1.Exploring Mechanism of Yiqi Huoxue Jiedu Formula in Alleviating Immune Cell Exhaustion in Sepsis Based on Transcriptomics and Metabolomics
Rui CHEN ; Qiusha PAN ; Kaiqiang ZHONG ; Shuqi MA ; Wei HUANG ; Jiahua LAI ; Ruifeng ZENG ; Xiaotu XI ; Jun LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):109-118
ObjectiveTo observe the effects of Yiqi Huoxue Jiedu formula(YHJF) on immune cell exhaustion in the spleen of septic mice and to explore and validate its potential intervention targets. MethodsMice were randomly divided into the sham-operated, model, low-dose YHJF(4.1 g·kg-1), and high-dose YHJF(8.2 g·kg-1) groups. Except for the sham-operated group, a cecal ligation and puncture(CLP) procedure was performed to establish a mouse sepsis model. The treatment groups received oral administration of the corresponding doses, while the sham-operated and model groups received an equal volume of physiological saline. After the intervention, the 7-day survival rate of each group was recorded, and spleen samples were collected 72 h post-intervention, and the spleen index was calculated. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate(dUTP) nick end labeling(TUNEL) staining was used to detect apoptosis in spleen cells. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the levels of interleukin(IL)-4 and IL-10 in the serum. Transcriptomics and metabolomics were used to screen for differentially expressed genes(DEGs) and differential metabolites in the spleen, followed by bioinformatics analysis to identify key targets. Real-time quantitative polymerase chain reaction(Real-time PCR), flow cytometry, and multiplex immunofluorescence were used to verify the expressions of key genes and proteins. ResultsThe high-dose YHJF group significantly improved the 7-day survival rate of septic mice(P0.05). Compared with the sham-operated group, the model group showed a significant increase in apoptosis of spleen cells and a decrease in the spleen index at 72 h post-modeling, with markedly elevated peripheral serum IL-4 and IL-10 levels(P0.01). Compared with the model group, the high-dose YHJF group showed a reduction in apoptosis of spleen cells, an increase in the spleen index, and a significant decrease in peripheral serum IL-4 and IL-10 levels(P0.05). Spleen transcriptomics identified 255 DEGs between groups, potentially serving as intervention targets for YHJF. Gene Ontology(GO) enrichment analysis revealed that DEGs were mainly involved in biological processes such as natural killer(NK) cell-mediated positive immune regulation, cell killing, cytokine production, positive regulation of innate immune cells, and interferon production. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis showed that DEGs were mainly involved in cytokine-cytokine receptor interactions, viral protein interactions with cytokines and cytokine receptors, chemokine signaling pathway, and nuclear transcription factor-κB(NF-κB) signaling pathway. Protein-protein interaction(PPI) network analysis identified CD160, granzyme B(GZMB), and chemokine ligand 4(CCL4) as key targets for YHJF in treating sepsis. Metabolomics identified 46 differential metabolites that were significantly reversed by YHJF intervention, and combined transcriptomics and metabolomics analysis identified 17 differential metabolites closely related to CD160. Pathway enrichment revealed that these metabolites were mainly involved in glycerophospholipid metabolism, arachidonic acid metabolism, glycosylphosphatidylinositol(GPI) anchor biosynthesis, linoleic acid metabolism, and α-linolenic acid metabolism pathways. Verification results showed that, compared with the sham-operated group, the model group exhibited significantly elevated CD160 mRNA expression level in the spleen, along with markedly decreased CCL4 and GZMB mRNA expression, and had a significant increase in CD160 expression on the surface of natural killer T(NKT) cells in the spleen(P0.01). Compared with the model group, the high-dose YHJF group had a significant decrease in CD160 mRNA expression in the spleen, a significant increase in CCL4 and GZMB mRNA expressions. Further flow cytometry and immunofluorescence revealed that compared with the sham-operated group, CD160 expression on the surface of splenic NKT cells in the model group was significantly increased(P0.01), while high-dose YHJF intervention significantly reduced CD160 expression(P0.01). ConclusionYHJF may alleviate NKT cell exhaustion in sepsis by downregulating the expression of the negative co-stimulatory molecule CD160, and this regulatory effect is closely related to fatty acid metabolism pathways. This study provides new insights and targets for further exploration of strengthening vital Qi and detoxifying strategy to improve immune cell exhaustion in acute deficiency syndrome of sepsis.
2.Exploring Mechanism of Yiqi Huoxue Jiedu Formula in Alleviating Immune Cell Exhaustion in Sepsis Based on Transcriptomics and Metabolomics
Rui CHEN ; Qiusha PAN ; Kaiqiang ZHONG ; Shuqi MA ; Wei HUANG ; Jiahua LAI ; Ruifeng ZENG ; Xiaotu XI ; Jun LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):109-118
ObjectiveTo observe the effects of Yiqi Huoxue Jiedu formula(YHJF) on immune cell exhaustion in the spleen of septic mice and to explore and validate its potential intervention targets. MethodsMice were randomly divided into the sham-operated, model, low-dose YHJF(4.1 g·kg-1), and high-dose YHJF(8.2 g·kg-1) groups. Except for the sham-operated group, a cecal ligation and puncture(CLP) procedure was performed to establish a mouse sepsis model. The treatment groups received oral administration of the corresponding doses, while the sham-operated and model groups received an equal volume of physiological saline. After the intervention, the 7-day survival rate of each group was recorded, and spleen samples were collected 72 h post-intervention, and the spleen index was calculated. Terminal deoxynucleotidyl transferase deoxyuridine triphosphate(dUTP) nick end labeling(TUNEL) staining was used to detect apoptosis in spleen cells. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the levels of interleukin(IL)-4 and IL-10 in the serum. Transcriptomics and metabolomics were used to screen for differentially expressed genes(DEGs) and differential metabolites in the spleen, followed by bioinformatics analysis to identify key targets. Real-time quantitative polymerase chain reaction(Real-time PCR), flow cytometry, and multiplex immunofluorescence were used to verify the expressions of key genes and proteins. ResultsThe high-dose YHJF group significantly improved the 7-day survival rate of septic mice(P0.05). Compared with the sham-operated group, the model group showed a significant increase in apoptosis of spleen cells and a decrease in the spleen index at 72 h post-modeling, with markedly elevated peripheral serum IL-4 and IL-10 levels(P0.01). Compared with the model group, the high-dose YHJF group showed a reduction in apoptosis of spleen cells, an increase in the spleen index, and a significant decrease in peripheral serum IL-4 and IL-10 levels(P0.05). Spleen transcriptomics identified 255 DEGs between groups, potentially serving as intervention targets for YHJF. Gene Ontology(GO) enrichment analysis revealed that DEGs were mainly involved in biological processes such as natural killer(NK) cell-mediated positive immune regulation, cell killing, cytokine production, positive regulation of innate immune cells, and interferon production. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis showed that DEGs were mainly involved in cytokine-cytokine receptor interactions, viral protein interactions with cytokines and cytokine receptors, chemokine signaling pathway, and nuclear transcription factor-κB(NF-κB) signaling pathway. Protein-protein interaction(PPI) network analysis identified CD160, granzyme B(GZMB), and chemokine ligand 4(CCL4) as key targets for YHJF in treating sepsis. Metabolomics identified 46 differential metabolites that were significantly reversed by YHJF intervention, and combined transcriptomics and metabolomics analysis identified 17 differential metabolites closely related to CD160. Pathway enrichment revealed that these metabolites were mainly involved in glycerophospholipid metabolism, arachidonic acid metabolism, glycosylphosphatidylinositol(GPI) anchor biosynthesis, linoleic acid metabolism, and α-linolenic acid metabolism pathways. Verification results showed that, compared with the sham-operated group, the model group exhibited significantly elevated CD160 mRNA expression level in the spleen, along with markedly decreased CCL4 and GZMB mRNA expression, and had a significant increase in CD160 expression on the surface of natural killer T(NKT) cells in the spleen(P0.01). Compared with the model group, the high-dose YHJF group had a significant decrease in CD160 mRNA expression in the spleen, a significant increase in CCL4 and GZMB mRNA expressions. Further flow cytometry and immunofluorescence revealed that compared with the sham-operated group, CD160 expression on the surface of splenic NKT cells in the model group was significantly increased(P0.01), while high-dose YHJF intervention significantly reduced CD160 expression(P0.01). ConclusionYHJF may alleviate NKT cell exhaustion in sepsis by downregulating the expression of the negative co-stimulatory molecule CD160, and this regulatory effect is closely related to fatty acid metabolism pathways. This study provides new insights and targets for further exploration of strengthening vital Qi and detoxifying strategy to improve immune cell exhaustion in acute deficiency syndrome of sepsis.
3.Effect of Yang-Reinforcing and Blood-Activating Therapy on the Long-Term Prognosis for Dilated Cardio-myopathy Patients with Yang Deficiency and Blood Stasis Syndrome:A Retrospective Cohort Study
Shiyi TAO ; Jun LI ; Lintong YU ; Ji WU ; Yuqing TAN ; Xiao XIA ; Fuyuan ZHANG ; Tiantian XUE ; Xuanchun HUANG
Journal of Traditional Chinese Medicine 2026;67(1):53-59
ObjectiveTo evaluate the impact of yang-reinforcing and blood-activating therapy on the long-term prognosis for patients with dilated cardiomyopathy (DCM) of yang deficiency and blood stasis syndrome. MethodsA retrospective cohort study was conducted involving 371 DCM patients with yang deficiency and blood stasis syndrome. The yang-reinforcing and blood-activating therapy was defined as the exposure factor. Patients were categorized into exposure group (186 cases) and non-exposure group (185 cases) according to whether they received yang-reinforcing and blood-activating therapy combined with conventional western medicine for 6 months or longer. The follow-up period was set at 48 months, and the Kaplan-Meier survival analysis was used to assess the cumulative incidence of major adverse cardiovascular events (MACE) in both groups. Cox regression analysis was used to explore the impact of yang-reinforcing and blood-activating therapy on the risk of MACE, and subgroup analysis was performed. Changes in traditional Chinese medicine (TCM) syndrome score, left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-diastolic diameter (LVEDD), and Minnesota Living with Heart Failure Questionnaire (MLHFQ) score were compared between groups at the time of first combined use of yang-reinforcing and blood-activating therapy (before treatment) and 1 year after receiving the therapy (after treatment). ResultsMACE occurred in 31 cases (16.67%) in the exposure group and 47 cases (25.41%) in the non-exposure group. The cumulative incidence of MACE in the exposure group was significantly lower than that in the non-exposure group [HR=0.559, 95%CI(0.361,0.895), P=0.014]. Cox regression analysis showed that yang-reinforcing and blood-activating therapy was an independent factor for reducing the risk of MACE in DCM patients [HR=0.623, 95%CI(0.396,0.980), P=0.041], and consistent results were observed in different subgroups. Compared with pre-treatment, the exposure group showed decreased TCM syndrome score and MLHFQ score, reduced LVEDD, and increased LVEF and LVFS after treatment (P<0.05); in the non-exposure group, TCM syndrome score decreased, LVEF and LVFS increased, and LVEDD reduced after treatment (P<0.05). After treatment, the exposure group had higher LVEF and LVFS, smaller LVEDD, and lower TCM syndrome score and MLHFQ score compared with the non-exposure group (P<0.05). ConclusionCombining yang-reinforcing and blood-activating therapy with conventional western medicine can reduce the risk of MACE in DCM patients with yang deficiency and blood stasis syndrome, meanwhile improving their clinical symptoms, cardiac function, and quality of life.
4.Correlation between liver fibrosis degree and carotid plaque in patients with lean metabolic dysfunction-associated fatty liver disease
Shuai ZHANG ; Shoulu JIN ; Wanqing LI ; Xijing SHI ; Hao LIANG ; Hao DONG ; Dailong LU ; Ying ZHU ; Xiaoxing XIANG ; Jun LIU
Journal of Clinical Hepatology 2026;42(2):319-325
ObjectiveTo investigate the association between noninvasive liver fibrosis markers and carotid plaque (CP) in patients with lean metabolic dysfunction-associated fatty liver disease (MAFLD), and to provide a basis for screening high-risk populations. MethodsA total of 957 patients with lean MAFLD who underwent physical examination in Subei People’s Hospital from January 2021 to June 2023 was enrolled as the observation cohort, with the presence or absence of CP as the outcome, and fibrosis-4 (FIB-4) index and nonalcoholic fatty liver disease fibrosis score (NFS) were used to assess liver fibrosis degree. The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. The multivariate logistic regression analysis, the restricted cubic spline analysis, the receiver operating characteristic curve, and the mediation effect analysis were used to investigate the association between liver fibrosis degree and CP. ResultsThe prevalence rate of CP was 36.6% in the lean MAFLD population. Compared with the non-CP group(n=607), the CP group (n=350) had a significantly higher proportion of male patients, a significantly higher proportion of patients with smoking/diabetes/hypertension, and significantly higher levels of age, creatinine, blood urea nitrogen, triglycerides, fasting blood glucose, aspartate aminotransferase, aspartate aminotransferase/alanine aminotransferase ratio, NFS, and FIB-4 index, as well as significantly lower levels of platelet count and albumin (all P<0.05). The multivariate logistic regression analysis showed that after adjustment for confounding factors, FIB-4 index (odds ratio[OR]=2.979, 95% confidence interval[CI]:2.141 — 4.219, P<0.001) and NFS (OR=1.747, 95%CI: 1.499 — 2.046, P<0.001) were positively correlated with CP. Both FIB-4 index and NFS had a good value in predicting CP. Hypertension had a significant indirect effect on the prevalence rate of CP through its impact on liver fibrosis markers, and its mediating effect accounted for 39.5% — 40.8% of the total effect (P<0.001). ConclusionIn patients with lean MAFLD, NFS and FIB-4 index are significantly positively correlated with the prevalence rate of CP, and they can be used as potential epidemiological predictive indicators. Liver fibrosis markers may play a mediating role in the association between hypertension and CP. Interventions targeting hypertension and liver fibrosis markers may help to prevent and delay the progression of CP.
5.Risk factors for acute kidney injury after liver transplantation and establishment of a predictive model
Journal of Clinical Hepatology 2026;42(2):380-386
ObjectiveTo investigate the risk factors for acute kidney injury (AKI) after liver transplantation, and to establish and validate a risk prediction model, and to provide a basis for early identification of high-risk patients and intervention in clinical practice. MethodsA single-center retrospective study was conducted, and clinical data were collected from 162 patients who received liver transplantation in Liver Transplantation Center of The First Hospital of Shanxi Medical University from March 2020 to June 2025. The patients were divided into AKI group with 69 patients and non-AKI group with 93 patients according to the diagnostic criteria for AKI established by the Kidney Disease: Improving Global Outcomes organization and the presence or absence of AKI within 7 days after surgery. The independent-samples t test was used for comparison of normally distributed continuous data between groups, while the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The univariate differential analysis was used to obtain the factors associated with AKI after liver transplantation, and the multivariate logistic regression analysis was used to identify the independent risk factors and establish a nomogram model; the Bootstrap method with 1 000 repeated samples was used to perform internal validation of the model. The dataset was randomly divided into a training set and a validation set at a ratio of 7∶3, and the receiver operating characteristic (ROC) curve, the calibration curve, and decision curve analysis (DCA) were used to assess the discriminatory ability, calibration, and clinical applicability of the predictive model. ResultsBody mass index (BMI) (odds ratio [OR]=1.281, 95% confidence interval [CI]: 1.037 — 1.582, P=0.022), serum creatinine (OR=1.097, 95%CI: 1.020 — 1.181, P=0.013), intraoperative blood loss (OR=1.005, 95%CI: 1.002 — 1.009, P=0.004), and cold ischemia time (OR=0.984, 95%CI: 0.976 — 0.991, P<0.001) were independent risk factors for the development of AKI after liver transplantation. The nomogram prediction model established based on the above factors had an area under the ROC curve (AUC) of 0.964 (95%CI: 0.931 — 0.997), with an optimal cutoff value of 0.319, a sensitivity of 0.971, and a specificity of 0.903. In the training set (n=113), the nomogram had an AUC of 0.969 (95% CI: 0.933 — 0.971), while in the validation set (n=49), the nomogram had an AUC of 0.941 (95%CI: 0.855 — 0.944). The calibration curve showed good consistency between the predicted incidence rate and the actual incidence rate, and DCA showed that it had good net clinical benefit. ConclusionBMI, serum creatinine, cold ischemia time, and intraoperative blood loss are independent risk factors for the development of AKI after liver transplantation, and the nomogram prediction model established based on these factors performs well and has a good value in predicting the development of AKI after liver transplantation.
6.Study on the contents of five active components and fingerprint of Gardenia jasminoides-Scutellaria baicalensis herb pairs before and after processing
China Pharmacy 2026;37(6):727-732
OBJECTIVE To establish the method for determining the contents of five active components in raw and charred herb pairs of Gardenia jasminoides-Scutellaria baicalensis , construct their fingerprints, and investigate the effects of G. jasminoides processing on chemical constituents in the h erb pairs. METHODS The HPLC method was used to determine the contents of genipin 1- β -D-gentiobioside, geniposide, crocin Ⅰ, crocin Ⅱ and baicalin in ten batches of raw G. jasminoides-S. baicalensis herb pairs and ten batches of charred G. jasminoides-S. baicalensis herb pairs. Using the same HPLC method, chromatographic fingerprints for the ten batches of raw herb pairs and ten batches of processed herb pairs were established with the Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicine (2012 edition). Principal component analysis and orthogonal partial least squares-discriminant analysis were performed. RESULTS Compared with the raw G. jasminoides-S. baicalensis herb pair, the average content of genipin 1- β -D-gentiobioside in the charred G. jasminoides-S. baicalensis herb pair increased by 12.65%; while the average contents of geniposide, crocin Ⅰ, crocin Ⅱ and baicalin decreased by 7.86%, 60.62%, 62.07% and 0.15%, respectively. Chromatographic fingerprints of ten batches of raw herb pairs and ten batches of processed herb pairs shared 18 common peaks with similarities ranging from 0.997 to 1.000 and 0.988 to 1.000, respectively. Five common peaks were identified: genipin 1- β -D-gentiobioside (peak 2), geniposide (peak 3), crocin Ⅰ (peak 6), crocin Ⅱ (peak 9) and baicalin (peak 10). Principal component analysis and orthogonal partial least squares-discriminant analysis results showed that the raw G. jasminoides-S. baicalensis herb pair and the charred G. jasminoides-S. baicalensis herb pair could be clearly distinguished. Variable importance in the projection (VIP) values for crocin Ⅰ and crocin Ⅱ were both greater than one. CONCLUSIONS A method has been successfully developed for the determination of five active c omponents, including genipin 1- β -D-gentiobioside, in the G. jasminoides-S. baicalensis herb pair, and its fingerprint has been drawn. Processing is found to increase the content of genipin 1- β -D-gentiobioside, while decreasing the levels of geniposide, crocin Ⅰ, crocin Ⅱ and baicalin in the herb pair. Furthermore, crocin Ⅰ and crocin Ⅱ could serve as potential quality markers for the quality control of this herb pair.
7.Quality evaluation of Heat-clearing and symptom-relieving formula based on multi-component quantification and screening of marker components
Jiahui CHEN ; Qiong LUO ; Lijun WEI ; Yuewu WANG ; Jun LI ; Chengdong LIU ; Jiajia HAO ; Liwen NIU
China Pharmacy 2026;37(6):740-745
OBJECTIVE To systematically evaluate the quality of the Heat-clearing and symptom-relieving formula and screen potential marker components that influence the quality of the formula. METHODS The contents of 11 components (calycosin-7- O - β -D-glucoside, ononin, hyperoside, isoquercitrin, baicalin, baicalein, cryptotanshinone, tanshinone Ⅱ A , tanshinone Ⅰ, senkyunolide A, ferulic acid) in the Heat-clearing and symptom-relieving formula were determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Using the contents of the aforementioned components as variables, cluster analysis (CA), principal component analysis (PCA), and orthogonal partial least squares-discriminant analysis (OPLS-DA) were conducted using OriginPro 2024 software and SIMCA 14.1 software; marker components affecting the quality of the Heat-clearing and symptom-relieving formula were then screened based on the criteria of variable importance in the projection (VIP) value>1 and P <0.05. The comprehensive evaluation of 20 batches of samples was carried out using the entropy weight-technique for order preference by similarity to ideal solution(TOPSIS) and grey correlation analysis (GCA) methods. RESULTS The contents of the above 11 components were 7.993-72.866, 4.542-31.228, 727.666-1 901.884, 496.846-1 293.279, 1 995.501-6 779.150, 54.500-241.280, 150.302-304.339, 79.698-189.206, 257.118-682.418, 5.498-21.687, 7.524-26.935 μg/g. CA, PCA and OPLS-DA results showed that 20 batches of samples were grouped into 2 categories. Q1, Q3, Q4, Q7-Q9, Q12, Q15, Q16 were grouped into one category, and the rest were grouped into another category; VIP values of ferulic acid, tanshinone Ⅱ A , baicalin, cryptotanshinone, calycosin-7- O - β -D-glucoside and ononin were all greater than 1 ( P <0.05). Both the entropy weight-TOPSIS and GCA methods showed that the samples ranked in the top 11 according to the euclidean distance and relative correlation degree were Q2, Q5, Q6, Q10, Q11, Q13, Q14, Q17-Q20. CONCLUSIONS The established HPLC-MS/MS method is rapid, accurate and highly sens itive. Combined with chemical pattern recognition analysis, entropy weight-TOPSIS and GCA methods, this method can be used to evaluate the quality of the Heat-clearing and symptom-relieving formula. Ferulic acid, tanshinone Ⅱ A , baicalin, cryptotanshinone, calycosin-7- O - β -D-glucoside and ononin may be the marker components that affect the quality of this formula. The overall quality of 11 batches of the Heat-clearing and symptom-relieving formula, including Q17, is relatively superior.
8.Conbercept therapy for neovascular age-related macular degeneration under the treat-and-extend regimen
Linrui LI ; Jun LI ; Yun LYU ; Mingyue ZHANG ; Moxiu GU
International Eye Science 2026;26(5):738-745
AIM:To assess the efficacy of intravitreal conbercept for treating neovascular age-related macular degeneration(nAMD)under a treat-and-extend(T & E)regimen.METHODS: A retrospective analysis was conducted on nAMD patients followed over a 2-year period(May 2020 to May 2022). All eyes received three monthly loading intravitreal injections of conbercept, followed by a T& E regimen in which the injection interval was extended by 2 or 4 wk according to disease activity, up to a maximum of 16 wk. When disease activity recurred, the interval was shortened. Patients were divided into initial and non-initial treatment groups based on treatment history. Best-corrected visual acuity(BCVA), central macular thickness(CMT), injection frequency, and intervals between injections over the 24-month follow-up were compared.RESULTS:Totally 27 patients(15 males and 12 females, 33 eyes)were enrolled. In the initial treatment group(18 eyes, mean age 65.72±12.32 y), BCVA significantly improved at 1, 3, and 6 mo(P<0.05), and CMT significantly improved at 1 and 3 mo(P<0.05). In the non-initial treatment group(15 eyes, mean age 69.00±9.21 y), BCVA improved significantly at 3 mo(P<0.05), whereas CMT remained stable(P >0.05). Baseline CMT was similar between the groups(P>0.05). However, significant differences were observed at multiple post-injection time points(P<0.05). The total number of injections did not differ between the groups(P>0.05). Intervals between injections varied, with the majority at 4 and 3-4 mo in the initial and non-initial treatment groups, respectively.CONCLUSION:Initiating intravitreal conbercept therapy under a T & E regimen results in superior visual and anatomical outcomes compared with non-initial treatment.
9.Regulatory Mechanisms of miRNA in Hepatocellular Carcinoma and Current Status of Traditional Chinese Medicine Intervention: A Review
Shiyi LI ; Hao CHENG ; Chunyan JI ; Jun SUN ; Juan XUE
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):323-332
Hepatocellular carcinoma(HCC), as one of the common malignant tumours, has seen a continuous rise in incidence and mortality worldwide, posing a serious threat to human health. However, traditional treatments have certain limitations, therefore, the exploration of new therapeutic strategies is particularly urgent. In recent years, with in-depth research on the regulatory mechanisms of microRNA(miRNA) in tumour occurrence and development, it has become new targets for HCC diagnosis and treatment. As a traditional treatment method, Chinese medicine, due to its multi-component, multi-pathway, and multi-target overall regulatory characteristics, shows broad prospects in treating HCC by regulating miRNAs. Accordingly, this paper reviews recent studies on the role of miRNAs in HCC and research advances in traditional Chinese medicine interventions, finding that various miRNAs play key roles in HCC cell cycle regulation, proliferation and apoptosis, invasion and metastasis, immune microenvironment, and drug resistance. It summarises how active ingredients, extracts, medicinal pairs, and formulas of Chinese medicine act on specific miRNAs to regulate their downstream target gene expression, affecting the malignant behaviour of HCC cells and exerting anti-cancer effects. This study aims to provide a theoretical basis for miRNAs as potential biomarkers and therapeutic targets for HCC, as well as to offer new ideas for developing miRNA-based targeted Chinese medicine therapies.
10.Effects of LINC02086 on proliferation, migration and invasion of gastric cancer cells by regulating Wnt/β-catenin pathway mediated M2 polarization of macrophages
Jun LI ; Yafei BU ; Jie CHEN ; Bo DING ; Lei WANG
Acta Universitatis Medicinalis Anhui 2026;61(2):192-201
ObjectiveTo investigate the effect and mechanism of long intergenic non-coding RNA02086 (LINC02086) overexpression mediated macrophage polarization on the proliferation, migration and invasion of gastric cancer cells. MethodsThe expression levels of LINC02086 in the human gastric epithelial cell line GES-1 and human gastric cancer cell lines HCG-27, NCI-N87, and AGS were determined by qRT-PCR. Human acute monocytic leukemia cells (THP-1) were induced to differentiate into M0 macrophages using phorbol 12-myristate 13-acetate (PMA). HGC-27 cells were infected with either LINC02086 overexpression lentivirus (OE-LINC02086) or its negative control lentivirus (Vector), and the culture supernatants were collected as conditioned medium (CM1). M0 macrophages were co-cultured with the infected HGC-27 cells, and the resulting supernatants were designated as conditioned medium 2 (CM2). M0 macrophages were treated with CM1 alone or in combination with Wnt/β-catenin pathway inhibitor IWR-1, forming the Vector+CM1, OE-LINC02086+CM1, and OE-LINC02086+CM1+IWR-1 groups, respectively. Flow cytometry was used to detect mannose receptor C-type 1 (CD206) expression, and qRT-PCR was employed to measure mRNA levels of interleukin-10 (IL⁃10), transforming growth factor-β (TGF⁃β), vascular endothelial growth factor (VEGF), and chemokine ligand 22 (CCL22). Western blot was performed to evaluate protein expression of CD206, VEGF, and key components of the Wnt/β-catenin pathway—Wnt family member 3a (Wnt3a), glycogen synthase kinase-3β (GSK-3β), and β-catenin. HGC-27 cells were treated with CM2 alone or combined with IWR-1, establishing the Vector+CM2, OE-LINC02086+CM2, and OE-LINC02086+CM2+IWR-1 groups. CCK-8 assay was used to evaluate cell proliferation, and Transwell assays were conducted to assess migration and invasion capabilities. ResultsCompared with GES-1 cells, the expression levels of LINC02086 were upregulated in HCG-27, NCI-N87, and AGS cells (P < 0.05), with the smallest increase observed in HCG-27 cells. Compared with Vector+CM1 group, the level of CD206 and the expression levels of IL⁃10, TGF⁃β, VEGF and CCL22 mRNA in macrophages stimulated by OE-LINC02086+CM1 increased (P<0.05). Meanwhile, the expression levels of Wnt3a and β-catenin proteins in cells increased (P<0.05), and the expression level of GSK-3β protein decreased (P<0.05). However, co-treatment with IWR-1 markedly reversed the promoting effects of LINC02086 overexpression on the expression of M2 polarization markers, including CD206, IL⁃10, and TGF⁃β mRNA, in macrophages (P<0.05), as well as its activation of the Wnt/β-catenin signaling pathway (P<0.05). Compared with Vector+CM2 group, HGC-27 cells infected with OE-LINC02086+CM2 had increased proliferation activity and increased number of migration and invasion cells (P<0.05). However, the combined intervention of IWR-1 significantly reversed the promotion of LINC02086 overexpression on the proliferation, migration and invasion of HGC-27 cells (P<0.05). ConclusionLINC02086 overexpression promotes the proliferation, migration and invasion of gastric cancer cells by activating Wnt/β-catenin pathway to mediate M2 polarization of macrophages.

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