OBJECTIVE To investigate the metabolic differences in roots， stems and leaves of Angelica dahurica （Fisch.ex Hoffm.） Benth. et Hook. f. ex Franch. et Savat. （shortened for A. dahurica ）， and to provide a basis for the development and utilization of its medicinal resources. METHODS UPLC-MS/MS untargeted metabolomics technology was employed to detect metabolites in roots， stems and leaves of A. dahurica . Multivariate statistical analysis was used to screen differential metabolites and perform cluster analysis. Furthermore， Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was conducted on these differential metabolites. RESULTS A total of 769 metabolites were identified in roots， stems and leaves of A. dahurica . Among t hem， lipids， alkaloids， amino acids and their derivatives accounted for the highest proportion， which accounted for 14.31%， 13.91% and 13.65%， respectively， and the coumarin compounds accounted for 3.25%. Results of principal component analysis， orthogonal partial least squares-discriminant analysis and cluster analysis indicated that there were certain differences in metabolites among the three tissues. A total of 205 differential metabolites were identified between stems and roots （82 up-regulated and 123 down-regulated）， 326 differential metabolites between leaves and roots （247 up-regulated and 79 down-regulated）， and 293 differential metabolites between the leaves and stems （263 up-regulated and 30 down-regulated）. Further analysis of the differential coumarin metabolites in different plant parts revealed that several compounds， including （ R ）-oxypeucedanin， 4-hydroxycoumarin， 4-methylumbelliferyl acetate， exhibited relatively high contents in the leaves. KEGG pathway enrichment analysis indicated that differential metabolites predominantly accumulated in the phenylpropanoid biosynthesis and ABC transporter pathways. CONCLUSIONS There are significant differences in metabolites among roots， stems and leaves of A. dahurica . Coumarin compounds are highly enriched in the leaves， and their synthesis and transport may be related to the synergistic effect of the phenylpropanoid biosynthesis pathway and the ABC transporter pathway.

To summarise the clinical experience of Professor TONG Xiaolin in treating prediabetes combined with overweight or obesity using the method of relieving depression and reducing turbidity. It is believed that prediabetes belongs to the category of "spleen-heat syndrome" in traditional Chinese medicine， and its core pathogenesis is center fullness with internal heat， while obesity is the initiating factor for exacerbating center fullness and internal heat， therefore， it is of great significance to reduce the risk of diabetes by interrupting the transformation between overweight， obesity and glucose metabolism abnormality. It is proposed that the main pathogenesis of prediabetes combined with overweight or obesity is qi depression and turbidity obstruction in middle jiao， with qi depression as the root and turbidity obstruction as the cause， forming a treatment idea with the method of relieving depression and reducing turbidity as the core. In clinic， Dahuang Huanglian Xiexin Decoction （大黄黄连泻心汤） is used as the basic prescription， with a primary focus on directing the turbid downward， supplemented by regulating qi， which embodies the concept of "promoting movement through descent， then figuring out the root of spleen-heat syndrome. Furthermore， the treatment is flexibly modified based on the patient's deficiency-excess syndrome to ensure individualized therapy.

The occurrence of diabetes mellitus （DM） is closely related to insulin resistance and islet β cell dysfunction. Modern studies have found that macrophages are widely present in the liver，fat，skeletal muscle，islets， and other tissues and organs. Macrophage M1/M2 polarization plays an important role in the occurrence and development of diabetes mellitus and its related complications by intervening in inflammatory response，improving insulin resistance，and promoting tissue repair. Most of the traditional Chinese medicines that regulate the activation and polarization of macrophages are Qi-replenishing and Yin-nourishing，heat-clearing， and detoxicating medicinal，which are consistent with the etiology and pathogenesis of diabetes and its related complications. Therefore，by summarizing the mechanisms between macrophage activation，polarization， and insulin resistance in various tissues，this paper reviewed traditional Chinese medicine and its effective components and compounds in improving diabetes mellitus and its related complications through multi-channel regulation of macrophage polarization and regulation of M1/M2 ratio，providing references for the future treatment of DM and its related complications with traditional Chinese medicine.

Purpose This study aims to explore the effect of peroxisomal membrane protein 4(PXMP4)on the migration and invasion of cervical cancer(CC)cells,as well as the epithelial-mesenchymal transition(EMT)process.Methods Bioinformatics and immunohistochemical analysis were employed to examine the expression of PXMP4 in CC tissues and its correlation with clinical pathological characteristics.Western blot and RT-qPCR were used to detect the expression of PXMP4 in CC cells.CCK-8 assay,scratch healing assay,and Transwell invasion assay were utilized to assess the proliferation,migration,and invasion capabilities of CC cells.Western blot was conducted to measure the expression of N-cadherin,E-cadherin,vimentin,phosphorylated ERK(p-ERK),and total ERK proteins in cervical CC.Results The TCGA database showed that the mRNA expression level of PXMP4 was significantly elevated in non-paired CC tissues(P=0.000 29),while the GEO database showed that the mRNA expression level of PXMP4 was sig-nificantly elevated in paired CC tissues(P=0.02).Immunohistochemical analysis showed that PXMP4 was primarily localized in the cytoplasm and cell membrane,with a positive rate of 70.31％(45/64)in CC tissues,significantly higher than 29.69％(19/64)in adjacent tissues.Clinical pathological analysis found that PXMP4 expression was as-sociated with maximum tumor differentiation(P=0.000 328)and lymph node metastasis(P=0.000 226),but not with age(P=0.637)or tumor diameter(P=0.304).CCK-8 assay,wound healing assay,and Transwell invasion as-say demonstrated that interference with PXMP4 inhibited the proliferation,invasion,and migration of CC cells,while overexpression of PXMP4 promoted these processes.Western blot results indicated that interference with PXMP4 signif-icantly increased E-cadherin expression and decreased N-cadherin,vimentin,and p-ERK expression(P＜0.05).Conversely,overexpression of PXMP4 led to a significant decrease in E-cadherin and an increase in N-cadherin,vim-entin,and p-ERK expression(P＜0.05).Additionally,stimulation of CC cells with different concentrations of the U0126 inhibitor significantly increased E-cadherin expression and decreased N-cadherin,vimentin,and p-ERK expres-sion(P＜0.05).Conclusion PXMP4 is highly expressed in CC tissues and is closely related to tumor differentiation and lymph node metastasis.PXMP4 promotes the EMT process of CC cells through the phosphorylated ERK1/2 signa-ling pathway.

OBJECTIVE To study and analyse the main components of Tongluo Muzu Powder transdermal absorption solution,as well as to investigate its mechanism of action in the treatment of osteoarthritis of the knee.METHODS The transdermal absorption solution of Tongluo Muzu Powder was extracted by Franz vertical diffusion cell,and its components were analyzed by UHPLC-MS/MS.Then TCMSP,Swiss target prediction,Gene Cards and other databases were introduced to predict the possible targets of the effec-tive components of transdermal absorption solution for the prevention and treatment of knee osteoarthritis,and Cytoscape software was used to construct the"drug-component-disease-target"visual network,and then the protein interaction network was obtained through the string database to find the core targets.Finally,AutoDock and PyMOL were used to verify the molecular docking of main active in-gredients and targets,and the gene ontology(GO)function analysis of core genes and the enrichment analysis of Kyoto Encyclopedia of genes and genomes(KEGG)pathway were conducted.Primary mouse chondrocytes were extracted,and the predicted targets of net-work pharmacology were verified by ELISA,Western blot,qPCR,etc.RESULTS A total of 48 effective components of the transder-mal absorption solution of Tongluo Muzu Powder and 88 possible targets for the treatment of knee osteoarthritis were screened out.The results of enrichment analysis showed that it was mainly involved in the process of apoptosis and oxidative stress.Molecular docking suggested that the main active ingredients and targets had good binding ability.The results showed that the lyophilized powder of the transdermal absorption solution of Tongluo Muzu Powder could reduce the concentration of inflammatory factors in the supernatant of chondrocytes after LPS intervention in a dose-dependent manner(P<0.05,P<0.01).The protein expression of p-PI3K/PI3K,p-AKT/AKT,MMP13 and p53 was decreased,and the protein expression of collagen Ⅱ was increased(P<0.05,P<0.01).At the same time,the mRNA expression of MMP13 and p53 was decreased and the mRNA expression of collagen Ⅱ was increased(P<0.05,P<0.01).In addition,it reduced the fluorescence intensity of TUNEL staining in cells(P<0.01).CONCLUSION By combining UH-PLC-MS/MS technology with network pharmacology,the main active ingredients of Tongluo Muzu Powder transdermal absorption solu-tion are preliminarily understood,and its potential mechanism of action in the treatment of knee osteoarthritis are predicted.