1.Mechanism of Paeoniflorin Regulating TLR4/NF-κB-IRS1 Inflammation-insulin Signaling Axis to Improve Metabolic Dysfunction Associated Fatty Liver Disease Combined with Insulin Resistance
Luyu LI ; Yiming FAN ; Wenlong YU ; Yiteng ZHANG ; Yaorui HU ; Huanxin DING ; Chuxuan LIU ; Xin JIN ; Hongyu ZHANG ; Qian XU ; Guangyong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):146-156
ObjectiveTo investigate the therapeutic effect of paeoniflorin on metabolic dysfunction-associated fatty liver disease (MASLD) combined with insulin resistance (IR), and to elucidate its regulatory mechanisms on the Toll-like receptor 4 (TLR4)/nuclear transcription factor (NF)-κB-insulin receptor substrate 1 (IRS1) inflammation-insulin signaling axis. MethodsMASLD mouse model was established using a 60% high-fat diet. Mice were randomly assigned to a normal control group, a MASLD model group, and paeoniflorin groups (low dose: 25 mg·kg-1·d-1, medium dose: 50 mg·kg-1·d-1, high dose: 100 mg·kg-1·d-1), receiving intragastric administration for consecutive 12 weeks. Concurrently, a palmitic acid/oleic acid (PA/OA)-induced lipid deposition model was established in HepG2 cells. Cell counting kit-8 (CCK-8) assay was performed to determine the optimal concentrations of PA/OA and paeoniflorin for intervention. Mice body weight, liver index, and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), and total cholesterol (TC) were measured. Fasting blood glucose (FBG) and fasting insulin (FINS) levels were measured, and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated, while an oral glucose tolerance test (OGTT) was performed to evaluate glucose metabolism. Hematoxylin and eosin (HE) staining was used to observe pathological changes and inflammatory cell infiltration in liver tissue, and oil red O staining was used to evaluate lipid droplet deposition in liver tissue and HepG2 cells. Potential targets were screened using network pharmacology and molecular docking. Western blot analysis was performed to detect the expression of HSP90AA1, TLR4, p-NF-κB p65, p-IRS1, and p-Akt proteins in liver tissue and HepG2 cells. ResultsCompared with the normal control group, mice in the MASLD model group exhibited significantly increased body weight, liver index, and serum levels of ALT, AST, TG, and TC, as well as markedly elevated FBG, FINS, and HOMA-IR, and impaired glucose tolerance (P<0.01). HE staining revealed marked hepatic steatosis and inflammatory cell infiltration, while oil red O staining showed a significant increase in lipid droplet deposition. Compared with the MASLD model group, after intervention with various doses of paeoniflorin, the increase in body weight and liver index was reduced, serum ALT, AST, TG, and TC levels decreased, and FBG, FINS, and HOMA-IR were significantly lowered, with glucose tolerance markedly improved (P<0.05, P<0.01), showing a certain dose-dependent trend. HE and oil red O staining results showed a marked reduction in hepatic steatosis and lipid deposition. In vitro experiments demonstrated that, compared with the control group, PA/OA treatment significantly induced increased lipid deposition in HepG2 cells. Compared with the model group, paeoniflorin intervention significantly reduced intracellular lipid droplets, and lipid deposition showed a dose-dependent decreasing trend. Mechanism studies indicated that, compared with the normal control group, the MASLD model group exhibited significantly elevated expression of TLR4, HSP90AA1, and p-NF-κB p65, while p-IRS1 (Ser307) expression was elevated and p-Akt (Ser473) expression was reduced (P<0.01). Compared with the model group, the expression of the aforementioned proteins was significantly reversed in all treatment groups following intervention (P<0.05, P<0.01). ConclusionPaeoniflorin significantly alleviates lipid deposition and insulin resistance in MASLD mice. Its mechanism of action may involve targeting HSP90AA1, TLR4, and NF-κB1 to regulate the TLR4/NF-κB-IRS1 inflammation-insulin signaling axis. This regulation suppresses inflammatory responses and restores insulin signaling, thereby ameliorating abnormalities in glucose and lipid metabolism.
2.Mechanism of Paeoniflorin Regulating TLR4/NF-κB-IRS1 Inflammation-insulin Signaling Axis to Improve Metabolic Dysfunction Associated Fatty Liver Disease Combined with Insulin Resistance
Luyu LI ; Yiming FAN ; Wenlong YU ; Yiteng ZHANG ; Yaorui HU ; Huanxin DING ; Chuxuan LIU ; Xin JIN ; Hongyu ZHANG ; Qian XU ; Guangyong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(21):146-156
ObjectiveTo investigate the therapeutic effect of paeoniflorin on metabolic dysfunction-associated fatty liver disease (MASLD) combined with insulin resistance (IR), and to elucidate its regulatory mechanisms on the Toll-like receptor 4 (TLR4)/nuclear transcription factor (NF)-κB-insulin receptor substrate 1 (IRS1) inflammation-insulin signaling axis. MethodsMASLD mouse model was established using a 60% high-fat diet. Mice were randomly assigned to a normal control group, a MASLD model group, and paeoniflorin groups (low dose: 25 mg·kg-1·d-1, medium dose: 50 mg·kg-1·d-1, high dose: 100 mg·kg-1·d-1), receiving intragastric administration for consecutive 12 weeks. Concurrently, a palmitic acid/oleic acid (PA/OA)-induced lipid deposition model was established in HepG2 cells. Cell counting kit-8 (CCK-8) assay was performed to determine the optimal concentrations of PA/OA and paeoniflorin for intervention. Mice body weight, liver index, and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), and total cholesterol (TC) were measured. Fasting blood glucose (FBG) and fasting insulin (FINS) levels were measured, and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated, while an oral glucose tolerance test (OGTT) was performed to evaluate glucose metabolism. Hematoxylin and eosin (HE) staining was used to observe pathological changes and inflammatory cell infiltration in liver tissue, and oil red O staining was used to evaluate lipid droplet deposition in liver tissue and HepG2 cells. Potential targets were screened using network pharmacology and molecular docking. Western blot analysis was performed to detect the expression of HSP90AA1, TLR4, p-NF-κB p65, p-IRS1, and p-Akt proteins in liver tissue and HepG2 cells. ResultsCompared with the normal control group, mice in the MASLD model group exhibited significantly increased body weight, liver index, and serum levels of ALT, AST, TG, and TC, as well as markedly elevated FBG, FINS, and HOMA-IR, and impaired glucose tolerance (P<0.01). HE staining revealed marked hepatic steatosis and inflammatory cell infiltration, while oil red O staining showed a significant increase in lipid droplet deposition. Compared with the MASLD model group, after intervention with various doses of paeoniflorin, the increase in body weight and liver index was reduced, serum ALT, AST, TG, and TC levels decreased, and FBG, FINS, and HOMA-IR were significantly lowered, with glucose tolerance markedly improved (P<0.05, P<0.01), showing a certain dose-dependent trend. HE and oil red O staining results showed a marked reduction in hepatic steatosis and lipid deposition. In vitro experiments demonstrated that, compared with the control group, PA/OA treatment significantly induced increased lipid deposition in HepG2 cells. Compared with the model group, paeoniflorin intervention significantly reduced intracellular lipid droplets, and lipid deposition showed a dose-dependent decreasing trend. Mechanism studies indicated that, compared with the normal control group, the MASLD model group exhibited significantly elevated expression of TLR4, HSP90AA1, and p-NF-κB p65, while p-IRS1 (Ser307) expression was elevated and p-Akt (Ser473) expression was reduced (P<0.01). Compared with the model group, the expression of the aforementioned proteins was significantly reversed in all treatment groups following intervention (P<0.05, P<0.01). ConclusionPaeoniflorin significantly alleviates lipid deposition and insulin resistance in MASLD mice. Its mechanism of action may involve targeting HSP90AA1, TLR4, and NF-κB1 to regulate the TLR4/NF-κB-IRS1 inflammation-insulin signaling axis. This regulation suppresses inflammatory responses and restores insulin signaling, thereby ameliorating abnormalities in glucose and lipid metabolism.
3.Mining molecular biomarkers regulating the occurrence of kidney renal clear cell carcinoma based on bioinformatics methods
Feng GUO ; Chenyu WANG ; Zhenfeng SHI ; Jianhua ZHAO ; Wenlong FAN ; Kadeer AIHEMAITI ; Zecheng NI
Journal of Modern Urology 2025;30(3):215-222
Objective: To identify biomolecular markers closely related to the occurrence of kidney renal clear cell carcinoma (KIRC) and verify their expression levels in clinical samples. Methods: Stage Ⅰ KIRC mRNA sequencing data were obtained from The Cancer Genome Atlas (TCGA).Principal component analysis (PCA) was used for dimensionality reduction to screen differentially expressed genes (DEGs),which then underwent GO and KEGG analyses.Weighted gene co-expression network analysis (WGCNA) was used to screen genes significantly related to KIRC,and a protein-protein interaction (PPI) network was constructed to screen hub genes.The diagnostic value of hub genes was evaluated with receiver operating characteristic (ROC) curve,and their prognostic value was analyzed using survival curve plots.The correlation between the mRNA expressions of hub genes and the pathological stages of KIRC was analyzed.Clinical samples of 20 patients with stage Ⅰ KIRC treated in our hospital were included,and the expressions of the hub genes in cancerous and adjacent tissues were detected with reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR),Western blotting,and enzyme-linked immunosorbent assay (ELISA). Results: A total of 8223 DEGs were screened out,including 4092 up-regulated ones and 4131 down-regulated ones.GO analysis showed that DEGs were related to bioadhesion,plasma membrane composition,and transporter activity.KEGG analysis showed that DEGs were related to pathways such as cell adhesion molecules,cytokine-cytokine receptor interactions,and interactions between viral proteins and cytokines and cytokine receptors.WGCNA analysis obtained 171 genes that were significantly related to stage Ⅰ KIRC.The hub gene,lymphocyte cytosolic protein 2 (LCP2),screened out by the PPI network,was significantly related to stage Ⅰ KIRC.The area under the ROC curve was 0.96.The expression level was negatively correlated with the overall survival rate of patients.The expression of LCP2 was related to the stage and lymph node metastasis.Clinical verification showed that the mRNA and protein relative expressions of LCP2 in KIRC tissues were significantly higher than those in adjacent tissues (P<0.000 1). Conclusion: LCP2 is significantly up-regulated in stage Ⅰ KIRC tissues and can be used as a potential biomarker for the early diagnosis and treatment of KIRC.
4.Measurement and analysis of radiation doses received by the human body and radiation levels in the CT room under digital miniature CT scanning conditions
Lin YIN ; Zhenhua YANG ; Yaqi XI ; Wenlong FAN ; Rui YANG ; Qisheng XIA ; Qiaoling WU
Chinese Journal of Radiological Health 2025;34(3):373-377
Objective To evaluate the radiation impact of a self-developed digital miniature CT on the human body and the environment under simulated scanning conditions, and verify its safety and regulatory compliance. Methods Under typical head scanning conditions with the digital miniature CT (70 kV/10 mA), the equivalent doses received at the body surface sites corresponding to the thyroid, breast, stomach, liver, kidney, and gonads of the phantom were measured without protection and with 0.5 mmPb equivalent protection using LiF (Mg, Cu, P) thermoluminescent dosimeters. The ambient dose equivalent rates at the bed level inside the CT room at different directions and distances from the scanning center were measured using a model AT1121 X/γ dosimeter. The equivalent doses of organs on both sides of the phantom and the ambient equivalent dose rates on the left and right sides of the longitudinal axis of the bed in the CT room were compared. The Mann-Whitney test was used at a significance level of P < 0.05. Results During a single scan of the head with the digital miniature CT, the equivalent doses at the body surface sites corresponding to the thyroid, breast, stomach, liver, kidney, and gonads without protection were 1.04, 0.95, 0.55, 0.57, 0.40, and 0.12 mSv, respectively, which were only 0.84% to 8.24% of the doses inside the irradiation field. With 0.5 mm Pb equivalent protection, the equivalent dose of the thyroid decreased from 8.24 mSv to 3.27 mSv with a reduction of 60.3%, and the doses of the other organs were reduced to 1.5-11.5 μSv with the maximum reduction of 14 times. In the longitudinal axis direction of the CT bed, the ambient dose equivalent rate at a distance of 2 m from the scanning center was reduced to 0.066 mSv/h, which was only 9.6% of the ambient equivalent dose rate at a distance of 50 cm from the scanning center. Conclusion The digital miniature CT has advantages in ensuring patient safety, optimizing imaging quality, and promoting technological development, demonstrating promising application potential. However, the radiation protection of personal and CT room should not be ignored.
5.Synergistic diagnostic potential of novel biomarkers SYWC and ADA for tuberculous pleural effusion
Chunhong FAN ; Wenlong HU ; Limei ZHU ; Ruifu YANG ; Daxia CAI ; Shaohua LU ; Xingdong CAI
The Journal of Practical Medicine 2025;41(15):2406-2411
Objective To evaluate the respective or synergistic value of cytoplasmic tryptophan-tRNA ligase(WARS1/SYWC)and adenosine deaminase(ADA)in diagnosing tuberculous pleural effusion(TPE).Methods A retrospective analysis was conducted on 120 patients with pleural effusion(64 cases of TPE,56 cases of non-TPE)admitted to the First Affiliated Hospital of Jinan University and its affiliated Shunde Hospital from January 2020 to December 2024.Pleural fluid SYWC levels were identified using enzyme-linked immunosorbent assay(ELISA).Univariate and multivariate logistic regression analyses were performed to identify diagnostic predictors,while receiver operating characteristic(ROC)curves were plotted to assess the diagnostic perfor-mance of individual and combined biomarkers.Results Compared to the non-TPE group,TPE group exhibited significantly younger age,lower pleural CEA,less serum CEA,and lower neutrophil-to-lymphocyte ratio(NLR),but significantly higher levels of pleural ADA,total protein,SYWC,and serum CRP(all P<0.05).Univariate analysis identified age,pleural CEA,carbohydrate antigen 199,ADA,SYWC,serum CEA,and NLR as potential predictors.Multivariate analysis confirmed pleural ADA(OR=1.064,95%CI:1.017~1.228)and SYWC(OR=6.695,95%CI:2.794~16.04)as independent diagnostic factors.At optimal cutoffs,SYWC(16.94 μg/L)demonstrated a sensitivity of 71.80%and specificity of 98.21%,while ADA(36.5 U/L)showed a sensitivity of 93.75%and a specificity of 89.29%.Combined detection increased the sensitivity to 95.56%,the specificity to 98.0%,and the accuracy to 97.87%.ROC analysis revealed an AUC of 0.973(95%CI:0.943~1.000)for the combination,outperforming ADA(0.897)and SYWC(0.938)alone.Conclusion The combi-nation of SYWC and ADA notably enhances diagnostic efficacy for TPE,providing high sensitivity and specificity as a reliable tool for clinical differentiation.
6.Geometric triangle relationship between Blumensaat line and tibial plateau may be an auxiliary indicator for diagnosing and evaluating anterior cruciate ligament injuries
Xiao FAN ; Wenlong XU ; Zichao XUE ; Tengbo YU
The Journal of Practical Medicine 2025;41(6):818-823
Objective To investigate whether the geometric triangular relationship between the Blumensaat line and the tibial plateau can serve as an auxiliary diagnostic index for identifying and evaluating anterior cruciate ligament(ACL)injuries,thereby enhancing diagnostic accuracy.Methods A retrospective self-controlled study was conducted involving 64 patients diagnosed with unilateral ACL injury via arthroscopy and treated with ACL reconstruction at Qingdao Municipal Hospital from January to August 2023.Ultimately,40 cases were included in the analysis.Preoperative MRI images of the affected knees and contralateral healthy knees were collected as the ACL injury group and control group,respectively.In the MRI images,point C,point D,and point E were defined as the anterior end,posterior end,and midpoint of the Blumensaat line,respectively;point A and point B were defined as the turning points of the anterior and posterior edges of the tibial plateau,respectively;and point C'was defined as the intersection of the extension line of DC and line AB.Based on these anatomical landmarks,angles ∠DAB,∠CEB,∠DC'B,and ∠CDB were established.The intra-class correlation coefficient(ICC)was calculated to assess measurement consistency and reproducibility.Differences between the aforementioned angles were compared,and the area under the receiver operating characteristic(ROC)curve was computed to evaluate diagnostic performance.Results For ∠CDB,∠DC'B,∠CEB,and ∠DAB,the intra-group and inter-group correlation coefficients all exceeded 0.80,indicating excellent consistency and reproducibility.Compared to the control group,the angles ∠CDB,∠CEB,and ∠DAB in the ACL injury group were significantly reduced(P<0.001).Among these,∠DAB appears to be the most reliable index for diagnosing and evaluating ACL injuries,with an area under the receiver operating characteristic curve(AUC)of 0.829,a cut-off value of 42.2°,a sensitivity of 82.5%,and a specificity of 80.0%.Conclusion The geometric triangular relationship between the Blumensaat line and the tibial plateau in MRI images,particularly the angle ∠DAB,can serve as an auxiliary indicator for diagnosing and evaluating ACL injuries,thereby enhancing diagnostic accuracy.
7.Synergistic diagnostic potential of novel biomarkers SYWC and ADA for tuberculous pleural effusion
Chunhong FAN ; Wenlong HU ; Limei ZHU ; Ruifu YANG ; Daxia CAI ; Shaohua LU ; Xingdong CAI
The Journal of Practical Medicine 2025;41(15):2406-2411
Objective To evaluate the respective or synergistic value of cytoplasmic tryptophan-tRNA ligase(WARS1/SYWC)and adenosine deaminase(ADA)in diagnosing tuberculous pleural effusion(TPE).Methods A retrospective analysis was conducted on 120 patients with pleural effusion(64 cases of TPE,56 cases of non-TPE)admitted to the First Affiliated Hospital of Jinan University and its affiliated Shunde Hospital from January 2020 to December 2024.Pleural fluid SYWC levels were identified using enzyme-linked immunosorbent assay(ELISA).Univariate and multivariate logistic regression analyses were performed to identify diagnostic predictors,while receiver operating characteristic(ROC)curves were plotted to assess the diagnostic perfor-mance of individual and combined biomarkers.Results Compared to the non-TPE group,TPE group exhibited significantly younger age,lower pleural CEA,less serum CEA,and lower neutrophil-to-lymphocyte ratio(NLR),but significantly higher levels of pleural ADA,total protein,SYWC,and serum CRP(all P<0.05).Univariate analysis identified age,pleural CEA,carbohydrate antigen 199,ADA,SYWC,serum CEA,and NLR as potential predictors.Multivariate analysis confirmed pleural ADA(OR=1.064,95%CI:1.017~1.228)and SYWC(OR=6.695,95%CI:2.794~16.04)as independent diagnostic factors.At optimal cutoffs,SYWC(16.94 μg/L)demonstrated a sensitivity of 71.80%and specificity of 98.21%,while ADA(36.5 U/L)showed a sensitivity of 93.75%and a specificity of 89.29%.Combined detection increased the sensitivity to 95.56%,the specificity to 98.0%,and the accuracy to 97.87%.ROC analysis revealed an AUC of 0.973(95%CI:0.943~1.000)for the combination,outperforming ADA(0.897)and SYWC(0.938)alone.Conclusion The combi-nation of SYWC and ADA notably enhances diagnostic efficacy for TPE,providing high sensitivity and specificity as a reliable tool for clinical differentiation.
8.Analysis of immune infiltration mechanism of dermatomyositis and prediction of therapeutic targets of traditional Chinese medicine based on CIBERSORT algorithm
Pu WANG ; Min HU ; Suyue PAN ; Qiao HUANG ; Dongyu CHEN ; Wenlong FAN ; Xiaoyu YANG ; Hong-xin WANG ; Yuqing HE
Chinese Journal of Immunology 2025;41(4):783-791,中插1
Objective:To analyze the gene chip related to dermatomyositis based on bioinformatics,to explore the immune in-filtration mechanism of key genes in dermatomyositis by CIBERSORT deconvolution algorithm,and to predict the therapeutic targets of dermatomyositis by network pharmacology.Methods:The gene microarray of dermatomyositis was searched in GEO database,and the differentially coexpressed genes were screened and analyzed.The differentially coexpressed genes were analyzed by GO analysis,KEGG analysis,protein interaction network construction(PPI)by R software package.Verify the expression levels of key genes,and the correlation of immune cell infiltration was analyzed by CIBERSORT deconvolution method.Through the medical ontology informa-tion retrieval platform Coremine medical database,the traditional Chinese medicine treatment targets of dermatomyositis were screened and summarized.Results:A total of 196 differentially expressed genes were screened.GO enrichment analysis showed that these differentially expressed genes were mainly concentrated in defense response to virus,blood particles,double-stranded RNA binding,polypeptide antigen binding,and so on.KEGG enrichment analysis showed that it was enriched in RIG-Ⅰ-like receptor sig-nal pathway,Toll-like receptor signal pathway and other signal pathways related to the pathogenesis of dermatomyositis.Finally,four key genes of dermatomyositis,STAT1,ISG15,IRF7 and IRF9 were obtained.Through CIBERSORT algorithm,M1 macrophages,M2 macrophages and CD8+T cells were the three kinds of cells with the highest average proportion and the most obvious immune infil-tration,and there was a significant positive correlation between activated natural killer cells and activated dendritic cells,while there was a significant negative correlation between resting mast cells and activated mast cells.The therapeutic targets of traditional Chinese medicine such as fish brain stone were predicted based on Coremine medical database;through channel analysis,it could be found that these traditional Chinese medicines are mainly attributed to liver meridian,lung meridian,spleen meridian;efficacy analysis is mainly focused on clearing heat,detoxification,promoting blood circulation and removing blood stasis,relieving cough and resolving phlegm and so on.Conclusion:Four key genes and some key signal pathways of dermatomyositis,STAT1,ISG15,IRF7 and IRF9 were obtained by bioinformatics method,the immune infiltration mechanism was analyzed by CIBERSORT algorithm,and the thera-peutic potential targets of traditional Chinese medicine were screened out to provide direction for the pathogenesis and treatment of der-matomyositis.
9.Geometric triangle relationship between Blumensaat line and tibial plateau may be an auxiliary indicator for diagnosing and evaluating anterior cruciate ligament injuries
Xiao FAN ; Wenlong XU ; Zichao XUE ; Tengbo YU
The Journal of Practical Medicine 2025;41(6):818-823
Objective To investigate whether the geometric triangular relationship between the Blumensaat line and the tibial plateau can serve as an auxiliary diagnostic index for identifying and evaluating anterior cruciate ligament(ACL)injuries,thereby enhancing diagnostic accuracy.Methods A retrospective self-controlled study was conducted involving 64 patients diagnosed with unilateral ACL injury via arthroscopy and treated with ACL reconstruction at Qingdao Municipal Hospital from January to August 2023.Ultimately,40 cases were included in the analysis.Preoperative MRI images of the affected knees and contralateral healthy knees were collected as the ACL injury group and control group,respectively.In the MRI images,point C,point D,and point E were defined as the anterior end,posterior end,and midpoint of the Blumensaat line,respectively;point A and point B were defined as the turning points of the anterior and posterior edges of the tibial plateau,respectively;and point C'was defined as the intersection of the extension line of DC and line AB.Based on these anatomical landmarks,angles ∠DAB,∠CEB,∠DC'B,and ∠CDB were established.The intra-class correlation coefficient(ICC)was calculated to assess measurement consistency and reproducibility.Differences between the aforementioned angles were compared,and the area under the receiver operating characteristic(ROC)curve was computed to evaluate diagnostic performance.Results For ∠CDB,∠DC'B,∠CEB,and ∠DAB,the intra-group and inter-group correlation coefficients all exceeded 0.80,indicating excellent consistency and reproducibility.Compared to the control group,the angles ∠CDB,∠CEB,and ∠DAB in the ACL injury group were significantly reduced(P<0.001).Among these,∠DAB appears to be the most reliable index for diagnosing and evaluating ACL injuries,with an area under the receiver operating characteristic curve(AUC)of 0.829,a cut-off value of 42.2°,a sensitivity of 82.5%,and a specificity of 80.0%.Conclusion The geometric triangular relationship between the Blumensaat line and the tibial plateau in MRI images,particularly the angle ∠DAB,can serve as an auxiliary indicator for diagnosing and evaluating ACL injuries,thereby enhancing diagnostic accuracy.
10.Analysis of immune infiltration mechanism of dermatomyositis and prediction of therapeutic targets of traditional Chinese medicine based on CIBERSORT algorithm
Pu WANG ; Min HU ; Suyue PAN ; Qiao HUANG ; Dongyu CHEN ; Wenlong FAN ; Xiaoyu YANG ; Hong-xin WANG ; Yuqing HE
Chinese Journal of Immunology 2025;41(4):783-791,中插1
Objective:To analyze the gene chip related to dermatomyositis based on bioinformatics,to explore the immune in-filtration mechanism of key genes in dermatomyositis by CIBERSORT deconvolution algorithm,and to predict the therapeutic targets of dermatomyositis by network pharmacology.Methods:The gene microarray of dermatomyositis was searched in GEO database,and the differentially coexpressed genes were screened and analyzed.The differentially coexpressed genes were analyzed by GO analysis,KEGG analysis,protein interaction network construction(PPI)by R software package.Verify the expression levels of key genes,and the correlation of immune cell infiltration was analyzed by CIBERSORT deconvolution method.Through the medical ontology informa-tion retrieval platform Coremine medical database,the traditional Chinese medicine treatment targets of dermatomyositis were screened and summarized.Results:A total of 196 differentially expressed genes were screened.GO enrichment analysis showed that these differentially expressed genes were mainly concentrated in defense response to virus,blood particles,double-stranded RNA binding,polypeptide antigen binding,and so on.KEGG enrichment analysis showed that it was enriched in RIG-Ⅰ-like receptor sig-nal pathway,Toll-like receptor signal pathway and other signal pathways related to the pathogenesis of dermatomyositis.Finally,four key genes of dermatomyositis,STAT1,ISG15,IRF7 and IRF9 were obtained.Through CIBERSORT algorithm,M1 macrophages,M2 macrophages and CD8+T cells were the three kinds of cells with the highest average proportion and the most obvious immune infil-tration,and there was a significant positive correlation between activated natural killer cells and activated dendritic cells,while there was a significant negative correlation between resting mast cells and activated mast cells.The therapeutic targets of traditional Chinese medicine such as fish brain stone were predicted based on Coremine medical database;through channel analysis,it could be found that these traditional Chinese medicines are mainly attributed to liver meridian,lung meridian,spleen meridian;efficacy analysis is mainly focused on clearing heat,detoxification,promoting blood circulation and removing blood stasis,relieving cough and resolving phlegm and so on.Conclusion:Four key genes and some key signal pathways of dermatomyositis,STAT1,ISG15,IRF7 and IRF9 were obtained by bioinformatics method,the immune infiltration mechanism was analyzed by CIBERSORT algorithm,and the thera-peutic potential targets of traditional Chinese medicine were screened out to provide direction for the pathogenesis and treatment of der-matomyositis.

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