1.Modified Xiehuangsan Regulates Microglial Polarization and TLR4/MyD88/NF-κB Pathway to Treat Tic Disorders in Rats
Mengjie ZHAO ; Qiong ZHAO ; Cuiling YANG ; Hongyun ZHOU ; Xiangjuan SUN ; Xinyi GUO ; Sajiyue HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):10-18
ObjectiveTo explore the mechanism of modified Xiehuangsan in treating tic disorders (TD) based on microglial polarization and the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor (NF)-κB pathway. MethodsSeventy-two Sprague-Dawley (SD) rats were randomly assigned into six groups: control, model, tiapride (0.025 g·kg-1), and low-, medium-, and high-dose (12, 24, 48 g·kg-1, respectively) modified Xiehuangsan, with 12 rats in each group. Except the control group, the other groups received intraperitoneal injection of 3,3'-iminodipropionitrile (IDPN) for 7 consecutive days for the modeling of TD. After successful modeling, the control and model groups were given normal saline via gavage, and the other groups were administrated with corresponding drugs by gavage. After 28 days of continuous intervention, rat behaviors were observed, and the modified Xiehuangsan group showing the best anti-TD effect was selected for deciphering the treatment mechanism. Hematoxylin and eosin staining was conducted to observe morphological changes in the rat striatum. Immunohistochemistry was employed to detect the expression of CD16 and CD206 in the striatum. Real-time PCR was employed to measure the mRNA levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), IL-4, TLR4, MyD88, and NF-κB p65 in the striatum. Western blot was employed to determine the protein levels of ionized calcium-binding adapter molecule 1 (Iba1), Fc receptor family for immunoglobulin (Ig)G type Ⅲ (CD16), mannose receptor (CD206), TLR4, MyD88, and NF-κB p65 in the striatum. ResultsCompared with the control group, the model group showed increased stereotyped behaviors, locomotor activity, total movement distance, and movement speed, shortened resting time (P<0.01), and noticeable pathological changes in the striatum. Compared with the model group, the tiapride group and modified Xiehuangsan groups exhibited reduced stereotyped behavior, locomotor activity, total movement distance, and movement speed, prolonged resting time (P<0.05, P<0.01), and alleviated pathological changes in the striatum. Among the modified Xiehuangsan groups, the high-dose group had the best intervention effect and the mildest pathological changes. Therefore, the high-dose group was selected for further research. Compared with the control group, the modeling of TD increased Iba1 and CD16 expression (P<0.05, P<0.01), up-regulated the mRNA levels of IL-1β and TNF-α (P<0.05, P<0.01), down-regulated the mRNA level of IL-4 (P<0.05), up-regulated the mRNA and protein levels of TLR4 and MyD88 (P<0.05, P<0.01), and up-regulated the protein level of NF-κB p65 (P<0.01). Compared with the model group, modified Xiehuangsan reduced Iba1 and CD16 expression (P<0.05, P<0.01), up-regulated the protein level of CD206 (P<0.05, P<0.01), down-regulated the mRNA levels of IL-1β and TNF-α (P<0.05), up-regulated the mRNA level of IL-4 (P<0.01), and down-regulated the mRNA and protein levels of TLR4, MyD88, and NF-κB p65 (P<0.05, P<0.01). ConclusionModified Xiehuangsan demonstrated a definite therapeutic effect on TD in rats. It may reduce neuroinflammation in TD rats by regulating the polarization of microglia in the striatum via the TLR4/MyD88/NF-κB signaling pathway.
2.Traditional Chinese Medicine Regulates Metabolic Reprogramming Mechanism to Intervene in Inflammation-cancer Transformation of Gastric Mucosa
Xinyi LIANG ; Jiale MA ; Huizhen LI ; Shuangmei ZHAO ; Mengtong LENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):252-260
Gastric cancer (GC) has an insidious onset and is mostly diagnosed in the middle and late stages after clinical detection. It is one of the malignant tumors with high incidence and mortality rates in the world. At present, the treatment plans are optimized mainly in terms of surgery, radiotherapy, and intervention, while the endpoints of clinical trials, such as patients' overall survival, progression-free survival, and disease-free survival, are still unsatisfactory. Therefore, effectively delaying the dynamic inflammation-cancer transformation has become an urgent bottleneck in the prevention and treatment of GC. In 1920s, Professor Otto Warburg discovered the phenomenon that tumor cells can accelerate glycolysis. Since then, the abnormal metabolic network inside tumor cells has gradually entered into researchers' view, and the hot academic research topic of metabolic reprogramming has been proposed. Tumor cells can meet their own energy consumption and adapt to external changes by adjusting their metabolic pathways to achieve rapid proliferation. In recent years, traditional Chinese medicine (TCM) is resolutely pursuing innovation in inheritance and the continuous refinement of research has led to the precision-oriented transition of TCM theories. Therefore, linking TCM with the treatment of tumors and precancerous diseases has certain research connotations. The searching and review of the publications in this field revealed that the number of publications in tumor-related metabolism increased dramatically, while there were only a few studies using TCM as a therapeutic solution. The research group has long been committed to the study of precancerous lesions of gastric cancer (PLGC) in Chinese and Western medicine. This article explained the dynamic process of inflammation-cancer transformation from the perspective of spleen deficiency-Qi stagnation-collateral stasis. The molecules of hypoxia-inducible factor (HIF)-1α, cancer-Myc (c-Myc), apolipoprotein E (APOE) and pyruvate kinase M2 (PKM2) were selected to reflect the biological connotation of inflammation-cancer transformation. The current achievements of TCM in regulating the metabolic reprogramming to intervene in inflammation-cancer transformation were summarized, with a view to providing more information for TCM to intervene in the inflammation-cancer transformation of gastric mucosa.
3.Correlation between ICAM-1, CD62P, and inflammatory factors and cerebral artery stenosis in patients with acute cerebral infarction
Yunying WU ; Tao HAN ; Yanbo CHENG ; Qian ZHAO
Journal of Public Health and Preventive Medicine 2025;36(5):89-92
Objective To investigate the correlation between levels of intercellular adhesion molecule-1 (ICAM-1), platelet surface P-selectin (CD62P), and inflammatory factors and cerebral artery stenosis in patients with acute cerebral infarction (ACI). Methods A total of 305 patients with ACI complicated with cerebral artery stenosis admitted to Zhongwu Hospital of Suqian City and Xinyi People's Hospital from January 2021 to December 2023 were selected as the research subjects. According to the degree of cerebral artery stenosis, they were divided into grade I group (stenosis degree<50%, n=85), grade II group (stenosis degree of 50%-75%, n=128), and grade III group (stenosis degree>75%, n=92). Sixty-eight ACI patients without cerebral artery stenosis during the same period were included in the reference group. The levels of serum inflammatory factors [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8)], ICAM-1 and CD62P were compared among the four groups. Spearman analysis was used to analyze the correlation between each factor and degree of cerebral artery stenosis. Results The levels of CRP, TNF-α, IL-6, IL-8, ICAM-1 and CD62P in the grade I, II and III groups were higher than those in the reference group. The levels of these factors were higher in the grade II and III groups than those in the grade I group, while the levels of various factors were higher in the grade III group than those in the grade II group (P<0.05). Spearman analysis showed that CRP, TNF-α, IL-6, IL-8, ICAM-1, and CD62P were positively correlated with the degree of cerebral artery stenosis in patients with ACI complicated with cerebral artery stenosis (P<0.05). Conclusion The levels of serum inflammatory factors, ICAM-1 and CD62P are significantly correlated with cerebral artery stenosis degree in patients with ACI.
4.Traditional Chinese Medicine Regulates Metabolic Reprogramming Mechanism to Intervene in Inflammation-cancer Transformation of Gastric Mucosa
Xinyi LIANG ; Jiale MA ; Huizhen LI ; Shuangmei ZHAO ; Mengtong LENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):252-260
Gastric cancer (GC) has an insidious onset and is mostly diagnosed in the middle and late stages after clinical detection. It is one of the malignant tumors with high incidence and mortality rates in the world. At present, the treatment plans are optimized mainly in terms of surgery, radiotherapy, and intervention, while the endpoints of clinical trials, such as patients' overall survival, progression-free survival, and disease-free survival, are still unsatisfactory. Therefore, effectively delaying the dynamic inflammation-cancer transformation has become an urgent bottleneck in the prevention and treatment of GC. In 1920s, Professor Otto Warburg discovered the phenomenon that tumor cells can accelerate glycolysis. Since then, the abnormal metabolic network inside tumor cells has gradually entered into researchers' view, and the hot academic research topic of metabolic reprogramming has been proposed. Tumor cells can meet their own energy consumption and adapt to external changes by adjusting their metabolic pathways to achieve rapid proliferation. In recent years, traditional Chinese medicine (TCM) is resolutely pursuing innovation in inheritance and the continuous refinement of research has led to the precision-oriented transition of TCM theories. Therefore, linking TCM with the treatment of tumors and precancerous diseases has certain research connotations. The searching and review of the publications in this field revealed that the number of publications in tumor-related metabolism increased dramatically, while there were only a few studies using TCM as a therapeutic solution. The research group has long been committed to the study of precancerous lesions of gastric cancer (PLGC) in Chinese and Western medicine. This article explained the dynamic process of inflammation-cancer transformation from the perspective of spleen deficiency-Qi stagnation-collateral stasis. The molecules of hypoxia-inducible factor (HIF)-1α, cancer-Myc (c-Myc), apolipoprotein E (APOE) and pyruvate kinase M2 (PKM2) were selected to reflect the biological connotation of inflammation-cancer transformation. The current achievements of TCM in regulating the metabolic reprogramming to intervene in inflammation-cancer transformation were summarized, with a view to providing more information for TCM to intervene in the inflammation-cancer transformation of gastric mucosa.
5.Molecular Mechanism of Endometrial Cell Senescence During Window of Implantation in Unexplained Recurrent Spontaneous Abortion and Intervention Effect of Bushen Huoxue Method
Xiaoxuan ZHAO ; Jing MA ; Xinyi DING ; Hongli ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):106-115
ObjectiveThis study aims to explore the molecular mechanism of endometrial cell senescence during the window of implantation (WOI) in unexplained recurrent spontaneous abortion (URSA) and the intervention effect of Bushen Huoxue method through the integrated research strategy of bioinformatics, machine learning, and animal experiments. MethodThe microarray gene sets of the endometrium of healthy women of childbearing age and patients with URSA during WOI were retrieved through the gene expression omnibus (GEO) database. The differentially expressed genes (DEGs) of URSA were screened by using the limma package of R language. Weighted gene co-expression network analysis (WGCNA) was used to obtain the most relevant module genes of URSA, and the gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis were performed. Gene sets related to cell senescence were obtained by the Human Gene Database (GeneCards) and Online Mendelian Inheritance in Man (OMIM). The Venn online mapping software was used to screen the intersection genes of DEGs of URSA, the most relevant module genes, and the genes related to cell senescence. Then, the search tool for the retrieval of interacting genes/proteins (STRING) was used to analyze the protein-protein interaction (PPI) network of the interacting genes, and the hub genes were screened through Cytohubba. In addition, the least absolute selection and shrinkage operator (LASSO) and random forest algorithm were used to screen diagnostic genes related to cell senescence of URSA. Finally, mouse models with URSA were established and randomly divided into the model group, Bushen Huoxue group, and aspirin group, with six mice in each group, and six normal pregnant mice were selected as a blank group. The Bushen Huoxue group was given Shoutai pill combined with Danggui powder formula granular liquid (12.35 g·kg-1) by gavage, and the aspirin group was gavaged with aspirin at a dose of 0.011 mL·g-1. The blank group and model group were given the same volume of distilled water by gavage. Drug administration began on the first day after the discovery of vaginal thrombus (recorded as the first day of gestation, i.e. GD1), and the mice were sacrificed 12 hours after administration at GD5. The endometrium samples were collected. Quantitative real-time polymerase chain reaction (Real-time PCR) and immunofluorescence were used to detect the expression of cell senescence-related diagnostic genes in the endometrium tissue of URSA mice during WOI and the intervention effect of the Bushen Huoxue method. ResultThe gene set of the GSE165004 microarray was included for bioinformatics analysis. According to the “limma” package of R language, 585 DEGs of URSA were selected (P<0.05). WGCNA results suggested that the gene in the magenta module was the most closely related to URSA (r=0.32, P<0.05). The results of the KEGG analysis of the magenta module suggested that the genes were mainly enriched in cell senescence, Hippo, and NF-κB signaling pathways (P<0.05). In addition, 2 138 genes related to cell senescence were obtained from Genecards and OMIM websites. The Venn online mapping tool was used to obtain 27 intersecting genes of DEGs of URSA, the magenta module genes, and cell senescence-related genes, namely, cell senescence-related DEGs in endometrium tissue during WOI of URSA. PPI analysis showed that synuclein alpha (SNCA), heme oxygenase 1 (HOMX1), and matrix metallopeptidase 1 (MMP1) were hub genes. Besides, four diagnostic genes were identified by LASSO regression and random forest, including gelsolin (GSN), cyclin2 (CCND2), RB binding protein 8 (RBBP8), and lysophosphatidic acid receptor 1 (LPAR1). Animal experiments confirmed that the mRNA level and fluorescence intensity of GSN were significantly increased (P<0.05), while the mRNA and fluorescence intensity of CCND2, LPAR1, and RBBP8 were significantly decreased (P<0.05) in the model group when compared with the blank group. The expression level of GSN was decreased (P<0.05), while the expression levels of CCND2, LPAR1, and RBBP8 were remarkably increased (P<0.05) in the Bushen Huoxue group when compared with the model group. ConclusionThe senescence of endometrial cells during WOI of URSA is related to multiple genes. Bushen Huoxue method can act on multiple targets that are related to cell senescence, which may be the key mechanism of improving endometrial receptivity in URSA.
6.Analysis on the differentiation and treatment of depression based on the theory of "yang moving and dispersing"
Yiming LI ; Xinyi XU ; Yueyun LIU ; Xin ZHAO
Journal of Beijing University of Traditional Chinese Medicine 2024;47(8):1070-1074
Depression,as a common mental illness in the world,has troubled hundreds of millions of patients,affecting the normal life and work of patients,and in serious cases,suicidal tendencies may occur. Depression can be classified into the categories of stagnation syndrome,running piglet,lily disease,and other diseases in traditional Chinese medicine,the mechanism of the disease is mostly related to depression and stagnation,and the clinical symptoms such as low mood and oppression in chest often appear. Based on ZHANG Jingyue's theory of "yang moving and dispersing",under the pathological state of "yang moving and dispersing",yang disperses and is deficient,leading to yang immobile,and then becomes depression,which ultimately leading to yang depression and the onset of the disease. Clinical treatment should be based on the basic therapeutic method of promoting yang and resolving depression,warming and tonifying yang qi,and regulating qi movement,so as to carry out the syndrome differentiation and treatment of depression.
7.Environmental and occupational health move forward together to create a new era of health: Minutes of the Eighteenth National Postgraduates Symposium on Environmental and Occupational Medicine
Yunjia ZHAO ; Yuan WANG ; Jiao CHEN ; Chenchen ZHANG ; Xinyi GU ; Di YI ; Xiaoyu WANG
Journal of Environmental and Occupational Medicine 2024;41(11):1297-1300
The 18th National Postgraduate Symposium on Environmental and Occupational Medicine, co-sponsored by the Editorial Board of Journal of Environmental and Occupational Medicine and the School of Public Health of Sun Yat-sen University, was successfully held on August 22 to 25, 2024 in Guangzhou, Guangdong Province, China. Adhering to the theme of “Research and practice: Healing the schism”, the symposium aims to enliven academic thinking, expand research horizons, encourage innovation, enhance inter-university exchanges, and strengthen talent cultivation, especially to promote the close integration of academic research and public health practice. A total of 105 papers were received from 38 universities. The symposium also gathered about 160 participants, mainly authors postgraduates from universities and experts and professors in the field of environmental and occupational medicine. All the participants discussed the latest research advances and future development trends of environmental and occupational medicine, and endeavor to apply the research results in public health practice.
8.Self Precipitation Analysis of Erhuang Powder and Its Effect on HeLa Cells
Xinyi WANG ; Shuyu ZHAO ; Xiufeng YU ; Feng GUAN ; Weinan LI ; Fengjuan HAN ; Yanhong WANG
Chinese Journal of Modern Applied Pharmacy 2024;41(12):1604-1614
OBJECTIVE
To explore the self precipitation source of Erhuang powder, determine the content of related components and its efficacy on HeLa cells.
METHODS
Bifurcation study to identify the main compatibility of precipitating. The self precipitation, supernatant and extract of Erhuang powder were analyzed by UHPLC-Q-Exactive MS. The main compounds in Coptidis Rhizoma and Catechu, catechin, epicatechin, epicberberine, coptisine, berberine and palmatine were selected as controls. A analysis method of UHPLC for self precipitation, supernatant and extract of Erhuang powder was established and the related components were quantitatively determined. The effects of self precipitation, supernatant and extract on HeLa cells were evaluated by MTT method and flow cytometry.
RESULTS
A slight flocculation precipitate appeared when the decoction of Erhuang powder was mixed in pairs, while a large amount of flocculation appeared when the decoction of Coptidis Rhizoma and Catechu water was mixed. The self precipitation, supernatant and extract samples contained 39 compounds, which were mainly alkaloids and phenolic acids. The contents of catechin and berberine in the 6 index components were mostly, which accounted for 73.56% of the total content of the index components in self precipitation and 61.89% of the total content of the index components in extract. Inhibition effect on HeLa cells: extract ≈ self precipitation > supernatant, and inducing apoptosis: self precipitate ≈ extract, supernatant had no apoptosis-inducing effect.
CONCLUSION
Coptidis Rhizoma-Catechu is the main compatible formula for precipitation formation. The self precipitation and extracts of Erhuang powder are mainly alkaloids and phenolic acids, among which berberine and catechin are high in content and can be used as representative components. The effect of self-precipitation and extract on HeLa cells was better than that of supernatant. This basically indicates that the self precipitation components and pharmacological effects of Erhuang powder are similar to those of the extract.
9.Opportunities and challenges of marginal donor liver
Xinyi LU ; Fei TENG ; Hong FU ; Yuanyu ZHAO ; Liye ZHU ; Jiayong DONG ; Jiaxi MAO ; Wenyuan GUO
Organ Transplantation 2024;15(3):463-468
With persistent breakthrough and maturity of surgical procedures and postoperative immunosuppressive therapy, the survival rate of liver transplant recipients and grafts has been significantly increased. The shortage of donor liver has become the main obstacle for clinical development of liver transplantation. How to expand the source of donor liver has become an urgent issue. Groundbreaking progresses have been made in the use of common marginal donor livers in clinical liver transplantation, such as elderly donor liver, steatosis donor liver, viral hepatitis donor liver and liver from donation after cardiac death. Nevertheless, multiple restrictions still exist regarding the use of marginal donor liver. Consequently, the definition of marginal donor liver and research progress in the application of common marginal donor livers were reviewed, and the opportunities and challenges of mariginal donoor liver were illustrated, aiming to provide reference for expanding the donor pool for clinical liver transplantation and bringing benefits to more patients with end-stage liver disease.
10.Expression and role of triggering receptor expressed on myeloid cells 2 in high glucose-treated microglia
Zhaohui WANG ; Xiao LIU ; Yue ZHOU ; Xinyi WEI ; Yue WANG ; Junfa LI ; Li ZHAO
Basic & Clinical Medicine 2024;44(2):167-173
Objective To explore the expression of triggering receptor expressed on myeloid cells 2(TREM2)in high-glucose microglia and to investigate the role of TREM2 in the proliferation,migration and phagocytosis of high-glucose microglia.Methods Microglia cells were divided into control group and high-glucose treatment group(67.5 mmol/L glucose,24 h).The microglia cells were counted and the expression of Iba1 and TREM2 was de-tected.TREM2 siRNA was transfected to detect the proliferation and migration of microglia.The amyloid β-peptide(Aβ)with a fluorescent tag was added to observe the phagocytosis of Aβ by microglia.Results Compared to normal microglia,the number of microglia significantly decreased after high-glucose treatment(P<0.001),while the ex-pression of TREM2 and Iba1 markedly increased(P<0.001).High glucose and TREM2 did not affect the prolifer-ation of microglia.Compared to the normal group,the migration of microglia significantly decreased after high-glu-cose treatment(P<0.05)and TREM2 did not affect the migration ability of high-glucose microglia.Compared to the normal group,the phagocytosis of Aβ by microglia significantly decreased in the high-glucose treated group(P<0.001).Furthermore,TREM2 knockdown further decreased the phagocytosis of Aβ by high-glucose microglia(P<0.001).Conclusions The expression of TREM2 in microglia significantly increases after high-glucose treat-ment,which significantly affects phagocytosis of Aβ by microglia.


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