1.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.
2.TIMP1 Participates in VEGFA-associated Endothelial Cell Activation and Aberrant Angiogenesis in Ulcerative Colitis
Zhi-Yu JIN ; Yi-Wei JIANG ; Zhen CAO
Progress in Biochemistry and Biophysics 2026;53(10):2665-2680
ObjectiveAbnormal intestinal angiogenesis and dysregulation of the mucosal immune microenvironment are important mechanisms underlying the occurrence and progression of ulcerative colitis (UC). This study aimed to identify biomarkers associated with angiogenesis in UC through integrated bioinformatics analysis and to validate their expression patterns and effects on vascular endothelial cell function through in vivo and in vitro experiments. MethodsSix UC-related datasets were retrieved from the GEO database. GSE48959, GSE59071, and GSE73661 were batch-corrected using the ComBat algorithm and used as the discovery cohort, while GSE47908, GSE92415, and GSE206285 were used as independent external validation cohorts. Differentially expressed genes were identified using the limma package, and a weighted gene co-expression network was constructed using WGCNA. The DEGs, WGCNA core module genes, and angiogenesis-related genes were intersected to obtain candidate genes. Multiple machine learning methods were further integrated to screen candidate features, followed by DNN and SHAP-based analysis of candidate gene feature contributions. PPI network topology analysis was further performed to identify hub genes, and the CIBERSORT algorithm was used to evaluate candidate genes and immune infiltration features. In addition, a DSS-induced mouse model of colitis and a TNF-α-stimulated HUVECs inflammatory model were established for experimental validation, combined with hematoxylin and eosin staining, immunofluorescence staining, Western blotting, wound healing assays, Transwell invasion assays, and Matrigel tube formation assays. ResultsA total of 481 upregulated and 285 downregulated genes were identified in the discovery cohort, and these genes were mainly enriched in pathways related to leukocyte migration and the complement and coagulation cascades. WGCNA identified the yellow module as the module most strongly associated with UC. The intersection of DEGs, WGCNA core module genes, and angiogenesis-related genes yielded 26 candidate genes. Four machine learning algorithms further identified C2, TIMP1, and TGM2 as common candidate features, while DNN-SHAP analysis and PPI network topology analysis further highlighted TIMP1 as a key hub gene. After multi-step screening, TIMP1 was ultimately identified as a key candidate gene. Validation across multiple datasets showed that TIMP1 was significantly upregulated in UC tissues and exhibited favorable discriminatory performance (all AUCs>0.85). In the DNN model, TIMP1 showed a relatively high feature contribution, supporting its potential relevance to UC classification. CIBERSORT analysis indicated that TIMP1 expression was positively correlated with neutrophils and resting NK cells, but negatively correlated with regulatory T cells and CD8⁺ T cells. In vivo and in vitro experiments further confirmed that TIMP1 expression was markedly increased under inflammatory conditions. In DSS-induced colitis mice, increased CD31-positive vascular signals were accompanied by elevated TIMP1 expression and reduced VE-cadherin expression. Moreover, TIMP1 knockdown significantly inhibited endothelial cell migration, invasion, and tube formation, accompanied by decreased expression of VEGFA, VEGFR-2, and VEGFR-3. ConclusionTIMP1 may participate in UC-associated abnormal angiogenesis and changes in vascular endothelial cell function under inflammatory conditions, highlighting its potential as a biomarker and a candidate for further therapeutic investigation.
3.Research progress in moxibustion for treating gastrointestinal dysfunction after laparoscopic cholecystectomy
Shuo LI ; Dongdong LU ; Qiuhui LIANG ; Quanxin LIU ; Weiwei JIAO ; Ying ZHEN ; Min DENG ; Lingyun WEN ; Jinbao WANG ; Yanxia CAO
International Journal of Traditional Chinese Medicine 2025;47(9):1327-1331
TCM believes that the main pathogenesis of gastrointestinal dysfunction (GD) after laparoscopic cholecystectomy (LC) is spleen and stomach weakness, liver and stomach disharmony, liver depression and spleen deficiency, and intestinal depression. Moxibustion in the treatment of GD after LC can avoid the aggravation of gastrointestinal burden caused by oral drugs. The intervention methods mainly include suspension moxibustion, umbilical moxibustion, heat sensitive moxibustion, thunder fire moxibustion, warm acupuncture, partition moxibustion, etc. Moxibustion is often performed on the acupoints in liver meridian, spleen meridian, stomach meridian, small intestine meridian, large intestine meridian and Conception Vessel, such as Taichong (LR3), Ganshu (BL18), Yinlingquan (SP9), Zusanli (ST36), Tianshu (ST25), Wangu (SI4), Hegu (LI4), Zhongwan (CV12), Shenque (CV8) and Qihai (CV6). At present, most studies combined with moxibustion on the basis of conventional Western medicine treatment can significantly improve the efficacy, and have certain advantages in improving gastrointestinal motility decline, intestinal flora imbalance, first exhaust time, gastrointestinal hormone level disorder and intestinal mucosal barrier dysfunction. However, there are still some problems in the existing research: small sample size of clinical research, not perfect scoring scale, not unified treatment plan and operation standard, relatively scarce basic research, relatively simple acupoint research, lack of biochemical evaluation indicators, and the research of national moxibustion needs to be explored and improved in the future.
4.Clinical study on meridian acupuncture combined with electromyographic biofeedback in spastic cerebral palsy
Ling YANG ; Jiang PAN ; Zhengliang CAO ; Zhen WANG ; Qian TIAN ; Bo LIU
International Journal of Traditional Chinese Medicine 2025;47(11):1527-1531
Objective:TTo evaluate the therapeutic effect of meridian acupuncture combined with electromyographic biofeedback therapy on spastic cerebral palsy.Methods:A randomized controlled trial study was conducted. Totally 128 children with spastic cerebral palsy in our hospital from September 2022 to September 2024 were divided into two groups using a random number table method, with 64 cases in each group. The control group received routine rehabilitation training and electromyographic biofeedback therapy, while the observation group received combined meridian acupoint therapy on the basis of the control group. Both groups received 3 weeks of treatment, making a total of 3 treatment courses. The Gross Motor Function Test (GMFM) was used to evaluate the motor function of children; the Developmental Behavior Assessment (DBA) was used to assess the psychological and behavioral development status of children aged 0-6, the Fine Motor Function Assessment (FMFM) was used to assess the fine motor skills of children; the Montreal Cognitive Assessment (MoCA) was used to assess the cognitive level of children; the Modified Ashworth Rating Scale (MAS) was used to assess the muscle strength level of children; the clinical efficacy was evaluated.Results:The total effective rate of the observation group was 92.19% (59/64), while that of the control group was 76.56% (49/64), with statistical significance ( χ2=5.93, P=0.015). The observation group had higher scores for lying down and turning over, sitting, crawling and kneeling, standing, walking, running, and jumping after treatment compared to the control group ( t-values of 2.82, 5.83, 4.97, 4.23, 4.41, respectively, P<0.01); the scores for gross motor skills, fine motor skills, adaptability, language, and social behavior were higher than thoes in the control group ( t values of 3.34, 3.73, 5.33, 3.75, 5.47, respectively, P<0.01); the FMFM and MoCA scores were higher than those in the control group ( t values of 5.23 and 4.41, respectively, P<0.01); the MAS grading level was lower than that of the control group ( t=8.46, P<0.01). Conclusion:The combination of meridian acupuncture and electromyographic biofeedback can improve the motor function, psychological and behavioral development, fine motor skills, cognitive development, and clinical efficacy of children with spastic cerebral palsy.
5.Exploration on the liver-protective effect of Peipi Shugan Decoction on liver fibrosis in rats based on network pharmacology
Guangshun CHEN ; Mingzhong CAO ; Rongming ZHANG ; Ruxia WU ; Zhen XIE ; Jiangfeng HAO
International Journal of Traditional Chinese Medicine 2025;47(12):1708-1717
Objective:To investigate the liver-protective effect of Peipi Shugan Decoction (PSD) in rats with liver fibrosis through network pharmacology and experimental animal models.Methods:TCMSP was used to retrieve the active components of Peipi Shugan Decoction, GeneCards database was used to obtain the liver fibrosis related targets, and Venny 2.1 was used to obtain the intersection targets. A protein-protein interaction (PPI) network was constructed using the STRING 12.0 database, and Go function and KEGG pathway enrichment analysis were performed through David database. A total of 60 male Sprague-Dawley (SD) rats were divided into two groups: a blank control group ( n=10) and a model establishment group ( n=50) with random number table method. Liver fibrosis models were induced in the model group by intraperitoneal injection of a 40% CCl?- olive oil solution. After successful modeling, the rats were randomly assigned to the following groups ( n=10 per group): model group, colchicine group, and Peipi Shugan Decoction low-, medium-, and high-dosage groups. The colchicine group received colchicine suspension at 0.2 ml/kg via intragastric administration. Peipi Shugan Decoction low-, medium-, and high-dosage groups were administered the decoction at dosages of 2.81, 5.63, and 11.25 g/kg, respectively. The blank control and model groups received an equal volume of normal saline. All treatments were administered once daily for 8 consecutive weeks. HE staining and Masson staining were used to observe the morphological changes of liver tissue and the deposition of collagen fibers. he levels of GPT, GOT and ALP were detected by automatic biochemical analyzer. The expressions of JAK2/STAT1 signaling pathway related proteins, α - smooth muscle actin (α-SMA) and Collagen Ⅰ in rat liver were detected by Western blot. The expression of α-SMA protein in liver tissue was detected by immunohistochemistry. The number and ratio of CD4 + T cells and CD8 + T cells in liver tissue were analyzed by flow cytometry. The levels of IL-6, IL-1β and TNF-α in serum were detected by ELISA. Results:A total of 94 active components were screened out from Peipi Shugan Decoction; the prediction analysis results revealed that this compound formula shared 122 common targets with liver fibrosis diseases; The top five core targets with degree values in the PPI network are AKT1, TNF, IL-6, TP53, and IL-1β. GO enrichment analysis further indicated that Peipi Shugan Decoction mainly achieved anti-liver fibrosis effects by regulating JAK2/STAT1 signaling pathway and other mechanisms. Compared with the model group, the colchicine group and Peipi Shugan Decoction low-, medium-, and high-dosage groups exhibited decreased serum levels of GPT, GOT, ALP, IL-6, TNF-α, and IL-1β ( P<0.05), as well as reduced expression of α-SMA in liver tissue ( P<0.05). Peipi Shugan Decoction medium- and high-dosage groups showed increased protein expression of p-STAT1/STAT1 in liver tissue ( P<0.05), while Peipi Shugan Decoction high-dosage group demonstrated decreased α-SMA protein expression ( P<0.05). Additionally, Peipi Shugan Decoction medium- and high-dosage groups exhibited reduced expressions of CD4 + and CD8 + ( P<0.05). Conclusions:Peipi Shugan Decoction has the characteristics of multi-component, multi-target and multi-pathway in the treatment of liver fibrosis. Its mechanism is mainly related to activating the JAK2/STAT1 signaling pathway, inhibiting cellular inflammatory responses and hindering the activation of hepatic stellate cells (HSC).
6.Application of pedagogies of PBL and CBL combined with ideological-political elements in surgical clinical ethics
Zhen CAO ; Jing XIE ; Jiashu HAN ; Jie YI ; Xisheng WENG ; Chen LIN ; Weibin WANG
Basic & Clinical Medicine 2025;45(3):413-416
Objective To evaluate the application of problem-based learning(PBL)and case-based learning(CBL)combined with ideological-political elements in surgical clinical ethics.Methods Eighty graduate students of grade 2022 majoring in surgery from Peking Union Medical College were selected as the subjects for the clinical ethics course offered in the first semester of the 2022-2023 academic year.They underwent the innovative pedago-gies of PBL and CBL combined with ideological-political elements.The satisfaction investigation and questionnaire surveys were performed to evaluate the effects.Results A total of 78 valid questionnaires were received.The results showed that 96.2%of students believed that this course supported them to understand the fundamental prin-ciples and knowledge of surgical clinical ethics and 94.9%of students expressed their willingness to expand their knowledge,indicating high satisfaction with the course.There were 91%of students acknowledged this model in terms of improving active learning and 93.6%stated that the course helped in developing good professional ethics.Most students responded positively to this model because of its contribution to enhance core clinical competencies.Conclusions The PBL and CBL combined with ideological-political elements have a better effect on surgical clini-cal ethics with high satisfaction of the students.
7.Effect of "Zhibian" (BL54) toward "Shuidao" (ST28) acupuncture on gut microbiota in mice with poor ovarian response.
Boya CHANG ; Jia REN ; Xu JIN ; Jianheng HAO ; Zhen GAO ; Yuxia CAO ; Haijun WANG
Chinese Acupuncture & Moxibustion 2025;45(6):770-780
OBJECTIVE:
To explore the possible mechanism by which the "Zhibian" (BL54) toward "Shuidao" (ST28) acupuncture improves ovarian function in mice with poor ovarian response (POR) by observing its effect on gut microbiota.
METHODS:
A total of 35 SPF-grade C57BL/6 female mice were screened for normal estrous cycles using vaginal smears, and 30 mice were selected. Ten mice were assigned to the blank group, while the remaining mice were used to establish the POR model by intragastric administration of tripterygium wilfordii suspension. The successfully modeled mice were randomly divided into a model group and an acupuncture group, with 10 mice in each group. After modeling, the acupuncture group received the "Zhibian" (BL54) toward "Shuidao" (ST28) acupuncture method once daily for 20 minutes per session. Ovulation induction began the day after the intervention, and samples were collected after ovulation induction. Vaginal cytology was used to observe estrous cycle changes, and the number of oocytes obtained, ovarian wet weight, and ovarian index were recorded. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH) were detected using ELISA. HE staining was used to observe ovarian histology. Gut microbiota was analyzed using 16S rRNA gene sequencing technology. Western blot was used to detect the relative protein expression levels of Occludin and zonula occludens-1 (ZO-1) in colonic tissue. Correlation analysis was conducted among serum hormone indexes, the number of oocytes obtained, ovarian index and gut microbiota.
RESULTS:
Compared with the blank group, the model group showed a higher estrous cycle disorder rate (P<0.01), increased serum FSH and LH levels, and a higher LH/FSH ratio (P<0.01), while the number of oocytes obtained, ovarian wet weight, ovarian index, and serum E2 and AMH levels were significantly reduced (P<0.01). Compared with the model group, the acupuncture group showed a lower estrous cycle disorder rate (P<0.01), decreased serum FSH and LH levels, and a lower LH/FSH ratio (P<0.01), along with an increased number of oocytes obtained, higher ovarian wet weight, ovarian index, and elevated serum AMH and E2 levels (P<0.01, P<0.05). The blank group had a large number of well-developed primordial follicles, with abundant and closely arranged follicles at various stages. In the model group, there was a significant increase in the number of atretic follicles, a reduction in the number of follicles at various stages, and loosely arranged ovarian tissue. Compared with the blank group, the model group showed a significant decrease in the number of normal follicles (P<0.01) and an increase in the number of atretic follicles (P<0.01). The acupuncture group showed a reduction in atretic follicles and an increase in the number of follicles at various stages compared with the model group, with a significant increase in normal follicles (P<0.01) and a decrease in atretic follicles (P<0.01). Compared with the blank group, the model group exhibited reduced gut microbiota diversity and richness, with significantly lower Chao1 and Shannon indices (P<0.01), and a greater clustering distance from the blank group. The model group also showed an increase in the relative abundance of Firmicutes_D, Verrucomicrobiota, Paramuribaculum, Dubosiella, and Muribaculum (P<0.01, P<0.05), while the relative abundance of Firmicutes_A and the relative protein expression of Occludin and ZO-1 in colonic tissue were decreased (P<0.01). Compared with the model group, the acupuncture group showed improved gut microbiota diversity and richness, with increased Chao1 and Shannon indices (P<0.05), and a clustering distance closer to the blank group. The acupuncture group exhibited reduced relative abundance of Firmicutes_D, Verrucomicrobiota, and Muribaculum (P<0.05, P<0.01), while the relative abundance of Firmicutes_A and the relative protein expression of Occludin and ZO-1 were significantly increased (P<0.01, P<0.05). Correlation analysis indicated a relationship between gut microbiota and serum hormone indicators, as well as the ovarian index. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis showed that the metabolic pathways of the intersecting species were related to amino acid biosynthesis and nucleotide metabolism.
CONCLUSION
The "Zhibian" (BL54) toward "Shuidao" (ST28) acupuncture method improves ovarian function in POR mice, and its mechanism may be related to regulating gut microbiota structure and maintaining intestinal barrier homeostasis.
Animals
;
Female
;
Gastrointestinal Microbiome
;
Mice
;
Acupuncture Therapy
;
Mice, Inbred C57BL
;
Humans
;
Ovary/physiopathology*
;
Acupuncture Points
;
Follicle Stimulating Hormone/metabolism*
;
Luteinizing Hormone/metabolism*
;
Estrous Cycle
;
Anti-Mullerian Hormone/blood*
8.Mechanism of Xiangmei Pills in treating ulcerative colitis based on UHPLC-Q-Orbitrap HRMS and 16S rDNA sequencing of intestinal flora.
Ya-Fang HOU ; Rui-Sheng WANG ; Zhen-Ling ZHANG ; Wen-Wen CAO ; Meng ZHAO ; Ya-Hong ZHAO
China Journal of Chinese Materia Medica 2025;50(4):882-895
The efficacy of Xiangmei Pills on rats with ulcerative colitis(UC) was investigated by characterizing the spectrum of the active chemical components of Xiangmei Pills. Rapid identification and classification of the main chemical components were performed,and the therapeutic effects of Xiangmei Pills on the proteins and intestinal flora of UC rats were analyzed to explore the mechanism of its action in treating UC. Fifty SD rats were acclimatized to feeding for 3 d and randomly divided into blank group, model group,mesalazine group(0. 4 g·kg~(-1)), low-dose group of Xiangmei Pills(1. 89 g·kg~(-1)), and high-dose group of Xiangmei Pills(5. 67 g·kg~(-1)), with 10 rats in each group. 5% dextrose sodium sulfate(DSS) was given by gavage to induce the male SD rat model with UC,and the corresponding medicinal solution was given by gavage after 10 days, respectively. The therapeutic effect of Xiangmei Pills on rats with UC was evaluated according to body mass, disease activity index(DAI), and hematoxylin-eosin(HE) staining, and the histopathological changes in the colon were observed. Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) technique was used to rapidly and accurately identify the main chemical constituents of Xiangmei Pills. Immunohistochemistry was used to detect the expression of aryl hydrocarbon receptor(AhR),interferon-γ(IFN-γ), mucin-2(MUC-2), and cytochrome P450 1A1(CYP1A1) in colon tissue. Interleukin-22(IL-22) expression in colon tissue was detected by immunofluorescence. The 16S r DNA high-throughput sequencing technique was used to study the modulatory effects of Xiangmei Pills on the intestinal flora structure of rats with UC. Pharmacodynamic results showed that compared with that of the blank group, the colon tissue of the model group was congested, and ulcers were visible in the mucosa; compared with that in the model group, the histopathology of the colon of the rats with UC in the groups of Xiangmei Pills were improved, with scattered ulcers and reduced inflammatory cell infiltration. Chemical analysis showed that a total of 45 components were identified by mass spectrometry information, including 15 phenolic acids, 8 coumarins, 15 organic acids, 3 amino acids, 2 flavonoids, and 2 other components. Compared with those in the blank group, the levels of Ah R, CYP1A1, MUC-2, and IL-22 proteins in the colon tissue of rats in the model group were significantly decreased, and the level of IFN-γ protein was significantly increased; the intestinal flora of rats in the model group was disorganized, with a decrease in the abundance of the flora; the relative abundance of Bacteroidetes,unclassified genera of Ascomycetes, Prevotella of the Prevotella family, and Prevotella decreased significantly, and that of Firmicutes decreased, but the difference was not statistically significant. The relative abundance of Bacteroidetes, Bifidobacterium, and Lactobacillus increased significantly. Compared with those of the model group, the levels of Ah R, CYP1A1, MUC-2, and IL-22proteins in the colonic tissue of the groups of Xiangmei Pills were significantly higher, and the levels of IFN-γ proteins were significantly lower. The recovery of the intestinal flora was accelerated, and the diversity of the intestinal flora was significantly increased. The relative abundance of Bacteroidetes was significantly increased, and that of unclassified genera of Ascomycetes,Lactobacillus, Prevotella of the Prevotella family, and Prevotella was significantly increased. The relative abundance of Bacteroidetes and Bifidobacterium was significantly decreased. This study demonstrated that Xiangmei Pills can effectively treat UC, mainly through the phenolic acid and organic acid components to stimulate the intestinal barrier, regulate protein expression and the relative abundance and diversity of intestinal flora, and play a role in the treatment of UC.
Animals
;
Colitis, Ulcerative/metabolism*
;
Drugs, Chinese Herbal/chemistry*
;
Rats, Sprague-Dawley
;
Male
;
Rats
;
Gastrointestinal Microbiome/genetics*
;
Chromatography, High Pressure Liquid
;
Humans
;
Mass Spectrometry
;
RNA, Ribosomal, 16S/genetics*
;
Bacteria/drug effects*
9.Polysaccharide extract PCP1 from Polygonatum cyrtonema ameliorates cerebral ischemia-reperfusion injury in rats by inhibiting TLR4/NLRP3 pathway.
Xin ZHAN ; Zi-Xu LI ; Zhu YANG ; Jie YU ; Wen CAO ; Zhen-Dong WU ; Jiang-Ping WU ; Qiu-Yue LYU ; Hui CHE ; Guo-Dong WANG ; Jun HAN
China Journal of Chinese Materia Medica 2025;50(9):2450-2460
This study aims to investigate the protective effects and mechanisms of polysaccharide extract PCP1 from Polygonatum cyrtonema in ameliorating cerebral ischemia-reperfusion(I/R) injury in rats through modulation of the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. In vivo, SD rats were randomly divided into the sham group, model group, PCP1 group, nimodipine(NMDP) group, and TLR4 signaling inhibitor(TAK-242) group. A middle cerebral artery occlusion/reperfusion(MCAO/R) model was established, and neurological deficit scores and infarct size were evaluated 24 hours after reperfusion. Hematoxylin-eosin(HE) and Nissl staining were used to observe pathological changes in ischemic brain tissue. Transmission electron microscopy(TEM) assessed ultrastructural damage in cortical neurons. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), interleukin-18(IL-18), tumor necrosis factor-α(TNF-α), interleukin-10(IL-10), and nitric oxide(NO) in serum. Immunofluorescence was used to analyze the expression of TLR4 and NLRP3 proteins. In vitro, a BV2 microglial cell oxygen-glucose deprivation/reperfusion(OGD/R) model was established, and cells were divided into the control, OGD/R, PCP1, TAK-242, and PCP1 + TLR4 activator lipopolysaccharide(LPS) groups. The CCK-8 assay evaluated BV2 cell viability, and ELISA determined NO release. Western blot was used to analyze the expression of TLR4, NLRP3, and downstream pathway-related proteins. The results indicated that, compared with the model group, PCP1 significantly reduced neurological deficit scores, infarct size, ischemic tissue pathology, cortical cell damage, and the levels of inflammatory factors IL-1β, IL-6, IL-18, TNF-α, and NO(P<0.01). It also elevated IL-10 levels(P<0.01) and decreased the expression of TLR4 and NLRP3 proteins(P<0.05, P<0.01). Moreover, in vitro results showed that, compared with the OGD/R group, PCP1 significantly improved BV2 cell viability(P<0.05, P<0.01), reduced cell NO levels induced by OGD/R(P<0.01), and inhibited the expression of TLR4-related inflammatory pathway proteins, including TLR4, myeloid differentiation factor 88(MyD88), tumor necrosis factor receptor-associated factor 6(TRAF6), phosphorylated nuclear factor-kappaB dimer RelA(p-p65)/nuclear factor-kappaB dimer RelA(p65), NLRP3, cleaved-caspase-1, apoptosis-associated speck-like protein(ASC), GSDMD-N, IL-1β, and IL-18(P<0.05, P<0.01). The protective effects of PCP1 were reversed by LPS stimulation. In conclusion, PCP1 ameliorates cerebral I/R injury by modulating the TLR4/NLRP3 signaling pathway, exerting anti-inflammatory and anti-pyroptotic effects.
Animals
;
Toll-Like Receptor 4/genetics*
;
NLR Family, Pyrin Domain-Containing 3 Protein/genetics*
;
Rats, Sprague-Dawley
;
Rats
;
Reperfusion Injury/genetics*
;
Male
;
Signal Transduction/drug effects*
;
Polysaccharides/isolation & purification*
;
Polygonatum/chemistry*
;
Brain Ischemia/genetics*
;
Drugs, Chinese Herbal/administration & dosage*
;
Mice
;
Humans
10.Frontier technologies and development trends of network pharmacology: a patent bibliometric analysis.
Li TAO ; Zhi-Peng KE ; Tuan-Jie WANG ; Zhen-Zhong WANG ; Liang CAO ; Wei XIAO
China Journal of Chinese Materia Medica 2025;50(11):3070-3078
This study systematically analyzed the global research landscape, technological composition, and core patents in the field of networks target and network pharmacology, and proposes further suggestions based on the IncoPat patent citation database and VOSviewer bibliometric network visualization tool. Using patent literature metrics and scientific knowledge mapping method, technological innovation pathways, research hotspots, and future directions in this field were further revealed. In particular, this field is moving towards data-driven, intelligent, and systematic approaches. Patent analysis indicated that most patent applications in this domain focused on traditional Chinese medicine(TCM), which have provided key engineering technical approaches to explore and solve complex problems of TCM. By integrating big data and artificial intelligence technologies, network targets and network pharmacology have conferred high-precision screening and quality control of key components and targets in herbal formulations and prescriptions, accelerating the clinical translation and industrialization of TCM-based new drugs and health products with medicine-food homology. Therefore, it is essential to optimize the patent protection system and establish integrated technology platforms in this field for ensuring the competitiveness of technological achievements in research and clinical application. These efforts will advance the widespread application and high-quality development of TCM modernization, precision medicine, and innovative drug discovery.
Bibliometrics
;
Patents as Topic
;
Humans
;
Medicine, Chinese Traditional
;
Network Pharmacology/trends*
;
Drugs, Chinese Herbal/pharmacology*

Result Analysis
Print
Save
E-mail