Aim To clarify the mechanism by which Qishen Yixin Granules improved microcirculation vas-cular endothelial dysfunction(VED)in mice,through activating the Nrf2/HO-1 signaling pathway to regulate oxidative stress.Methods C57 mice were randomly divided into six groups:blank group,model group,pos-itive drug group,and low-,medium-,and high-dose groups of Qishen Yixin Granules.The VED model was established by long-term infusion of Ang Ⅱ combined with a high-fat diet.Each treatment group received the corresponding drug intervention.After four weeks of drug intervention,cardiac function was assessed by echocardiography.Carstairs staining was used to ob-serve the formation of microthrombi in myocardial tis-sue.The micro vascular ischemia was evaluated by Hei-denhain staining.The ultrastructure of endothelial cells was observed by electron microscopy.The levels of EMPs,ROS,NO,ET-1,TF,TM,VWF,and TXA2 in serum were measured by ELISA.The expression levels of MDA,SOD,and GSH-Px in mouse heart tissue were determined by chemical methods.Cardiac microvascu-lar density and the expression of Nrf2,Keap1,and HO-1 proteins were detected by Immunohistochemical stai-ning.The protein expressions of Keap1,cytoplasmic Nrf2,nuclear Nrf2,and HO-1 in myocardial tissue were detected by Western blot.Results Qishen Yixin Granules could effectively improve the cardiac function of mice,alleviate the damage of endothelial cells and endothelial function.They could up-regulate serum NO levels and the activities of antioxidant enzymes SOD and GSH-Px,while down-regulating the expression of ROS and vascular inflammatory injury factors such as ET-1,VWF,TXA2,TF,TM,and EMPs.Qishen Yixin Granules also increased the positive counts of CD34,Nrf2,and HO-1,as well as microvessel density.Fur-thermore,they inhibited the expression of MDA,Keap1,and cytoplasmic Nrf2 protein in myocardial tis-sue,while increasing the expression of nuclear proteins HO-1 and Nrf2.Conclusions Qishen Yixin Granules may inhibit oxidative stress and inflammatory response by regulating the Nrf2/HO-1 signaling pathway,thereby improving vascular endothelial damage and cardiac function in VED mice.

Aim To explore the mechanism of the syn-ergistic effect of the ferroptosis inducer erastin com-bined with shikonin in promoting ferroptosis in human hypertrophic scar fibroblasts(HSFBs).Methods Hypertrophic scar tissues provided by the General Hos-pital of Ningxia Medical University were collected,and HSFBs were extracted.HSFBs were identified by HE staining and immunofluorescence.The inhibitory rates of Era and SHK on HSFBs at different concentrations were detected by CCK-8 assay,and the IC50 value was calculated.CompuSyn software was used to calculate the co-use index(CI).Control group,Erastin(Era)group,shikonin(SHK)group and Era+SHK group were set up,and the number and morphological chan-ges of cells were observed after 24 hours of interven-tion.The ability of cell migration and invasion was de-tected by scratch test and Transwell test.The changes of malondialdehyde(MDA),total iron ion and reactive oxygen species(ROS)were detected by corresponding biochemical kits.The expressions of collagen I,α-SMA and GOT1,SLC7A11,GPX4 and FTH1 were detected by Western blot.Results The IC50 value of Era and SHK of primary HSFBs was 2.22 μmol·L-1 and 3.94μmol·L-1 respectively,which was used as the single drug concentration for subsequent experiments.The CompuSyn software was employed to calculate the CI value when the two drugs were used in combination,and the concentrations corresponding to CI=0.39597(Era:1.2 μmol·L-1+SHK:1.5 μmol·L-1)were selected as subsequent combination concentrations(Because when CI was equal to 0.395 97,the concen-tration of each drug was lower than the concentration of single drug,and the inhibition rate of combined drug was greater than 50％).Compared with the monother-apy group,the number of HSFBs in the SHK+Era group was significantly reduced,cell membrane showed breakage and vesiculation,cell wrinkling became smal-ler,and cytoplasm was concentrated.The migration and invasion ability of HSFBs in the SHK+Era group were obviously weakened(P＜0.05),and the expres-sion of fibrosis-related proteins collagen Ⅰ and α-SMA was reduced(P＜0.05);the contents of MDA,total i-ron ions,and ROS in HSFBs of the SHK+Era group increased(P＜0.05),and the protein expression lev-els of SLC7A11,GOT1,GPX4,and FTH1 further de-creased(P＜0.05).Conclusions Erastin in combi-nation with shikonin can synergistically inhibit the pro-liferation,migration and fibrosis levels of HSFBs.The mechanism may be that erastin enhances the inhibition of shikotin on GOT1,increases the levels of cellular i-ron ions,ROS,and lipid peroxides,thereby promoting ferroptosis in HSFBs.

Aim To study the possibility of luteolin(LUT)as a new drug of traditional Chinese medicine and its improving effect on glucose and lipid metabo-lism and liver oxidative stress injury in db/db mice,and to explore the possible mechanism.Methods AI was used to predict the drug toxicity,evaluate the phys-ical and chemical properties and segment the molecular structure of LUT.Molecular docking was used to verify the binding ability of LUT with Nrf2 and HMOX1;db/m mice were divided into the group C,and db/db mice were randomly divided into the T,L,M,H and P groups.The body weight and FBG changes were ob-served within 12 weeks of intervention.The expres-sions of FBG,HbA1c,Fins,TC,TG,HDL-C,LDL-C were detected.The pathomorphological changes and steatosis of mouse liver were observed by HE and oil red O staining.The expression of MDA,SOD and GSH-Px in liver was detected by Kit.The protein and mRNA expressions of Nrf2 and HMOX1 were detected by immunohistochemistry,WB and qPCR.Results AI algorithm predicted the safety and easy synthesis of LUT.LUT intervention had no significant effect on the body weight of db/db mice.After 12 weeks,compared with the group C,the livers of mice in group T showed disordered structure of hepatic lobules,irregular ar-rangement of hepatocytes,and a large number of fat vacuoles and lipid droplets in the cytoplasm.Compared with the group T,LUT intervention could improve the pathological changes of liver,reduce the expression of FBG,HbA1c,fins,TC,TG,LDL-C,MDA,improve the level of HOMA-IR,and upregulate the activities of SOD and GSH-Px.Molecular docking results showed LUT had strong binding with Nrf2 and HMOX1,and could increase the expression of Nrf2 and HMOX1.Conclu-sion LUT can correct the disorder of glucose and lip-id metabolism in db/db mice,and improve the level of oxidative stress in liver of mice through Nrf2/HMOX1 pathway,which has the development prospect as a new Chinese medicine for the treatment of T2DM.

Aim To clarify the mechanism by which Qishen Yixin Granules improved microcirculation vas-cular endothelial dysfunction(VED)in mice,through activating the Nrf2/HO-1 signaling pathway to regulate oxidative stress.Methods C57 mice were randomly divided into six groups:blank group,model group,pos-itive drug group,and low-,medium-,and high-dose groups of Qishen Yixin Granules.The VED model was established by long-term infusion of Ang Ⅱ combined with a high-fat diet.Each treatment group received the corresponding drug intervention.After four weeks of drug intervention,cardiac function was assessed by echocardiography.Carstairs staining was used to ob-serve the formation of microthrombi in myocardial tis-sue.The micro vascular ischemia was evaluated by Hei-denhain staining.The ultrastructure of endothelial cells was observed by electron microscopy.The levels of EMPs,ROS,NO,ET-1,TF,TM,VWF,and TXA2 in serum were measured by ELISA.The expression levels of MDA,SOD,and GSH-Px in mouse heart tissue were determined by chemical methods.Cardiac microvascu-lar density and the expression of Nrf2,Keap1,and HO-1 proteins were detected by Immunohistochemical stai-ning.The protein expressions of Keap1,cytoplasmic Nrf2,nuclear Nrf2,and HO-1 in myocardial tissue were detected by Western blot.Results Qishen Yixin Granules could effectively improve the cardiac function of mice,alleviate the damage of endothelial cells and endothelial function.They could up-regulate serum NO levels and the activities of antioxidant enzymes SOD and GSH-Px,while down-regulating the expression of ROS and vascular inflammatory injury factors such as ET-1,VWF,TXA2,TF,TM,and EMPs.Qishen Yixin Granules also increased the positive counts of CD34,Nrf2,and HO-1,as well as microvessel density.Fur-thermore,they inhibited the expression of MDA,Keap1,and cytoplasmic Nrf2 protein in myocardial tis-sue,while increasing the expression of nuclear proteins HO-1 and Nrf2.Conclusions Qishen Yixin Granules may inhibit oxidative stress and inflammatory response by regulating the Nrf2/HO-1 signaling pathway,thereby improving vascular endothelial damage and cardiac function in VED mice.

BACKGROUND:Knee osteoarthritis is a common degenerative disease that significantly impacts patients'quality of life and increases the societal healthcare burden.Early and accurate diagnosis of knee osteoarthritis is crucial for the treatment and prognosis of patients.Traditional diagnostic methods are not only subjective and time-consuming but also do not guarantee consistently high accuracy.OBJECTIVE:To develop an automatic diagnostic method for knee osteoarthritis based on deep learning,utilizing deep learning networks to improve diagnostic accuracy and efficiency.METHODS:A new network model,YOLOV8-ViT,was proposed by replacing the backbone network of YOLOv8n with the Efficient-ViT network and incorporating attention mechanisms for the automatic identification and classification of X-ray images of knee osteoarthritis.The experimental dataset included 5 078 X-ray images of patients with knee osteoarthritis obtained from the Third Affiliated Hospital of Guangzhou University of Chinese Medicine.Three imaging physicians annotated the sites of knee osteoarthritis and classified them according to the Kellgren-Lawrence grading standard using Labelme software,and the results were combined.The evaluation indicators used in this study included Precision,F1 score,mean average precision(mAP),Recall,val/box_loss,val/cls_loss,and val/dfl_loss.RESULTS AND CONCLUSION:The experimental results showed that the YOLOV8-ViT model outperformed the YOLOv5n,YOLOv8n,and YOLOv9n models in terms of precision,mAP50,mAP50-95,F1 score,and Recall,while lowering val/box_loss,val/cls_loss,and val/dfl_loss by 0.496,0.45,and 0.523;1.037,0.305,and 0.728;and 0.267,0.654,and 0.854,respectively.These experimental data validate that this model has high detection accuracy.

Objective To explore the role of miR-204-3p in silicosis and to elucidate the mechanism by which it affects silicosis fibers by regulating silica dust-induced alveolar epithelial-mesenchymal transition(EMT)in rats.Methods Forty SD rats were divided randomly into 4 groups:Control,Silicosis,AAV-Control,and AAV-miR-204-3p groups.The pathology of lung tissue damage was detected by hematoxylin and eosin(HE)and Masson staining.Relative expression levels of miR-204-3p and EMT marker genes in lung tissues from rats in each group were analyzed by real-time fluorescence reverse transcription quantitative PCR(RT-qPCR),and protein expression levels of EMT-related markers in lung tissues were detected by Western blot.Results The alveolar structure was damaged,the lung septa showed interstitial fibrosis,and expression levels of mesenchymal markers were elevated in the Silicosis group compared with the Control group(P＜0.05,P＜0.01,P＜0.001).The alveolar structure was more complete,the EMT process was alleviated,fibrosis was improved,and mesenchymal marker expression was reduced in the AAV-miR-204-3p group compared with the AAV-Control group(P＜0.05,P＜0.01,P＜0.001).Conclusions Free silica dust induces EMT in rat lung tissue.Overexpression of miR-204-3p can attenuate the EMT process induced by free silica dust in rats,and may thus affect silicosis fibrosis.

Objective To establish human colorectal cancer(CRC)organoids and to evaluate the efficacy of chem-otherapy drugs.Methods Patient-derived CRC cells were cultured to form organoids.The CRC organoids and origi-nal tissues were stained with molecular markers of CRC immunohishtochemically.CRC organoids were used to test drug sensitivity and different concentrations of chemotherapy drugs 5-fluorouracil,oxaliplatin and irinotecan were given respectively;Organoid activity before and after drug treatment was measured by 3D cell viability assay.Results The patient-derived organoids(PDO)from 5 CRC tissues were successfully established.The expression of CK20,Ki67 and Villin proteins was similar in organoids and in original tumor.The organoids retained histologcial features similar to those of the original tumors.Different PDO showed differential sensitivity to different chemothera-py drugs.Conclusions CRC-PDO can dispaly their different sensitivities to different chemotherapy drugs,and could provide valuble reference for personalized treatment for CRC patients.

Objective:To investigate the epidemiological dynamics and spatiotemporal diffusion trend of brucellosis in China from 2010 to 2024.Methods:Data on reported human brucellosis cases in mainland China from January 1, 2010, to December 31, 2024, were collected via the"China Information System for Disease Control and Prevention", including detailed information on the date of onset, gender, age, occupation, and residential address of the cases. The Joinpoint regression and spatial interpolation techniques were used to investigate the spatiotemporal dynamics and population distribution characteristics of human brucellosis in pastoral/semi-pastoral areas and other regions, as well as urban and rural areas, and explore the epidemic trends of the disease.Results:From 2010 to 2024, pastoral/semi-pastoral regions reported 252 094 brucellosis cases, with a mean annual incidence rate of 36.57±7.28 per 100 000. In contrast, other regions cumulatively recorded 519 748 cases during the same period, demonstrating a significantly lower mean annual incidence rate of 2.54±0.74 per 100 000. The incidence rate of human brucellosis in pastoral/semi-pastoral regions exhibited a declining-rebounding-declining trend. Specifically, the incidence rate decreased significantly from 2010 to 2017 (APC=-7.20; P<0.001) and increased notably from 2017 to 2021 (APC=18.00; P=0.015) with a decline again from 2021 to 2024 (APC=-7.53; P=0.027). In other regions, the incidence rate showed a fluctuating upward trend. Specifically, the incidence rate increased significantly from 2010 to 2015 (APC=20.37; P<0.001) and decreased notably from 2015 to 2018 (APC=-21.78; P<0.001), followed by an increase again from 2018 to 2024, a significant upward trend in incidence rate from 2018 to 2021 (APC=26.73; P<0.001) and a non-significant decline from 2021 to 2024 (APC=-0.99; P=0.735), resulting in the maintenance of a relatively high incidence level. Rural areas demonstrated significantly higher brucellosis incidence rates than urban settings (all P<0.001). Brucellosis exhibited a diffusion trend from the northern epidemic areas of China to neighboring regions, along with sporadic diffusion in southern regions between 2010 and 2024. The age structure of patients in pastoral/semi-pastoral areas differed significantly from that in other regions. Specifically, in pastoral/semi-pastoral areas, the incidence rate was higher among the 35-49 age groups, while in other regions, the incidence rate was higher among those aged 55-64. Conclusion:There are notable disparities in the incidence of human brucellosis between pastoral/semi-pastoral areas and other regions in China. Human brucellosis exhibits a diffusion trend from the northern epidemic areas of China to neighboring regions, along with sporadic diffusion in southern regions.

BACKGROUND:Knee osteoarthritis is a common degenerative disease that significantly impacts patients'quality of life and increases the societal healthcare burden.Early and accurate diagnosis of knee osteoarthritis is crucial for the treatment and prognosis of patients.Traditional diagnostic methods are not only subjective and time-consuming but also do not guarantee consistently high accuracy.OBJECTIVE:To develop an automatic diagnostic method for knee osteoarthritis based on deep learning,utilizing deep learning networks to improve diagnostic accuracy and efficiency.METHODS:A new network model,YOLOV8-ViT,was proposed by replacing the backbone network of YOLOv8n with the Efficient-ViT network and incorporating attention mechanisms for the automatic identification and classification of X-ray images of knee osteoarthritis.The experimental dataset included 5 078 X-ray images of patients with knee osteoarthritis obtained from the Third Affiliated Hospital of Guangzhou University of Chinese Medicine.Three imaging physicians annotated the sites of knee osteoarthritis and classified them according to the Kellgren-Lawrence grading standard using Labelme software,and the results were combined.The evaluation indicators used in this study included Precision,F1 score,mean average precision(mAP),Recall,val/box_loss,val/cls_loss,and val/dfl_loss.RESULTS AND CONCLUSION:The experimental results showed that the YOLOV8-ViT model outperformed the YOLOv5n,YOLOv8n,and YOLOv9n models in terms of precision,mAP50,mAP50-95,F1 score,and Recall,while lowering val/box_loss,val/cls_loss,and val/dfl_loss by 0.496,0.45,and 0.523;1.037,0.305,and 0.728;and 0.267,0.654,and 0.854,respectively.These experimental data validate that this model has high detection accuracy.

Objective:To identify and synthesize the best available evidence for the prevention and management of enteral nutrition intolerance in postoperative patients with gastric cancer.Methods:Following the hierarchical structure of the "6S Evidence Resource Pyramid" model, evidence was systematically retrieved from evidence-based databases, clinical guidelines and professional societies' websites, and comprehensive literature databases. Studies related to the prevention and management of enteral nutrition intolerance in postoperative gastric cancer patients were screened. Two researchers, both trained in evidence-based nursing, independently conducted quality appraisal, evidence extraction, and integration. The search covered literature published from database inception to February 25, 2025.Results:A total of 23 studies were included, comprising 2 clinical guidelines, 1 evidence summary, 2 systematic reviews, 4 expert consensuses, 9 randomized controlled trials, 1 quasi-experimental study, 1 cohort study, 2 analytical cross-sectional studies, and 1 case-control study. Based on 6 key aspects (including preparation by Medical staff before surgery, postoperative patient assessment, formulation of feeding, rehabilitation exercises, traditional Chinese medicine interventions, and management of enteral nutrition intolerance), a total of 26 best evidence recommendations were summarized.Conclusions:The evidence summarized in this study provides an evidence-based foundation for clinical medical staff, contributing to the reduction of enteral nutrition intolerance in postoperative patients with gastric cancer.