1.Construction of Saikosaponin D Multifunctional Liposomes and Evaluation of Its Anti-liver Cancer Efficacy and Targeting
Kun YU ; Guochun YANG ; Yaliang JIANG ; Yunting XIAO ; Congxian WANG ; Qionge SUN ; Ziyue LI ; Yikun SHANG ; Yu MAO ; Xin CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):205-216
ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol(Chol) in conventional liposomes with saikosaponin D(SSD) and modifying with poloxamer 407(P407) for co-delivery of curcumin(Cur). The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes, and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes(P407-DiR-Chol-LPs, PDCL) and novel SSD-based liposomes(P407-DiR-SSD-LPs, PDSL) were prepared by the optimized formulation process, and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups, including blank group, model group, free doxorubicin(DOX) group(2 mg·kg-1), free Cur group(8 mg·kg-1), free SSD group(10 mg·kg-1), P407-Cur-Chol-LPs(PCCL) group, P407-SSD-LPs(PSL) group, and P407-Cur-SSD-Lps(PCSL) group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change, organ indices, tumor volume and mass, relative tumor proliferation rate(T/C), and tumor growth inhibition rate(TGI). Histopathological analysis of liver, kidney, and tumor tissues was performed using hematoxylin-eosin(HE) staining. Serum levels of aspartate aminotransferase(AST), alanine aminotransferase (ALT), blood urea nitrogen(BUN), and creatinine(Crea)in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur, SSD, and P407 to soybean phosphatidylcholine(SPC) as 1∶25, 1∶20, and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm, a Zeta potential of -47.25 mV, and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics, demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group(P<0.05, P<0.01). Among the treatment groups, PCSL group showed superior efficacy over free Cur group, free SSD group, PCCL group, and PSL group, with TGI>40% and T/C<60%, indicating pronounced anti-hepatocellular carcinoma effects(P<0.05, P<0.01). Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy, achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma, providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.
2.Mechanism of Taishan Panshisan in Inhibiting Oxidative Stress Injury of Trophoblast Cells by Regulating KEAP1/Nrf2/FoxO3 Signaling Pathway
Yangyang DUAN ; Xianglun JI ; Jiahong CHEN ; Jinghang YANG ; Xinyu XIAO ; Shutao CHEN ; Chaorui LIN ; Fan LIN ; Shu JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):12-22
ObjectiveTo explore the effect and mechanism of Taishan Panshi powder (TSPSP) on inhibiting oxidative stress injury in human chorionic trophoblast cells (HTR-8/SVneo), and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion (SA). MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus (GEO) database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP, and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments, HTR-8/SVneo cells were divided into blank group, model group, TSPSP-containing serum 2.5%, 5%, 10% groups, and nuclear factor E2-related factor 2 (Nrf2) inhibitor group (ML385, 30 μmol·L-1). Except for the blank group, other groups were stimulated with 150 μmol·L-1 H2O2 for 3 h to establish a cell oxidative stress injury model. After successful modeling, the blank group and model group were given 10% blank serum, each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum, and the Nrf2 inhibitor group was additionally given 30 μmol·L-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h, and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde (MDA), Fe2+, and Glutathione (GSH) were detected by enzyme-linked immunosorbent assay (ELISA). Intracellular reactive oxygen species (ROS) level was detected by a fluorescent probe (DCF-DA). The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 (KEAP1), Nrf2, and forkhead box protein O3 (FoxO3) in cells were detected by immunofluorescence (IF) and real-time quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of KEAP1, Nrf2, FoxO3, Glutathione peroxidase 4 (GPX4), and superoxide dismutase (SOD) in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1, Nrf2, and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway, nine significantly differential pathways were identified (P<0.05), among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology, and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response, FOXO and MAPK signaling pathways, etc. In in vitro experiments, compared with the blank group, the cell viability in the model group was significantly decreased (P<0.01). Compared with the model group, the cell viability in each TSPSP-containing serum group was significantly increased (P<0.01). Compared with the 10% TSPSP-containing serum group, the cell viability in the ML385 group decreased to approximately 70% (P<0.01). Compared with the blank group, the model group showed significantly increased contents of MDA, Fe2+, and ROS, decreased GSH expression (P<0.01), significantly reduced cell migration rate (P<0.01), and increased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.01), while decreased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.01). Compared with the model group, each TSPSP-containing serum group showed significantly decreased contents of MDA, Fe²⁺, and ROS, increased GSH expression (P<0.01), significantly increased migration rate (P<0.01), significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.05, P<0.01), and significantly increased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.05, P<0.01). Compared with the 10% TSPSP-containing serum group, the ML385 group showed reversed trends in all indicators (P<0.05, P<0.01). ConclusionTSPSP can inhibit H2O2-induced oxidative stress injury of trophoblast cells, and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.
3.Mechanism of Taishan Panshisan in Inhibiting Oxidative Stress Injury of Trophoblast Cells by Regulating KEAP1/Nrf2/FoxO3 Signaling Pathway
Yangyang DUAN ; Xianglun JI ; Jiahong CHEN ; Jinghang YANG ; Xinyu XIAO ; Shutao CHEN ; Chaorui LIN ; Fan LIN ; Shu JIANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):12-22
ObjectiveTo explore the effect and mechanism of Taishan Panshi powder (TSPSP) on inhibiting oxidative stress injury in human chorionic trophoblast cells (HTR-8/SVneo), and to uelucidate the underlying mechanism of TSPSP in the treatment of spontaneous abortion (SA). MethodsGene differential analysis of SA was performed using the Gene Expression Omnibus (GEO) database and correlated with oxidative stress. Network pharmacology was employed to screen the active components of TSPSP, and a "Chinese medicine-component-target-disease" network was constructed to predict the mechanism of action of TSPSP. For in vitro validation experiments, HTR-8/SVneo cells were divided into blank group, model group, TSPSP-containing serum 2.5%, 5%, 10% groups, and nuclear factor E2-related factor 2 (Nrf2) inhibitor group (ML385, 30 μmol·L-1). Except for the blank group, other groups were stimulated with 150 μmol·L-1 H2O2 for 3 h to establish a cell oxidative stress injury model. After successful modeling, the blank group and model group were given 10% blank serum, each TSPSP-containing serum group was treated with the corresponding concentration of drug-containing serum, and the Nrf2 inhibitor group was additionally given 30 μmol·L-1 ML385 on the basis of 10% TSPSP-containing serum. All groups of cells were continuously cultured under the above conditions for 24 h, and then samples were collected for subsequent detection. Cell viability in each group was detected by CCK-8 assay. Cell migration rate was detected by scratch test. The contents of malondialdehyde (MDA), Fe2+, and Glutathione (GSH) were detected by enzyme-linked immunosorbent assay (ELISA). Intracellular reactive oxygen species (ROS) level was detected by a fluorescent probe (DCF-DA). The protein and mRNA expression levels of Kelch-like ECH-associated protein 1 (KEAP1), Nrf2, and forkhead box protein O3 (FoxO3) in cells were detected by immunofluorescence (IF) and real-time quantitative polymerase chain reaction (Real-time PCR). The protein expression levels of KEAP1, Nrf2, FoxO3, Glutathione peroxidase 4 (GPX4), and superoxide dismutase (SOD) in cells were detected by Western blot. ResultsThe GSE76862 and GSE22490 datasets were obtained from the GEO database. Differential gene analyses showed that the KEAP1, Nrf2, and FoxO3 genes were all associated with the disease. After matching with the oxidative stress pathway, nine significantly differential pathways were identified (P<0.05), among which three contained the target genes Nrf2 and FoxO3. A total of 246 active ingredient targets of TSPSP and 2 804 SA-related targets were obtained through network pharmacology, and 154 potential action targets were obtained after taking the intersection. Topological analysis showed that targets such as KEAP1 and Nrf2 exhibited high degree values. GO and KEGG enrichment analyses indicated that the intersection targets were mainly involved in oxidative stress response, FOXO and MAPK signaling pathways, etc. In in vitro experiments, compared with the blank group, the cell viability in the model group was significantly decreased (P<0.01). Compared with the model group, the cell viability in each TSPSP-containing serum group was significantly increased (P<0.01). Compared with the 10% TSPSP-containing serum group, the cell viability in the ML385 group decreased to approximately 70% (P<0.01). Compared with the blank group, the model group showed significantly increased contents of MDA, Fe2+, and ROS, decreased GSH expression (P<0.01), significantly reduced cell migration rate (P<0.01), and increased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.01), while decreased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.01). Compared with the model group, each TSPSP-containing serum group showed significantly decreased contents of MDA, Fe²⁺, and ROS, increased GSH expression (P<0.01), significantly increased migration rate (P<0.01), significantly decreased protein and mRNA expression levels of KEAP1 and FoxO3 (P<0.05, P<0.01), and significantly increased protein and mRNA expression levels of Nrf2, GPX4, and SOD (P<0.05, P<0.01). Compared with the 10% TSPSP-containing serum group, the ML385 group showed reversed trends in all indicators (P<0.05, P<0.01). ConclusionTSPSP can inhibit H2O2-induced oxidative stress injury of trophoblast cells, and its mechanism of action may be related to the drug activating the KEAP1/Nrf2/FoxO3 signaling pathway.
4.Integrating Transcriptomics and 3D Organoids to Investigate Mechanism of Periplaneta americana Extract Against Lung Adenocarcinoma
Qiong MA ; Chunxia HUANG ; Jiawei HE ; Yuting BAI ; Xingyue LIU ; Yuxuan XIONG ; Yang ZHONG ; Hengzhou LAI ; Yuling JIANG ; Xueke LI ; Qian WANG ; Yifeng REN ; Xi FU ; Funeng GENG ; Taoqing WU ; Ping XIAO ; Fengming YOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):124-132
ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract(PAE) against human-derived lung adenocarcinoma organoids(LUAD-PDOs) and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid(Nor-PDOs) models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8(CCK-8) assay. Experimental groups included the model group(LUAD-PDOs), normal group, model administration group(LUAD-PDOs+PAE), and normal administration group(Nor-PDOs+PAE). Hematoxylin-eosin(HE) staining was used to observe the pathological structures of PDOs, immunohistochemistry(IHC) was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7(CK-7) and Napsin A, TUNEL staining was applied to detect cell apoptosis. RNA sequencing(RNA-Seq) was conducted to identify differentially expressed genes(DEGs), followed by Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes(KEGG), and Gene Set Enrichment Analysis(GSEA), alongside protein-protein interaction(PPI) network analysis to screen core mechanisms. Finally, key targets were validated by integrating external database analysis with immunofluorescence(IF). ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures, whereas LUAD-PDOs displayed dense, solid structures. CCK-8 and TUNEL assays revealed that, compared with the model group, PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells, while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention(347 up-regulated and 372 down-regulated)(P<0.05). GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism, including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway(P<0.05). PPI network analysis indicated that breast cancer type 1 susceptibility protein(BRCA1) and checkpoint kinase 1(CHEK1) were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention(P<0.05). Furthermore, survival analysis based on The Cancer Genome Atlas(TCGA) database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD(P<0.05). ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis, its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway, with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.
5.Spatiotemporal Electrical Impedance Tomography for Speech Respiratory Assessment in Cleft Palate: an Interpretable Machine Learning Study
Yang WU ; Xiao-Jing ZHANG ; Hao YU ; Cheng-Hui JIANG ; Bo SUN ; Jia-Feng YAO
Progress in Biochemistry and Biophysics 2026;53(2):485-500
ObjectiveCleft palate (CP) is a common congenital deformity often associated with velopharyngeal insufficiency (VPI), which disrupts the physiological coupling between respiration and speech. Conventional clinical assessments, such as nasometry and spirometry, provide limited static data and fail to visualize the dynamic spatiotemporal distribution of lung ventilation during phonation. This study introduces spatiotemporal electrical impedance tomography (ST-EIT) to evaluate speech-respiratory functional features in CP patients compared to normal controls (NC). The aim is to characterize multi-domain respiratory patterns and to validate an interpretable machine learning framework for providing objective, quantitative evidence for clinical assessment. MethodsSeventy-five participants were enrolled in this study, comprising 37 patients with surgically repaired CP and 38 healthy volunteers matched for age, gender, and body mass index (BMI). All subjects performed standardized sustained phonation tasks while undergoing synchronous monitoring with a 16-electrode EIT system and a pneumotachograph. A comprehensive feature engineering pipeline was developed to extract physiological parameters across 3 complementary domains. (1) Temporal domain: including inspiratory/expiratory phase duration (tPhase), time constants (Tau), and inspiratory-to-expiratory time ratios (TI/TE); (2) airflow domain: comprising mean flow, peak flow, and instantaneous flow at 25%, 50%, and 75% of tidal volume; and (3) spatial domain: quantifying global and regional tidal impedance variation (TIV), global inhomogeneity (GI), and center of ventilation (CoV). Extreme Gradient Boosting (XGBoost) classifiers were trained using 5 distinct data sources (Spirometry, Nasometry, Inspiratory-EIT, Expiratory-EIT, and fused ST-EIT). Model performance was rigorously evaluated via stratified 5-fold cross-validation, and Shapley additive explanations (SHAP) were employed to quantify global and local feature contributions. ResultsThe CP group exhibited a distinct respiratory phenotype compared to controls. In the temporal domain, CP patients showed significantly shorter inspiratory (1.60 s vs.1.85 s, P<0.001) and expiratory phase durations (2.45 s vs. 3.95 s, P<0.001), indicating a rapid, shallow breathing rhythm. In the airflow domain, while inspiratory flows were comparable, the CP group demonstrated significantly elevated mean and peak flows during the expiratory phase (P<0.001), reflecting compensatory respiratory effort. Spatially, CP patients presented significant ventilation redistribution, characterized by higher regional TIV in the right-anterior (ROI1) and left-posterior (ROI4) quadrants, but lower TIV in the left-anterior (ROI2) quadrant. In terms of diagnostic accuracy, the multi-modal ST-EIT model achieved the highest performance (AUC: 0.915±0.012, Accuracy: 0.843±0.019, F1-score: 0.872±0.017), substantially outperforming models based on spirometry (AUC: 0.721) or nasometry (AUC: 0.625) alone. Interpretability analysis revealed that spatial domain features were the most critical, contributing 53.4% to the model’s decision-making, followed by temporal (25.0%) and airflow (21.6%) features. ConclusionST-EIT successfully captures the temporal, airflow, and spatial deviations in CP speech respiration that are undetectable by conventional methods—specifically, rapid phase transitions, hyperdynamic expiratory airflow, and regional ventilation heterogeneity. This study validates ST-EIT as a robust, non-invasive, and radiation-free tool for characterizing speech-respiratory dysfunction, offering high clinical value for bedside screening, rehabilitation planning, and longitudinal monitoring of patients with cleft palate.
6.Spatiotemporal Electrical Impedance Tomography for Speech Respiratory Assessment in Cleft Palate: an Interpretable Machine Learning Study
Yang WU ; Xiao-Jing ZHANG ; Hao YU ; Cheng-Hui JIANG ; Bo SUN ; Jia-Feng YAO
Progress in Biochemistry and Biophysics 2026;53(2):485-500
ObjectiveCleft palate (CP) is a common congenital deformity often associated with velopharyngeal insufficiency (VPI), which disrupts the physiological coupling between respiration and speech. Conventional clinical assessments, such as nasometry and spirometry, provide limited static data and fail to visualize the dynamic spatiotemporal distribution of lung ventilation during phonation. This study introduces spatiotemporal electrical impedance tomography (ST-EIT) to evaluate speech-respiratory functional features in CP patients compared to normal controls (NC). The aim is to characterize multi-domain respiratory patterns and to validate an interpretable machine learning framework for providing objective, quantitative evidence for clinical assessment. MethodsSeventy-five participants were enrolled in this study, comprising 37 patients with surgically repaired CP and 38 healthy volunteers matched for age, gender, and body mass index (BMI). All subjects performed standardized sustained phonation tasks while undergoing synchronous monitoring with a 16-electrode EIT system and a pneumotachograph. A comprehensive feature engineering pipeline was developed to extract physiological parameters across 3 complementary domains. (1) Temporal domain: including inspiratory/expiratory phase duration (tPhase), time constants (Tau), and inspiratory-to-expiratory time ratios (TI/TE); (2) airflow domain: comprising mean flow, peak flow, and instantaneous flow at 25%, 50%, and 75% of tidal volume; and (3) spatial domain: quantifying global and regional tidal impedance variation (TIV), global inhomogeneity (GI), and center of ventilation (CoV). Extreme Gradient Boosting (XGBoost) classifiers were trained using 5 distinct data sources (Spirometry, Nasometry, Inspiratory-EIT, Expiratory-EIT, and fused ST-EIT). Model performance was rigorously evaluated via stratified 5-fold cross-validation, and Shapley additive explanations (SHAP) were employed to quantify global and local feature contributions. ResultsThe CP group exhibited a distinct respiratory phenotype compared to controls. In the temporal domain, CP patients showed significantly shorter inspiratory (1.60 s vs.1.85 s, P<0.001) and expiratory phase durations (2.45 s vs. 3.95 s, P<0.001), indicating a rapid, shallow breathing rhythm. In the airflow domain, while inspiratory flows were comparable, the CP group demonstrated significantly elevated mean and peak flows during the expiratory phase (P<0.001), reflecting compensatory respiratory effort. Spatially, CP patients presented significant ventilation redistribution, characterized by higher regional TIV in the right-anterior (ROI1) and left-posterior (ROI4) quadrants, but lower TIV in the left-anterior (ROI2) quadrant. In terms of diagnostic accuracy, the multi-modal ST-EIT model achieved the highest performance (AUC: 0.915±0.012, Accuracy: 0.843±0.019, F1-score: 0.872±0.017), substantially outperforming models based on spirometry (AUC: 0.721) or nasometry (AUC: 0.625) alone. Interpretability analysis revealed that spatial domain features were the most critical, contributing 53.4% to the model’s decision-making, followed by temporal (25.0%) and airflow (21.6%) features. ConclusionST-EIT successfully captures the temporal, airflow, and spatial deviations in CP speech respiration that are undetectable by conventional methods—specifically, rapid phase transitions, hyperdynamic expiratory airflow, and regional ventilation heterogeneity. This study validates ST-EIT as a robust, non-invasive, and radiation-free tool for characterizing speech-respiratory dysfunction, offering high clinical value for bedside screening, rehabilitation planning, and longitudinal monitoring of patients with cleft palate.
7.Pre-operative risk assessment of hepatocellular carcinoma recurrence in liver transplant recipients by non-invasive detection of pre-existing genetic lesions
Suqin YANG ; Sunbin LING ; Jianhua LI ; Yan WANG ; Jiapei WANG ; Qiwei HUANG ; Fanming LIU ; Yiqi ZHUANG ; Yingyu ZHENG ; Rui WANG ; Zhe YANG ; Xiaoping ZHENG ; Kai WANG ; Zhikun LIU ; Jun CHEN ; Jianguo WANG ; Haiyang XIE ; Lin ZHOU ; Leiming CHEN ; Guoqiang CAO ; Dandan CHEN ; Junfang JI ; Bin ZHAO ; Chao JIANG ; Di LU ; Xuyong WEI ; Hangjin JIANG ; Qiaonan SHAN ; Hengbo SHI ; Yong-Zhen XU ; Shusen ZHENG ; Zhengxin WANG ; Shengda LIN ; Xiao XU
Clinical and Molecular Hepatology 2026;32(2):884-903
Background/Aims:
Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy.
Methods:
We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues.
Results:
We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts.
Conclusion
Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.
8.Electrical stimulation induces miR-741-3p to regulate Radil and promote Schwann cell migration
Qing LIU ; Bo GAO ; Xiao YANG ; Yu JIANG ; Pei WANG
Chinese Journal of Tissue Engineering Research 2025;29(19):4038-4043
BACKGROUND:More and more animal experiments and clinical studies have confirmed that electrical stimulation can promote the repair of peripheral nerve injury,but the specific mechanism is not yet fully understood. OBJECTIVE:To investigate the effect of electrical stimulation-induced miR-741-3p regulating Radil on Schwann cell migration. METHODS:(1)Twelve male SD rats were randomly divided into electrical stimulation group and control group.The electrical stimulation group received continuous electrical stimulation for 7 days after sciatic nerve compression injury,while the control group was not treated after sciatic nerve compression.The injured nerves were taken on day 7 after operation.The expression difference of miR-741-3p between the two groups was verified by fluorescence in situ hybridization.(2)The target genes of miR-741-3p were predicted by miRDB,TargetScan,and miRWalk databases.(3)Schwann cells were transfected with miR-741-3p mimetic and its control,miR-741-3p inhibitor and its control,Radil siRNA and its control,miR-741-3p inhibitor+Radil siRNA and miR-741-3p inhibitor+siRNA control.The transfection efficiency was detected by RT-PCR.The migration ability of Schwann cells was detected by Transwell chamber. RESULTS AND CONCLUSION:(1)The fluorescence intensity of miR-741-3p in the electrical stimulation group was lower than that in the control group.(2)The results of database prediction showed that 69 genes might be the target genes of miR-741-3p.Radil was one of the predicted target genes,which was mainly involved in cell adhesion and migration.(3)Compared with the miR-741-3p inhibitor control group,the number of Schwann cell migration increased in the miR-741-3p inhibitor group(P<0.05).Compared with the miR-741-3p mimic control group,the number of Schwann cell migration in the miR-741-3p mimic group decreased(P<0.05).Compared with the siRNA control group,the number of Schwann cell migration was decreased in the Radil siRNA group(P<0.05).(4)Compared with miR-741-3p inhibitor control group,the expression level of Radil was increased in miR-741-3p inhibitor group.Compared with miR-741-3p mimic control group,the expression level of Radil was decreased in miR-741-3p mimic group.(5)Compared with miR-741-3p inhibitor+siRNA control group,the number of Schwann cell migration was reduced in miR-741-3p inhibitor+Radil siRNA group(P<0.05).The results showed that electrical stimulation promoted the migration of Schwann cells by down-regulating miR-741-3p and targeting Radil gene.
9.Exploration and Practice of a Comprehensive Model of"Teaching,Science and Ideology Trinity"to Enhance the Scientific Research Comprehensive Ability of Medical Students
Xiao-Hong YANG ; Chun-Hong HUANG ; Da-Ya LUO ; Wei-Feng ZHU ; Mu-Ying YING ; Yi JIANG ; Jing-Chong GUO ; Hao-Tang LIAO ; Xiao-Li TANG
Chinese Journal of Biochemistry and Molecular Biology 2025;41(9):1360-1368
The integration of science and education is not only an important strategy for promoting social progress and technological development,but also a modern form of higher education aiming at cultivating innovative talents.Conducting scientific research training for undergraduate medical students is one of the important ways to cultivate their innovative abilities and comprehensive qualities.Our team proposed a"teaching,science,and ideology trinity"teaching model to comprehensively cultivate students' scientific research comprehensive abilities under the value orientation of ideological and political education by or-ganically integrating molecular biology experimental teaching with the scientific research training of under-graduate medical students.In this teaching activity,taking the experiment of gene polymorphism as an example,our team selected students with research potential from the whole grade and divided them into 4 project groups that were instructed by 4 teachers.The students were trained in the whole process of scien-tific research,including topic selection,project writing,experimental designing,application for research ethics,and project summary.Our team has always adhered to student-contentedness of educational con-cepts to stimulate students' intrinsic motivation throughout the teaching process.Students are the design-ers and implementers of the project,and teachers are only guides and promoters of learning.After this training,students not only became familiar with the writing and implementation of scientific research pro-jects,but also improved their literature reading,experimental designing,experimental skills,and prob-lem-solving abilities.More importantly,this teaching activity also cultivated students' awareness of re-search ethics and academic moral standards.
10.Analgesic effect of ultrasound-guided quadratus lumborum block combined with patient-controlled intravenous analgesia after lower abdominal surgery
Shu-ting LI ; Tan-guang WU ; Guo-jiang YIN ; Kun LI ; Xiao-yang SONG
Journal of Regional Anatomy and Operative Surgery 2025;34(10):904-907
Objective To investigate the analgesic effect of ultrasound-guided quadratus lumborum block combined with patient-controlled intravenous analgesia after lower abdominal surgery.Methods A total of 134 patients who underwent lower abdominal surgery in General Hospital of Central Theater Command from April 2021 to April 2024 were prospectively selected and randomly divided into the observation group and the control group,with 67 patients in each group.Patients in the observation group received ultrasound-guided quadratus lumborum block combined with patient-controlled intravenous analgesia.Patients in the control group underwent only patient-controlled intravenous analgesia.The number of analgesic pump compressions and the cumulative sufentanil consumption 4 hours,6 hours,12 hours,and 24 hours after surgery,the visual analogue score(VAS)of pain at rest and exercise,and the incidence of adverse reactions during postoperative analgesia were compared between the two groups.Results Compared with the control group,the number of analgesic pump compressions and the cumulative sufentanil consumption of patients were fewer/less at 6 hours,12 hours and 24 hours after surgery in the observation group(P<0.05).The VAS scores of patients at exercise 4 hours,6 hours,12 hours and 24 hours after surgery in the observation group were significantly lower than those in the control group(P<0.05).The incidence of nausea,vomiting and vertigo in the observation group was significantly lower than that in the control group(P<0.05).Conclusion Compared with patient-controlled intravenous analgesia,ultrasound-guided quadratus lumborum block combined with patient-controlled intravenous analgesia can significantly reduce the number of analgesia pump compressions and the cumulative sufentanil consumption in postoperative analgesia of lower abdominal surgery,and has a better effect in relieving exercise pain,it can also reduce the occurrence of adverse reactions such as nausea and vomiting.

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