1.Efficacy of chemotherapy combined with targeted therapy and immunotherapy versus chemotherapy alone in advanced pancreatic cancer:a retrospective cohort study
Ziyan CUI ; Jiayue DUAN ; Ziyan SUN ; Zegao ZHOU ; Cheng QI ; Changqing YAN
Chinese Journal of Surgery 2026;64(1):55-63
Objective:To explore the efficacy and safety of combining targeted therapy and immunotherapy with standard chemotherapy in patients with advanced pancreatic cancer.Methods:This is a single-center retrospective cohort study. A total of 123 patients with advanced pancreatic cancer who received first-line systemic treatment at the Second Hospital of Hebei Medical University between January 2022 and December 2024 were retrospectively enrolled. There were 65 males and 58 females,with a mean age of (65.1±10.1) years (range:22 to 88 years). According to whether targeted therapy combined with immunotherapy was added to chemotherapy,patients were divided into a triplet group ( n=46) and a standard chemotherapy group ( n=77). The primary endpoints were overall survival (OS) and progression-free survival (PFS); secondary endpoints included radiological efficacy indicators (objective response rate (ORR), disease control rate (DCR),clinical benefit rate,etc.) and treatment-related adverse events. Propensity score matching (PSM,caliper=0.2) was used to balance baseline characteristics between groups. Kaplan-Meier curves were used to estimate survival,and Cox regression models were applied to analyze factors influencing OS and PFS. Results:In the original cohort,the median OS was 11 months in the triplet group and 8 months in the chemotherapy group,with no statistically significant difference ( P=0.056). The median PFS was 5 months in the triplet group and 3 months in the chemotherapy group,also without statistical significance ( P>0.05). Multivariate Cox regression analysis indicated that the triplet regimen was an independent prognostic factor for both OS and PFS ( P<0.05). After PSM,baseline balance between groups was good. The median OS was 10.0 months in the triplet group and 7.0 months in the chemotherapy group, with no significant difference ( P=0.094). In terms of efficacy, the ORR was 26.1% (12/46) in the triplet group versus 7.8% (6/77) in the chemotherapy group,with a statistically significant difference ( χ2=6.320, P=0.012). The DCR was 54.3% (25/46) in the triplet group and 33.8% (26/77) in the chemotherapy group,also statistically significant ( χ2=4.214, P=0.037). The incidence of adverse events was similar between groups,mostly grade 1 to 2. Conclusions:The triplet regimen of chemotherapy,targeted therapy,and immunotherapy shows potential in improving efficacy and prolonging survival with acceptable safety in patients with advanced pancreatic cancer. However, its definitive benefits require further investigation.
2.Clinical efficacy of minimally invasive robot-assisted coronary artery bypass grafting for multivessel coronary artery disease
Jiahui LI ; Chenyi CUI ; Haoqi LI ; Jizhong XUAN ; Zhao LI ; Sheng WANG ; Junjie SUN ; Zhaoyun CHENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(05):728-733
Objective To explore the clinical efficacy of robot-assisted coronary artery bypass grafting through a small incision in the left intercostal space in the treatment of multivessel coronary disease. Methods A retrospective analysis was conducted on the clinical data of patients who underwent coronary artery bypass grafting through a small incision in the left intercostal space at Central China Fuwai Hospital of Zhengzhou University from January 1, 2023 to October 15, 2024. Patients were divided into a robotic group and a minimally invasive group based on whether the surgery was assisted by the Da Vinci robot. Results A total of 81 patients were included, with 57 in the minimally invasive group, including 41 males and 16 females, with a median age of 65.0 (57.5, 69.5) years; and 24 in the robotic group, including 17 males and 7 females, with a median age of 61.0 (56.0, 69.0) years. There was no statistically significant difference in baseline data between the two groups (P>0.05). The robotic group had less intraoperative bleeding [300 (200, 438) mL vs. 500 (375, 600) mL, P=0.006], shorter postoperative mechanical ventilation time [15.0 (13.3, 23.5) h vs. 22.0 (15.5, 39.5) h, P=0.037], and lower incidence of postoperative pain [8 (33.3%) vs. 33 (57.9%), P=0.043]. The hospitalization cost in the robotic group was higher than that in the minimally invasive group [130491 (123298, 135691) yuan vs. 123892 (115543, 133449) yuan, P=0.023]. There was no statistical difference in postoperative laboratory indicators between the two groups (P>0.05). There was also no statistical difference in the duration of surgery, postoperative 24 h drainage volume, ICU stay time, postoperative hospital stay or incidences of perioperative compications including pleural effusion, transfusion, new-onset atrial fibrillation, acute kidney injury, non-union of incision, major cardiovascular and cerebrovascular adverse events, and reoperation between the two groups (P>0.05). Conclusion Compared with the minimally invasive group, the robotic group shows satisfactory efficacy and can effectively reduce postoperative pain and intraoperative bleeding, and shorten postoperative mechanical ventilation time.
3.Establishment and preliminary evaluation of a fluorescent recombinase-aided amplification assay for detection of Strongyloides stercoralis
Xiaodan CHEN ; Wanqiong CHENG ; Xiaoyin FU ; Jiayin LÜ ; Jiayue SUN ; Qiuhua BAI ; Xue HAN ; Yunliang SHI ; Dengyu LIU
Chinese Journal of Schistosomiasis Control 2026;38(2):160-168
Objective To establish a fluorescent recombinase-aided amplification (RAA) assay for detection of Strongyloides stercoralis nucleic acid and to preliminarily evaluate its performance. Methods Six sets of specific primers targeting S. stercoralis 18S ribosomal RNA (18S rRNA) gene and one fluorescent probe were designed and synthesized. The optimal primer-probe set was determined through systematic screening and optimization to establish the fluorescent RAA assay. The assay was evaluated using S. stercoralis genomic DNA at concentrations of 100, 10, and 1 pg/μL, and 100, 10, and 1 fg/μL, as well as recombinant pUC57 plasmids containing the target gene fragments at 1 × 105, 1 × 104, 1 × 103, 1 × 102, 1 × 101, 1 × 100 copies/reaction, to determine the analytical sensitivity. Genomic DNA from Ascaris lumbricoides, Ancylostoma duodenale, Enterobius vermicularis, Angiostrongylus cantonensis, Trichinella spiralis, Clonorchis sinensis, Schistosoma japonicum, and Taenia saginata was used to assess assay specificity. A total of 25 stool samples from patients suspected of S. stercoralis infection were tested by the modified Baermann funnel technique, PCR, and the established fluorescent RAA assay. The sensitivity, specificity, concordance rate and their 95% confidence intervals (CI) of these three techniques were estimated, and agreement between methods was evaluated using the Kappa coefficient. Results Exo-4 was identified as the optimal primer set screened from the six primer sets, and the best amplification performance was achieved when the final concentrations of the forward and reverse primers were 0.44 μmol/L and a probe concentration was 0.20 μmol/L. The limit of detection of the fluorescent RAA assay was 100 fg/μL for genomic DNA of S. stercoralis and 1 × 100 copies/reaction for recombinant plasmids. Specific fluorescence signals were detected within 5 min, with no cross-reactivity observed with A. lumbricoides, A. duodenale, E. vermicularis, A. cantonensis, T. spiralis, C. sinensis, S. japonicum, or T. saginata. Among the 25 clinical stool samples from patients suspected of S. stercoralis infections, the modified Baermann funnel technique and fluorescent RAA assay detected 19 positives and 6 negatives, whereas PCR detected 18 positives and 7 negatives. The fluorescent RAA assay showed a sensitivity of 100.00% [95% CI: (82.35%, 100.00%)], specificity of 100.00% [95% CI: (54.07%, 100.00%)], concordance rate of 100.00% [95% CI: (86.28%, 100.00%)], and a Kappa coefficient of 1.00 [95% CI: (1.00, 1.00)] (P < 0.001) relative to the modified Baermann funnel technique, and a sensitivity of 100.00% [95% CI: (81.47%, 100.00%)], specificity of 85.71% [95% CI: (42.13%, 99.64%)], concordance rate of 96.00% [95% CI: (79.65%, 99.90%)], and a Kappa coefficient of 0.90 [95% CI: (0.70, 1.00)] (P < 0.001). Positive amplification products emitted green fluorescence under a portable blue-light device, enabling visual interpretation of results. Conclusions The fluorescent RAA assay established in this study is rapid, highly sensitive, and highly specific. It enables detection of S. stercoralis nucleic acid under isothermal conditions and allows visual interpretation of results, providing a novel tool for rapid clinical diagnosis and field screening of S. stercoralis infections.
4.Eccentric Cycling Improves Cardiopulmonary Fitness, Respiratory Function, and Quality of Life in Chronic Kidney Disease: A Randomized Controlled Trial
Yu-Ting HUANG ; Hsin-Yeh LEE ; Hui-Ching CHENG ; Hsin-Lun YANG ; Ching-Hsia HUNG ; Chien-Chou SU ; Yu-Tzu CHANG ; Chien-Yao SUN ; Kun-Ling TSAI
Annals of Rehabilitation Medicine 2026;50(2):105-116
Objective:
To compare the effects of eccentric cycling (ECC), concentric cycling (CON), and standard care (CTL) on cardiopulmonary capacity, respiratory health, and quality of life (QoL) in patients with chronic kidney disease (CKD).
Methods:
Thirty-one CKD patients were divided into the CTL, CON, and ECC groups. The CON and ECC groups participated in 8-week, 24-session cycling programs. Outcomes were assessed through cardiopulmonary exercise tests, respiratory function tests, and the 36-Item Short Form Survey Instrument questionnaire.
Results:
The ECC group achieved significant improvements in maximal oxygen uptake, while the CTL group showed a decline. For oxygen uptake efficiency slope, significant changes were observed only in the ECC group, with a group-by-time interaction effect compared to CTL. Furthermore, the ECC group demonstrated the most significant increase in diaphragm movement and a significant increase in diaphragm thickness, with comparisons indicating that ECC outperformed both CTL and CON. Regarding QoL, the ECC group exhibited significantly greater improvements in Physical Component Summary and Mental Component Summary, with statistically significant differences compared with the CTL and CON groups.
Conclusion
ECC is a low-effort, high-benefit exercise modality that significantly enhances cardiopulmonary fitness, respiratory function, and QoL in patients with CKD.
5.Application of chitosan in repair and regeneration of oral hard and soft tissues
Zhuo WANG ; Panpan SUN ; Huanzhi CHENG ; Tingting CAO
Chinese Journal of Tissue Engineering Research 2026;30(2):459-468
BACKGROUND:Chitosan has a place in the biomedical field due to its good biological properties and unique physicochemical properties,especially in tissue engineering and drug delivery with good application prospects.OBJECTIVE:To summarize the research progress of the role of chitosan in the repair and regeneration of oral soft and hard tissues.METHODS:A computerized search of CNKI and PubMed databases was performed with the search terms"chitosan,oral mucosal diseases,periodontal diseases,tissue regeneration,bacteriostatic,drug carrier,wound healing"in Chinese and English.The search time limit was from 2010 to 2024.After screening according to the inclusion and exclusion criteria,88 articles were finally included for summary analysis.RESULTS AND CONCLUSION:Chitosan is a promising biomaterial in bone and pulp regeneration as it has the ability to stimulate the recruitment and adhesion of osteogenic progenitor cells and dental pulp stem cells.Chitosan prevents caries,periodontal disease,and candidiasis by inhibiting Streptococcus pyogenes,Porphyromonas gingivalis,and Candida in the oral cavity.Chitosan nanocomposites have higher stability,better biocompatibility,and slow-release properties of drugs and can be enhanced by combining with other chemical reagents to enhance their anticancer properties.Chitosan possesses drug delivery,antibacterial activity,hemostasis and wound healing,which in turn can block the erosion of wounds by saliva and oral flora,relieve pain,repair and promote wound healing.Chitosan promotes the deposition of calcified material,which is conducive to the remineralisation of enamel and dentin.
6.Tracing Development of LIU Wansu's Theory of ''Fire-heat Inducing Stroke''
Xin LAN ; Changxiang LI ; Haojia ZHANG ; Jialin CHENG ; Zijin SUN ; Liyang DONG ; Zilin REN ; Xueqian WANG ; Fafeng CHENG ; Qingguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):32-41
LIU Wansu, as the foremost of the four great masters of the Jin-Yuan period, established the "theory of fire-heat'' and extended the fire-heat pathogenesis framework to the field of stroke, thereby forming the theory of ''fire-heat inducing stroke''. This achieved a paradigmatic shift in stroke etiology from ''exogenous wind inducing stroke'' to ''fire-heat inducing stroke''. This paper systematically reviews the developmental trajectory of LIU Wansu's ''fire-heat inducing stroke'' theory and explores the social background, academic origins, and core connotations of its theoretical construction. The study found that, based on the ''Nineteen Pathomechanisms'' in the Huangdi's Internal Classic (Huang Di Nei Jing) and combined with clinical practice, LIU Wansu proposed that fire-heat is the fundamental cause of stroke, and that the Six Climatic Factors and the Five Zhi-Emotions can all transform into fire. He further constructed a stratified syndrome differentiation and therapeutic system centered on clearing heat and purging fire, emphasizing differentiated treatment of exterior and interior syndromes, Six Meridians syndrome differentiation, and seasonally adjusted medication. This theory not only resolved the diagnostic and therapeutic dilemmas of febrile epidemic diseases during the Jin-Yuan period, but also exerted a profound influence on later physicians such as ZHANG Zihe and ZHU Danxi, thereby promoting the pluralistic development of stroke theory in traditional Chinese medicine (TCM). Modern pharmacological research provides solid scientific evidence, confirming that the ''fire-heat'' pathological state is highly associated with key mechanisms such as excessive inflammatory responses, oxidative stress, and excitatory amino acid toxicity following cerebral ischemia. Heat-clearing and fire-purging prescriptions and agents, such as Huanglian Jiedu Tang and baicalin, can exert multi-target neuroprotective effects by regulating inflammatory signaling, enhancing antioxidant enzyme activity, and balancing neurotransmitters. This not only verifies the scientific basis of the ''fire-heat inducing stroke'' theory from a modern biological perspective but also provides conclusive evidence for the clinical application of heat-clearing and fire-purging therapy. LIU Wansu's ''fire-heat inducing stroke'' theory represents a major milestone in the historical understanding of stroke pathogenesis, and its academically transitional insights continue to hold core guiding value for the pattern identification and treatment of ischemic stroke today.
7.Effects of Huanglian Jiedutang on Neutrophil Infiltration in Brain of MCAO Mice via Regulation of Chemokine Expression in Exosomes
Haojia ZHANG ; Kai WANG ; Zijin SUN ; Chunyu WANG ; Wei SHAO ; Kunjing LIU ; Liyang DONG ; Dan CHEN ; Wenxiu XU ; Chuanzun WANG ; Wen WANG ; Changxiang LI ; Xueqian WANG ; Fafeng CHENG ; Qingguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):42-53
ObjectiveTo investigate whether Huanglian Jiedutang can inhibit neutrophil infiltration in the brains of middle cerebral artery occlusion (MCAO) mice by regulating the expression of neutrophil-related chemokines in exosomes, thereby achieving therapeutic effects. MethodsA total of 130 male specific pathogen-free (SPF) C57BL/6J mice were randomly divided into four groups: Sham-operated group, MCAO model group, Huanglian Jiedutang group (6 g·kg-1), and Ginaton group (21.6 mg·kg-1), with 10 mice in the Ginaton group and 40 mice in each of the remaining three groups. Mice in the Huanglian Jiedutang group and the Ginaton group were administered the corresponding drugs by oral gavage once daily at a volume of 0.15 mL·(10 g)-1 for 7 consecutive days, while the sham-operated and model groups received an equal volume of saline via the same route. After 7 days, MCAO surgery was performed. The distal and proximal ends of the right common carotid artery (CCA) were ligated, a small incision was made between the two ligatures, and a silicone rubber-coated monofilament with a rounded tip was inserted into the lumen to occlude the CCA. The filament was left in place for 1 h to establish a focal cerebral ischemia model. At 24 h after modeling, mice were evaluated. Neurological function was assessed using the Longa score. Cerebral infarct volume was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Cerebral blood flow was observed by laser speckle imaging. Hematoxylin and eosin (HE) staining and Nissl staining were used to observe pathological changes in brain tissues. Exosomes were isolated from mouse plasma and brain tissues by ultracentrifugation and molecular size exclusion and identified by electron microscopy, particle size analysis, and protein blotting. Long-chain RNA libraries of exosomes were constructed and sequenced. Real-time quantitative reverse transcription polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of inflammatory factors and neutrophil-related chemokines in exosomes from plasma and brain tissues of each group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the protein expression of inflammatory factors and neutrophil-related chemokines in exosomes from brain tissues of each group. Immunohistochemistry was used to detect the expression of the neutrophil-specific protein myeloperoxidase (MPO) in the brains of mice in each group. ResultsCompared with the sham-operated group, the model group showed decreased neurological function scores (P<0.01), obvious cerebral infarction (P<0.01), reduced cerebral blood flow (P<0.01), neuronal necrosis in the brain, and decreased numbers of Nissl bodies (P<0.01). The mRNA expression levels of IL-1β, MPO, CXCL1, CXCL2, CXCL3, CXCL10, CCL2, and CCL3 in exosomes from plasma and brain tissues were significantly increased (P<0.05, P<0.01). The protein expression levels of IL-1β, MPO, CXCL2, and CXCL10 in exosomes from brain tissues were increased (P<0.05, P<0.01), and MPO-positive rates and mean optical density values in brain tissues were elevated (P<0.01). Compared with the model group, the Huanglian Jiedutang group and the Ginaton group showed increased neurological function scores (P<0.05), reduced cerebral infarct volume (P<0.01), restored cerebral blood flow (P<0.01), reduced necrotic cells in the brain, and increased numbers of Nissl bodies (P<0.01). In the Huanglian Jiedutang group, the mRNA expression levels of IL-1β, MPO, CXCL1, CXCL2, CXCL3, CXCL10, CCL2, and CCL3 in exosomes from plasma and brain tissues were decreased (P<0.05, P<0.01). The protein expression levels of IL-1β, MPO, CXCL2, and CXCL10 in exosomes from brain tissues were reduced (P<0.05, P<0.01), and MPO-positive rates and mean optical density values in brain tissues were decreased (P<0.01). ConclusionHuanglian Jiedutang can effectively regulate the expression of neutrophil-related chemokines in exosomes from plasma and brain tissues of MCAO mice, thereby reducing neutrophil infiltration in the brain and achieving therapeutic effects.
8.Effect of Huanglian Jiedutang on Focal Cerebral Ischemia-reperfusion Injury in Mice and Its Impact on Oligodendrocyte-related Gene Expression
Zijin SUN ; Kai WANG ; Haojia ZHANG ; Linjing SONG ; Zhaoyi WANG ; Wenxiu XU ; Jing JI ; Yonglin SHAN ; Qianqian SHI ; Xueqian WANG ; Fafeng CHENG ; Qingguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):54-63
ObjectiveTo evaluate the therapeutic effects of Huanglian Jiedutang on cerebral infarction injury in a mouse model of middle cerebral artery occlusion (MCAO) and to explore its mechanism of action on oligodendrocytes, particularly its potential in myelin repair. MethodsMultiple experimental approaches were used to evaluate cerebral ischemic injury and the effects of drug intervention. Laser speckle imaging was used to detect changes in cerebral blood flow, 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to measure infarct volume, and neurological function was scored according to the Zea-Longa criteria. Brain tissues were routinely embedded in paraffin and subjected to HE and Nissl staining to observe tissue structure and neuronal damage. Animals were divided into a sham group (n=24), model group (n=24), Huanglian Jiedutang group (n=24), and Ginkgo biloba extract (GBE) group (n=18). After 1 week of acclimatization, intragastric administration was initiated. The sham and model groups received normal saline, the Huanglian Jiedutang group was administered 1.82 g·kg-1, and the GBE group was administered 0.432 g·kg-1 after preparation as a 2.16 g·L-1 solution. All groups were treated for 5 consecutive days at a dose of 0.2 mL·(10 g)-¹·d-¹. The MCAO model was established after the final administration on day 6. Single-cell RNA sequencing was used to analyze brain tissue cellular composition and changes in oligodendrocyte subpopulations. Distinct subpopulations were identified by Uniform manifold approximation and projection (UMAP) dimensionality reduction and unsupervised clustering, and marker gene expression was analyzed. Pathway enrichment and causal inference were further performed using IPA. Finally, real-time quantitative PCR was used to verify mRNA expression changes of myelin-related genes. ResultsCompared with the sham group, the model group showed significantly increased neurological function scores (P<0.01), significantly impaired blood flow (P<0.01), significantly enlarged cerebral infarct area (P<0.01), and pathological changes including disordered cortical structural arrangement, aggravated cytoplasmic vacuolization, and increased Nissl bodies. Compared with the model group, the Huanglian Jiedutang and GBE groups showed significantly decreased neurological function scores (P<0.01), markedly restored blood flow levels (P<0.01), significantly reduced cerebral infarct area (P<0.01), and improvement in cortical structural disorder, alleviation of cytoplasmic vacuolization, and a reduction in Nissl bodies. Single-cell data showed that a myelin-associated oligodendrocyte (Mye-OL) subpopulation existed among oligodendrocytes, which was closely related to myelin generation. Compared with the sham group, the number of Mye-OL cells decreased in the model group. Compared with the model group, the number of Mye-OL cells increased in the Huanglian Jiedutang group. This subpopulation promoted the expression of myelin-related genes, including MOG, MBP, and MAG, via transcription factors such as OLIG1, OLIG2, NKX2-2, and SOX10, thereby regulating myelin generation, restoring cognition, and exerting therapeutic effects on acute cerebral infarction. Compared with the sham group, the mRNA expression levels of OLIG1, OLIG2, NKX2-2, and SOX10 were significantly downregulated in the model group (P<0.01), and the mRNA expression levels of myelin-related genes, including MOG, MBP, and MAG, were also significantly downregulated (P<0.01). In contrast, compared with the model group, the Huanglian Jiedutang and GBE groups showed significantly upregulated mRNA expression levels of OLIG1, OLIG2, NKX2-2, and SOX10 (P<0.01), and significantly upregulated mRNA expression levels of myelin-related genes, including MOG, MBP, and MAG (P<0.01). ConclusionHuanglian Jiedutang exerts therapeutic effects on acute cerebral infarction by regulating the OLIG1/2-NKX2-2-SOX10 signaling pathway to promote myelin generation by Mye-OL cells.
9.Regulatory Role of Huanglian Jiedutang in Microglial Metabolic Reprogramming to Suppress Neuroinflammatory Damage Based on Single-cell Transcriptomics
Zijin SUN ; Haojia ZHANG ; Kai WANG ; Linjing SONG ; Chuanzun WANG ; Wen WANG ; Jing JI ; Zhaoyi WANG ; Wenxiu XU ; Qingguo WANG ; Xueqian WANG ; Fafeng CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):64-73
ObjectiveTo investigate the characteristics of metabolic reprogramming during cerebral ischemia-reperfusion injury using single-cell transcriptome sequencing, analyze the heterogeneity of microglial populations, and evaluate the interventional effects of Huanglian Jiedutang on metabolic abnormalities and neuroinflammation. MethodsA transient middle cerebral artery occlusion (tMCAO) model was used to establish ischemic stroke in mice. Local cerebral blood flow changes were monitored by laser speckle imaging. Neurological impairment was evaluated using the Zea-Longa score, and histopathological damage in brain tissue was observed by HE and Nissl staining. Animals were divided into a sham group, model group, Huanglian Jiedutang group, and Ginkgo biloba extract (GBE) group. After 1 week of acclimatization, intragastric administration was initiated. The sham and model groups received normal saline, the Huanglian Jiedutang group was administered 1.82 g·kg-1, and the GBE group was administered 0.432 g·kg-1 after preparation as a 2.16 mg/mL solution. All groups were treated for 5 consecutive days (0.2 mL/10 g/day), and the tMCAO model was established on day 6 after the final administration. At the molecular level, single-cell RNA sequencing was performed on ischemic hemisphere tissue. Non-negative matrix factorization (NMF) was used to cluster microglial subpopulations, combined with differential expression analysis, metabolic reprogramming assessment, and inflammatory factor correlation analysis to elucidate their functional characteristics in ischemia-reperfusion injury. Transcription factor enrichment analysis was further conducted to identify key regulatory nodes. Finally, PCR was used to detect mRNA expression changes of relevant genes to validate the single-cell sequencing results. ResultsCompared with the sham group, the model group showed increased neurological function scores (P<0.01), decreased blood flow levels (P<0.01), disordered cortical structure, increased cytoplasmic vacuolization, and increased Nissl bodies. Compared with the model group, the Huanglian Jiedutang and GBE groups showed decreased neurological function scores (P<0.01), increased blood flow levels (P<0.01), alleviated cortical structural disorder, reduced cytoplasmic vacuolization, and decreased Nissl bodies. Single-cell analysis showed that microglia could be divided into five subpopulations. Among them, clusters 3 and 5 exhibited significant pro-inflammatory phenotypes, with marked activation of hypoxia and NF-κB signaling pathways, and were identified as pro-inflammatory subpopulations. Clusters 1 and 2 were enriched in Wnt/β-catenin and transforming growth factor(TGF)-β signaling pathways and exhibited prominent anti-inflammatory and reparative characteristics. Meanwhile, glycolysis-related genes, such as HK2, PFKP, and LDHA, were significantly upregulated in the pro-inflammatory subpopulations. Correlation analysis showed that the expression levels of inflammatory molecules were positively correlated with glycolysis-related gene expression levels, whereas the expression levels of reparative and anti-inflammatory molecules were negatively correlated with glycolysis-related gene expression levels, indicating that microglia rely on the glycolytic pathway for energy acquisition under ischemic conditions. Further single-cell transcriptome analysis revealed that Huanglian Jiedutang effectively downregulated key genes driving metabolic reprogramming (such as HK2, PFKP, and LDHA), significantly reduced the proportion of microglial subpopulations accompanied by glycolytic reprogramming, and inhibited their transformation toward a damage phenotype, thereby reducing inflammatory injury. Meanwhile, compared with the sham group, the mRNA expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor(TNF)-α, CCL2, CXCL2, and CSF3 were significantly upregulated (P<0.01) in the model group, whereas the mRNA expression levels of endothelial- and pericyte-related functional genes, including RGS5, PECAM1, VEGFB, and NOS3, were significantly downregulated (P<0.01). In contrast, compared with the model group, the Huanglian Jiedutang and GBE groups showed significantly decreased mRNA expression levels of IL-1β, IL-6, TNF-α, CCL2, CXCL2, and CSF3 (P<0.01), and significantly increased mRNA expression levels of endothelial- and pericyte-related functional genes, including RGS5, PECAM1, VEGFB, and NOS3 (P<0.01). ConclusionHuanglian Jiedutang exerts neuroprotective effects by regulating the metabolic reprogramming state of microglia and modulating their inflammatory levels, thereby inhibiting neuroinflammatory injury.
10.Treatment of Liver Cancer by Intervening TGF-β Signaling Pathway with Traditional Chinese Medicine: A Review
Hao CHENG ; Haohao GUO ; Jun SUN ; Juan XUE ; Chunyan JI ; Shiyi LI ; Yuxue DING ; Huaqiang YUE
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):318-326
Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β (TGF-β) regulates cell differentiation, proliferation, apoptosis, and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years, with the continuous exploration of the mechanism of liver cancer, it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine (TCM) provides a unique perspective for the classification, diagnosis, and treatment of liver cancer with its comprehensive regulatory effects of multi-components, multi-targets, and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest, apoptosis, autophagy, et al, while the pro-cancerous mechanisms included promoting cancer cell proliferation, invasion and metastasis, immunosuppression, angiogenesis, et al. The TCM compounds intervening this pathway were sorted out, including Jianpi Huayu compound, Fuyang Baoyuan compound, Yipi Yanggan compound, Fuzheng Jiedu compound, compound Astragalus and Salvia, Biejia Jianwan, Dahuang Zhechong pill, and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea, Dendrobii Caulis, Gleditsia sinensis, and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids, alkaloids, glycosides, phenolics, terpenoids, polysaccharides, and other kinds of compounds. At the same time, it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells, blocking the cell cycle, and inhibiting liver cancer cell proliferation, migration, invasion, angiogenesis, immune escape, etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal, thereby exerting positive anti-tumor effects, opening up a new direction for the precise targeted treatment of liver cancer, and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

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