Colorectal cancer （CRC） is one of the most common cancers， with its incidence ranking high among cancers. It stands as the second leading cause of cancer-related death worldwide. In the early stages， CRC lacks specific symptoms， and most patients are diagnosed at advanced stages， making it a major research focus in the field of gastrointestinal tumors. Currently， clinical CRC treatments face several common challenges， including high surgical risks， frequent metastasis and recurrence， drug resistance， and significant side effects from chemotherapy and radiation therapy. With the development and application of traditional Chinese medicine （TCM）， it has been found that TCM and its active ingredients can effectively inhibit CRC cell proliferation， invasion， migration， and angiogenesis， and promote apoptosis and autophagy， thereby slowing the progression of CRC. This has become a key focus of CRC treatment research. Salvia Miltiorrhiza has multiple pharmacological effects， including activating blood circulation to dispel blood stasis， unlocking meridians to relieve pain， clearing heat to calm irritability， and cooling blood to reduce abscesses. It contains a variety of chemical components， including diterpenoids， phenolic acids， flavonoids， polysaccharides， nitrogen-containing compounds， steroids， and lactone compounds. This review summarized the molecular mechanisms of Salvia miltiorrhiza and its active ingredients in the treatment of CRC. It is found that these ingredients exert anti-CRC effects through various molecular mechanisms， including cell cycle arrest， promotion of apoptosis， inhibition of cell invasion and migration， induction of autophagy， suppression of tumor angiogenesis， and remodeling of the tumor microenvironment. The review aims to provide new insights for the drug development and clinical application of Salvia miltiorrhiza in CRC treatment.

[Objective]To explore the patterns of diagnosis and prescription in traditional Chinese medicine(TCM),specifically using Polygala tenuifolia Willd formulas,for the treatment of Alzheimer's disease(AD),grounded in the fundamental theories of TCM.[Methods]The medical case documents containing"Poly gala tenuifolia Willd formula for dementia"were included in China National Knowledge Infrastructure(CNKI),VIP,Wanfang and Gujin Medical Case Cloud Platform databases.Furthermore,an Excel 2019 database was created and subsequently standardized.The database was then mined for patterns related to the administration and utilization of medications,by utilizing the Gujin Medical Case Cloud Platform and the Python programming language.Following standardization,the drug application rules were explored by using the Ancient and Modern Medical Case Cloud Platform and Python.[Results]It employed the Ancient and Modern Medical Case Cloud Platform and Python following standardization.A total of 211 kinds of drugs were recorded in 165 medical records,with warm being the most prevalent,followed by neutral.These drugs were mainly sweet,pungent and bitter in taste,and the main effects of the drugs were attributed to the liver,heart,kidney,spleen and lung meridians,and most of the drugs that were paired with Poly gala tenuifolia Willd had functions of opening the orifices,inducing drainage and seepage of dampness,invigorating blood circulation,removing blood stasis and tonifying the deficiency.Acorus calamus and Poly gala tenuifolia Willd were the core pair of drugs with the common dosage of 10 g and 15 g respectively,and the proportion of the two was mostly 1︰1,2︰3.Acorus calamus-Poly gala tenuifolia Willd was often paired with Poria,commonly used pairs were Radix Rehmanniae Preparata-Cornu Cervi,Ligusticum Chuanxiong-Salviae Miltiorrhizae,the complex network analysis showed that the core composition of treating AD was the prescription of Kaixin Powder which removed ginseng but added with the participation of the Radix Rehmanniae Preparata,Salviae Miltiorrhizae,Ligusticum Chuanxiong and Glycyrrhiza glabra.[Conclusion]In this study,among the formulas containing Polygala tenuifolia Willd for AD,the highest correlation was found between Polygala tenuifolia Willd and Acorus calamus,which was mainly used to replenish deficiency and for diarrhea,and focused on strengthening the spleen,resolving dampness and expelling phlegm,regulating the liver and activating the blood,and benefiting the kidneys and filling in the marrow on the basis of tranquilizing the spirit and opening up the aperture to awaken the mind.The preliminary clarification of the medication law of the formulas containing Polygala tenuifolia Willd for the treatment of AD can provide a basis for the clinical use of medication and the development of new prescriptions.

OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.

OBJECTIVE To explore the intervention mechanism of Shangke Lengtongtie on cold hyperalgesia in KOA mice based on the HMGB1/CXCL12/CXCR4 signaling axis.METHODS Monosodium iodoacetate(MIA)was used for the intra-articular injec-tion into the knee joint to establish mice model of knee osteoarthritis(KOA).Peripheral blood monocytes were extracted from mice,cultured,and then reinfused into the tail vein of the mice.Subsequently,in vivo animal imaging was used to observe the recruitment sites of these monocytes.The cold hyperalgesia threshold was measured at various time points in each group of mice.Hematoxylin and eosin(HE)staining was used to evaluate the level of synovial pathological changes.ELISA was employed to detect the expression of in-flammatory factors IL-1β,TNF-α,and pain mediators CGRP and Substance P in mouse serum.Western blot and qPCR methods were used to detect the protein and gene expression of cold hyperalgesia-related indicators such as TRPA1,TRPM8,HMGB1,CXCL12,CXCR4,Collagen Ⅰ,and Netrin-1 in synovial tissue,as well as DCC in dorsal root ganglia(DRG)tissue.RESULTS In vivo ima-ging showed that after the monocytes were reinfused into KOA mice,they were recruited to the knee joint area,with the HMGB1 group exhibiting a greater recruitment of circulating monocytes at the knee joint.Additionally,compared to the control group,the KOA group and HMGB1 group showed inflammatory pathological changes in the synovium,increased expression of serum inflammatory factors and pain mediators,reduced cold hyperalgesia threshold,and upregulated protein and gene expression of cold hyperalgesia-related indica-tors in synovial and DRG tissues.The changes were more significant in the HMGB1 group compared to the KOA group(P<0.05).Af-ter treatment with Shangke Lengtongtie or GL intervention,synovial inflammation was alleviated,serum inflammatory factors and pain mediators decreased,cold hyperalgesia threshold increased,and the upregulation of cold hyperalgesia-related indicator protein and gene expression levels was significantly reversed(P<0.05).CONCLUSION Shangke Lengtongtie exerts a beneficial effect on the mitigation of synovitis and cold hyperalgesia in KOA mice,a therapeutic mechanism that possibly mediated through the inhibition of the HMGB1/CXCL12/CXCR4 signaling axis.

[Objective]To explore the patterns of diagnosis and prescription in traditional Chinese medicine(TCM),specifically using Polygala tenuifolia Willd formulas,for the treatment of Alzheimer's disease(AD),grounded in the fundamental theories of TCM.[Methods]The medical case documents containing"Poly gala tenuifolia Willd formula for dementia"were included in China National Knowledge Infrastructure(CNKI),VIP,Wanfang and Gujin Medical Case Cloud Platform databases.Furthermore,an Excel 2019 database was created and subsequently standardized.The database was then mined for patterns related to the administration and utilization of medications,by utilizing the Gujin Medical Case Cloud Platform and the Python programming language.Following standardization,the drug application rules were explored by using the Ancient and Modern Medical Case Cloud Platform and Python.[Results]It employed the Ancient and Modern Medical Case Cloud Platform and Python following standardization.A total of 211 kinds of drugs were recorded in 165 medical records,with warm being the most prevalent,followed by neutral.These drugs were mainly sweet,pungent and bitter in taste,and the main effects of the drugs were attributed to the liver,heart,kidney,spleen and lung meridians,and most of the drugs that were paired with Poly gala tenuifolia Willd had functions of opening the orifices,inducing drainage and seepage of dampness,invigorating blood circulation,removing blood stasis and tonifying the deficiency.Acorus calamus and Poly gala tenuifolia Willd were the core pair of drugs with the common dosage of 10 g and 15 g respectively,and the proportion of the two was mostly 1︰1,2︰3.Acorus calamus-Poly gala tenuifolia Willd was often paired with Poria,commonly used pairs were Radix Rehmanniae Preparata-Cornu Cervi,Ligusticum Chuanxiong-Salviae Miltiorrhizae,the complex network analysis showed that the core composition of treating AD was the prescription of Kaixin Powder which removed ginseng but added with the participation of the Radix Rehmanniae Preparata,Salviae Miltiorrhizae,Ligusticum Chuanxiong and Glycyrrhiza glabra.[Conclusion]In this study,among the formulas containing Polygala tenuifolia Willd for AD,the highest correlation was found between Polygala tenuifolia Willd and Acorus calamus,which was mainly used to replenish deficiency and for diarrhea,and focused on strengthening the spleen,resolving dampness and expelling phlegm,regulating the liver and activating the blood,and benefiting the kidneys and filling in the marrow on the basis of tranquilizing the spirit and opening up the aperture to awaken the mind.The preliminary clarification of the medication law of the formulas containing Polygala tenuifolia Willd for the treatment of AD can provide a basis for the clinical use of medication and the development of new prescriptions.

[Objective]To explore the clinical efficacy of Qingre Jiedu Decoction in the treatment of acute mastitis during lactation.[Methods]The clinical data of lactating mastitis patients who presented to the Galactophore Department of Beijing Hospital of Traditional Chinese Medicine,Capital Medical University from January 2019 to December 2020 were retrospectively analyzed.In the treatment group,80 patients received internal decoction;in control group,no decoction was taken.The severity index of mastitis,disease improvement rate,breast pain score,milk patency,nipple cracking condition and traditional Chinese medicine(TCM)systemic symptom score were observed.[Results]There were significant statistic differences in the severity index of mastitis,disease improvement rate,breast pain score,milk patency and TCM systemic symptoms scores(P＜0.05).The therapeutic effect of the treatment group was better than that of the control group.[Conclusion]Qingre Jiedu Decoction can effectively release pain,reduce the size of lumps,release swelling and milk stasis of lactation acute mastitis,and the curative effect is good.

BACKGROUND:Yougui Pill is a famous formula of the Chinese traditional medicine,which has good efficacy for lumbar disc herniation due to kidney yang insufficiency. OBJECTIVE:To investigate the potential targets and mechanism of action of Yougui Pill in the treatment of lumbar disc herniation by using network pharmacology and molecular docking technology,and verified by animal experiments. METHODS:(1)Network pharmacological analysis:We obtained the active ingredients and targets of Yougui Pill from TCMSP and other databases,collected genes related to lumbar disc herniation from GeneCards database,and took the intersection of the two for the topological analysis to derive the main active ingredients and core therapeutic targets.Gene ontology function analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis were performed using R software.(2)Molecular docking:Autodock and Pymol software were utilized for the prediction of molecular binding energy of TCM active ingredients to core therapeutic targets.(3)Animal experiments:Eighteen Sprague-Dawley rats were randomly divided into a control group,a degeneration group and a Yougui Pill group,with 6 rats in each group.A rat model of intervertebral disc degeneration was prepared by fiber puncture method in the degeneration and Yougui Pill groups.At 2 weeks after modeling,Yougui Pill was given by gavage in the Yougui Pill group,once a day for 2 consecutive weeks.The level of tumor necrosis factor-α in serum was detected by the ELISA method,and morphological changes of the annulus fibrosus and nucleus pulposus cells were observed using hematoxylin-eosin staining. RESULTS AND CONCLUSION:There were 90 active ingredients and 64 targets,and the main active ingredients were found to be quercetin,kaempferol,β-carotene,soybean flavonoid,and 4'-O-methylnyasol.The core targets of Yougui Pill for the treatment of lumbar disc herniation were interleukin 6,tumor necrosis factor-α,AKT1,interleukin 1B,and vascular endothelial growth factor A.Enrichment analysis revealed that the intersecting genes might be expressed through the interleukin-17 signaling pathway,tumor necrosis factor signaling pathway,MAPK signaling pathway,PI3K-AKT signaling pathway,and other signaling pathways to improve intervertebral disc degeneration.The molecular docking test verified that quercetin,kaempferol,and β-carotene had strong binding ability to the core targets.Animal experiments showed that the level of serum tumor necrosis factor α in the degeneration group was higher than that in the control group(P<0.05),and the level of serum tumor necrosis factor α in the Yougui Pill group was lower than that in the degeneration group(P<0.05).Hematoxylin-eosin staining showed that the fibrous annulus of the intervertebral discs and the structure of the nucleus pulposus in the degeneration group were destroyed,and the number of nucleus pulposus cells was reduced;there was a tendency to reconstructing the fibrous annulus of the intervertebral discs in the Yougui Pill group,and the number of nucleus pulposus cells increased compared with the degeneration group.To conclude,Yougui Pill may treat lumbar disc herniation by improving disc degeneration through the effects of quercetin,kaempferol,beta-carotene and other key active ingredients on core targets such as tumor necrosis factor.

Background and Aims:Kaempferol is a natural flavonoid compound that can regulate various processes and activities associated with cancer,such as the cell cycle,oxidative stress,apoptosis,proliferation,metastasis,and angiogenesis. Its potential for treating breast cancer has been validated in some studies,but its mechanism of action remains unclear. Therefore,this study was conducted to explore the potential targets and pathways of kaempferol in the treatment of breast cancer and establish a prognostic model.Methods:Using network pharmacology and bioinformatics approaches,the intersection targets of kaempferol for the treatment of breast cancer were obtained from databases such as HERB,GeneCards,STRING,PubChem,RCSB PDB,and TCGA. Protein interaction,GO analysis,and KEGG pathway enrichment analysis were performed,followed by molecular docking for validation. Prognostic-related genes were identified through LASSO-Cox regression analysis to establish a risk score model. The prognostic analysis for each gene,and the correlation between risk score and immune infiltration were analyzed. Results:Network pharmacology analysis identified 55 intersection targets. Protein interaction analysis revealed five potential key genes (Akt1,Bcl2,CASP3,ESR1,AR). GO analysis showed that kaempferol treatment of breast cancer involved 1604 biological process entries,20 cellular component entries,and 121 molecular function entries. KEGG pathway enrichment mainly included pathways related to chemical carcinogenesis,reactive oxygen species signaling,AGE-RAGE signaling in diabetic complications,TNF signaling,and IL-17 signaling. Molecular docking results indicated that kaempferol had a strong affinity for key targets,with the best binding effect observed with ESR1 (-9.1 kcal/mol). Ten prognostic genes (Bcl2,CYP1B1,DPP4,GSTM1,GSTM2,MMP1,NCOA2,NOS2,NR1I3,PTGS2) were obtained through LASSO-Cox regression analysis,and a risk score model was established. The AUC of this model for predicting breast cancer patient prognosis was greater than 0.5. Single-gene survival analysis indicated that higher expression of Bcl2 (HR=0.61,95％ CI=0.43-0.86,P=0.005),CYP1B1 (HR=0.68,95％ CI=0.49-0.94,P=0.022),GSTM1 (HR=0.68,95％ CI=0.47-0.98,P=0.037),GSTM2 (HR=0.64,95％ CI=0.46-0.90,P=0.010),and PTGS2 (HR=0.62,95％ CI=0.44-0.86,P=0.005) correlated with a higher overall survival (OS),while higher expression of MMP1 (HR=1.72,95％ CI=1.22-2.41,P=0.002),NCOA2 (HR=1.71,95％ CI=1.12-2.60,P=0.013),NOS2 (HR=1.67,95％ CI=1.20-2.32,P=0.002),and NR1I3 (HR=1.69,95％ CI=1.21-2.37,P=0.002) was associated with worse OS. The risk score was negatively correlated with the infiltration of T cells,CD8+T cells,myeloid dendritic cells,NK cells,and B cells,and positively correlated with monocyte/macrophage infiltration (all P<0.05).Conclusion:Kaempferol exerts therapeutic effects on breast cancer through multiple targets and pathways. The prognostic genes identified based on its related targets,along with the established prognostic model,can guide clinical treatment of breast cancer. The correlation between the prognostic model and immune infiltration provides direction for future experimental studies.

Background and Aims:Kaempferol is a natural flavonoid compound that can regulate various processes and activities associated with cancer,such as the cell cycle,oxidative stress,apoptosis,proliferation,metastasis,and angiogenesis. Its potential for treating breast cancer has been validated in some studies,but its mechanism of action remains unclear. Therefore,this study was conducted to explore the potential targets and pathways of kaempferol in the treatment of breast cancer and establish a prognostic model.Methods:Using network pharmacology and bioinformatics approaches,the intersection targets of kaempferol for the treatment of breast cancer were obtained from databases such as HERB,GeneCards,STRING,PubChem,RCSB PDB,and TCGA. Protein interaction,GO analysis,and KEGG pathway enrichment analysis were performed,followed by molecular docking for validation. Prognostic-related genes were identified through LASSO-Cox regression analysis to establish a risk score model. The prognostic analysis for each gene,and the correlation between risk score and immune infiltration were analyzed. Results:Network pharmacology analysis identified 55 intersection targets. Protein interaction analysis revealed five potential key genes (Akt1,Bcl2,CASP3,ESR1,AR). GO analysis showed that kaempferol treatment of breast cancer involved 1604 biological process entries,20 cellular component entries,and 121 molecular function entries. KEGG pathway enrichment mainly included pathways related to chemical carcinogenesis,reactive oxygen species signaling,AGE-RAGE signaling in diabetic complications,TNF signaling,and IL-17 signaling. Molecular docking results indicated that kaempferol had a strong affinity for key targets,with the best binding effect observed with ESR1 (-9.1 kcal/mol). Ten prognostic genes (Bcl2,CYP1B1,DPP4,GSTM1,GSTM2,MMP1,NCOA2,NOS2,NR1I3,PTGS2) were obtained through LASSO-Cox regression analysis,and a risk score model was established. The AUC of this model for predicting breast cancer patient prognosis was greater than 0.5. Single-gene survival analysis indicated that higher expression of Bcl2 (HR=0.61,95％ CI=0.43-0.86,P=0.005),CYP1B1 (HR=0.68,95％ CI=0.49-0.94,P=0.022),GSTM1 (HR=0.68,95％ CI=0.47-0.98,P=0.037),GSTM2 (HR=0.64,95％ CI=0.46-0.90,P=0.010),and PTGS2 (HR=0.62,95％ CI=0.44-0.86,P=0.005) correlated with a higher overall survival (OS),while higher expression of MMP1 (HR=1.72,95％ CI=1.22-2.41,P=0.002),NCOA2 (HR=1.71,95％ CI=1.12-2.60,P=0.013),NOS2 (HR=1.67,95％ CI=1.20-2.32,P=0.002),and NR1I3 (HR=1.69,95％ CI=1.21-2.37,P=0.002) was associated with worse OS. The risk score was negatively correlated with the infiltration of T cells,CD8+T cells,myeloid dendritic cells,NK cells,and B cells,and positively correlated with monocyte/macrophage infiltration (all P<0.05).Conclusion:Kaempferol exerts therapeutic effects on breast cancer through multiple targets and pathways. The prognostic genes identified based on its related targets,along with the established prognostic model,can guide clinical treatment of breast cancer. The correlation between the prognostic model and immune infiltration provides direction for future experimental studies.

A transcriptional regulatory network for wild-type and ATP7B-knockout HepG2 cells exposed to copper was constructed by bioinformatics methods to explore the potential mechanism of key transcription factors in the pathogenesis of hepatolenticular degeneration. The differentially expressed genes (DEGs) for wild-type and ATP7B-knockout HepG2 cell lines without copper and exposed to copper were collected from the gene expression omnibus (GEO) database. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were performed for DEGs induced by copper. The key functional modules and genes were identified based on the protein-protein interaction (PPI) network. Moreover, the enrichment analysis of genes in functional modules was performed. Finally, a transcriptional regulatory network was constructed to screen the core transcription factors. A total of 1 034 genes, including 509 down-regulated genes and 525 up-regulated genes, were selected as DEGs. The up-regulated and down-regulated functional modules based on PPI network included 3 785 and 3 931 genes, respectively. Genes in key functional modules were enriched in cell-substrate junction, chromosomal region, spliceosomal complex and ribosome. They were involved in mRNA processing, histone modification, RNA splicing, regulation of DNA metabolic process, protein phosphorylation and other biological processes. Moreover, they were correlated to transcriptional coregulator activity, DNA-binding transcription factor binding, ubiquitin-like protein ligase binding and other molecular functions. KEGG analysis showed that genes in key functional modules were significantly enriched in hepatitis B, MAPK signaling pathway, cellular senescence and apoptosis, neurotrophin signaling pathway and pathways of neurodegeneration-multiple diseases. The transcriptional regulatory network contained 11 differentially expressed transcription factors and 96 DEGs. Among them, U2AF1, NFRKB, FUS, MAX, SRSF1, CEBPA and RXRA were the core transcription factors, which may facilitate the study of the biological function of relevant molecules in transcriptional regulation of hepatolenticular degeneration.
Humans ; Transcriptome ; Gene Expression Profiling/methods* ; Hepatolenticular Degeneration/genetics* ; Copper ; Gene Regulatory Networks ; Computational Biology/methods* ; Transcription Factors/genetics* ; DNA ; DNA-Binding Proteins/genetics* ; Serine-Arginine Splicing Factors/genetics*