Background: Diabetic pain patients have increased pain at night. Exosomes can relieve neuropathic pain. This study aimed to investigate the efficacy of exosome administration at different time points in relieving diabetic neuropathic pain (DNP) in rats. Methods: M2 macrophages from bone marrow were induced in mice and exosomes were extracted. A diabetic rat model was induced using streptozotocin, with the mechanical withdrawal threshold (MWT) of the rats beingmeasured at ≤ 80% of the basal value after 14 days, indicating successful construction of the DNP rat model.Exosomes were administered on three consecutive days at ZT0 (zeitgeber time) and ZT12. Parameters including blood glucose levels, body weight, MWT, and thermal withdrawal latency (TWL) were assessed in the rats. The lumbar spinal cord of rats was examined on days 21 and 28 to measure inflammatory factors and observe the expression of M1 and M2 microglia. Furthermore, microglia were exposed to lipopolysaccharide (LPS) and LPS + exosomes in a controlled in vitro setting to assess alterations in microglia phenotype involving the NF-kB p65 andIKBα inflammatory signaling pathways. Results: The findings revealed that administration of exosomes during the rat resting period at ZT12 resulted in increased MWT and TWL, as well as a shift in microglia polarization towards the M2 phenotype. In vitro analysis indicated that exosomes influenced microglia polarization and suppressed the phosphorylation of NF-kB p65 andIKBα.  Conclusions Temporal therapy with exosomes effectively reduces pain in DNP rats by polarizing microglia andaffecting NF-kB p65 and IKBα signaling pathways.

Background: Diabetic pain patients have increased pain at night. Exosomes can relieve neuropathic pain. This study aimed to investigate the efficacy of exosome administration at different time points in relieving diabetic neuropathic pain (DNP) in rats. Methods: M2 macrophages from bone marrow were induced in mice and exosomes were extracted. A diabetic rat model was induced using streptozotocin, with the mechanical withdrawal threshold (MWT) of the rats beingmeasured at ≤ 80% of the basal value after 14 days, indicating successful construction of the DNP rat model.Exosomes were administered on three consecutive days at ZT0 (zeitgeber time) and ZT12. Parameters including blood glucose levels, body weight, MWT, and thermal withdrawal latency (TWL) were assessed in the rats. The lumbar spinal cord of rats was examined on days 21 and 28 to measure inflammatory factors and observe the expression of M1 and M2 microglia. Furthermore, microglia were exposed to lipopolysaccharide (LPS) and LPS + exosomes in a controlled in vitro setting to assess alterations in microglia phenotype involving the NF-kB p65 andIKBα inflammatory signaling pathways. Results: The findings revealed that administration of exosomes during the rat resting period at ZT12 resulted in increased MWT and TWL, as well as a shift in microglia polarization towards the M2 phenotype. In vitro analysis indicated that exosomes influenced microglia polarization and suppressed the phosphorylation of NF-kB p65 andIKBα.  Conclusions Temporal therapy with exosomes effectively reduces pain in DNP rats by polarizing microglia andaffecting NF-kB p65 and IKBα signaling pathways.

Background: Diabetic pain patients have increased pain at night. Exosomes can relieve neuropathic pain. This study aimed to investigate the efficacy of exosome administration at different time points in relieving diabetic neuropathic pain (DNP) in rats. Methods: M2 macrophages from bone marrow were induced in mice and exosomes were extracted. A diabetic rat model was induced using streptozotocin, with the mechanical withdrawal threshold (MWT) of the rats beingmeasured at ≤ 80% of the basal value after 14 days, indicating successful construction of the DNP rat model.Exosomes were administered on three consecutive days at ZT0 (zeitgeber time) and ZT12. Parameters including blood glucose levels, body weight, MWT, and thermal withdrawal latency (TWL) were assessed in the rats. The lumbar spinal cord of rats was examined on days 21 and 28 to measure inflammatory factors and observe the expression of M1 and M2 microglia. Furthermore, microglia were exposed to lipopolysaccharide (LPS) and LPS + exosomes in a controlled in vitro setting to assess alterations in microglia phenotype involving the NF-kB p65 andIKBα inflammatory signaling pathways. Results: The findings revealed that administration of exosomes during the rat resting period at ZT12 resulted in increased MWT and TWL, as well as a shift in microglia polarization towards the M2 phenotype. In vitro analysis indicated that exosomes influenced microglia polarization and suppressed the phosphorylation of NF-kB p65 andIKBα.  Conclusions Temporal therapy with exosomes effectively reduces pain in DNP rats by polarizing microglia andaffecting NF-kB p65 and IKBα signaling pathways.

Background: Diabetic pain patients have increased pain at night. Exosomes can relieve neuropathic pain. This study aimed to investigate the efficacy of exosome administration at different time points in relieving diabetic neuropathic pain (DNP) in rats. Methods: M2 macrophages from bone marrow were induced in mice and exosomes were extracted. A diabetic rat model was induced using streptozotocin, with the mechanical withdrawal threshold (MWT) of the rats beingmeasured at ≤ 80% of the basal value after 14 days, indicating successful construction of the DNP rat model.Exosomes were administered on three consecutive days at ZT0 (zeitgeber time) and ZT12. Parameters including blood glucose levels, body weight, MWT, and thermal withdrawal latency (TWL) were assessed in the rats. The lumbar spinal cord of rats was examined on days 21 and 28 to measure inflammatory factors and observe the expression of M1 and M2 microglia. Furthermore, microglia were exposed to lipopolysaccharide (LPS) and LPS + exosomes in a controlled in vitro setting to assess alterations in microglia phenotype involving the NF-kB p65 andIKBα inflammatory signaling pathways. Results: The findings revealed that administration of exosomes during the rat resting period at ZT12 resulted in increased MWT and TWL, as well as a shift in microglia polarization towards the M2 phenotype. In vitro analysis indicated that exosomes influenced microglia polarization and suppressed the phosphorylation of NF-kB p65 andIKBα.  Conclusions Temporal therapy with exosomes effectively reduces pain in DNP rats by polarizing microglia andaffecting NF-kB p65 and IKBα signaling pathways.

Background and aims:Metabolic dysfunction-associated fatty liver disease(MAFLD)is a common chronic condition that can lead to cancer due to its complex pathogenesis.Therapeutic agents targeting AMP-activated protein kinase(AMPK)activation have been suggested as potential treatments for metabolic disorders such as metabolic dysfunction-associated steatohepatitis(MASH).Rhizoma Atractylodis Mac-rocephalae(RAM)has been clinically used to treat obesity-related health problems,but its therapeutic effects on MAFLD and the underlying mechanism remain unclear.Therefore,this study was conducted to evaluate the function and underlying mechanism of RAM in the treatment of MAFLD.Methods:The effect of RAM decoction on MAFLD was evaluated using a high-fat diet(HFD)-induced MAFLD mouse model.In vitro studies were conducted using a palmitic acid/oleic acid-induced lipid accumulation model in the alpha mouse liver 12 cells and RAM-containing serum.The underlying mechanisms were elucidated through a combination of network pharmacology analysis,immunohis-tochemistry,western blotting,and polymerase chain reaction analysis.Results:Administration of RAM decoction significantly reduced body weight gain in MAFLD mice without changing food intake.The weights of the liver and inguinal adipose tissues were also reduced after RAM treatment.Additionally,RAM administration decreased serum levels of alanine aminotrans-ferase,aspartate transaminase,total cholesterol,triglyceride,low-density lipoprotein cholesterol,and glucose,while reducing lipid droplet accumulation in the liver tissues of MAFLD mice.The underlying mechanisms included the activation of the phosphorylation of AMPK and acetyl-CoA carboxylase(ACC),and inhibition of the expression of sterol regulatory element binding protein 1(SREBP1).However,RAM did not alter the protein expression levels of peroxisome proliferator-activated receptor α and carnitine palmitoyltransferase-1α.Furthermore,the RAM-induced upregulation of phosphorylated AMPK,phos-phorylated ACC,and SREBP1 expression,as well as the downregulation of fatty acid synthase expression,were reversed by using an AMPK inhibitor.Conclusions:Through a combination of network pharmacology and experimental validation,we demonstrated that RAM may exert therapeutic effects on MAFLD by inhibiting lipid synthesis and activating phosphorylated AMPK pathways.

Background: Diabetic pain patients have increased pain at night. Exosomes can relieve neuropathic pain. This study aimed to investigate the efficacy of exosome administration at different time points in relieving diabetic neuropathic pain (DNP) in rats. Methods: M2 macrophages from bone marrow were induced in mice and exosomes were extracted. A diabetic rat model was induced using streptozotocin, with the mechanical withdrawal threshold (MWT) of the rats beingmeasured at ≤ 80% of the basal value after 14 days, indicating successful construction of the DNP rat model.Exosomes were administered on three consecutive days at ZT0 (zeitgeber time) and ZT12. Parameters including blood glucose levels, body weight, MWT, and thermal withdrawal latency (TWL) were assessed in the rats. The lumbar spinal cord of rats was examined on days 21 and 28 to measure inflammatory factors and observe the expression of M1 and M2 microglia. Furthermore, microglia were exposed to lipopolysaccharide (LPS) and LPS + exosomes in a controlled in vitro setting to assess alterations in microglia phenotype involving the NF-kB p65 andIKBα inflammatory signaling pathways. Results: The findings revealed that administration of exosomes during the rat resting period at ZT12 resulted in increased MWT and TWL, as well as a shift in microglia polarization towards the M2 phenotype. In vitro analysis indicated that exosomes influenced microglia polarization and suppressed the phosphorylation of NF-kB p65 andIKBα.  Conclusions Temporal therapy with exosomes effectively reduces pain in DNP rats by polarizing microglia andaffecting NF-kB p65 and IKBα signaling pathways.

Objectives:To explore the predictive value of angiography-derived index of microcirculatory resistance(Angio-IMR)for early prognosis in patients with acute ST-segment elevation myocardial infarction(STEMI)after percutaneous coronary intervention(PCI).Methods:This multicenter study enrolled 1 629 consecutive STEMI patients who underwent successful PCI at three grade A tertiary hospitals(The Second Affiliated Hospital,Zhejiang University School of Medicine;Shengjing Hospital of China Medical University;Renji Hospital,Shanghai Jiao Tong University School of Medicine)from June 1,2017,to May 31,2020.According to postoperative Angio-IMR,patients was stratified into two groups:the Angio-IMR>40 group(n=508)and the Angio-IMR≤40 group(n=1 121).The incidence of major adverse cardiovascular events(MACE;defined as a composite endpoint including cardiac death,heart failure rehospitalization,cardiogenic shock,malignant arrhythmia,cardiopulmonary resuscitation and stent thrombosis)within 1-month post-PCI was compared between the two groups.Results:The median Angio-IMR after PCI was 32.4(22.3,42.6).The cumulative incidence of early-term MACE was significantly higher in patients with Angio-IMR>40,compared to those with Angio-IMR≤40(5.5%vs.2.3%,log-rank P<0.001).Multivariate Cox regression analysis showed that Angio-IMR>40 was an independent predictor of early-term MACE(HR=2.07,95%CI:1.20-3.58,P=0.009).The addition of Angio-IMR enhanced the predicting performance of the clinical risk model to predict early adverse outcomes(AUC:0.820 vs.0.794,P=0.043).Conclusions:In patients with STEMI after PCI,Angio-IMR can predict the occurrence of early-term MACE.The incorporation of Angio-IMR to clinical models significantly improves the model ability to predict early adverse outcomes in these patients.

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.

Objectives:To explore the predictive value of angiography-derived index of microcirculatory resistance(Angio-IMR)for early prognosis in patients with acute ST-segment elevation myocardial infarction(STEMI)after percutaneous coronary intervention(PCI).Methods:This multicenter study enrolled 1 629 consecutive STEMI patients who underwent successful PCI at three grade A tertiary hospitals(The Second Affiliated Hospital,Zhejiang University School of Medicine;Shengjing Hospital of China Medical University;Renji Hospital,Shanghai Jiao Tong University School of Medicine)from June 1,2017,to May 31,2020.According to postoperative Angio-IMR,patients was stratified into two groups:the Angio-IMR>40 group(n=508)and the Angio-IMR≤40 group(n=1 121).The incidence of major adverse cardiovascular events(MACE;defined as a composite endpoint including cardiac death,heart failure rehospitalization,cardiogenic shock,malignant arrhythmia,cardiopulmonary resuscitation and stent thrombosis)within 1-month post-PCI was compared between the two groups.Results:The median Angio-IMR after PCI was 32.4(22.3,42.6).The cumulative incidence of early-term MACE was significantly higher in patients with Angio-IMR>40,compared to those with Angio-IMR≤40(5.5%vs.2.3%,log-rank P<0.001).Multivariate Cox regression analysis showed that Angio-IMR>40 was an independent predictor of early-term MACE(HR=2.07,95%CI:1.20-3.58,P=0.009).The addition of Angio-IMR enhanced the predicting performance of the clinical risk model to predict early adverse outcomes(AUC:0.820 vs.0.794,P=0.043).Conclusions:In patients with STEMI after PCI,Angio-IMR can predict the occurrence of early-term MACE.The incorporation of Angio-IMR to clinical models significantly improves the model ability to predict early adverse outcomes in these patients.

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.