Objective To analyze the clinical efficacy of real-world bulleyaconitine A tablets combined with salt and pepper seven-seed hot package in the treatment of knee osteoarthritis(KOA).Methods 110 outpatient patients from the Department of Orthopedics,Shenzhen Traditional Chinese Medicine Hospital from December 2023 to August 2024 were selected,they were randomly divided into control group of 53 cases and treatment group of 57 cases.The patients in control group were treated with flurbiprofen gel paste,the patients in treatment group received oral administration of bulleyaconitine A tablets and external application of Jiaoyan Qizi hot package,the treatment course were all 4 weeks.All patients were followed up for 2 weeks after the end of treatment.Western Ontario and McMaster University osteoarthritis index(WOMAC)score,Lequesne score,12-item short form health survey(SF-12)score and clinical efficacy were compared between two groups,and adverse events were recorded.Results The total effective rate of treatment group was 87.7％,which was significantly higher than 71.7％of control group(P＜0.05);After treatment,WOMAC score,Lequesne score and SF-12 score in two groups were better than before treatment(P＜0.05).The improvement of WOMAC score,Lequesne score and SF-12 score in treatment group were more obvious(P＜0.05).Conclusion For KOA patients with cold and damp obstruction syndrome,the use of bulleyaconitine A tablets combined with Jiaoyan Qizi hot package can alleviate knee joint pain,improve knee joint mobility,and enhance patients'quality of life.

Objective To analyze the clinical efficacy of real-world bulleyaconitine A tablets combined with salt and pepper seven-seed hot package in the treatment of knee osteoarthritis(KOA).Methods 110 outpatient patients from the Department of Orthopedics,Shenzhen Traditional Chinese Medicine Hospital from December 2023 to August 2024 were selected,they were randomly divided into control group of 53 cases and treatment group of 57 cases.The patients in control group were treated with flurbiprofen gel paste,the patients in treatment group received oral administration of bulleyaconitine A tablets and external application of Jiaoyan Qizi hot package,the treatment course were all 4 weeks.All patients were followed up for 2 weeks after the end of treatment.Western Ontario and McMaster University osteoarthritis index(WOMAC)score,Lequesne score,12-item short form health survey(SF-12)score and clinical efficacy were compared between two groups,and adverse events were recorded.Results The total effective rate of treatment group was 87.7％,which was significantly higher than 71.7％of control group(P＜0.05);After treatment,WOMAC score,Lequesne score and SF-12 score in two groups were better than before treatment(P＜0.05).The improvement of WOMAC score,Lequesne score and SF-12 score in treatment group were more obvious(P＜0.05).Conclusion For KOA patients with cold and damp obstruction syndrome,the use of bulleyaconitine A tablets combined with Jiaoyan Qizi hot package can alleviate knee joint pain,improve knee joint mobility,and enhance patients'quality of life.

Objective To investigate the mechanism by which Huangqi Guizhi Wuwu decoction(HQGZWWD)regulates nerve injury(NI)through vascular endothelial growth factor(VEGF)pathway based on a combination of network pharmacology and molecular docking techniques.Methods Active ingredients and targets of HQGZWWD were identified through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.A drug-ingredient-target network was constructed by integrated with data from OMIM,GeneCards,and CTD databases to identify VEGF/NI-related targets.Protein-protein interaction analyses were conducted by using STRING network platform,which were further analyzed by using the DAVID database for Gene Ontology/Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment.A"compound-target-pathway"network was constructed by using Cytoscape.Molecular docking was performed to validate the binding ability of core components with the targets.Results The primary constituents(quercetin,kaempferol)and principal targets[signal transducer and activator of transcription 3(STAT3),caspase 3,epidermal growth factor receptor(EGFR),etc.]of HQGZWWD were identified.KEGG analysis revealed that the targets were enriched cancer,EGFR inhibitor resistance,and advanced glycation end-products-receptor for advanced glycation end-products etc.signaling pathways.Molecular docking demonstrated binding energy between core components and STAT3,caspace 3,EGFR,etc.,specifically,the core components exhibited strong binding energy such as STAT3(≤-7.37kcal/mol).Conclusion HQGZWWD shows potency in suppressing inflammation,oxidative stress,and apoptosis,while promoting neural repair through VEGF regulation.The integration of network pharmacology and molecular docking offers a foundational framework for mechanistic investigations.

Objective To analyze the modeling and evaluation method for vascular restenosis animal models in the last 10 years,to provide a reference for improving animal models of vascular restenosis.Methods Literature related to vascular restenosis was retrieved from mainstream Chinese and English databases from 2013 to 2023.Data on experimental animal strains,modeling method,modeling cycles,and detection method were extracted from the included literature,and a database was established using Excel for summary analysis.Results Among the 122 identified articles,the main experimental animals were rats,rabbits,and pigs,and most animals were male.The most common modeling method was balloon injury,and the modeling cycle was mainly within 4～8 weeks.The main detection indexes were histopathology,accounting for 37.18％,including routine hematoxylin-eosin,Masson,and Elastica van Gieson(EVG)staining.Conclusions The translatability of porcine vascular restenosis models is currently more in line with expectations,but their cost is high and they are unpopular,and rats and rabbits thus remain the main animal models.Balloon injury is the main mode of modeling.Different animal models and modeling method for vascular restenosis have advantages and disadvantages,and the model should be selected according to the experimental purpose.Animal models of vascular restenosis still have some limitations,however,and better animal models are required in the future.

Objective To analyze the modeling and evaluation method for vascular restenosis animal models in the last 10 years,to provide a reference for improving animal models of vascular restenosis.Methods Literature related to vascular restenosis was retrieved from mainstream Chinese and English databases from 2013 to 2023.Data on experimental animal strains,modeling method,modeling cycles,and detection method were extracted from the included literature,and a database was established using Excel for summary analysis.Results Among the 122 identified articles,the main experimental animals were rats,rabbits,and pigs,and most animals were male.The most common modeling method was balloon injury,and the modeling cycle was mainly within 4～8 weeks.The main detection indexes were histopathology,accounting for 37.18％,including routine hematoxylin-eosin,Masson,and Elastica van Gieson(EVG)staining.Conclusions The translatability of porcine vascular restenosis models is currently more in line with expectations,but their cost is high and they are unpopular,and rats and rabbits thus remain the main animal models.Balloon injury is the main mode of modeling.Different animal models and modeling method for vascular restenosis have advantages and disadvantages,and the model should be selected according to the experimental purpose.Animal models of vascular restenosis still have some limitations,however,and better animal models are required in the future.

Objective:To explore the protocol for handgrip exercise stress echocardiography by comparing different maximal voluntary contraction（MVC）handgrip groups with bicycle exercise stress.Methods:Forty-one healthy volunteers were enrolled prospectively from June to October 2024 in Tangdu Hospital and utilized a color Doppler echocardiography system，supine cycle ergometer，and handgrip dynamometer to collect echocardiographic data at baseline，during handgrip exercises at 20%（3 min），30%（3 min），and 40%（2 min）of MVC，and spine bicycle exercise stress at peak. Parameters measured included left ventricular ejection fraction（EF），stroke volume（SV），cardiac output（CO），mitral inflow E-wave and A-wave velocities，lateral and septal mitral annular e' velocities，E/A and E/e' ratios，global longitudinal strain（GLS），left atrial reservoir strain（LAS R），conduit strain（LAS CD），and contractile strain（LAS CT）. The non-invasive myocardial work indices were also assessed，including global work index（GWI），global constructive work（GCW），global wasted work（GWW），and global work efficiency（GWE）. Statistical analyses were performed using repeated measures analysis of variance，with corrected paired t-test for comparisons between two exercise stress states. Results:Compared with the baseline state，heart rate，blood pressure，CO、GWI、GCW、GWW and LAS CT gradually increased，while EF、E/A、GLS、GWE、LAS R and LAS CD gradually decreased under 20%，30% and 40% of MVC states. The changes were most obvious at 40% of MVC state，which was selected for the handgrip exercise stress echocardiography protocol.Compared with the peak of bicycle exercise，at 40% of MVC，heart rate was significantly lower［（81.2 ± 9.7）bpm vs.（164.6 ± 11.3）bpm， P<0.05）］，systolic blood pressure was slightly lower［（152.9 ± 13.2）mmHg vs.（165.1 ± 20.4）mmHg， P<0.05］，diastolic blood pressure was higher［（96.0 ± 9.5）mmHg vs.（89.5 ± 10.9）mmHg， P<0.05］，GLS was lower［（19.1 ± 1.5）% vs.（23.5 ± 1.7）%， P<0.05］，GWI was similar［（2 254.2 ± 417.3）mmHg% vs.（2 227.5 ± 389.0）mmHg%， P>0.05］，but GWE was higher［（95.3 ± 2.0）% vs.（93.7 ± 2.0）%， P<0.05］，and LAS R was lower［（39.4 ± 4.2）% vs.（43.9 ± 4.1）%， P<0.05］. Conclusions:The 40% of MVC lasting 2 min can cause the most significant handgrip-related changes in cardiac function and can be used as the standard protocol for handgrip exercise stress echocardiography. Handgrip stress exercise can cause significant changes in cardiac systole，diastole，and work performance，showing different characteristics compared with bicycle exercise stress.

OBJECTIVE: To evaluate the effect of biodegradable magnesium alloy materials in promoting tendon-bone healing during rotator cuff tear repair and to investigate their potential underlying biological mechanisms. METHODS: Forty-eight 8-week-old Sprague Dawley rats were taken and randomly divided into groups A, B, and C. Rotator cuff tear models were created and repaired using magnesium alloy sutures in group A and Vicryl Plus 4-0 absorbable sutures in group B, while only subcutaneous incisions and sutures were performed in group C. Organ samples of groups A and B were taken for HE staining at 1 and 2 weeks after operation to evaluate the safety of magnesium alloy, and specimens from the supraspinatus tendon and proximal humerus were harvested at 2, 4, 8, and 12 weeks after operation. The specimens were observed macroscopically at 4 and 12 weeks after operation. Biomechanical tests were performed at 4, 8, and 12 weeks to test the ultimate load and stiffness of the healing sites in groups A and B. At 2, 4, and 12 weeks, the specimens were subjected to the following tests: Micro-CT to evaluate the formation of bone tunnels in groups A and B, HE staining and Masson staining to observe the regeneration of fibrocartilage at the tendon-bone interface after decalcification and sectioning, and Goldner trichrome staining to evaluate the calcification. Immunohistochemical staining was performed to detect the expressions of angiogenic factors, including vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP-2), as well as osteogenic factors at the tendon-bone interface. Additionally, immunofluorescence staining was used to examine the expressions of Arginase 1 and Integrin beta-2 to assess M1 and M2 macrophage polarization at the tendon-bone interface. The role of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway in tendon-bone healing was further analyzed using real-time fluorescence quantitative PCR. RESULTS: Analysis of visceral sections revealed that magnesium ions released during the degradation of magnesium alloys did not cause significant toxic effects on organs such as the heart, liver, spleen, lungs, and kidneys, indicating good biosafety. Histological analysis further demonstrated that fibrocartilage regeneration at the tendon-bone interface in group A occurred earlier, and the amount of fibrocartilage was significantly greater compared to group B, suggesting a positive effect of magnesium alloy material on tendon-bone interface repair. Additionally, Micro-CT analysis results revealed that bone tunnel formation occurred more rapidly in group A compared to group B, further supporting the beneficial effect of magnesium alloy on bone healing. Biomechanical testing showed that the ultimate load in group A was consistently higher than in group B, and the stiffness of group A was also greater than that of group B at 4 weeks, indicating stronger tissue-carrying capacity following tendon-bone interface repair and highlighting the potential of magnesium alloy in enhancing tendon-bone healing. Immunohistochemical staining results indicated that the expressions of VEGF and BMP-2 were significantly upregulated during the early stages of healing, suggesting that magnesium alloy effectively promoted angiogenesis and bone formation, thereby accelerating the tendon-bone healing process. Immunofluorescence staining further revealed that magnesium ions exerted significant anti-inflammatory effects by regulating macrophage polarization, promoting their shift toward the M2 phenotype. Real-time fluorescence quantitative PCR results demonstrated that magnesium ions could facilitate tendon-bone healing by modulating the PI3K/AKT signaling pathway. CONCLUSION Biodegradable magnesium alloy material accelerated fibrocartilage regeneration and calcification at the tendon-bone interface in rat rotator cuff tear repair by regulating the PI3K/AKT signaling pathway, thereby significantly enhancing tendon-bone healing.
Animals ; Rotator Cuff Injuries/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Wound Healing/drug effects* ; Alloys/pharmacology* ; Rats ; Proto-Oncogene Proteins c-akt/metabolism* ; Rotator Cuff/metabolism* ; Macrophages/metabolism* ; Magnesium/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Vascular Endothelial Growth Factor A/metabolism* ; Male ; Biocompatible Materials ; Bone Morphogenetic Protein 2/metabolism*

Objective:To develop habitat radiomics models to predict early treatment responses to the hepatic arterial infusion chemotherapy (HAIC) combined with targeted therapy or immunotherapy in advanced hepatocellular carcinoma (HCC) patients, and to guide clinical diagnosis and treatment.Methods:From October 2021 to Decemeber 2023, at Army Characteristic Medical Center of PLA (Chongqing Daping Hospital) and the First Affiliated Hospital of Chongqing Medical University, 94 patients with advanced HCC who received HAIC combined with targeted therapy or immunotherapy were retrospectively enrolled. According to the treatment results, the patients were divided into response group and non-response group. Univariate and multivariate logistic regression were performed to analyze the clinical data of the patients. Based on contrast-enhanced CT images, tumor habitats were delineated and habitat features were extracted with k-means clustering, and the imaging features of arterial and venous phases were also extracted. The least absolute shrinkage and selection operator (LASSO) was used for dimensionality reduction. Feature selection was performed using LASSO to reduce dimensions, and then the selected features were further refined through stepwise logistic regression analysis.Binary logistic regression models were conducted to develop the habitat radiomics model, arterial phase radiomics model (APRM), venous phase radiomics model (VPRM), clinical data model, as well as the combination of radiomics model and clinical data model to predict early treatment (after 2 treatment cycles) response. Receiver operating characteristic curves (ROC) were plotted, and model performance was evaluated by the area under the curve (AUC), calibration curves, and decision curve. The models were validated through Bootstrap methods (1 000 times). DeLong test was used to compare AUC values.Results:The results of cluster analysis identified 3 characteristic habitats in HCC imaging: low-, medium-, and high-enhancement tumor habitats. The proportion of high-enhancement habitats was higher than that in the non-response group. A predictive model was established based on the proportions of these 3 habitats. Based on the proportion of low-, medium-, and high-enhancement habitats within the tumor, a habitat radiomics model was constructed. After LASSO selection and logistic regression analysis, 3 arterial phase and 3 venous phase radiomic features were selected to build the APRM and VPRM, respectively. Logistic regression analysis identified the following factors for the clinical data model: comorbidities ( OR=0.275, P=0.031), maximum tumor diameter ( OR=1.149, P=0.019), red blood cell count ( OR=0.463, P=0.022), alpha fetoprotein >400 μg/L ( OR=3.452, P=0.017), and tyrosine kinase inhibitor therapy ( OR=3.072, P=0.048). Among the single predictive model′s comparison, the AUC of habitat radiomics model was 0.860 (95% confidence interval(95% CI): 0.789 to 0.932), while those of the APRM、VPRM and clinical data model were 0.850 (95% CI: 0.773 to 0.926), 0.855 (95% CI: 0.782 to 0.928), and 0.774 (95% CI: 0.681 to 0.867), respectively, and there were no statistically significant among these models (all P>0.05). Among the combination models, the AUC of the habitat rediomic-clinical data combination model was 0.881 (95% CI: 0.814 to 0.947); the AUC of arterial phase rediomic-clinical data combination model was 0.897 (95% CI: 0.833 to 0.961); and the AUC of venous phase rediomic-clinical data combination model was 0.888 (95% CI: 0.826 to 0.951), but there were no statistically significant among the 3 models (all P>0.05). The calibration curve showed that the habitat rediomic-clinical data combination model had the most accurate predictive probability. Internal validation showed that the AUC of habitat rediomic-clinical data combination model was 0.848 (95% CI: 0.772 to 0.922), and the predictive performance was better than that of the clinical-data model (0.733 (95% CI: 0.670 to 0.863)). Conclusion:The habitat radiomics model based on enhanced CT can effectively predict early treatment responses to the HAIC combined with targeted therapy or immunotherapy in advanced HCC patients, which provides theoretical basis for individualized treatment in advanced HCC.

Sepsis is a life-threatening organ dysfunction caused by the body's dysregulated response to infection. Reversible myocardial dysfunction caused by sepsis is known as septic cardiomyopathy. A thorough understanding of the pathogenesis of septic cardiomyopathy is crucial for early intervention to prevent its progression and improve the success rate of sepsis treatment. At present, the research on the pathogenesis of septic cardiomyopathy mainly focuses on two aspects: the systemic neuroimmune mechanism and the local changes of cardiomyocytes. The former mainly includes the autonomic nervous dysfunction mainly caused by sympathetic overactivation and the inflammatory storm induced by immune response disorder. The latter covers the dysregulation of calcium homeostasis, mitochondrial dysfunction and energy metabolism disorder of cardiomyocytes. Immune dysfunction is one of the key factors that cause the poor prognosis of patients with septic cardiomyopathy. Macrophages are sentinel cells of the body's innate immunity. Cardiac macrophages have been confirmed to be one of the most heterogeneous immune cells in the heart. According to their origin and differentiation, they can be divided into bone marrow-derived tissue infiltrating macrophages and cardiac resident macrophages, which have roles of polarization, phagocytosis, regulation of inflammatory response, and participate in innate and adaptive immunity. In the occurrence and development of septic cardiomyopathy, cardiac macrophages recruited from the blood participate in balancing the inflammation and repair of myocardial tissue through the conversion of pro-inflammatory phenotype and anti-inflammatory phenotype. Cardiac resident macrophages mediate immune phagocytosis to maintain the local homeostasis of cardiomyocytes, and the glycometabolic reprogramming of macrophages regulates the release of inflammatory factors, while macrophage metabolic reprogramming regulates the release of inflammatory factors. A deeper understanding of the biological behavior of macrophages, and regulating the polarization, metabolism and phagocytosis of cardiac macrophages, could serve as new target for the prevention and treatment of septic cardiomyopathy. Therefore, this article reviews the key pathogenesis of septic cardiomyopathy and the role of macrophages of different origins and differentiation, revealing the possibility of developing new strategies for the prevention and treatment of septic cardiomyopathy.
Humans ; Cardiomyopathies/pathology* ; Macrophages/immunology* ; Sepsis/complications* ; Myocytes, Cardiac

Objective To investigate the mechanism by which Huangqi Guizhi Wuwu decoction(HQGZWWD)regulates nerve injury(NI)through vascular endothelial growth factor(VEGF)pathway based on a combination of network pharmacology and molecular docking techniques.Methods Active ingredients and targets of HQGZWWD were identified through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.A drug-ingredient-target network was constructed by integrated with data from OMIM,GeneCards,and CTD databases to identify VEGF/NI-related targets.Protein-protein interaction analyses were conducted by using STRING network platform,which were further analyzed by using the DAVID database for Gene Ontology/Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment.A"compound-target-pathway"network was constructed by using Cytoscape.Molecular docking was performed to validate the binding ability of core components with the targets.Results The primary constituents(quercetin,kaempferol)and principal targets[signal transducer and activator of transcription 3(STAT3),caspase 3,epidermal growth factor receptor(EGFR),etc.]of HQGZWWD were identified.KEGG analysis revealed that the targets were enriched cancer,EGFR inhibitor resistance,and advanced glycation end-products-receptor for advanced glycation end-products etc.signaling pathways.Molecular docking demonstrated binding energy between core components and STAT3,caspace 3,EGFR,etc.,specifically,the core components exhibited strong binding energy such as STAT3(≤-7.37kcal/mol).Conclusion HQGZWWD shows potency in suppressing inflammation,oxidative stress,and apoptosis,while promoting neural repair through VEGF regulation.The integration of network pharmacology and molecular docking offers a foundational framework for mechanistic investigations.