Aβ_1-42， IL-6， TNF-α， and IBA1 were significantly reduced （P<0.05， P<0.01）. ConclusionXixintang may improve cognitive function and alleviate AD pathology in AD model rats by regulating AQP4 polarity distribution， thereby breaking the vicious cycle of "Aβ deposition-neuroinflammation-BBB damage" and restoring the homeostasis of the microenvironment in the brain.

ObjectiveThis study aims to investigate whether Xixintang could ameliorate cognitive dysfunction in an Alzheimer's disease （AD） rat model induced by D-galactose and β-amyloid （Aβ_25-35）， by means of repairing the colonic mucosal barrier， regulating the Toll-like receptor 4 （TLR4）/nuclear factor-κB p65 （NF-κB p65） signaling pathway， and intervening in the pathological process mediated by the gut-brain axis. MethodsSixty specific pathogen-free （SPF） male Sprague-Dawley （SD） rats were randomly divided to five groups （n=12）： A control group， a model group， a donepezil group， an Xixintang group， and a probiotic group. Except for those in the control group， rats in all other groups received daily intraperitoneal injections of D-galactose for six consecutive weeks. Subsequently， aggregated Aβ_25-35 was injected stereotactically into the bilateral ventricles to establish the AD model. During the intervention periods， the rats in all groups were administered their respective drugs and normal saline by gavage. The Morris water maze test was used to assess the capacity for spatial learning and memory. Hematoxylin-eosin （HE） staining was employed to observe the histopathological changes in the colon tissues. Immunofluorescence was used to detect Aβ_1-41 deposition in the hippocampal region and Mucin 2 （MUC2） expression in the colonic mucosa. Western blot was performed to measure the protein expression levels of FFAR2，TLR4， NF-κB p65， occludin （OCLN）， zonula occludens-1 （ZO-1）， and MUC2 in the colonic tissues. Enzyme-linked immunosorbent assay （ELISA） was used to determine the contents of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， serum amyloid A （SAA）， and Aβ_1-42 in the hippocampal region from the colonic tissues. The lipopolysaccharide （LPS） concentrations in colon tissues of rats were measured by using a dynamic chromogenic limulus assay. ResultsCompared with those in the control group， the rats in the model group exhibited a significantly prolonged escape latency and a markedly shorter duration in the target quadrant （P<0.01）. The integrity of the colonic mucosal structure was compromised， with disordered gland arrangement and a reduced number of goblet cells. The Aβ_1-42 deposition in the hippocampal region was significantly increased （P<0.01）. The protein expression levels of TLR4 and NF-κB p65 in colonic tissues were significantly upregulated （P<0.01）， while those of occludin and ZO-1 were downregulated （P<0.01）. The contents of inflammatory factors such as IL-6， TNF-α， and SAA were significantly elevated （P<0.01）， and the LPS level in the serum was markedly increased （P<0.01）. In comparison to those in the model group， the rats in the Xixintang group showed a significantly shortened escape latency and a prolonged duration in the target quadrant （P<0.01）. The colonic mucosal structure was ameliorated， with neat gland arrangement and an increased number of goblet cells. The Aβ_1-42 deposition in the hippocampal region was reduced （P<0.01）. The protein expressions of TLR4 and NF-κB p65 in the colon tissues were decreased （P<0.05，P<0.01）， while the protein levels of occludin and ZO-1 were increased （P<0.01）. The contents of IL-6， TNF-α， and serum amyloid A （SAA） were decreased （P<0.01）， and the LPS level was reduced （P<0.01）. ConclusionXixintang can significantly ameliorate cognitive dysfunction of AD model rats， by means of restoring the colonic mucosal barrier structure， reducing cerebral Aβ deposition， and suppressing peripheral and central inflammatory response. Its mechanism of action may be closely associated with the suppression of the TLR4/NF-κB signaling pathway activation， reduction of endotoxin levels， and regulation of the gut-brain axis.

ObjectiveThis study aims to investigate whether Xixintang could ameliorate cognitive dysfunction in an Alzheimer's disease （AD） rat model induced by D-galactose and β-amyloid （Aβ_25-35）， by means of repairing the colonic mucosal barrier， regulating the Toll-like receptor 4 （TLR4）/nuclear factor-κB p65 （NF-κB p65） signaling pathway， and intervening in the pathological process mediated by the gut-brain axis. MethodsSixty specific pathogen-free （SPF） male Sprague-Dawley （SD） rats were randomly divided to five groups （n=12）： A control group， a model group， a donepezil group， an Xixintang group， and a probiotic group. Except for those in the control group， rats in all other groups received daily intraperitoneal injections of D-galactose for six consecutive weeks. Subsequently， aggregated Aβ_25-35 was injected stereotactically into the bilateral ventricles to establish the AD model. During the intervention periods， the rats in all groups were administered their respective drugs and normal saline by gavage. The Morris water maze test was used to assess the capacity for spatial learning and memory. Hematoxylin-eosin （HE） staining was employed to observe the histopathological changes in the colon tissues. Immunofluorescence was used to detect Aβ_1-41 deposition in the hippocampal region and Mucin 2 （MUC2） expression in the colonic mucosa. Western blot was performed to measure the protein expression levels of FFAR2，TLR4， NF-κB p65， occludin （OCLN）， zonula occludens-1 （ZO-1）， and MUC2 in the colonic tissues. Enzyme-linked immunosorbent assay （ELISA） was used to determine the contents of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， serum amyloid A （SAA）， and Aβ_1-42 in the hippocampal region from the colonic tissues. The lipopolysaccharide （LPS） concentrations in colon tissues of rats were measured by using a dynamic chromogenic limulus assay. ResultsCompared with those in the control group， the rats in the model group exhibited a significantly prolonged escape latency and a markedly shorter duration in the target quadrant （P<0.01）. The integrity of the colonic mucosal structure was compromised， with disordered gland arrangement and a reduced number of goblet cells. The Aβ_1-42 deposition in the hippocampal region was significantly increased （P<0.01）. The protein expression levels of TLR4 and NF-κB p65 in colonic tissues were significantly upregulated （P<0.01）， while those of occludin and ZO-1 were downregulated （P<0.01）. The contents of inflammatory factors such as IL-6， TNF-α， and SAA were significantly elevated （P<0.01）， and the LPS level in the serum was markedly increased （P<0.01）. In comparison to those in the model group， the rats in the Xixintang group showed a significantly shortened escape latency and a prolonged duration in the target quadrant （P<0.01）. The colonic mucosal structure was ameliorated， with neat gland arrangement and an increased number of goblet cells. The Aβ_1-42 deposition in the hippocampal region was reduced （P<0.01）. The protein expressions of TLR4 and NF-κB p65 in the colon tissues were decreased （P<0.05，P<0.01）， while the protein levels of occludin and ZO-1 were increased （P<0.01）. The contents of IL-6， TNF-α， and serum amyloid A （SAA） were decreased （P<0.01）， and the LPS level was reduced （P<0.01）. ConclusionXixintang can significantly ameliorate cognitive dysfunction of AD model rats， by means of restoring the colonic mucosal barrier structure， reducing cerebral Aβ deposition， and suppressing peripheral and central inflammatory response. Its mechanism of action may be closely associated with the suppression of the TLR4/NF-κB signaling pathway activation， reduction of endotoxin levels， and regulation of the gut-brain axis.

Chronic heart failure （CHF） refers to a clinical syndrome in which the function or structure of the heart is changed due to damage to the original myocardium， resulting in reduced pumping and/or filling functions of the heart. In recent years， the mechanisms， pathways， and targets of traditional Chinese medicine （TCM） in the treatment of CHF have been continuously confirmed， and the application of TCM theories in guiding the syndrome differentiation and precise treatment of CHF is currently a research hotspot. On the basis of the syndrome differentiation and treatment in TCM， Professor LI Candong innovatively proposed the thinking of five differentiation： Disease differentiation， syndrome differentiation， pathogenesis differentiation， symptom differentiation， and individual differentiation. This article explores the clinical diagnosis and treatment of CHF from this thinking， emphasizing comprehensive syndrome differentiation， objective analysis， dynamic assessment， and individualized treatment. In terms of diagnosis， the first is to identify the disease name， cause， location， severity， and type of CHF， determine the type and its evolution， and clarify the process of transmission and transformation between deficiency and excess. Secondly， it is necessary to distinguish the authenticity， severity， primary and secondary， urgency and complexity of CHF syndromes， providing scientific guidance for syndrome differentiation and treatment. Thirdly， according to the symptoms and the principles of deficiency and excess， the physician should identify the core pathogenesis of CHF from the perspectives of Qi， blood， Yin， Yang， deficiency， stasis， phlegm， water， and toxins. Fourthly， from the macro， meso and micro levels， the physician should carefully distinguish the presence or absence， severity， authenticity， and completeness of the symptoms to guide the diagnosis and treatment process of CHF. Finally， personalized medication for CHF should be promoted based on the patient's gender， age， constitution， and living habits. In terms of treatment， based on the thinking of five differentiation， we propose that the treatment of CHF should integrate the disease and syndrome， clarify the pathogenesis， and apply precise treatment. The treatment should be people-oriented， staged， and typed， and the medication should be adjusted according to symptoms. This diagnostic and therapeutic approach is based on the holistic concept and syndrome differentiation and treatment， and combines the three causes for appropriate treatment， providing new ideas and insights for the diagnosis and treatment of CHF.

Background: and Purpose Live cell-based assays (LCBA) are increasingly used for serological antibody detection due to their ability to preserve antigen conformation, offering moderately higher sensitivity than fixed cell-based assays. However, the clinical necessity of prioritizing LCBA for the detection of aquaporin-4 immunoglobulin G (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) remains unclear, especially when compared to its established role in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease. Methods: We compared the performance of live cell-based assays using immunofluorescence (LCBA-IF) and fixed cell-based assays using immunofluorescence (FCBA-IF) in detecting AQP4-IgG in 90 cases of NMOSD meeting 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, alongside 40 controls. Additionally, we further investigated the relationship between AQP4-IgG titers as measured by LCBA-IF and FCBA-IF and clinical parameters in NMOSD patients. Results: Results showed 96.9% agreement between LCBA-IF and FCBA-IF (Cohen’s κ=0.935), with a strong Spearman correlation (0.977, p<0.001). Both methods demonstrated 100% specificity, with LCBA-IF showing slightly higher sensitivity compared to FCBA-IF. Within LCBAIF-tested groups, statistically significant differences in annualized relapse rates were observed across all pairwise comparisons (low-titer vs. moderate-titer, low-titer vs. high-titer, and moderate-titer vs. high-titer; all p<0.050). However, this association reached statistical significance in some FCBA-IF-tested groups. Conclusions Overall, there is a strong concordance between LCBA-IF and FCBA-IF in detecting AQP4-IgG, where LCBA-IF shows slightly higher sensitivity. Furthermore, there is a potential link between elevated AQP4-IgG titers and an increased risk of relapse, and this correlation may appear more pronounced when using LCBA-IF.

Objective To explore the impact of tumor-associated myeloid cell infiltration signatures on postoperative overall survival (OS) in patients with gastric cancer. Methods A retrospective analysis was performed on patients who underwent radical gastrectomy at Zhongshan Hospital, Fudan University from January 2005 to December 2019. Patients were randomly divided into a training set (n＝167) and an internal validation set (n＝168) at a 1:1 ratio. Meanwhile, 147 patients with gastric cancer treated at Zhongshan Hospital (Xiamen), Fudan University during the same period were enrolled as the external validation set (n＝147). Immunohistochemistry was used in all patients to evaluate the distribution characteristics of 18 immune markers in three regions of gastric cancer tissues, namely primary tumor (PT), invasive margin (IM), and normal tissue (NT). These markers include 11 myeloid cell markers (CD11b, CD33, CD11c, CD14, CD15, CD16, CD68, CD86, CD163, CD206, and CD66b) and 7 immune checkpoints (CD73, IDO, LAG3, PD-1, SIGLEC9, SIRPA, and TIM3). LASSO regression and Cox proportional hazards model were applied to screen immune markers associated with postoperative OS in gastric cancer patients, and a predictive model for 1-, 3-, and 5-year postoperative OS was established. Data from the internal and external validation set were used for internal and external verification of the predictive model. Receiver operating characteristic (ROC) curves were plotted and the area under the curve (AUC) was calculated to assess the discriminative ability of the model. Results In the training set, LASSO regression and Cox proportional hazards model identified 4 immune marker signatures (CD14_PT, CD15_PT, CD206_PT, and SIGLEC9_PT) to construct the predictive model. ROC curve analysis showed that the AUCs of the model for predicting 1-, 3-, and 5-year postoperative OS were 0.74, 0.75, and 0.84, respectively. When the model was applied to the internal and external validation sets, the AUCs for 1-, 3-, and 5-year postoperative OS were 0.74, 0.72, 0.72 (internal validation set) and 0.72, 0.71, 0.74 (external validation set), respectively. Cox multivariate regression analysis showed that the risk score was an independent risk factor for postoperative OS in patients with gastric cancer. Conclusion The model constructed based on LASSO-Cox regression exhibits good predictive performance and can effectively predict postoperative OS in gastric cancer patients, which may serve as a basis for intensive treatment of high-risk patients after surgery.

Objective: To assess the status of sexual behaviors, HIV/AIDS knowledge awareness, and novel synthetic drug use among school attending young students in Guangdong Province, so as to provide evidence base for formulating targeted intervention strategies. Methods: From September to December 2024, a convenience sampling method was employed to conduct an anonymous online survey among 41 119 students from 20 higher education institutions and vocational colleges in Guangdong Province. Chi square test was utilized for rate comparisons and univariate analysis, and a multivariate Logistic regression model was applied to analyze factors associated with novel synthetic drug use. Results: The self reported rate of sexual behavior was 5.2%. Among sexually active students, the rates of unprotected sexual intercourse, having temporary sexual partners, and having commercial sexual partners were 32.4%, 34.5%, and 26.3%, respectively. The awareness rate of HIV related knowledge was 75.7%. The overall use rate of novel psychoactive substances(NPS) was 1.0%, and among sexually active students it was 6.5%. Multivariate Logistic regression analysis showed that students with sexual experience ( OR =4.15) and those with HIV testing history ( OR =9.38) had higher risks of NPS use; among sexually active students, those with unprotected sexual intercourse ( OR =6.83) and those with commercial sexual partners ( OR = 4.68 ) had higher risks of NPS use (all P <0.05). Conclusions The HIV/AIDS knowledge level among surveyed students needs further improvement, and high risk sexual behaviors are cross linked with novel synthetic drug use. It is recommended to carry out integrated health education for all students and implement comprehensive targeted interventions for sexually active students.

Objective:To analyze the current status of red blood cell transfusion in very preterm infants (VPI) (gestational age at birth <32 weeks) from Chinese Neonatal Network (CHNN) in 2022.Methods:This cross-sectional study was based on the CHNN VPI cohort. It included 6 985 VPI admitted to CHNN 89 participating centers within 24 hours after birth in 2022. VPI with major congenital anomalies or those transferred to non-CHNN centers for treatment or discharged against medical advice were excluded. VPI were categorized based on whether they received red blood cell transfusions, their gestational age at birth, the type of respiratory support received during transfusion, and whether the pre-transfusion hemoglobin levels exceeded the thresholds. General characteristics, red blood cell transfusion rates, number of transfusions, timing of the first transfusion, and pre-transfusion hemoglobin levels were compared among different groups. The incidence of adverse outcomes between the group of VPI who received transfusions above the threshold and those who received transfusions below the threshold were compared. Comparison among different groups was conducted using χ2 tests, Kruskal-Wallis H tests, Mann-Whitney U test, and so on. Trends by gestational age at birth were evaluated by Cochran-Armitage tests and Jonckheere-Terpstra tests for trend. Results:Among the 6 985 VPI, 3 865 cases(55.3%) were male, with a gestational age at birth of 30.0 (28.6, 31.0) weeks and a birth weight of (1 302±321) g. Overall, 3 617 cases (51.8%) received red blood cell transfusion, while 3 368 cases (48.2%) did not. The red blood cell transfusion rate was 51.8% (3 617/6 985), with rates of 77.7% (893/1 150) for those born before 28 weeks gestational age and 46.7% (2 724/5 835) for those born between 28 and 31 weeks gestational age. A total of 9 616 times red blood cell transfusions were administered to 3 617 VPI, with 632 times missing pre-transfusion hemoglobin data, and 8 984 times included in the analysis. Of the red blood cell transfusions, 25.6% (2 459/9 616) were administered when invasive respiratory support was required, 51.3% (4 934/9 616) were receiving non-invasive respiratory support, while 23.1% (2 223/9, 616) were given when no respiratory support was needed. Compared to the non-transfusion group, the red blood cell transfusion group had a higher rate of pregnancy-induced hypertension in mothers, lower rates of born via cesarean section and mother′s antenatal steroid administration, smaller gestational age, lower birth weight, a higher proportion of small-for-gestational-age, multiple births, and proportions of Apgar score at the 5 th minute after birth ≤3 (all P<0.05). They were also less likely to be female, born in hospital or undergo delayed cord clamping (all P<0.01). Additionally, higher transport risk index of physiologic stability score at admission were observed in the red blood cell transfusion group ( P<0.001). The number of red blood cell transfusion was 2 (1, 3) times, with the first transfusion occurring at an age of 18 (8, 29) days, and a pre-transfusion hemoglobin level of 97 (86, 109) g/L. For VPI ≤7 days of age, the pre-transfusion hemoglobin levels for invasive respiratory support, non-invasive respiratory support, or no respiratory support, respectively, with no statistically significant differences between groups ( H=5.59, P=0.061). For VPI aged 8 to 21 days and≥22 days, the levels with statistically differences between groups (both P<0.01). Red blood cell transfusions above recommended thresholds were observed in all respiratory support categories at different stages of life, with the highest prevalence in infants aged 8 to 21 days and≥22 days who did not require respiratory support, at 90.1% (264/273) and 91.1%(1 578/1 732), respectively. The rate of necrotizing enterocolitis was higher in the above-threshold group ( χ2=10.59, P=0.001), and the duration of hospital stay was longer in the above-threshold group ( Z=4.67, P<0.001) compared to the below-threshold group. Conclusions:In 2022, the red blood cell transfusion rate was relatively high among VPI from CHNN. Pre-transfusion hemoglobin levels frequently exceeded recommended transfusion thresholds.

BACKGROUND:Rheumatoid arthritis is an inflammatory disease.Many studies have shown that wogonin has a good anti-inflammatory effect on rheumatoid arthritis,but its exact efficacy and specific mechanism of action remain to be clarified. OBJECTIVE:To investigate the mechanism of wogonin ameliorating joint inflammation by regulating endoplasmic reticulum stress pathway in rats with collagen-induced arthritis. METHODS:(1)At the animal level:Female Wistar rats were divided into healthy control group,arthritis model group and wogonin treatment group.Rat models of arthritis in the latter two groups were established by subcutaneous injection of bovine type Ⅱ collagen and adjuvant.In the wogonin group,wogonin was given by gavage for 28 consecutive days after modeling.During this period,the rats in each group were weighed,and arthritis score and ankle swelling were measured every 7 days.After the experiment,the pathological changes of the joint were observed,the mRNA and protein levels of endoplasmic reticulum stress pathway GRP78 and CHOP were detected by qRT-PCR,western blot,and immunohistochemistry.(2)At the cellular level,cell counting kit-8 was used to detect the cytotoxic effect of wogonin on fibroblast-like synoviocytes from rats with collagen-induced arthritis.The fibroblast-like synoviocytes induced by thapsigargin were treated with different concentrations of wogonin.The levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant were detected by ELISA,and the intracellular reactive oxygen species in each group were determined by DCFH-DA probe method.The mRNA and protein levels of GRP78,IRE1α,XBP1s and CHOP were detected by qRT-PCR and western blot,respectively. RESULTS AND CONCLUSION:Compared with the healthy control group,arthritis index score and ankle swelling degree in the arthritis model group were increased(P<0.01),synovial hyperplasia,inflammatory cell infiltration,cartilage destruction and bone erosion were observed in pathological sections,and the mRNA and protein expressions of GRP78 and CHOP in the ankle were significantly increased(P<0.01),which were mainly located in synovial tissue and articular surface.Compared with the arthritis model group,the arthritis index score and ankle swelling degree in the wogonin treatment group were decreased(P<0.05),synovial hyperplasia and the number of inflammatory cells were decreased,cartilage destruction and bone erosion were alleviated,the mRNA and protein expression levels of GRP78 and CHOP in the ankle were decreased(P<0.05),particularly in synovial tissue and on the articular surface.There was no significant difference in body mass among the three groups(P>0.05).In the cell experiment,200 μmol/L wogonin significantly reduced the survival rate of fibroblast-like synoviocytes(P<0.01).Compared with the blank control group,the levels of interleukin-1β,tumor necrosis factor-α,content of reactive oxygen species,and mRNA and protein expression of GRP78,IRE1α,XBP1s,and CHOP in the thapsigargin group were significantly increased(P<0.05);compared with the thapsigargin group,50 and 100 μmol/L wogonin significantly reduced the levels of interleukin-1β and tumor necrosis factor-α in the cell supernatant(P<0.05,P<0.01),and 100 μmol/L wogonin significantly reduced the content of reactive oxygen species(P<0.01)and down-regulated the mRNA and protein expression levels of GRP78,IRE1α,XBP1s and CHOP(all P<0.05).These results suggest that wogonin can effectively alleviate joint inflammatory responses in rats with collagen-induced arthritis,and the endoplasmic reticulum stress pathway may be the key target of its intervention.