Objective To evaluate the short-term effects of comprehensive health management interventions for stroke high-risk population screening on the prevention and treatment of ischemic stroke, and to provide reference and basis for improving and exploring health management and prevention strategies for stroke high-risk population. Methods From 2018 to 2022, 13 community health service centers in Jiading District, Shanghai were selected in the present study. Based on information push platform, stroke risk assessment and health intervention follow-up were conducted for community residents through convenience sampling. The residents were divided into a full course intervention group (intervention group) and a routine intervention group (control group) according to different health intervention measures and forms. The incidence of ischemic stroke in the two groups of survey subjects was tracked within 36 months. Results A total of 52144 subjects were included in the study. The total number of patients in the full course intervention group was 14227, with an incidence density of 577.32/100 000 (556.49/100 000-598.12/100 000), which was lower than that of the conventional intervention group (37 917), with an incidence density of 1 485.47/100 000 (1 464.99/100 000-1 505.94/100 000) (χ²=2490.212, P<0.001). The relative risk of the full course intervention group was 0.39, and the relative risk of stroke risk factors in the full course intervention group from low to high was 0.33, 0.43, 0.45, and 0.49, respectively. The incidence density of males in the full course intervention group was 660.76 (627.46/100 000 - 694.05/100 000), with a relative risk of 0.43, and the incidence density of female patients was 509.71/100 000 (483.37/100 000 - 536.05/100 000), with a relative risk of 0.35. The overall incidence density of the population under 62 years old gourp, 62-75 years old group and over 75 years old group was 197.45/100 000 (173.09/100 000 -221.80/100 000), 608.36/100 000 (580.19/100 000-636.54/100 000), and 1 025.06/100 000 (958.51/100 000-1 091.61/100 000), with relative risks of 0.51, 0.44, and 0.38, respectively. Conclusion Comprehensive health management measures can effectively reduce the short-term risk of ischemic stroke, and should be further promoted and improved to enhance the effectiveness of stroke prevention and control.

Treatment resistance, recurrence, and metastasis of breast cancer remain critical issues affecting long-term patient survival. Chronic psychological stress may act as a host biological driver of breast cancer treatment resistance rather than a mere comorbidity. Through the sustained activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis, also referred to as the "brain-tumor axis", stress signaling reshapes inflammatory, immune, and metabolic networks within the tumor microenvironment and thereby influences chemotherapy, endocrine therapy, anti-HER2 therapy, immunotherapy, and radiotherapy. Current evidence indicates that the key pathways with translational potential are mainly the β-adrenergic axis and the glucocorticoid receptor (GR) pathway. The former is more involved in amplifying inflammatory responses, promoting immunosuppression and metastasis, whereas the latter is closely associated with anti-apoptosis, maintenance of tumor stemness, and reprogramming of estrogen receptor function. This review focuses on the discrepancies in evidence regarding these pathways between population-based studies and preclinical models, and discusses clinically operable non-pharmacologic interventions such as cognitive behavioral stress management, nurse navigation and treatment adherence support, and exercise interventions during the neoadjuvant phase. Although high-level evidence for direct survival benefit remains limited, these interventions have shown favorable effects on cortisol levels, depressive symptoms, quality of life, adherence, relative dose intensity, and some biology-related intermediate endpoints, making them valuable complementary approaches in comprehensive breast cancer management.

Objective To investigate the efficacy of lenalidomide combined with bortezomib and dexamethasone in the treatment of multiple myeloma(MM)and their effects on heat shock protein 90(HSP90)mRNA,miR-28-5p,anti-tartrate acid phosphatase 5b(TRACP-5b)and high mobility group protein B1(HMGB1).Methods Eighty patients with newly diagnosed MM were selected and divided into the two-combination group(40 patients treated with bortezomib and dexamethasone)and the three-combination group(40 patients treated with bortezomib and dexamethasone combined with lenalidomide)according to the treatment modalities.Real-time fluorescence quantitative polymerase chain reaction was used to detect HSP90 mRNA and miR-28-5p levels.Enzyme-linked immunosorbent assay was used to detect TRACP-5b and HMGB1 levels.The clinical efficacy of the 2 groups was compared.Levels of HSP90 mRNA,miR-28-5p,TRACP-5b,HMGB1,the immune cell function,renal function indexes and the incidence of adverse reactions were compared before and after treatment.Results The total effective rate of the three-combination group was higher than that of the two-combination groups(92.50%vs.75.00%,P＜0.05).Compared with the pretreatment,the levels of HSP90 mRNA,TRACP-5b,blood creatinine(SCr),and urea nitrogen(BUN)decreased in the 2 groups after treatment,and which was lower in the three-combination group than that in the two-combination groups.The levels of miR-28-5p,HMGB1,CD4+,CD3+and CD4+/CD8+were elevated in the 2 groups,and the levels were higher in the three-combination group than those in the two-combination group(P＜0.05).There was no significant difference in the incidence of adverse reactions between the two groups.Conclusion Lenalidomide combined with bortezomib and dexamethasone is clinically effective,safe and reliable in the treatment of MM.

Objective:To establish a mouse model of liver cancer resistant to PD-1 monoclonal antibody and analyze the changes in its metabolomics to explore the potential mechanism of drug resistance.Methods:BALB/c mice were randomly divided into control and treatment groups after being loaded with tumor,and a normal group was additionally set up.The normal and control groups were injected with saline,and the treatment group was injected with PD-1 monoclonal antibody,after which the mice in the treatment group were screened for drug resistant and response groups.Observed the drug-resistant situation,body mass,tumor growth and survival rate of mice in each group,calculate the spleen index.The pathological features of tumor tissues were observed by HE staining method.Serum metabolites were detected by non-targeted metabolomics.Finally,a bivariate Pearson correlation analysis was conducted between the differential serum metabolites and tumor size.Results:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established,and the drug resistance rate of the mice was 50％.Compared with the normal and response groups,mice in the resistant group showed an increase in body weight,a significant increase in tumor volume,a decrease in survival rate,and a significant increase in splenic index.There was less lymphocyte infiltration in the tumor tissue.Metabolomics analysis showed that the serum levels of glutamic acid and aspartic acid increased and malic acid decreased in the resistant mice compared with the response group,and these changes were closely related to the arginine biosynthesis pathway.Conclusions:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established.The changes in its peripheral serum metabolomics mainly involve arginine metabolism and the related changes of aspartate,malate and glutamate.

BACKGROUND:Metformin is currently considered the first-line medication for the treatment of type 2 diabetes.Metformin may delay the progression of osteoarthritis,but its specific mechanism of action remains unclear.OBJECTIVE:To evaluate the therapeutic effects and the related action mechanisms of metformin on osteoarthritis in rats.METHODS:(1)Network pharmacology:Potential common targets for metformin,osteoarthritis,and ferroptosis were screened using the CTD,SwissTargetPrediction,GeneCards,and OMIM databases.After importing the targets into the STRING database,protein-protein interaction analysis was conducted to identify the key targets for metformin,osteoarthritis,and ferroptosis.(2)Molecular docking:P53 and its downstream factor SLC7A11 protein structures in PDB format were downloaded from the PDB database.The 2D structure of metformin was converted to a 3D structure,and molecular docking of metformin with the proteins was performed using Discovery Studio 2019 Client.(3)In vivo experiments:Thirty male SD rats were randomly divided into three groups(n=10).The blank group did not receive surgery.The osteoarthritis model was established using the modified Hulth method for the model and metformin groups.One day after the surgery,rats in the metformin group were gavaged with metformin 200 mg/kg per day,while the blank and model groups were gavaged with physiological saline.Treatment continued for 4 weeks.Hematoxylin-eosin staining and Safranin O-fast green staining were used to observe the pathological morphology and structure of the knee cartilage,and Mankin scoring was performed.ELISA was used to measure the levels of tumor necrosis factor-α and interleukin-6 in the serum.The microplate method was used to measure serum ferroptosis-related indicators,including glutathione,malondialdehyde,and Fe2+.Immunofluorescence staining,western blot assay,and real-time qPCR were used to detect the protein and mRNA expression of P53,SLC7A11,glutathione peroxidase 4,proteoglycans,and matrix metalloproteinase 13 in the cartilage tissue of the rats.RESULTS AND CONCLUSION:(1)A total of 96 intersecting targets among metformin,osteoarthritis,and ferroptosis were identified.After protein-protein interaction analysis,77 potential targets were found.Further screening identified the core targets as TP53,AKT1,JUN,interleukin-6,MYC,interleukin-1β,and tumor necrosis factor-α,among others.(2)Docking analysis results showed that metformin bound strongly and stably with P53 and its downstream factor SLC7A11.(3)In the model group,the knee cartilage surface was irregular,with cartilage tissue defects and reduced chondrocyte numbers.Compared to the model group,the knee cartilage structure damage in the metformin group was significantly improved,with a smoother cartilage surface and increased chondrocyte numbers.The Mankin score in the model group was significantly higher than that in the blank group,while the Mankin score in the intervention group was significantly lower than that in the model group.(4)Compared with the model group,the metformin group had significantly lower levels of tumor necrosis factor-α,interleukin-6,malondialdehyde,and Fe2+,and significantly higher glutathione levels.(5)Compared to the model group,the metformin group had significantly increased protein and mRNA expression of SLC7A11,glutathione peroxidase 4,and proteoglycans,and significantly decreased protein and mRNA expression of P53 and matrix metalloproteinase 13 in their cartilage tissue.(6)The results indicate that metformin can effectively improve cartilage damage in osteoarthritis rats and alleviate chondrocyte ferroptosis by inhibiting the aberrantly activated P53/SLC7A11/glutathione peroxidase 4 signaling pathway.This improvement in chondrocyte iron metabolism and lipid peroxidation response further reduces cartilage matrix degradation and prevents further cartilage damage and inflammatory response.

Purpose To investigate the correlation between tumor budding in penile squamous cell carcinoma(SCC)and its clinicopathological features.Methods Clinical data and pathological slides from 69 cases of penile SCC were collected.Tumor budding was examined microscopically,and statistical analyses were performed to assess the relationship between tumor budding and various clinicopathological features.Results Among the 69 cases of pe-nile SCC,41 cases exhibited low-grade tumor budding and 28 cases displayed high-grade tumor budding.Tumor bud-ding was significantly correlated with tumor size,urethral invasion,invasion of the urethral corpus spongiosum,inva-sion of the penile corpus cavernosum,tumor necrosis,nerve invasion,vascular tumor thrombus,and pathological T stage(all P＜0.05).In contrast,no significant association was found between tumor budding and HPV-related versus non-HPV-related penile SCC(P＞0.05).Log-rank survival analysis indicated that patients with high-grade tumor bud-ding had a significantly lower survival rate compared to those with low-grade tumor budding(P＜0.05).Conclusion Tumor budding is a distinct pathological feature of penile SCC,and high-grade tumor budding is associated with a more aggressive biological behavior.

Objective:To compare the differences in the evaluation of hemolysis performance of cellulose hemostatic materials using different detection methods and test media,and to explore a m ore reasonable testing plan for such products.Methods:Hemolysis tests were conducted on cellulose hemostatic materials using the absorbance measurement hemolysis method and hemoglobin concentration measurement hemolysis method in accordance with YY/T 1651.1-2019 standard.We compared the changes in hemolysis rate,pH value,and osmotic pressure under different experimental media.Results:Under the same experimental method,compared to SC,the hemolysis results using PBS as the extraction medium are smaller,and the changes in pH and osmotic pressure are closer to the normal range of human body changes.Conclusions:The changes in pH and osmotic pressure may be one of the reasons for the high hemolysis rate of cellulose hemostatic materials.Choosing PBS with buffering effect as the leaching medium may be more suitable for evaluating the hemolysis performance of cellulose hemostatic materials.

Brucellosis,a zoonotic infectious disease caused by Brucella,leads to persistent infections in both animals and humans.This disease not only substantially affects the health and development of the livestock industry,but also poses a major threat to human health and public safety.Currently,vaccination remains the most effective method for preventing animal bru-cellosis.Compared with smooth strains,rough Brucella strains lack the O-chain antigens,thus offering advantages such as lower virulence,higher safety,and no interference with clinical diagnostics.Consequently,rough Brucella vaccines have prom-ising potential for brucellosis prevention and control.Researchers are now focusing on the development of Brucella abortus vac-cines as an important direction in brucellosis vaccine research and development.An urgent need exists for the development of Brucella abortus vaccines.This article provides a brief review of current research on vaccines for rough Brucella and candidate strains,and summarizes developed vaccine applications and their effectiveness,to provide insights for brucellosis prevention and control,and further development of vaccines for rough Brucella.

Objective:To establish a mouse model of liver cancer resistant to PD-1 monoclonal antibody and analyze the changes in its metabolomics to explore the potential mechanism of drug resistance.Methods:BALB/c mice were randomly divided into control and treatment groups after being loaded with tumor,and a normal group was additionally set up.The normal and control groups were injected with saline,and the treatment group was injected with PD-1 monoclonal antibody,after which the mice in the treatment group were screened for drug resistant and response groups.Observed the drug-resistant situation,body mass,tumor growth and survival rate of mice in each group,calculate the spleen index.The pathological features of tumor tissues were observed by HE staining method.Serum metabolites were detected by non-targeted metabolomics.Finally,a bivariate Pearson correlation analysis was conducted between the differential serum metabolites and tumor size.Results:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established,and the drug resistance rate of the mice was 50％.Compared with the normal and response groups,mice in the resistant group showed an increase in body weight,a significant increase in tumor volume,a decrease in survival rate,and a significant increase in splenic index.There was less lymphocyte infiltration in the tumor tissue.Metabolomics analysis showed that the serum levels of glutamic acid and aspartic acid increased and malic acid decreased in the resistant mice compared with the response group,and these changes were closely related to the arginine biosynthesis pathway.Conclusions:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established.The changes in its peripheral serum metabolomics mainly involve arginine metabolism and the related changes of aspartate,malate and glutamate.

BACKGROUND:Metformin is currently considered the first-line medication for the treatment of type 2 diabetes.Metformin may delay the progression of osteoarthritis,but its specific mechanism of action remains unclear.OBJECTIVE:To evaluate the therapeutic effects and the related action mechanisms of metformin on osteoarthritis in rats.METHODS:(1)Network pharmacology:Potential common targets for metformin,osteoarthritis,and ferroptosis were screened using the CTD,SwissTargetPrediction,GeneCards,and OMIM databases.After importing the targets into the STRING database,protein-protein interaction analysis was conducted to identify the key targets for metformin,osteoarthritis,and ferroptosis.(2)Molecular docking:P53 and its downstream factor SLC7A11 protein structures in PDB format were downloaded from the PDB database.The 2D structure of metformin was converted to a 3D structure,and molecular docking of metformin with the proteins was performed using Discovery Studio 2019 Client.(3)In vivo experiments:Thirty male SD rats were randomly divided into three groups(n=10).The blank group did not receive surgery.The osteoarthritis model was established using the modified Hulth method for the model and metformin groups.One day after the surgery,rats in the metformin group were gavaged with metformin 200 mg/kg per day,while the blank and model groups were gavaged with physiological saline.Treatment continued for 4 weeks.Hematoxylin-eosin staining and Safranin O-fast green staining were used to observe the pathological morphology and structure of the knee cartilage,and Mankin scoring was performed.ELISA was used to measure the levels of tumor necrosis factor-α and interleukin-6 in the serum.The microplate method was used to measure serum ferroptosis-related indicators,including glutathione,malondialdehyde,and Fe2+.Immunofluorescence staining,western blot assay,and real-time qPCR were used to detect the protein and mRNA expression of P53,SLC7A11,glutathione peroxidase 4,proteoglycans,and matrix metalloproteinase 13 in the cartilage tissue of the rats.RESULTS AND CONCLUSION:(1)A total of 96 intersecting targets among metformin,osteoarthritis,and ferroptosis were identified.After protein-protein interaction analysis,77 potential targets were found.Further screening identified the core targets as TP53,AKT1,JUN,interleukin-6,MYC,interleukin-1β,and tumor necrosis factor-α,among others.(2)Docking analysis results showed that metformin bound strongly and stably with P53 and its downstream factor SLC7A11.(3)In the model group,the knee cartilage surface was irregular,with cartilage tissue defects and reduced chondrocyte numbers.Compared to the model group,the knee cartilage structure damage in the metformin group was significantly improved,with a smoother cartilage surface and increased chondrocyte numbers.The Mankin score in the model group was significantly higher than that in the blank group,while the Mankin score in the intervention group was significantly lower than that in the model group.(4)Compared with the model group,the metformin group had significantly lower levels of tumor necrosis factor-α,interleukin-6,malondialdehyde,and Fe2+,and significantly higher glutathione levels.(5)Compared to the model group,the metformin group had significantly increased protein and mRNA expression of SLC7A11,glutathione peroxidase 4,and proteoglycans,and significantly decreased protein and mRNA expression of P53 and matrix metalloproteinase 13 in their cartilage tissue.(6)The results indicate that metformin can effectively improve cartilage damage in osteoarthritis rats and alleviate chondrocyte ferroptosis by inhibiting the aberrantly activated P53/SLC7A11/glutathione peroxidase 4 signaling pathway.This improvement in chondrocyte iron metabolism and lipid peroxidation response further reduces cartilage matrix degradation and prevents further cartilage damage and inflammatory response.