1.Mechanistic Study on Tougu Xiaotong Capsules in Regulating PANoptosis to Delay Degeneration of Chondrocytes in Knee Osteoarthritis
Jinxia YE ; Yixin LIN ; Xiaoqing LEI ; Yanfeng HUANG ; Changlong FU ; Desen LI ; Wenyi WANG ; Lan WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):149-161
ObjectiveTo investigate the effect of Tougu Xiaotong capsules (TGXTC) on the regulation of chondrocyte PANoptosis, delay of chondrocyte degeneration, and improvement of the symptoms in knee osteoarthritis (KOA). MethodsIn vivo experiments: 50 male C57BL/6 mice were randomly assigned into five groups (n=10 per group): sham operation group, model group, low-dose TGXTC group (7.2 g·kg-1), high-dose TGXTC group (14.4 g·kg-1), and diclofenac sodium group (0.05 g·kg-1). Except for the sham group, KOA models were established in all other groups using the modified Hulth method. Following successful model induction, the TGXTC groups received daily oral gavage of 7.2 or 14.4 g·kg-1 for 6 weeks, while the diclofenac sodium group received 0.05 g·kg-1 solution daily over the same duration. Model evaluation was performed using Lequesne MG score; micro-computed tomography (micro-CT) was used to scan the knee, hematoxylin-eosin (HE) staining and safranin O-fast green staining were used to observe the morphology of cartilage, transmission electron microscopy (TEM) was used to determine ultrastructural changes of PANoptosis. Multiple immunofluorescence (IF) co-localization assays was performed to detect the co-localization of cleaved Caspase-3, receptor-interacting protein 3 (RlPK3), and the N-terminal domain of gasdermin D (GSDMD-N) in cartilage tissue, while western blot was employed to detect the expression levels of cleaved Caspase-3, RIPK3, and GSDMD-N. In vitro experiments: The knee cartilages of 4-week-old SD rats were isolated, and a chondrocyte in vitro culture system was established through mechanical digestion with 0.2% type Ⅱ collagenase. Second-generation chondrocytes were divided into three groups: the control group, the model group (pretreated with 10 mg·L-1 lipopolysaccharide (LPS) for 24 h followed by treatment with 1 μmol·L-1 nigericin for 4 h), and the TGXTC treatment group (pretreated with 10 mg·L-1 LPS for 24 h, followed by exposure to 1 μmol·L-1 nigericin for 4 h and subsequently treated with 100 mg·L-1 TGXTC for an additional 24 h). The levels of reactive oxygen species (ROS), apoptosis, necroptosis, and pyroptosis of chondrocytes were evaluated via fluorescence microscopy following staining with ROS detection, AO/EB and YO-PRO-1/PI staining kits. Transmission electron microscopy was utilized to investigate the ultrastructural changes associated with PANoptosis in cartilage tissue of KOA mice. Inflammatory cytokine levels (IL-1β and IL-18) were measured using ELISA. Western blot was conducted to assess protein expressions related to PANoptosis, including cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3. ResultsCompared with the sham group, the Lequesne MG scores were significantly up-regulated(P<0.01) in the model group, and the pathological changes of cartilage were significantly, with joint spaces narrower, osteophyte formation increased, secere abrasion of cartilage surface. Ultrastructural analysis revealed pronounced chondrocyte apoptosis, necroptosis, and pyroptosis, along with markedly elevated expression of cleaved Caspase-3, RlPK3, and GSDMD-N in cartilage tissue (P<0.01). In addition, The mean fluorescence intensities of ROS, orange-red fluorescence in AO/EB staining, green fluorescence and red fluorescence in YO-PRO-1/PI staining were increased of chondrocyte in the model group (P<0.01) . The levels of inflammatory factors IL-1β and IL-18 in the supernatant were increased (P<0.01). The expression of PANoptosis related proteins (cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3) were also significantly upregulated(P<0.05). Compared to the model group, the TGXTC group demonstrated a significant improvement in various parameters of mice. These included a reduction in the Lequesne MG score, an increase in joint space, a decrease in osteophyte formation, diminished cartilage damage, reduced release of ROS, and alleviation of apoptotic, necroptotic, and pyroptotic processes in chondrocytes. Additionally, mitochondrial swelling and endoplasmic reticulum dilation were also mitigated. The levels of ROS as well as IL-1β and IL-18 were significantly decreased (P<0.05). Furthermore, the expression levels of proteins associated with PANoptosis in cartilage tissue showed marked reductions (P<0.05). Similar results were observed in chondrocytes: cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3 exhibited significant decreases as well (P<0.05). ConclusionTGXTC may mitigate chondrocytes degeneration and alleviate KOA symptoms by reducing oxidative stress and suppressing the activation of PANoptosis pathways.
2.Mechanistic Study on Tougu Xiaotong Capsules in Regulating PANoptosis to Delay Degeneration of Chondrocytes in Knee Osteoarthritis
Jinxia YE ; Yixin LIN ; Xiaoqing LEI ; Yanfeng HUANG ; Changlong FU ; Desen LI ; Wenyi WANG ; Lan WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):149-161
ObjectiveTo investigate the effect of Tougu Xiaotong capsules (TGXTC) on the regulation of chondrocyte PANoptosis, delay of chondrocyte degeneration, and improvement of the symptoms in knee osteoarthritis (KOA). MethodsIn vivo experiments: 50 male C57BL/6 mice were randomly assigned into five groups (n=10 per group): sham operation group, model group, low-dose TGXTC group (7.2 g·kg-1), high-dose TGXTC group (14.4 g·kg-1), and diclofenac sodium group (0.05 g·kg-1). Except for the sham group, KOA models were established in all other groups using the modified Hulth method. Following successful model induction, the TGXTC groups received daily oral gavage of 7.2 or 14.4 g·kg-1 for 6 weeks, while the diclofenac sodium group received 0.05 g·kg-1 solution daily over the same duration. Model evaluation was performed using Lequesne MG score; micro-computed tomography (micro-CT) was used to scan the knee, hematoxylin-eosin (HE) staining and safranin O-fast green staining were used to observe the morphology of cartilage, transmission electron microscopy (TEM) was used to determine ultrastructural changes of PANoptosis. Multiple immunofluorescence (IF) co-localization assays was performed to detect the co-localization of cleaved Caspase-3, receptor-interacting protein 3 (RlPK3), and the N-terminal domain of gasdermin D (GSDMD-N) in cartilage tissue, while western blot was employed to detect the expression levels of cleaved Caspase-3, RIPK3, and GSDMD-N. In vitro experiments: The knee cartilages of 4-week-old SD rats were isolated, and a chondrocyte in vitro culture system was established through mechanical digestion with 0.2% type Ⅱ collagenase. Second-generation chondrocytes were divided into three groups: the control group, the model group (pretreated with 10 mg·L-1 lipopolysaccharide (LPS) for 24 h followed by treatment with 1 μmol·L-1 nigericin for 4 h), and the TGXTC treatment group (pretreated with 10 mg·L-1 LPS for 24 h, followed by exposure to 1 μmol·L-1 nigericin for 4 h and subsequently treated with 100 mg·L-1 TGXTC for an additional 24 h). The levels of reactive oxygen species (ROS), apoptosis, necroptosis, and pyroptosis of chondrocytes were evaluated via fluorescence microscopy following staining with ROS detection, AO/EB and YO-PRO-1/PI staining kits. Transmission electron microscopy was utilized to investigate the ultrastructural changes associated with PANoptosis in cartilage tissue of KOA mice. Inflammatory cytokine levels (IL-1β and IL-18) were measured using ELISA. Western blot was conducted to assess protein expressions related to PANoptosis, including cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3. ResultsCompared with the sham group, the Lequesne MG scores were significantly up-regulated(P<0.01) in the model group, and the pathological changes of cartilage were significantly, with joint spaces narrower, osteophyte formation increased, secere abrasion of cartilage surface. Ultrastructural analysis revealed pronounced chondrocyte apoptosis, necroptosis, and pyroptosis, along with markedly elevated expression of cleaved Caspase-3, RlPK3, and GSDMD-N in cartilage tissue (P<0.01). In addition, The mean fluorescence intensities of ROS, orange-red fluorescence in AO/EB staining, green fluorescence and red fluorescence in YO-PRO-1/PI staining were increased of chondrocyte in the model group (P<0.01) . The levels of inflammatory factors IL-1β and IL-18 in the supernatant were increased (P<0.01). The expression of PANoptosis related proteins (cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3) were also significantly upregulated(P<0.05). Compared to the model group, the TGXTC group demonstrated a significant improvement in various parameters of mice. These included a reduction in the Lequesne MG score, an increase in joint space, a decrease in osteophyte formation, diminished cartilage damage, reduced release of ROS, and alleviation of apoptotic, necroptotic, and pyroptotic processes in chondrocytes. Additionally, mitochondrial swelling and endoplasmic reticulum dilation were also mitigated. The levels of ROS as well as IL-1β and IL-18 were significantly decreased (P<0.05). Furthermore, the expression levels of proteins associated with PANoptosis in cartilage tissue showed marked reductions (P<0.05). Similar results were observed in chondrocytes: cleaved Caspase-3, cleaved Caspase-8, RIPK3, ZBP1, GSDMD-N, and NLRP3 exhibited significant decreases as well (P<0.05). ConclusionTGXTC may mitigate chondrocytes degeneration and alleviate KOA symptoms by reducing oxidative stress and suppressing the activation of PANoptosis pathways.
3.Current Status,Challenges,and Strategies of Basic Research on the Brain-Gut Interaction Theory for Spleen and Stomach Diseases in Traditional Chinese Medicine
Ting CHEN ; Jinxia ZHU ; Xiaohua HOU ; Xiaoli ZHANG ; Lifei ZHENG ; Lei ZHANG ; Xinxin WANG ; Xuan LI ; Xudong TANG
Journal of Traditional Chinese Medicine 2026;67(5):517-522
The brain-gut interaction theory is a multidimensional integrative concept based on the brain-gut axis, involving neural, endocrine, and immune regulatory networks as well as the gut microbiota. Zang-fu organs (脏腑) theory in traditional Chinese medicine (TCM) shows a high degree of consistency with the brain-gut interaction theory, and the core functions such as the spleen and stomach governing the ascending of the clear and descending of the turbid, the liver governing the free flow of qi, and the heart governing mental and emotional activities are closely associated with the multi-level regulatory mechanisms of the brain-gut axis. TCM therapy can modulate brain-gut interactions through multiple pathways in the treatment of spleen and stomach diseases, including the regulation of gastrointestinal hormone secretion, neurotransmitter levels, the hypothalamic-pituitary-adrenal (HPA) axis, immune homeostasis and inflammatory responses, as well as the gut microecology. However, current basic research on the brain-gut interaction theory in TCM for spleen and stomach diseases still faces several challenges, such as difficulties in integrating TCM spleen-stomach theory with modern pathophysiology, lack of innovation in research concepts, and limitations in research methodologies. It is therefore proposed that multidisciplinary collaboration, multi-omics technologies, and targeted research approaches should be adopted to provide more comprehensive methods for basic research on TCM spleen and stomach diseases, thereby promoting the in-depth development of brain-gut interaction theory.
4.Parameters of MR diffusion kurtosis imaging for predicting human epidermal growth factor receptor 2-positive breast cancer
Jinxia QIU ; Yongbo YIN ; Lili YANG ; Na QI ; Hongsha WANG
Chinese Journal of Interventional Imaging and Therapy 2025;22(8):529-533
Objective To investigate the value of parameters of MR diffusion kurtosis imaging(DKI)for predicting human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC).Methods A total of 122 cases of BC diagnosed by pathology were retrospectively enrolled,including 37 cases of HER2-positive(HER2-positive group)and 85 cases of HER2-negative(HER2-negative group).Parameters obtained based on MR DKI(mean diffusivity[MD]and mean kurtosis[MK]values)and the results of immunohistochemical detection(expression of matrix metalloproteinase-2[MMP-2],vascular endothelial growth factor receptor 2[VEGFR-2])were compared between groups.Then maltivariable logistic regression was used to analyze the independent predictors of HER2-positive BC based on DKI parameters being statistically different between groups,and a combined model was constructed.Receiver operating characteristic(ROC)curve was drawn,and the area under the curve(AUC)were calculated to assess the efficacy of each single DKI parameter and their combined model for predicting HER2-positive BC,and the correlations of these DKI parameters with MMP-2 or VEGFR-2 expressions were analyzed.Results Compared with HER2-negative group,MD value,MK value,positive expression proportion of MMP-2 and VEGFR-2 increased in HER2-positive group(all P<0.05).Both MD(OR=1.423)and MK(OR=1.624)values were independent predictors of HER2-positive BC(both P<0.05),with AUC for predicting HER2-positive BC of 0.819 and 0.836,respectively,while the AUC of combined model of MD and MK values was 0.916.MD value of BC was positively correlated with MMP-2(rs=0.222)and VEGFR-2 expression(rs=0.232)(both P<0.05),while MK value of BC was not significantly correlated with MMP-2 or VEGFR-2 expression(both P>0.05).Conclusion As parameters of MR DKI,MD and MK values could be used to effectively predict HER2-positive BC.
5.Exploration on Fine Operation Management of Low Value Consumables under SPD Management Model
Hong-bin WANG ; Yi XU ; Qing ZHENG ; Xuezhi HONG ; Chunrong TAN ; Yongqin ZHANG ; Li WANG ; Jinxia ZHANG
Chinese Health Economics 2025;44(9):80-83
Objective:To strengthen the management of low-value consumables in public hospitals by introducing the Supply Processing Distribution(SPD)management model,and to explore refined operational management strategies and path optimization for low-value consumables.Methods:The SPD management model was introduced,and the entire process of hospital consumables was refinedly managed using third-party supply chain information management platforms,visualized tertiary department warehouses,Radio Frequency Identification(RFID)technology and intelligent cabinet systems,Unique Device Identification(UDI)coding,"four-code integration"and other supporting technologies.Results:Based on the analysis of the current situation in the target Hospital,specific measures related to the management of low-value consumables were introduced after the introduction of the SPD model.Conclusion:It provides a reference and guidance for the hospital's medical consumables management department to promote refined management of medical consumables under the SPD model.
6.Reform and practice of"Topic-based"experimental teaching in course of Clinical Immunological Test Technology in the perspective of new quality productivity
Wei YANG ; Gang WANG ; Jinxia AI ; Xuesong WANG ; Miao WANG ; Liyuan SUN
Chinese Journal of Immunology 2025;41(5):1228-1231
From the perspective of new quality productivity,it is a new direction and opportunity to train innovative talents with modern technology and professional knowledge.This paper introduces the practice of"Topic-based"experimental teaching in the course of Clinical Immunology Laboratory Technology,and explores the possible ways to train new qualified personnel of medical labo-ratory technology.
7.A case report and literature review on mechanical thrombectomy for ectopic embolism caused by carotid web and restenosis after carotid endarterectomy
Peng ZHAO ; Ping ZHANG ; Jinxia WANG ; Shaoguang WU ; Jie LIU
Chinese Journal of Cerebrovascular Diseases 2025;22(4):252-255
The carotid web is a double-layered membranous structure protruding into the lumen,primarily affecting the carotid bifurcation and bulb.It is considered as a potential risk factors for ischemic stroke.Carotid web can alter the structure of the carotid artery lumen,leading to hemodynamic abnormalities that increase the risk of thrombus formation.Once detached,it can cause intracranial arterial embolism,making it a common cause of stroke in young adults.This case report presents a case of restenosis after mechanical thrombectomy and carotid endarterectomy for carotid web-induced ectopic embolism.It provides references and insights for clinicians to recognize,diagnose and treat this disease.
8.The effect of short-term exposures to atmospheric fine particulate matter and its components on cognitive function in middle-aged and older people aged 40-89
Huiting LING ; Yu WANG ; Chen CHEN ; Jinxia YANG ; Changzhen XIANG ; Yiqi QIU ; Jianan LI ; Jianlong FANG ; Jiaonan WANG ; Xiaoming SHI
Chinese Journal of Preventive Medicine 2025;59(4):416-424
Objective:To assess the effect of short-term exposures to atmospheric fine particulate matter (PM 2.5) and its components on cognitive function in middle-aged and older people aged 40-89 and identify key components that affect cognitive function. Methods:From October 2018 to March 2019, a cross-sectional survey of middle-aged and older people aged 40-89 was conducted across 10 cities in Beijing-Tianjin-Hebei and neighboring regions of China. Data on PM 2.5 and its components were collected from the nearest air supermonitoring stations to the residential addresses. The cognitive function was assessed using the Min-Mental State Examination (MMSE) scale. Multiple linear regression models were used to assess the effect of short-term exposures to PM 2.5 and its components on cognitive function in middle-aged and older people. The restricted cubic spline function was used to fit the exposure-response relationship between different components and changes in MMSE scores. Results:The age of the 1 978 respondents was (65.1±13.4) years, and 976 (49.34%) were males. During the study period, the daily mean concentration of PM 2.5 was (71.2±43.2) μg/m 3, and the MMSE score was (28.2±3.7). The results of the multiple linear regression model showed that short-term exposures to PM 2.5 and its components were associated with cognitive decline in middle-aged and older people after adjusting for confounding factors, and the effect was higher at lag 0-28 days. For an interquartile range (64.3 μg/m 3) increase in PM 2.5 at lag 0-28 d, the MMSE score decreased by 5.91 (95% CI: 0.04, 11.77). For an interquartile range increase in organic carbon (OC), antimony (Sb), chromium (Cr), zinc (Zn), tin (Sn), and cadmium (Cd), the MMSE scores of middle-aged and older people decreased by 5.71 (95% CI: 1.69, 9.73), 4.67 (95% CI: 2.50, 6.84), 4.49 (95% CI: 1.05, 7.92), 3.65 (95% CI: 0.89, 6.42), 2.76 (95% CI: 1.22, 4.30), and 1.72 (95% CI: 0.53, 2.92). Conclusions:Short-term exposures to atmospheric PM 2.5 and its components (OC, Sb, Cr, Zn, Sn, and Cd) are associated with cognitive decline in middle-aged and older people.
9.Reform and practice of"Topic-based"experimental teaching in course of Clinical Immunological Test Technology in the perspective of new quality productivity
Wei YANG ; Gang WANG ; Jinxia AI ; Xuesong WANG ; Miao WANG ; Liyuan SUN
Chinese Journal of Immunology 2025;41(5):1228-1231
From the perspective of new quality productivity,it is a new direction and opportunity to train innovative talents with modern technology and professional knowledge.This paper introduces the practice of"Topic-based"experimental teaching in the course of Clinical Immunology Laboratory Technology,and explores the possible ways to train new qualified personnel of medical labo-ratory technology.
10.Tougu Xiaotong Capsules for treating arthritis according to the principle of"Same Treatment for Different Diseases":analysis based on integrated pharmacology,molecular docking techniques and molecular dynamics simulation
Yixin LIN ; Wenyi WANG ; Xiaoqing LEI ; Dezun MA ; Yanfeng HUANG ; Changlong FU ; Jinxia YE
Chinese Journal of Tissue Engineering Research 2025;29(24):5093-5101
BACKGROUND:Our previous research found that Tougu Xiaotong Capsules can be used not only for the treatment of osteoarthritis,but also for rheumatoid arthritis and gouty arthritis.However,the specific mechanism of action of"Same Treatment for Different Diseases"is still unclear.OBJECTIVE:To identify the main effects and mechanisms of Tougu Xiaotong Capsules in the treatment of osteoarthritis,rheumatoid arthritis and gouty arthritis with the treating principle of"Same Treatment for Different Diseases"by the methodologies of integrated pharmacology,molecular docking techniques and molecular dynamics simulation.METHODS:The active chemical components of Tougu Xiaotong Capsules and their corresponding targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and the Swiss Target Prediction database.The disease genes for osteoarthritis,rheumatoid arthritis and gouty arthritis were obtained from the GeneCards and OMIM databases.Cytoscape 3.7.2 software was used to construct a drug-component-disease-target network diagram and a protein-protein interaction network.Gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were conducted using the Daivd database.Molecular docking simulations were performed on the CB-DOCK2 website,and molecular dynamics simulations were carried out using the GROMACS 2020.6 software.RESULTS AND CONCLUSION:(1)A total of 50 active components of Tougu Xiaotong Capsules were screened,with 184 potential targets and 29 intersection targets across the three types of arthritis.(2)The gene ontology enrichment analysis of the intersection targets indicated that the key gene functions of Tougu Xiaotong Capsules in treating the three types of arthritis were found to be cellular response to lipopolysaccharide,inflammatory response,extracellular matrix,protein binding,and zinc ion binding.(3)Kyoto Encyclopedia of Genes and Genomes enrichment analysis identified key pathways as interleukin-17 signaling pathway,tumor necrosis factor signaling pathway,NOD-like receptor and Toll-like receptor signaling pathways.(4)Six core targets[interleukin-6,interleukin-1β,prostaglandin endoperoxide synthase 1,prostaglandin endoperoxide synthase 2,cytochrome P450 1A2(CYP1A2)and C-X-C chemokine ligand 8]were determined based on the protein-protein interaction network.(5)Molecular docking results confirmed that(+)-catechin,β-sitosterol,kaempferol,myricetin,and wallichilide had good structure-activity relationships.Molecular dynamics simulations further confirmed the stable binding of CYP1A2 with wallichilide,corroborating the network pharmacology and molecular docking results.Therefore,Tougu Xiaotong Capsules may regulate the interleukin-17 signaling pathway,tumor necrosis factor signaling pathway,and other signaling pathways by targeting interleukin-1β,prostaglandin endoperoxide synthase 1,prostaglandin endoperoxide synthase 2 and CYP1A2,exert an effect of"Same Treatment for Different Diseases"on osteoarthritis,rheumatoid arthritis and gouty arthritis.

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