Objective To explore the impact of Shexiang Baoxin Pill(SXBXP,a traditional Chinese patent medicine,broadly applied for the treatment of cardiovascular diseases)on coronary microvascular disease(CMD)and investigate the role and underlying mechanisms of muscone,a key bioactive component of the pills,in the treatment.Methods A total of 16 ob/ob mice(8 weeks old)were randomly and equally divided into an ob/ob-SXBXP group and a ob/ob-Control group,receiving 10 mg/kg·d SXBXP or PBS via oral gavage,and another 8 wild-type mice with the same genetic background(WT group)were subjected as a negative control group.Cell model of CMD was established based on mouse coronary microvascular endothelial cells(MCMEC)under ischemia and hypoxic(HI)condition,and the cells were further treated with 20 μg/mL SXBXP(HI+SX)and 30 μmol/L muscone(HI+Muscone),respectively.Echocardiography was carried out for coronary flow reserve(CFR)and left ventricular function,and laser speckle imaging was applied to evaluate myocardial blood flow(MBF).Microvascular density in the heart was evaluated with CD31 immunofluorescence staining.The expression levels of vascular endothelial growth factor(VEGF)in cardiac microvascular endothelial cells of both mouse and cell models were detected by immunofluorescence staining and Western blot analysis.The proliferation and angiogenesis of MCMEC were observed by 5-ethynyl-2'-deoxyuridine staining and angiogenesis experiments.Results In the ob/ob-Control group of mice,the levels of CFR,MBF,and cardiac microvascular density were significantly lower than those in the WT group(P<0.05),and these indicators were significantly improved in the ob/ob-SXBXP group when compared with the ob/ob-Control group(P<0.05),which indicates that SXBXP improves the CMD phenotype.The expression level of VEGF in cardiac microvascular endothelial cells was significantly lower in the ob/ob-Control mice than the WT mice(P<0.05),while the level in the ob/ob-SXBXP group was significantly higher than that in the ob/ob-Control group(P<0.05),illustrating that SXBXP may ameliorate CMD through VEGF-mediated microvascular angiogenesis.In vitro experiments further revealed that the VEGF expression level and the proliferation and angiogenesis abilities in MCMEC were significantly lower in the HI group than the cells under the normoxia control condition(P<0.05).Both SXBXP and muscone treatment resulted in enhanced expression of VEGF and improved proliferative and angiogenesis abilities of MCMEC(P<0.05).These results suggest that muscone could improve CMD by VEGF-mediated microvascular angiogenesis.Conclusion SXBXP can improve CMD.Muscone,as a key component of SXBXP,promotes microvascular angiogenesis by inducing the expression of VEGF,then enhances myocardial perfusion,and consequently alleviates CMD.

Gallbladder cancer is a highly aggressive malignancy of the biliary system, often diagnosed at the advanced stage due to its insidious early symptoms, leading to poor overall progno-sis. In recent years, the rapid advancement of artificial intelligence (AI) technologies and their inte-gration into medicine have opened new avenues for the early diagnosis and precision treatment of gallbladder cancer. Currently, AI incorporating deep learning algorithm has significantly improved diagnostic sensitivity and specificity in ultrasound, computed tomography, and pathological analysis. However, clinical translation of AI models remains limited by challenges such as insufficient annota-ted data and limited model interpretability. Future research should focus on establishing multi-center data-sharing mechanisms, developing interpretability tools, and optimizing multimodal data integration strategies, thereby promoting the transformation of AI technologies from an auxiliary diagnostic tool to a core component of clinical decision-making.

Gallbladder cancer is a highly aggressive malignancy of the biliary system, often diagnosed at the advanced stage due to its insidious early symptoms, leading to poor overall progno-sis. In recent years, the rapid advancement of artificial intelligence (AI) technologies and their inte-gration into medicine have opened new avenues for the early diagnosis and precision treatment of gallbladder cancer. Currently, AI incorporating deep learning algorithm has significantly improved diagnostic sensitivity and specificity in ultrasound, computed tomography, and pathological analysis. However, clinical translation of AI models remains limited by challenges such as insufficient annota-ted data and limited model interpretability. Future research should focus on establishing multi-center data-sharing mechanisms, developing interpretability tools, and optimizing multimodal data integration strategies, thereby promoting the transformation of AI technologies from an auxiliary diagnostic tool to a core component of clinical decision-making.

Objective:To investigate the regulatory mechanism of miR-29a-3p/ SGMS2 axis on the inflammatory response of ovarian granulosa cells (KGN). Methods:By constructing and validating overexpression and knockdown of miR-29a-3p and SGMS2 transfected KGN cell models, dual luciferase reporter gene assay was used to detect the binding of miR-29a-3p to SGMS2. MTT assay was used for detecting the cell proliferation. Fluorescence intensity of proliferating cell nuclear antigen (PCNA) and Ki67 protein were detected by immunofluorescence. Apoptosis was detected by flow cytometry. The expression levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β and sphingomyelin in cell supernatant were detected by enzyme-linked immunosorbent assay. The protein expression levels of Caspase-3, cleaved-Caspase-3, SGMS2 and p-p65 in KGN were detected by Western blotting. Results:miR-29a-3p had site-specific binding to SGMS2 and can negatively regulated SGMS2 expression level. Overexpression of SGMS2 in KGN cells was able to increase their levels of absorbance ( P=0.007) and enhanced the immunofluorescence intensity of the protein of PCNA and Ki67 (all P<0.001). Overexpression of SGMS2 could reduce the apoptosis rate of KGN cells ( P=0.001). Overexpression of SGMS2 increased the expression levels of TNF-α, IL-6, IL-1β and sphingomyelin (all P<0.001). The expressions of cleaved-Caspase-3, p-p65 and SGMS2 proteins were elevated in KGN cells when SGMS2 was overexpressed ( P=0.001, P<0.001, P<0.001), while knock down SGMS2, the above results had a trend of change opposite to overexpression of SGMS2. Conclusion:There is a targeted negative regulatory relationship between miR-29a-3p and SGMS2, which can promote the inflammatory response of KGN and may provide a target for the treatment of polycystic ovary syndrome.

Objective:To investigate the regulatory mechanism of miR-29a-3p/ SGMS2 axis on the inflammatory response of ovarian granulosa cells (KGN). Methods:By constructing and validating overexpression and knockdown of miR-29a-3p and SGMS2 transfected KGN cell models, dual luciferase reporter gene assay was used to detect the binding of miR-29a-3p to SGMS2. MTT assay was used for detecting the cell proliferation. Fluorescence intensity of proliferating cell nuclear antigen (PCNA) and Ki67 protein were detected by immunofluorescence. Apoptosis was detected by flow cytometry. The expression levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β and sphingomyelin in cell supernatant were detected by enzyme-linked immunosorbent assay. The protein expression levels of Caspase-3, cleaved-Caspase-3, SGMS2 and p-p65 in KGN were detected by Western blotting. Results:miR-29a-3p had site-specific binding to SGMS2 and can negatively regulated SGMS2 expression level. Overexpression of SGMS2 in KGN cells was able to increase their levels of absorbance ( P=0.007) and enhanced the immunofluorescence intensity of the protein of PCNA and Ki67 (all P<0.001). Overexpression of SGMS2 could reduce the apoptosis rate of KGN cells ( P=0.001). Overexpression of SGMS2 increased the expression levels of TNF-α, IL-6, IL-1β and sphingomyelin (all P<0.001). The expressions of cleaved-Caspase-3, p-p65 and SGMS2 proteins were elevated in KGN cells when SGMS2 was overexpressed ( P=0.001, P<0.001, P<0.001), while knock down SGMS2, the above results had a trend of change opposite to overexpression of SGMS2. Conclusion:There is a targeted negative regulatory relationship between miR-29a-3p and SGMS2, which can promote the inflammatory response of KGN and may provide a target for the treatment of polycystic ovary syndrome.