1.Application of frontal electroencephalogram in assessment of anxiety, depression,and sleep quality in adolescents with emotional disorders
Ying YANG ; Haiting XU ; Weigang PAN ; Xinpeng XU ; Siyuan LIU ; Xiaohong LI
Sichuan Mental Health 2026;39(2):112-118
BackgroundEmotional disorders in adolescents have emerged as a prominent issue in recent years. Current mainstream clinical assessment approaches for such conditions predominantly rely on interviews and rating scales, which are limited by inherent drawbacks such as high subjectivity and recall bias. Accordingly, there exists an urgent clinical need for the development of objective, quantifiable auxiliary diagnostic tools.In previous studies, frontal electroencephalography (EEG) has demonstrated significant value in assessing depressive and anxiety. However, the lack of standardized quantitative metrics and intuitive visual analytical approaches has severely restricted clinical interpretability of EEG data and diminished patient engagement. To address these key limitations, the present study proposes an innovative analytical framework that converts frontal EEG signals into quantifiable visual metrics to enhance clinical comprehension and acceptance. ObjectiveTo explore the value of frontal EEG in assessing anxiety, depression, and sleep quality in adolescents with emotional disorders, with the aim of providing objective auxiliary tools for clinical diagnosis and assessment of adolescents with emotional disorders. MethodsThis cross-sectional study recruited 105 adolescents aged 12-18 years who visited the outpatient department of a specialized mental hospital in Beijing from April 2023 to April 2024. All participants met the diagnostic criteria for mood (affective) disorders or anxiety disorders in the International Classification of Diseases, tenth edition (ICD-10). Frontal EEG signals were collected within a big data analytics-driven framework and further processed by EEG system to generate six quantitative cerebral function indices, namely brain load, tension and excitement, emotional stress, sleepiness index, cerebral vitality, and cerebral fatigue. In addition, validated standardized scales, including the Self-rating Anxiety Scale (SAS), the Self-rating Depression Scale (SDS), and the Pittsburgh Sleep Quality Index (PSQI), were administered for anxiety, depressive symptoms, and sleep quality, respectively. ResultsIn adolescent patients with emotional disorders, the SAS score exhibited significant positive correlations with brain load (rs=0.328, P<0.01), emotional stress (rs=0.341, P<0.01), and cerebral fatigue (rs=0.286, P<0.01). The SDS score was positively correlated with brain load (rs=0.275, P<0.01), emotional stress (rs=0.241, P<0.05), and cerebral fatigue (rs=0.311, P<0.01), while showing a significant negative correlation with cerebral vitality (rs=-0.212, P<0.05). Additionally, the PSQI total score demonstrated positive correlations with brain load (rs=0.340, P<0.01), emotional stress (rs=0.322, P<0.01), and cerebral fatigue (rs=0.229, P<0.05). ConclusionFrontal EEG-derived indices, including brain load, emotional stress, cerebral fatigue and cerebral vitality, may serve as objective markers for reflecting anxiety, depression, and sleep quality in adolescents with emotional disorders. [Funded by Beijing High level Innovation and Entrepreneurship Talent Support Program (number, 202504841041); Horizontal Joint Project]
2.Serial mediating roles of cognitive distortion and hopelessness in the associations of stressful life events with subclinical depressive and anxiety symptoms
Xiaolin SUN ; Xinpeng XU ; Weigang PAN ; Ying YANG ; Siyuan LIU ; Xiaohong LI
Sichuan Mental Health 2026;39(4):375-380
BackgroundStressful life events are associated with subclinical depressive and anxious symptoms, which may increase the risk of subsequent depressive and anxiety disorders. However, the mechanisms linking stressful life events to subclinical emotional symptoms remain unclear. ObjectiveTo explore the clinical characteristics of individuals with subclinical depression and anxiety following stressful events, and to analyze the mechanisms by which stressful events affect subclinical depressive and anxious symptoms, so as to provide a reference for the early identification and intervention of emotional symptoms in individuals under stress. MethodsFrom December 2024 to April 2025, 80 individuals with subclinical depression and/or anxiety (study group) and 80 healthy controls were recruited via the online official accounts of Beijing Anding Hospital, Capital Medical University and Beijing Huilongguan Hospital, Capital Medical University. Participants completed the Patients' Health Questionnaire Depression Scale-9 item (PHQ-9), the Generalized Anxiety Disorder Scale-7 item (GAD-7), the Life Event Scale (LES), the Self-rating Idea of Suicide Scale (SIOSS), and the Dysfunctional Attitude Scale (DAS). Spearman rank correlation analysis was used to examine the associations in the study group. Serial mediation analyses were conducted using model 6 of Process version 4.1, to test whether cognitive distortion and hopelessness mediated the associations of stressful life events with subclinical depressive and anxious symptoms. ResultsCompared with healthy controls, participants with subclinical depressive and anxious symptoms had higher scores on PHQ-9, GAD-7, LES, SIOSS hopelessness subscale, and DAS scores (Z/t=10.294, 9.197, 4.659, 6.918, 3.517, P<0.01). In the study group, GAD-7 score was positively correlated with LES, DAS, and SIOSS hopelessness subscale scores (rs=0.233, 0.465, 0.588, P<0.05); SIOSS hopelessness subscale score was positively correlated with DAS and LES scores (rs=0.393, 0.309, P<0.01) and cognitive distortion was positively correlated with stressful life events(rs=0.432, P<0.01). Stressful life events were directly associated with subclinical anxiety symptoms (β=0.040, 95% CI: 0.015–0.065, P<0.05), and showed a significant serial indirect association with subclinical anxiety symptoms (indirect effect=0.006, 95% CI: 0.001–0.017, P<0.01), accounting for 7.15% of the total effect. Stressful life associated with subclinical depressive symptoms (β=0.087, 95% CI: 0.060–0.115, P<0.01), however, the indirect effect through cognitive distortion and hopelessness were not statistically significant. ConclusionAfter experiencing stressful events, individuals with subclinical depression and anxiety exhibit more pronounced cognitive distortions and hopelessness. Stressful events can both directly affect subclinical anxiety symptoms and indirectly affect them through the serial mediating effects of cognitive distortion and hopelessness. Stressful events have a direct effect on subclinical depressive symptoms, whereas the mediating effects of cognitive distortion and hopelessness are no statistically significant. [Funded by the Training Program for the Development of High-level Public Health Technical Talents (number, Academic Leader-01-22); www.chictr.org.cn number, ChiCTR2400093516]
3.Correlation between serum lncRNA ANRIL and CNOT2 and clinicopathological characteristics and prognosis in elderly patients with breast cancer
Weigang MOU ; Li GAO ; Guojun QIU
International Journal of Laboratory Medicine 2025;46(19):2391-2396
Objective To analyze serum levels of long chain non coding RNA(lncRNA)ANRIL,CCR4-NOT transcription complex subunit 2(CNOT2)in breast cancer patients and their relationship with clinico-pathological characteristics and prognosis.Methods From February 2018 to February 2021,a total of 126 eld-erly patients with breast cancer in the hospital were selected as the breast cancer group.According to whether tumor progression occurred during follow-up,the patients were divided into poor prognosis group(n=26)and good prognosis group(n=100).60 old healthy female people who underwent physical examination during the same time were taken as control group.Statistical analysis was used to study the differences of serum lncRNA ANRIL and CNOT2 levels in patients with different clinical and pathological characteristics.The prognostic factors of elderly patients with breast cancer were conducted by Kaplan-Meier curve and Cox regression analy-sis.Receiver operating characteristic curve was drawn to assess the prognostic value of serum lncRNA ANRIL and CNOT2 in elderly patients with breast cancer.Results The levels of serum lncRNA ANRIL and CNOT2 in the breast cancer group were higher than those in the control group(P<0.05).The serum lncRNA AN-RIL and CNOT2 levels in patients with TNM stage Ⅲ and histological grade Ⅲ were higher than those in pa-tients with TNM stage Ⅰ-Ⅱ and histological grade Ⅰ—Ⅱ(P<0.05).The level of serum lncRNA ANRIL and CONT2 in poor prognosis group were higher than that in the good prognosis group(P<0.05).The 3-year progression free survival rates of lncRNA ANRIL high and low expression group,CNOT2 high and low expression group were 66.67%(40/60),90.91%(60/66)and 66.13%(41/62),92.19%(59/64),respective-ly,with statistically significant differences(P<0.05).TNM stage Ⅲ,histological grade Ⅲ,serum lncRNA ANRIL and CNOT2 were risk factors affecting the prognosis of elderly patients with breast cancer(P<0.05).The area under the curve of serum lncRNA ANRIL and CNOT2 combined in assessment of prognosis in elderly patients with breast cancer was higher than that of lncRNA ANRIL and CNOT2 alone(P<0.05).Conclusion The expression of serum lncRNA ANRIL and CNOT2 in elderly breast cancer are up-regulated,which are related to TNM stage and histological grading,and are markers to evaluate the prognosis of elderly patients with breast cancer.
4.Trends of Brain Tumor Incidence and Onset Age in Can-cer Registration Areas of Jiangsu Province from 2009 to 2019
De LIU ; Pan ZHANG ; Cheng QIAO ; Ting LI ; Peipei CHEN ; Zongmei DONG ; Jinyi ZHOU ; Ran TAO ; Weigang MIAO ; Renqiang HAN
China Cancer 2025;34(2):116-124
[Purpose]To analyze the trends of brain tumor incidence and age of onset in cancer registration areas of Jiangsu Province from 2009 to 2019.[Methods]The incidence data of brain tumors from 2009 to 2019 were obtained from 16 national cancer registration areas of Jiangsu Province.The crude incidence rate,age-standardized incidence rate by Chinese standard popula-tion(ASIRC),average age of onset,standardized age-specific incidence rate,and annual average percentage change(AAPC)by sexes and regions were calculated.[Results]The incidence rate of brain tumor in Jiangsu Province from 2009 to 2019 showed an increasing trend(AAPC=4.12%,95%CI:3.31%~4.95%),and the increase in female(AAPC=5.79%,95%CI:4.44%~7.15%)was higher than that in male(AAPC=2.31%,95%CI:1.66%~2.97%);and the increase in urban areas(AAPC=4.84%,95%CI:3.52%~6.18%)was higher than that in rural areas(AAPC=3.04%,95%CI:2.12%~3.98%).The ASIRC also showed an increasing trend(AAPC=2.14%,95%CI:1.27%~3.02%).Birth cohort analysis showed that within the same age group,the incidence rate of brain tumors increased with increasing birth years.The average age of onset for crude incidence showed a delaying trend of 0.43 years old per year(t=7.09,P<0.001);that for ASIRC was 0.20 years old per year(t=3.33,P=0.009).The proportion of patients in the age group of 60 years old and above increased from 35.79%in 2009 to 44.18%in 2019.[Conclusion]The incidence of brain tumor in cancer registration areas of Jiangsu Province showed an increasing trend from 2009 to 2019 with a delaying trend of average age of onset.
5.Trends of Incidence and Age at Onset of Bone Malignant Tumors in Jiangsu Cancer Registration Areas from 2009 to 2019
Pei ZHAO ; Ye XIE ; Qiumei LI ; Qiwei WANG ; Renqiang HAN ; Weigang MIAO ; Ran TAO ; Jinyi ZHOU
China Cancer 2025;34(8):618-625
[Purpose]To analyze the trends of incidence and age at onset of bone malignant tumors in cancer registration areas of Jiangsu Province from 2009 to 2019.[Methods]Incidence data of bone malignant tumors from 2009 to 2019 were collected from 16 consecutive and quality-con-trolled cancer registries in Jiangsu Province.The incidence rates,average age at onset,and inci-dence composition of bone malignant tumors were calculated.A birth cohort model was constructed to analyze the changes in the incidence of bone malignant tumors in the population born from 1929 to 2019.Joinpoint regression models were used to analyze the average annual percentage change(AAPC)in the incidence rates and the incidence composition of bone malignant tumors for each year in those aged 60 years old and above.A general linear regression model was used to ana-lyze the trend of the average age of onset.[Results]The crude incidence rate of bone malignant tumors in women in Jiangsu cancer registration areas decreased from 2009 to 2019,with an AAPC of-2.62%(P=0.025).After adjusting the population composition,except for urban areas,the incidence of bone malignant tumors in the whole province,men,women and rural areas all decreased significantly,with AAPC of-3.15%,-2.49%,-4.31%and-2.23%,respectively.The average age at onset of bone malignant tumors in the whole province,men and urban areas de-creased significantly yearly,with an average annual decrease of 0.365,0.504 and 0.469 years old,respectively.In the same period,the incidence of malignant bone tumors in the whole province,men,women and urban areas of age groups of 50~59,60~69 and 70~79 years old showed a decreasing trend,the AAPC ranged from-9.06%to-4.14%(all P<0.05),and the inci-dence decreased gradually with the year of birth.The incidence of malignant bone tumors in men<30 years old increased yearly with an AAPC of 4.30%(P<0.05).Compared with 2009,the com-position of incidence in men aged 15~39 years old and in urban population increased in 2019,while the incidence of bone malignant tumors in the age group of 60~79 years old in the province generally decreased.After age structure adjustment,the incidence of bone malignant tumors in people over 60 years old in urban areas decreased with an AAPC of-1.42%(P<0.05).[Conclu-sion]The incidence of bone malignant tumors in Jiangsu Province is decreasing and the age at on-set is moving forward,indicating that the prevention and control measures of bone malignant tu-mors should be adjusted accordingly.
6.Incidence trends and age distribution of cutaneous melanoma in Jiangsu province from 2010 to 2019
Yuancheng LI ; Renqiang HAN ; Weigang MIAO ; Pengfei LUO
Chinese Journal of Dermatology 2025;58(3):228-233
Objective:To analyze incidence trends and age distribution of cutaneous melanoma in Jiangsu province from 2010 to 2019.Methods:In this cross-sectional study, data on the reported incidence of cutaneous melanoma from 2009 to 2019 were obtained from 16 cancer registries in Jiangsu Province, which had complete and continuous records after quality control. The Jointpoint log-linear regression model was used, and the average annual percentage change (AAPC) was calculated to analyze incidence trends of cutaneous melanoma in different genders and areas (urban or rural). Data from the Chinese population census in 2000 were used for calculation of age-standardized incidence rates by Chinese standard population. The Jointpoint regression model was used to evaluate the trends in the average age at onset over time. If there were no inflection points, a t test was used to compare changes in the average age at onset and age-specific proportions among different years. The age-period-cohort model was used to analyze changes of the incidence in birth cohorts in different years. Results:The age-standardized incidence rate of cutaneous melanoma in Jiangsu province was 0.26/100 000 in 2009 and 0.49/100 000 in 2019. Overall, the provincial incidence rates showed an increasing trend (AAPC in age-standardized incidence rates: 6.17%, P < 0.001). In the subgroup analyses, increasing trends were observed in different genders and areas (AAPC in age-standardized incidence rates: 4.24% for males, 8.01% for females, 5.17% for urban areas, 7.62% for rural areas, all P < 0.001). The standardized average age at onset of cutaneous melanoma was 59.95 years in 2009 and 58.84 years in 2019, with no significant trend in average age at onset over time ( P = 0.196). People aged 60 years and above had an AAPC of 1.20% ( P = 0.020) in the actual incidence proportion of cutaneous melanoma in 2019 compared with 2009. The age-period-cohort model showed that the incidence progressively increased with the year of birth in age groups among patients of different genders and in different areas (all P < 0.05) . Conclusions:The overall incidence of cutaneous melanoma was relatively low in Jiangsu province from 2009 to 2019, however, an upward trend was observed. Patients in both rural and urban areas, as well as female and male populations, all exhibited increasing incidence rates. The incidence rates of cutaneous melanoma increased with age.
7.Qingre sanzhuo decoction treats hyperuricemia complicated with gouty arthritis via TLR4/Myd88/NF-κB signaling pathway
Weigang CHENG ; Haolin LI ; Juanjuan YANG ; Qian BAI ; Luoyang JING ; Lele HU ; Fangmei JIN ; Haidong WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(4):456-463
AIM:To investigate the therapeutic effect of Qingre sanzhuo decoction on rats with hyperuri-caemia combined with gouty arthritis and its effect on TLR4/Myd88/NF-κB signalling pathway.METHODS:Forty-eight SD male rats were randomly divided into blank,model,and colchicine groups(0.3 mg·kg-1·d-1),and Origre sanzhou decotion low,medium and high-dosage groups(7.42,14.85,29.70 g·kg-1·d-1),which were treated with the modified Coderre method for hyperuricemia combined with acute gouty arthritis via gavage of yeast paste combined with potassium oxa-late,which was used for the treatment of acute gouty arthritis combined with hyperuricemia.A composite rat model of acute gouty arthritis was constructed by combining yeast paste with potassium oxalate gavage to cause hyperuricaemia,combined with the modified Coderre method.After 7 days of intervention,the circumference of the right ankle joint of rats was measured and the swelling of the ankle joint was calculated,the blood uric acid(HUA)level of rats was determined by biochemical method,the histopatho-logical and morphological changes of the synovial membrane of the ankle joint of rats were examined by HE staining,and the serum levels of inflammatory factors,tumour necrosis factor-alpha(TNF-α),inter-leukin-6(IL-6),and IL-1β were determined by enzyme-linked immunosorbent assay(ELISA),and Western blotting was performed to determine the levels of inflammatory factors,TNF-α,and IL-1β.The protein expression levels of Toll-like receptor 4(TLR4),myeloid differentiation factor 88(Myd88),and nuclear factor-κB(NF-κB)in the synovial tissues of the ankle joints of the rats were determined by Western blot method,and the mRNA expression of TLR4,Myd88,and NF-κB in the rat was determined by real-time fluorescence quantitative polymerase chain reaction(Real-time PCR).RESULTS:Compared with the blank group,rats in the model group showed significantly lower ankle joint swelling(P<0.01),increased levels of HUA,dis-organised synovial tissue structure,large number of inflammatory cells infiltration,and significantly higher serum levels of TNF-α,IL-6,and IL-1β(P<0.01),and the protein and mRNA expression levels of TLR4,Myd88,and NF-κB in the synovial membrane of the ankle joints of the model group were significantly increased(P<0.01).levels were significantly increased(P<0.01);compared with the model group,joint swelling was significantly reduced in the colchicine group,and the medium-and high-dose groups of Qingre sanzhuo decoction(P<0.05);synovial hyperplasia and inflam-matory cell infiltration were improved in the colchicine group and the medium-and high-dose groups of Qingre sanzhuo decoction,and the HUA and the levels of TNF-α,IL-6,and IL-1β were significantly decreased in the dosing groups(P<0.05,P<0.01),and compared with the model group,the medium-and high-dose groups of Qingre sanzhuo decoction could significantly reduce the expression of TLR4,Myd88,and NF-κB protein and mRNA(P<0.01).CONCLUSION:Qingre sanzhuo decoction reduces the release of inflamma-tory factors by inhibiting the TLR4/Myd88/NF-κB pathway,and plays a role in the treatment of hyper-uricaemia combined with gouty arthritis.
8.Sesquiterpene ZH-13 from Aquilariae Lignum Resinatum Improves Neuroinflammation by Regulating JNK Phosphorylation
Ziyu YIN ; Yun GAO ; Junjiao WANG ; Weigang XUE ; Xueping PANG ; Huiting LIU ; Yunfang ZHAO ; Huixia HUO ; Jun LI ; Jiao ZHENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):139-145
ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide (LPS) to induce neuroinflammation. The cells were divided into the normal group, the model group, and the ZH-13 low- and high-dose treatment groups (10, 20 μmol·L-1). The model group was treated with 1 μmol·L-1 LPS. Cell viability was assessed using the cell proliferation and activity assay (CCK-8 kit). Nitric oxide (NO) release in the cell supernatant was measured using a nitric oxide kit (Griess method). The mRNA expression levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and interleukin-6 (IL-6) were detected by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The phosphorylation of mitogen-activated protein kinase (MAPK) pathway proteins was assessed by Western blot. ResultsCompared with the model group, ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation (P<0.05, P<0.01). In the 20 μmol·L-1 ZH-13 treatment group, the mRNA expression levels of IL-1β, TNF-α, iNOS, and IL-6 were significantly reduced compared to the model group (P<0.05, P<0.01). In both the low- and high-dose ZH-13 groups, the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase (JNK) in the upstream MAPK pathway were significantly reduced (P<0.05). After stimulation with the JNK agonist anisomycin (Ani), both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group (P<0.01). ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.
9.Effect of Wulao Qisun Prescription on Proliferation and Osteogenic Differentiation of AS Fibroblasts by Regulating Wnt/β-catenin Signaling Pathway
Juanjuan YANG ; Ping CHEN ; Haidong WANG ; Zhendong WANG ; Haolin LI ; Zhimin ZHANG ; Yuping YANG ; Weigang CHENG ; Jin SU ; Jingjing SONG ; Dongsheng LU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):67-73
ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis (AS). MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group, low drug-containing serum group, medium drug-containing serum group, high drug-containing serum group, and positive drug group. After drug intervention, cell proliferation was measured using the cell counting kit-8 (CCK-8) assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase (ALP) activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin (OCN), osteopontin (OPN), and runt-related transcription factor 2 (Runx2) was detected by Western blot. The mRNA expression levels of Wnt5a, β-catenin, and Dickkopf-1 (DKK-1) were measured by real-time quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the blank group, each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression (P<0.01). Compared with the blank group, the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression (P<0.05). The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression (P<0.05, P<0.01), with the positive drug group showing the most pronounced effect (P<0.01). The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression (P<0.01). Compared with the blank group, the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins (P<0.05, P<0.01), while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN, OPN, and Runx2 proteins (P<0.05, P<0.01). ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts, thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression, further inhibiting the transcription of downstream target genes.
10.Qingre Sanzhuo Decoction Treats Gouty Arthritis Combined with Hyperuricaemia in Rats via NLRP3/ASC/Caspase-1 Pathway
Haolin LI ; Qian BAI ; Weigang CHENG ; Weiqing LI ; Juanjuan YANG ; Peixin HE ; Huijun YANG ; Haidong WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):49-57
ObjectiveTo investigate the effect and mechanism of Qingre Sanzhuo decoction in treating gouty arthritis (GA) combined with hyperuricaemia (HUA). MethodsSixty male SD rats were randomized into normal, model, colchicine (0.5 mg·kg-1), and low-, medium-, and high-dose (17, 34, 68 g·kg-1, respectively) Qingre Sanzhuo decoction groups (n=10). The rats in other groups except the normal group were treated with the modified method for the modeling of GA combined with HUA. The drug intervention groups were administrated with corresponding drugs by gavage in the afternoon every day and the normal group and the model group were administrated with an equal volume of sterile normal saline by gavage. The level of uric acid (SUA) in the serum was measured 2 h after the last administration. The degree of ankle joint swelling was calculated 0.5, 12, 24, 48 h after modeling, and joint inflammation was scored. The pathological changes of ankle joints were observed by hematoxylin-eosin staining, and the serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), C reactive protein (CRP), and interleukin-18 (IL-18) were measured by enzyme-linked immunosorbent assay. Real-time PCR was performed to determine the mRNA levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), cysteinyl aspartate-specific protease-1 (Caspase-1), gasdermin D (GSDMD), and nuclear factor-kappa B (NF-κB) in the synovial tissue of ankle joints. Western blot was employed to determine the protein levels of NLRP3, ASC, and Caspase-1 in ankle joints. The immunohistochemical method was used to detect the expression of GSDMD and NF-κB in the synovial tissue of ankle joints. ResultsCompared with the normal group, the model group showed increased SUA in the serum (P<0.05), ankle joint swelling and joint inflammation (P<0.05), increased number of blood vessels in the synovium, inflammatory cell foci in the synovial bursa, elevated serum levels of TNF-α, IL-1β, CRP, and IL-18 (P<0.05), and up-regulated mRNA and protein levels of NLRP3, ASC, Caspase-1, GSDMD, and NF-κB in the synovial tissue of ankle joints (P<0.05). Compared with the model group, the medium- and high-dose Qingre Sanzhuo decoction groups showed reduced SUA in the serum (P<0.05), alleviated ankle joint swelling and joint inflammation (P<0.05), lowered serum levels of TNF-α, IL-1β, CRP, and IL-18 (P<0.05), and down-regulated mRNA and protein levels of NLRP3, ASC, Caspase-1, GSDMD, and NF-κB in the synovial tissue of ankle joints (P<0.05). However, in terms of ameliorating the pathological changes of ankle joints, only the high-dose Qingre Sanzhuo decoction group showed normal morphology of the synovial membrane of ankle joints and no obvious lesion in the articular cartilage. ConclusionQingre Sanzhuo decoction may play a role in preventing and controlling GA combined with HUA by down-regulating the activity of NLRP3/ASC/Caspase-1 pathway and inhibiting the expression of inflammatory cytokines, such as TNF-α, IL-1β, CRP, and IL-18.

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