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.

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.

OBJECTIVE To evaluate the efficacy and safety of Weiyan Tongluo Granules in treating chronic atrophic gastritis(CAG)and explore its potential mechanisms.METHODS From June 2020 to December 2022,100 CAG patients with spleen defi-ciency and blood stasis syndrome were enrolled and randomly divided into a trial group(n=50)and a control group(n=50)using a random number table.The trial group received Weiyan Tongluo Granules plus a folic acid placebo,while the control group received fo-lic acid tablets plus a traditional Chinese medicine granule placebo.The treatment course for both groups was 24 weeks,with 8 and 10 dropouts in the trial and control groups,respectively.Post-treatment comparisons included OLGA/OLGIM staging reversal rates,low-grade intraepithelial neoplasia regression rate,SSDPRO-CG(Patient-Reported Outcome Scale for Chronic Gastritis in Spleen-Stomach Diseases)scores,TCM syndrome scores,and safety indicators.Serum levels of PG I,PGⅡ,PGR,and G-17 were measured via ELISA before and after treatment.Gastric mucosal p-NF-κB and CDX2 protein expression levels were analyzed by Western blot,while mRNA levels of IL-1β,IL-6,VIL1,and MUC2 were quantified via qPCR.RESULTS After treatment,the trial group showed sig-nificantly higher OLGA and OLGIM stage reversal rates than the control group(P<0.05,P<0.01),though no significant difference was observed in low-grade intraepithelial neoplasia regression.Both groups exhibited significant improvements in physiological domain scores and total SSDPRO-CG scores(P<0.01),with the trial group outperforming the control group in physiological,independence,psychological domains,and total scores(P<0.05,P<0.01).TCM syndrome scores(total and sub-items:gastric distension,pain,poor appetite,bloating)decreased significantly in both groups(P<0.01),while the trial group showed greater reductions in loose stools and dull complexion(P<0.01).After-treatment,the trial group had significantly lower TCM syndrome scores than the control group(P<0.05,P<0.01).Serum PG I,PGⅡ,PGR,G-17,gastric mucosal p-NF-κB,CDX2,and IL-1β,IL-6,VIL1,MUC2 mRNA levels improved significantly in the trial group(P<0.05,P<0.01),while the control group improved only in PGⅡ(P<0.05,P<0.01).The trial group's improvements in these biomarkers surpassed the control group's(P<0.05,P<0.01).No treatment-related adverse events occurred in either group.CONCLUSION Weiyan Tongluo Granules ameliorate gastric mucosal pathology,clinical symptoms,psychological state,and quality of life in CAG patients without significant adverse effects.Its mechanism may involve sup-pressing the NF-κB pathway to reduce IL-1β and IL-6 expression,downregulating CDX2 to inhibit VIL1 and MUC2 transcription,thereby reversing the vicious cycle of inflammation-intestinal metaplasia.

Objective:To observe and analyze the abnormal gait characteristics and lower limb kinematic chain in patients with bilateral moderate-to-severe hallux valgus(HV)during adaptive walking.Method:From September 2022 to August 2023,33 patients with moderate-and-severe HV were selected from the department of arthrology,Wangjing Hospital,Chinese Academy of Traditional Chinese Medicine and en-rolled in the observation group.A group of 29 healthy subjects were matched and enrolled in the control group.DC-G-150-F2 three-dimensional gait analysis system was used to collect gait characteristics and lower limb motion chain of two groups during a 10m adaptive walking test.Temporal-spatial gait parameters and ki-nematic changes in the hip,knee,and ankle joints were observed and analyzed.Result:The gait time-space parameters of left and right support phase,total double support phase,left lateral foot deviation angle,step length,stride length and pace in the observation group were significantly lower than those in the control group(P＜0.05).In contrast,the time-space parameters of left and right swing phase and stride frequency in the observation group were significantly higher than those in the control group(P＜0.05).The two groups had no significant difference in right lateral foot deviation angle and step width(P＞0.05).The range of flexion and extension of the right hip joint,rotation of the left hip joint,rotation of the left and right knee joint and flexion and extension of the left and right ankle joint in the observation group were significantly lower than those in the control group(P＜0.05).There were no significant differences be-tween the two groups in the range of motion of left hip flexion and extension,right hip rotation,left versus right hip spreading,left versus right knee flexion and extension,and left versus right ankle rotation(P＞0.05).However,the range of motion of right hip rotation and right knee flexion and extension was lower than that of the control subjects(P=0.084,P=0.093).Conclusion:Gait changes in patients with bilateral moderate-to-severe bunions are characterized by shortened sin-gle and double support phases,prolonged swing phase,increased step frequency,reduced step length and stride length,and a"broken stride and slow catching up"walking pattern.The range of motion of each lower limb joint in the sagittal plane and horizontal plane is reduced,resulting in a rigid and twisted state through-out the lower limb kinematic chain.

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.

Objective To investigate the expression and clinical significance of serum microRNA-144-3p(miR-144-3p)and microRNA-126-3p(miR-126-3p)in patients with intracerebral hemorrhage(ICH).Methods From February 2022 to April 2023,120 ICH patients who underwent treatment at our hospital were recruited as the ICH group.They were separated into a good prognosis group and a poor prognosis group based on the modified Rankin Scale(mRS)score After 6 months treatment Additionally,110 healthy individuals who underwent physical examination at our hospital were included as the control group.Clinical data of patients were collected and analyzed.Enzyme linked immunosorbent assay(ELISA)was applied to detect serum levels of tumor necrosis factor-α(TNF-α)and vascular endothelial growth factor(VEGF)indicators.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was applied to detect the expression levels of serum miR-144-3p and miR-126-3p.Pearson method was applied to analyze the correlation between serum miR-144-3p,miR-126-3p,TNF-α,and VEGF levels in ICH patients.Multivariate Logistic regression was applied to analyze the factors affecting the prognosis of ICH patients.ROC curve was applied to analyze the predictive value of serum miR-144-3p and miR-126-3p for the prognosis of ICH patients.Results In the control group,the serum miR-144-3p was 1.02±0.02,the TNF-α was(19.15±6.79)pg/ml,the VEGF level was(1.05±0.18)ng/ml,and the serum miR-126-3p level was 1.04±0.05.The values in the ICH group were 2.12±0.23,(48.32±8.43)pg/ml,(6.56±1.49)ng/ml,and(0.53±0.12),respectively.There was a statistically significant difference between the two groups(P＜0.05).Pearson analysis results showed that serum miR-144-3p was positively correlated with TNF-α and VEGF levels in ICH patients(r=0.496,0.542,P＜0.05),while serum miR-126-3p was negatively correlated with TNF-α and VEGF levels(r=-0.493,-0.526,P＜0.05).There were significant differences in the serum levels of miR-144-3p,miR-126-3p,TNF-α,VEGF,and NIHSS score between different prognostic groups(P＜0.05).Multivariate logistic analysis revealed that serum miR-144-3p,miR-126-3p,TNF-α,and VEGF were all factors affecting the poor prognosis of ICH patients(P＜0.05).The area under the curve(AUC)of serum miR-144-3p,miR-126-3p,and combined prediction of prognosis in ICH patients was 0.851,0.886,and 0.952,respectively,the combined prediction of the two was more valuable(Zcombination-miR-144-3p=3.371,Zcombination-miR-126-3p=2.791,P＜0.05).Conclusion The expression of miR-144-3p in the serum of ICH patients increases,while the expression of miR-126-3p decreases.The two may serve as biological markers for predicting the prognosis of ICH patients,and the combination of the two is more valuable in predicting the prognosis of ICH patients.

Objective To investigate the expression and clinical significance of serum microRNA-144-3p(miR-144-3p)and microRNA-126-3p(miR-126-3p)in patients with intracerebral hemorrhage(ICH).Methods From February 2022 to April 2023,120 ICH patients who underwent treatment at our hospital were recruited as the ICH group.They were separated into a good prognosis group and a poor prognosis group based on the modified Rankin Scale(mRS)score After 6 months treatment Additionally,110 healthy individuals who underwent physical examination at our hospital were included as the control group.Clinical data of patients were collected and analyzed.Enzyme linked immunosorbent assay(ELISA)was applied to detect serum levels of tumor necrosis factor-α(TNF-α)and vascular endothelial growth factor(VEGF)indicators.Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was applied to detect the expression levels of serum miR-144-3p and miR-126-3p.Pearson method was applied to analyze the correlation between serum miR-144-3p,miR-126-3p,TNF-α,and VEGF levels in ICH patients.Multivariate Logistic regression was applied to analyze the factors affecting the prognosis of ICH patients.ROC curve was applied to analyze the predictive value of serum miR-144-3p and miR-126-3p for the prognosis of ICH patients.Results In the control group,the serum miR-144-3p was 1.02±0.02,the TNF-α was(19.15±6.79)pg/ml,the VEGF level was(1.05±0.18)ng/ml,and the serum miR-126-3p level was 1.04±0.05.The values in the ICH group were 2.12±0.23,(48.32±8.43)pg/ml,(6.56±1.49)ng/ml,and(0.53±0.12),respectively.There was a statistically significant difference between the two groups(P＜0.05).Pearson analysis results showed that serum miR-144-3p was positively correlated with TNF-α and VEGF levels in ICH patients(r=0.496,0.542,P＜0.05),while serum miR-126-3p was negatively correlated with TNF-α and VEGF levels(r=-0.493,-0.526,P＜0.05).There were significant differences in the serum levels of miR-144-3p,miR-126-3p,TNF-α,VEGF,and NIHSS score between different prognostic groups(P＜0.05).Multivariate logistic analysis revealed that serum miR-144-3p,miR-126-3p,TNF-α,and VEGF were all factors affecting the poor prognosis of ICH patients(P＜0.05).The area under the curve(AUC)of serum miR-144-3p,miR-126-3p,and combined prediction of prognosis in ICH patients was 0.851,0.886,and 0.952,respectively,the combined prediction of the two was more valuable(Zcombination-miR-144-3p=3.371,Zcombination-miR-126-3p=2.791,P＜0.05).Conclusion The expression of miR-144-3p in the serum of ICH patients increases,while the expression of miR-126-3p decreases.The two may serve as biological markers for predicting the prognosis of ICH patients,and the combination of the two is more valuable in predicting the prognosis of ICH patients.

Objective:To observe and analyze the abnormal gait characteristics and lower limb kinematic chain in patients with bilateral moderate-to-severe hallux valgus(HV)during adaptive walking.Method:From September 2022 to August 2023,33 patients with moderate-and-severe HV were selected from the department of arthrology,Wangjing Hospital,Chinese Academy of Traditional Chinese Medicine and en-rolled in the observation group.A group of 29 healthy subjects were matched and enrolled in the control group.DC-G-150-F2 three-dimensional gait analysis system was used to collect gait characteristics and lower limb motion chain of two groups during a 10m adaptive walking test.Temporal-spatial gait parameters and ki-nematic changes in the hip,knee,and ankle joints were observed and analyzed.Result:The gait time-space parameters of left and right support phase,total double support phase,left lateral foot deviation angle,step length,stride length and pace in the observation group were significantly lower than those in the control group(P＜0.05).In contrast,the time-space parameters of left and right swing phase and stride frequency in the observation group were significantly higher than those in the control group(P＜0.05).The two groups had no significant difference in right lateral foot deviation angle and step width(P＞0.05).The range of flexion and extension of the right hip joint,rotation of the left hip joint,rotation of the left and right knee joint and flexion and extension of the left and right ankle joint in the observation group were significantly lower than those in the control group(P＜0.05).There were no significant differences be-tween the two groups in the range of motion of left hip flexion and extension,right hip rotation,left versus right hip spreading,left versus right knee flexion and extension,and left versus right ankle rotation(P＞0.05).However,the range of motion of right hip rotation and right knee flexion and extension was lower than that of the control subjects(P=0.084,P=0.093).Conclusion:Gait changes in patients with bilateral moderate-to-severe bunions are characterized by shortened sin-gle and double support phases,prolonged swing phase,increased step frequency,reduced step length and stride length,and a"broken stride and slow catching up"walking pattern.The range of motion of each lower limb joint in the sagittal plane and horizontal plane is reduced,resulting in a rigid and twisted state through-out the lower limb kinematic chain.

OBJECTIVE To evaluate the efficacy and safety of Weiyan Tongluo Granules in treating chronic atrophic gastritis(CAG)and explore its potential mechanisms.METHODS From June 2020 to December 2022,100 CAG patients with spleen defi-ciency and blood stasis syndrome were enrolled and randomly divided into a trial group(n=50)and a control group(n=50)using a random number table.The trial group received Weiyan Tongluo Granules plus a folic acid placebo,while the control group received fo-lic acid tablets plus a traditional Chinese medicine granule placebo.The treatment course for both groups was 24 weeks,with 8 and 10 dropouts in the trial and control groups,respectively.Post-treatment comparisons included OLGA/OLGIM staging reversal rates,low-grade intraepithelial neoplasia regression rate,SSDPRO-CG(Patient-Reported Outcome Scale for Chronic Gastritis in Spleen-Stomach Diseases)scores,TCM syndrome scores,and safety indicators.Serum levels of PG I,PGⅡ,PGR,and G-17 were measured via ELISA before and after treatment.Gastric mucosal p-NF-κB and CDX2 protein expression levels were analyzed by Western blot,while mRNA levels of IL-1β,IL-6,VIL1,and MUC2 were quantified via qPCR.RESULTS After treatment,the trial group showed sig-nificantly higher OLGA and OLGIM stage reversal rates than the control group(P<0.05,P<0.01),though no significant difference was observed in low-grade intraepithelial neoplasia regression.Both groups exhibited significant improvements in physiological domain scores and total SSDPRO-CG scores(P<0.01),with the trial group outperforming the control group in physiological,independence,psychological domains,and total scores(P<0.05,P<0.01).TCM syndrome scores(total and sub-items:gastric distension,pain,poor appetite,bloating)decreased significantly in both groups(P<0.01),while the trial group showed greater reductions in loose stools and dull complexion(P<0.01).After-treatment,the trial group had significantly lower TCM syndrome scores than the control group(P<0.05,P<0.01).Serum PG I,PGⅡ,PGR,G-17,gastric mucosal p-NF-κB,CDX2,and IL-1β,IL-6,VIL1,MUC2 mRNA levels improved significantly in the trial group(P<0.05,P<0.01),while the control group improved only in PGⅡ(P<0.05,P<0.01).The trial group's improvements in these biomarkers surpassed the control group's(P<0.05,P<0.01).No treatment-related adverse events occurred in either group.CONCLUSION Weiyan Tongluo Granules ameliorate gastric mucosal pathology,clinical symptoms,psychological state,and quality of life in CAG patients without significant adverse effects.Its mechanism may involve sup-pressing the NF-κB pathway to reduce IL-1β and IL-6 expression,downregulating CDX2 to inhibit VIL1 and MUC2 transcription,thereby reversing the vicious cycle of inflammation-intestinal metaplasia.

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.