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 define the mechanism by which swine TRIM25 restricts vesicular stomatitis virus replication. Methods: Porcine 3D4/21 cells with TRIM25 overexpression or knockdown were infected with vesicular stomatitis virus. Viral replication was quantified by immunoblotting, quantitative reverse transcription polymerase chain reaction, and 50% tissue culture infectious dose assays. Type I interferon signaling was assessed by transcript quantification, interferon-beta and interferon-stimulated response element reporter assays, and co-immunoprecipitation.Viral RNA binding was tested by RNA immunoprecipitation. Results: TRIM25 overexpression reduced viral RNA and infectious titers, whereas TRIM25 knockdown increased replication (p < 0.01). TRIM25 increased interferon-beta and interferon-stimulated gene expression and enhanced interferon-beta and interferonstimulated response element promoter activity (p < 0.01). Mechanistically, TRIM25 promoted Lys63-linked ubiquitination of RIG-I and increased phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3. TRIM25 also bound vesicular stomatitis virus genomic RNA, and binding required the C-terminal region. Conclusions and Relevance: Porcine TRIM25 restricts vesicular stomatitis virus replication by amplifying type I interferon signaling and directly binding viral RNA.

The global incidence rate of cancer is increasing yearly,and chemotherapy-induced gastrointestinal mucosal injury has become a crucial factor affecting patients'therapeutic prognosis;however,there is currently a lack of effective therapeutic drugs to address this issue.There is thus an urgent need to establish more ideal animal models of chemotherapy-induced gastrointestinal mucosal injury,to support the exploration of its pathogenesis and the development of therapeutic drugs.This review considered relevant literature published during the period from 2019 to 2024,to provide a comprehensive summary and analysis from several perspectives,including the selection of experimental animals,chemotherapeutic drugs and modeling method,evaluation indicators,and practical applications.Furthermore,we highlight several existing issues with current models,including the lack of standardized modeling method,insufficient research on models with a tumor background,and inadequate exploration of novel cell death mechanisms.This collation of the literature also revealed the gradual emergence of traditional Chinese medicine as a research hotspot,with potential for the treatment of gastrointestinal mucosal injury.Further studies of effective medicines are warranted to identify interventional strategies for chemotherapy-induced gastrointestinal mucosal injury.

Objective:To construct dynamic cycle management mode of medical equipment,so as to analyze the influence of that on management effect of medical equipment in the department of neurosurgery,and improve the management effect of neurosurgery equipment.Method:Based on the full-process monitoring,full participation and all-round management of the dynamic cycle management mode,the full life cycle management was implemented on medical instruments and equipment.A total of 1,269 used medical equipment in the department of neurosurgery of the Second Affiliated Hospital of Air Force Medical University from January 2022 to December 2023 were selected.During the period from January 2022 to December 2022,the conventional management mode was adopted to manage these equipment.From January and December 2023,the dynamic cycle management mode was adopted to manage them.The management effects of equipment failure and the incidence of risk events of the two management modes were compared.A self-made satisfaction questionnaire was used to investigate the satisfaction scores of medical staffs,who used the equipment,for maintaining and using the equipment.Results:The time of average internal reporting for repair,the time of external reporting for repair,the time of diagnosing fault,total time of reporting repair and total maintenance time in dynamic cycle management mode were respectively(3.15±1.04)min,(19.34±2.81)min,(22.66±3.73)min,(10.04±1.11)min and(5.38±1.92)d,which were significantly lower than those in conventional management mode(t=15.878,21.553,18.755,20.486,7.636,P<0.05).The incidence of risk events of equipment in dynamic cycle management mode was significantly lower than that in conventional management group(x2=8.635,P<0.05).The satisfaction scores of medical staffs who used equipment in dynamic cycle management mode were significantly higher than those in conventional management mode in the timeliness of reporting repair,the speed of diagnosis and maintenance,the used effect after maintenance for failure of equipment,and the differences were significant(t=7.364,7.381,5.413,P<0.05).Conclusion:The application of dynamic cycle management mode for medical equipment in the management for instrument and equipment of the department of neurosurgery in hospital can improve management effect for equipment,and reduce incidence of risk events of equipment,and enhance the satisfaction of staffs who use equipment.

Objective:To construct dynamic cycle management mode of medical equipment,so as to analyze the influence of that on management effect of medical equipment in the department of neurosurgery,and improve the management effect of neurosurgery equipment.Method:Based on the full-process monitoring,full participation and all-round management of the dynamic cycle management mode,the full life cycle management was implemented on medical instruments and equipment.A total of 1,269 used medical equipment in the department of neurosurgery of the Second Affiliated Hospital of Air Force Medical University from January 2022 to December 2023 were selected.During the period from January 2022 to December 2022,the conventional management mode was adopted to manage these equipment.From January and December 2023,the dynamic cycle management mode was adopted to manage them.The management effects of equipment failure and the incidence of risk events of the two management modes were compared.A self-made satisfaction questionnaire was used to investigate the satisfaction scores of medical staffs,who used the equipment,for maintaining and using the equipment.Results:The time of average internal reporting for repair,the time of external reporting for repair,the time of diagnosing fault,total time of reporting repair and total maintenance time in dynamic cycle management mode were respectively(3.15±1.04)min,(19.34±2.81)min,(22.66±3.73)min,(10.04±1.11)min and(5.38±1.92)d,which were significantly lower than those in conventional management mode(t=15.878,21.553,18.755,20.486,7.636,P<0.05).The incidence of risk events of equipment in dynamic cycle management mode was significantly lower than that in conventional management group(x2=8.635,P<0.05).The satisfaction scores of medical staffs who used equipment in dynamic cycle management mode were significantly higher than those in conventional management mode in the timeliness of reporting repair,the speed of diagnosis and maintenance,the used effect after maintenance for failure of equipment,and the differences were significant(t=7.364,7.381,5.413,P<0.05).Conclusion:The application of dynamic cycle management mode for medical equipment in the management for instrument and equipment of the department of neurosurgery in hospital can improve management effect for equipment,and reduce incidence of risk events of equipment,and enhance the satisfaction of staffs who use equipment.

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.

The global incidence rate of cancer is increasing yearly,and chemotherapy-induced gastrointestinal mucosal injury has become a crucial factor affecting patients'therapeutic prognosis;however,there is currently a lack of effective therapeutic drugs to address this issue.There is thus an urgent need to establish more ideal animal models of chemotherapy-induced gastrointestinal mucosal injury,to support the exploration of its pathogenesis and the development of therapeutic drugs.This review considered relevant literature published during the period from 2019 to 2024,to provide a comprehensive summary and analysis from several perspectives,including the selection of experimental animals,chemotherapeutic drugs and modeling method,evaluation indicators,and practical applications.Furthermore,we highlight several existing issues with current models,including the lack of standardized modeling method,insufficient research on models with a tumor background,and inadequate exploration of novel cell death mechanisms.This collation of the literature also revealed the gradual emergence of traditional Chinese medicine as a research hotspot,with potential for the treatment of gastrointestinal mucosal injury.Further studies of effective medicines are warranted to identify interventional strategies for chemotherapy-induced gastrointestinal mucosal injury.

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 analyze the expression and prognosis of B-cell lymphoma 7 protein family member A (BCL7A) in hepatocellular carcinoma, as well as the effect and mechanism of BCL7A expression on the invasion and migration of hepatocellular carcinoma cells.Methods:The cancer tissues and adjacent tissues of 40 patients with hepatocellular carcinoma who underwent radical hepatobiliary resection in the Department of Hepatobiliary Surgery, Affiliated Hospital of Nantong University from November 2017 to March 2018 were prospectively collected for protein extraction, including 29 males and 11 females, aged (58.5±10.4) years. The information of 374 cases of hepatocellular carcinoma and 50 cases of adjacent tissues were downloaded from The Cancer Genome Atlas (TCGA) database, and the hepatocellular carcinoma cell lines Hep3B and SMMC-7721 were transfected with overexpressing BCL7A plasmid and empty vector plasmid (negative control), respectively. Western blotting and immunohistochemistry were used to detect the expression of BCL7A, and Western blotting was also used to detect the expression of proteins related to epithelial-mesenchymal transition (N-cadherin, E-cadherin, snail). Transwell and cell scratch assays were used to detect cell invasion and migration.Results:Compared with adjacent tissues, the mRNA expression of BCL7A in 50 patients with hepatocellular carcinoma in TCGA was significantly increased ( t=13.38, P<0.001). According to the median mRNA expression level of BCL7A, 374 patients were divided into BCL7A high expression group ( n=187) and low expression group ( n=187), and the cumulative survival rate of BCL7A high expression patients was lower than that of low expression group, and the difference was statistically significant ( χ2=6.95, P=0.009). Western blot was used to detect the relative expression of BCL7A protein in cancer tissues, and found it was higher compared to adjacent tissues. Compared with the negative control group, the number of cells invaded by the BCL7A overexpression group of hepatoma cells Hep3B and SMMC-7721 was more than the negative control group respectively, (153.7±1.3) vs (63.7±4.7) and (307.7±25.14) vs (72.3±12.5), and the differences were statistically significant ( t=7.97, 8.38, both P=0.001) .The results of the cell scratch assay were consistent with the results of the Transwell invasion assay. The expressions of N-cadherin and snail in the BCL7A overexpression group were higher than those in the negative control group, and the E-cadherin was lower, and the difference was statistically significant (all P<0.05). Conclusions:The expression of BCL7A in cancer tissues of patients with hepatocellular carcinoma is elevated and is associated with poor prognosis. BCL7A may promote hepatocellular carcinoma cell metastasis and invasion by promoting epithelial-mesenchymal transition.