1.Compound Xishu Granules Inhibit Proliferation of Hepatocellular Carcinoma Cells by Regulating Ferroptosis
Yuan TIAN ; Yuxi WANG ; Zhen LIU ; Yuncheng MA ; Hongyu ZHU ; Xiaozhu WANG ; Qian LI ; Jian GAO ; Weiling WANG ; Wenhui XU ; Ting WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):37-45
ObjectiveTo study the mechanism of compound Xishu granules (CXG) in inhibiting the proliferation of hepatocellular carcinoma cells by regulating ferroptosis. MethodsThe transplanted tumor model of human Huh7 was established with nude mice and the successfully modeled mice were randomized into model, Fufang Banmao (0.21 g·kg-1), low-dose (1.87 g·kg-1) CXG, medium-dose (3.74 g·kg-1) CXG, and high-dose (7.49 g·kg-1) CXG groups. Mice were administrated with drinking water or CXG for 28 days, and the body weight and tumor volume were measured every 4 days. Hematoxylin-eosin staining was employed to observe the histopathological changes of tumors. The cell-counting kit-8 (CCK-8) was used to examine the survival rate of Huh7 cells treated with different concentrations (0, 31.25, 62.5, 125, 250, 500, 1 000 mg·L-1) of CXG for 24 h and 48 h. CA-AM, DCFH-DA, and C11-BODIPY581/591 fluorescent probes were used to determine the intracellular levels of ferrous ion (Fe2+), reactive oxygen species (ROS), and lipid peroxide (LPO), respectively. The colorimetric method was employed to measure the levels of glutathione (GSH) and superoxide dismutase (SOD). Western blot was employed to determine the protein levels of glutathione peroxidase 4 (GPX4), transferrin receptor 1 (TFR1), and ferritin heavy chain 1 (FTH1), respectively. ResultsIn the animal experiment, compared with the model group, the drug treatment groups showed reductions in the tumor volume from day 12 (P<0.01). After treatment, the Fufang Banmao and low-, medium-, and high-dose CXG groups had lower tumor volume, relative tumor volume, and tumor weight than the model group (P<0.05), with tumor inhibition rates of 48.99%, 79.93%, 91.38%, and 97.36%, respectively. Moreover, the CXG groups had lower tumor volume and relative tumor volume (P<0.05 in all the three dose groups) and lower tumor weight (P<0.05 in medium-dose and high-dose groups) than the Fufang Banmao group. Compared with the model group, the drug treatment groups showed reduced number of tumor cells, necrotic foci with karyopyknosis, nuclear fragmentation, and nucleolysis, and the high-dose CXG group showed an increase in the proportion of interstitial fibroblasts. In the cell experiment, compared with the blank group, CXG reduced the survival rate of Huh7 cells in a dose-dependent manner after incubation for 24 h and 48 h (P<0.05). Compared with the blank group, the RSL3 group and the low-, medium-, and high-dose CXG groups showed a decrease in the relative fluorescence intensity of CA-AM and increases in the fluorescence intensity of DCFH-DA and fluorescence ratio of C11-BODIPY581/591, which indicated elevations in the levels of Fe2+ (P<0.01), ROS (P<0.05), and LPO (P<0.01), respectively. Compared with the blank group, the RSL3 and low-, medium-, and high-dose CXG groups showed lowered levels of GSH and SOD (P<0.05). In addition, the RSL3 group and the medium- and high-dose CXG groups showed down-regulated expression of GPX4 and FTH1 (P<0.05), and the low- and high-dose CXG groups presented up-regulated expression of TFR1 (P<0.05). ConclusionCXG suppresses the proliferation of hepatocellular carcinoma cells by inducing ferroptosis via downregulating the GSH-GPX4 signaling axis and increasing intracellular Fe2+and LPO levels.
2.Evaluation of Effect of Tongnaoyin on Blood-brain Barrier Injury in Acute Ischemic Stroke Patients Based on Dynamic Contrast-enhanced Magnetic Resonance Imaging
Yangjingyi XIA ; Shanshan LI ; Li LI ; Xiaogang TANG ; Xintong WANG ; Qing ZHU ; Hui JIANG ; Cuiping YUAN ; Yongkang LIU ; Zhaoyao CHEN ; Wenlei LI ; Yuan ZHU ; Minghua WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):140-146
ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke (AIS) patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method,the patients were assigned into a control group (32 cases) and an observation group (31 cases). The control group received conventional Western medical treatment,and the observation group took 200 mL Tongnaoyin after meals,twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment,the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans,rKep,and rVe values were obtained from the region of interest (ROI) of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment,the NIHSS and mRS scores declined in both groups,and the observation group had lower scores than the control group (P<0.05). After treatment,the rKtrans and rVe in the observation group were lower than those in the control group (P<0.01). ConclusionCompared with conventional Western medical treatment alone,conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients,thereby ameliorating neurological impairment after AIS to improve the prognosis.
3.Traditional Chinese Medicine Treats Sepsis by Regulating PI3K/Akt Pathway: A Review
Zhu LIU ; Jiawei WANG ; Jing YAN ; Jinchan PENG ; Mingyao XU ; Liqun LI ; Sheng XIE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):314-322
Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms such as bacteria. In addition to the manifestations of systemic inflammatory response syndrome and primary infection lesions, critical cases often have manifestations of organ hypoperfusion. The morbidity and mortality of sepsis have remained high in recent years, which seriously affect the quality of life of the patients. The pathogenesis of sepsis is complicated, in which uncontrollable inflammation is a key mechanism. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway plays a key role in mediating inflammation in sepsis. The available therapies of sepsis mainly include resuscitation, anti-infection, vasoactive drugs, intensive insulin therapy, and organ support, which show limited effects of reducing the mortality. Therefore, finding new therapeutic drugs is a key problem to be solved in the clinical treatment of sepsis. In recent years, studies have shown that traditional Chinese medicine (TCM) can regulate the PI3K/Akt pathway via multiple pathways, multiple effects, and multiple targets to inhibit inflammation and curb the occurrence and development of sepsis, which has gradually become a hot spot in the prevention and treatment of sepsis. Moreover, studies have suggested that TCM has unique advantages in the treatment of sepsis. TCM can regulate the PI3K/Akt signaling pathway to inhibit inflammation, reduce oxidative stress, and control apoptosis in the prevention and treatment of sepsis. Despite the research progress, a systematic review remains to be performed regarding the TCM treatment of sepsis by regulating the PI3K/Akt signaling pathway. After reviewing relevant papers published in recent years, this study systematically summarizes the relationship between PI3K/Akt pathway and sepsis and the role of TCM in the treatment of sepsis, aiming to provide new ideas for the potential treatment of sepsis and the development of new drugs.
4.Seasonal distribution characteristics, source analysis and health risk assessment of polycyclic aromatic hydrocarbons in PM2.5 in Lianyungang City in 2019-2023
Shengnan GAO ; Jinkun LI ; Li CHEN ; Zhengdong XYU ; Hongru ZHU ; Jian WANG ; Zhiyang YAO
Journal of Public Health and Preventive Medicine 2025;36(1):65-69
Objective To study the seasonal distribution characteristics of polycyclic aromatic hydrocarbons (PAHs) in PM2.5 in Lianyungang City, and analyze the sources of PAHs pollution, and to evaluate the health risks of PAHs in different seasons. Methods PM2.5 samples were collected regularly from January 2019 to December 2023, and 16 types of PAHs were determined by HPLC. Kruskal-Wallis H test was used to compare the concentrations of PM2.5 and PAHs in different years and seasons. The source of PAHs was analyzed by characteristic ratio and principal component analysis (PCA). Health risks were assessed using the BaP equivalent method and the incremental lifetime cancer risk (ILCR) model. Results The annual exceedance rates of PM2.5 and BaP in Lianyungang showed a decreasing trend from 2019 to 2023. PM2.5, total PAHs and PAHs monomers (except Ace, Flu and Acy) all showed significant seasonal differences, with the highest concentration in winter (P<0.001). The average proportion of 4-ring PAHs was the highest and the average proportion of 2-ring PAHs was the lowest. The proportion of 5-6 ring PAHs was relatively high in winter and spring. PM2.5and PAHs were negatively correlated with temperature, relative humidity and precipitation, and were positively correlated with atmospheric pressure. PM2.5 was negatively correlated with wind speed, while some PAHs monomers were positively correlated with wind speed. The characteristic ratio and PCA results showed that the main sources of PAHs in Lianyungang City were mixed sources of road dust and vehicle emissions, oil pollution sources and biomass combustion sources. The results of ILCR showed that the highest risk was found in adults, with males slightly higher than females. In Lianyungang, the maximum value of ILCR in winter was more than 10-6 in people over 9 years old. Conclusion The main sources of PAHs in PM2.5 in Lianyungang City are mixed sources of road dust and vehicle emissions, oil pollution sources, and biomass combustion sources. Under the current exposure level of PAHs in PM2.5, residents have a certain potential carcinogenic risk.
5.Mechanism of Intervening with Diarrhea-predominant Irritable Bowel Syndrome in Rats with Spleen Deficiency by Xingpi Capsules Through Regulating 5-HT-RhoA/ROCK2 Pathway
Gang WANG ; Lingwen CUI ; Xiangning LIU ; Rongxin ZHU ; Mingyue HUANG ; Ying SUN ; Boyang JIAO ; Ran WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):60-69
ObjectiveTo investigate the efficacy of Xingpi capsules (XPC) in treating diarrhea-predominant irritable bowel syndrome (IBS-D) with spleen deficiency and elucidate its potential molecular mechanisms. MethodsA rat model of IBS-D with spleen deficiency was established by administering senna leaf in combination with restrained stress and swimming fatigue for 14 d. Ten specific pathogen free (SPF)-grade healthy rats were used as the normal control group. After successful modeling, SPF-grade rats were randomly divided into a model group, a pinaverium bromide group (1.5 mg·kg-1), and low- and high-dose XPC groups (0.135 and 0.54 g·kg-1), with 10 rats in each group. Rats in the normal control group and the model group were given distilled water by gavage, while the remaining groups were administered corresponding drug solutions by gavage once a day for 14 consecutive days. The rat body weights and fecal condition were observed every day, and the Bristol score was recorded. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of 5-hydroxytryptamine (5-HT) in serum and colon tissue. Transmission electron microscopy was used to observe the microvilli and tight junctions in the colon. The integrity of the colonic barrier, intestinal motility, and expression of related pathway proteins were evaluated by hematoxylin-eosin (HE) staining, immunohistochemistry, and Western blot. ResultsCompared with those in the normal control group, rats in the model group showed a significantly decreased body weight and increased diarrhea rate, diarrhea grade, and Bristol score (P<0.01). HE staining revealed incomplete colonic mucosa in the model group, with evident congestion and edema observed. Electron microscopy results indicated decreased density and integrity of the colonic barrier, shedding and disappearance of microvilli, and significant widening of tight junctions. The expression levels of colonic tight junction proteins Occludin and Claudin-5 were downregulated (P<0.01), and the levels of 5-HT in serum and colon tissue were elevated (P<0.01). The small intestine propulsion rate significantly increased (P<0.01), and the expression of contractile proteins Ras homolog family member A (RhoA) and Rho-associated coiled-coil containing protein kinase 2 (ROCK2) in colon and phosphorylation of myosin light chain (MLC20) were upregulated (P<0.01). Compared with the model group, the treatment groups showed alleviated diarrhea, diarrhea-associated symptoms, and pathological manifestations of colon tissue to varying degrees. Specifically, high-dose XPC exhibited effectively relieved diarrhea, promoted recovery of colonic mucosal structure, significantly reduced congestion and edema, upregulated expression of Occludin and Claudin-5 (P<0.01), decreased levels of 5-HT in serum and colon tissue (P<0.05,P<0.01), significantly slowed small intestine propulsion rate (P<0.01), and significantly downregulated expression of contractile proteins RhoA and ROCK2 in colon and phosphorylation of MLC20 (P<0.05,P<0.01). ConclusionXPC effectively alleviates symptoms of spleen deficiency and diarrhea and regulates the secretion of brain-gut peptide. The characteristics of XPC are mainly manifested in alleviating IBS-D with spleen deficiency from the aspects of protecting intestinal mucosa and inhibiting smooth muscle contraction, and the mechanism is closely related to the regulation of the 5-HT-RhoA/ROCK2 pathway expression.
6.Analysis of Dynamic Change Patterns of Color and Composition During Fermentation of Myristicae Semen Koji
Zhenxing WANG ; Mengmeng FAN ; Le NIU ; Suqin CAO ; Hongwei LI ; Zhenling ZHANG ; Hanwei LI ; Jianguang ZHU ; Kai LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):222-229
ObjectiveTo explore the changes in volatile components, total polysaccharides, enzyme activity, and chromaticity value of Myristicae Semen Koji(MSK) during the fermentation process, and conduct correlation analysis. MethodsBased on gas chromatography-mass spectrometry(GC-MS), the changes of volatile components in MSK at different fermentation times were identified. The phenol sulfuric acid method, dinitrosalicylic acid method(DNS), and carboxymethyl cellulose sodium salt method(CMC-Na) were used to investigate the total polysaccharide content, amylase activity, and cellulase activity during the fermentation process. Visual analysis technology was used to explore the changes in chromaticity values, revealing the fermentation process of MSK and the dynamic changes of various measurement indicators, partial least squares-discriminant analysis(PLS-DA) was used to explore the differential compounds of MSK at different fermentation degrees, and Pearson correlation analysis was used to explore the correlation between volatile components of MSK and total polysaccharides, enzyme activity, and chromaticity values. ResultsA total of 60 volatile compounds were identified from MSK, the relative contents of components such as (+)-α-pinene, β-phellandrene, β-pinene, (+)-limonene, and p-cymene obviously increased, while the relative contents of components such as safrole, methyl isoeugenol, methyleugenol, myristicin, and elemicin significantly decreased. During the fermentation process, the total polysaccharide content showed an upward trend, while the activities of amylase and cellulase showed an initial increase followed by a decrease, and reached their maximum value at 40 h. the overall brightness(L*) and total color difference(ΔE*) gradually increased, while the changes in red-green value(a*) and yellow-blue value(b*) were not obvious. PLS-DA results showed that MSK could be clearly distinguished at different fermentation times, and 13 differential biomarkers were screened out. Pearson correlation analysis results showed that the contents of α-terpinene, β-phellandrene, methyleugenol, β-cubebene and myristic acid had an obvious correlation with chromaticity values. ConclusionAfter fermentation, the volatile components, total polysaccharides, amylase activity, and cellulase activity of MSK undergo significant changes, and there is a clear correlation between them and chromaticity values, which reveals the dynamic changes in the fermentation process and related indicators of MSK, laying a foundation for the quality control.
7.Regulation of Signaling Pathways Related to Myocardial Infarction by Traditional Chinese Medicine: A Review
Wenjun WU ; Chidao ZHANG ; Jingjing WEI ; Xue LI ; Bin LI ; Xinlu WANG ; Mingjun ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):321-330
The pathological changes of myocardial infarction (MI) are mainly characterized by progressive myocardial ischemic necrosis, decline in cardiac diastolic function, thinning of the ventricular wall, and enlargement of the ventricles. The clinical manifestations include myocardial ischemia, heart failure, arrhythmia, shock, and even sudden cardiac death, rendering MI one of the most perilous cardiovascular diseases. Currently, the clinical treatment for MI primarily involves interventional procedures and drug therapy. However, due to their significant side effects and high complication rates associated with these treatments, they fail to ensure a satisfactory quality of life and long-term prognosis for patients. On the other hand, traditional Chinese medicine has demonstrated remarkable potential in improving patient prognosis while reducing side effects. Research has elucidated that various signaling pathways such as nuclear transcription factor-κB (NF-κB), adenosine 5̒-monophosphate-activated protein kinase (AMPK), transforming growth factor-β (TGF-β)/Smads, mitogen-activated protein kinase (MAPK), Wnt/β-catenin (β-catenin), and phosphatidylinositol 3-kinase (PI3K)/protein kinase B(Akt) play crucial roles in regulating the occurrence and development of MI. Effectively modulating these signaling pathways through its therapeutic interventions, traditional Chinese medicine can enhance MI management by inhibiting apoptosis, providing anti-inflammatory properties, alleviating oxidative stress levels, and resisting myocardial ischemia. Due to its notable efficacy and favorable safety, it has become an area of focus in clinical practice.
8.Exploring the Correlation between Pyroptosis and Immune Microenvironment Dysregulation in Rheumatoid Arthritis from the Perspective of "Ying Decline and Wei Attack"
Yancun LI ; Shu ZHU ; Yuhan WANG ; Yuan QU ; Yuan LIU ; Ping JIANG
Journal of Traditional Chinese Medicine 2025;66(5):464-467
As a complex autoimmune disease, rheumatoid arthritis (RA) involves immune microenvironment dysregulation resulting from excessive activation of pyroptosis, which is a crucial factor in disease progression. Based on the theory of ying-wei in traditional Chinese medicine, "ying decline and wei attack" is considered the fundamental pathogenesis of RA. Pyroptosis serves as a microscopic manifestation of this concept, suggesting a potential correlation between "ying decline and wei attack" and pyroptosis nd immune microenvironment dysregulation in RA. Accordingly, treatment principles based on this theory are proposed: in the early stage of the disease, boosting wei to consolidate the exterior, and regulating ying to dispel pathogens; in the middle and late stages, harmonizing ying to remove stagnation, and nourishing its transformational source.
9.Safety analysis of Yttrium-90 resin microsphere selective internal radiation therapy on malignant liver tumors
Jia CAI ; Shiwei TANG ; Rongli LI ; Mingxin KONG ; Hongyan DING ; Xiaofeng YUAN ; Yuying HU ; Ruimei LIU ; Xiaoyan ZHU ; Wenjun LI ; Haibin ZHANG ; Guanwu WANG
Chinese Journal of Clinical Medicine 2025;32(1):24-29
Objective To explore the safety of Yttrium-90 resin microsphere selective internal radiation therapy (90Y-SIRT) on malignant liver tumors. Methods A retrospective analysis was conducted on 64 patients with malignant liver tumors who underwent 90Y-SIRT from February 2023 to November 2024 at Weifang People’s Hospital. The clinical characteristics of the patients and the occurrence of adverse reactions after treatment were analyzed to assess the safety of 90Y-SIRT. Results Among the 64 patients, there were 52 males (81.25%) and 12 females (18.75%); the average age was (56.29±11.08) years. Seven patients (10.94%) had tumors with maximum diameter of less than 5 cm, 38 patients (59.38%) had tumors with maximum diameter of 5-10 cm, and 19 patients (29.68%) had tumors with maximum diameter of greater than 10 cm. There were 47 cases (73.44%) of solitary lesions and 17 cases (26.56%) of multiple lesions; 53 cases (82.81%) were primary liver cancers and 11 cases (17.19%) were metastatic liver cancers. Of the 64 patients, 63 successfully completed the Technetium-99m macroaggregated albumin (99mTc-MAA) perfusion test and received the 90Y-SIRT; one patient received 90Y-SIRT after the second 99mTc-MAA perfusion test due to a work error. The most common adverse reactions included grade 1 alanine aminotransferase (ALT) elevation in 26 cases (40.62%) and grade 2 in 2 cases (9.37%), grade 1 aspartate aminotransferase (AST) elevation in 27 cases (42.18%) and grade 2 in 7 cases (10.93%); grade 1 nausea in 17 cases (26.56%) and grade 2 in 6 cases (9.37%); grade 1 abdominal pain in 12 cases (18.75%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%); grade 1 vomiting in 11 cases (17.18%), grade 2 in 5 cases (7.81%), and grade 3 in 1 case (1.56%). Conclusion The adverse reactions of 90Y-SIRT for treating malignant liver tumors are mild, indicating good safety.
10.Analysis and evaluation of platelet bank establishment strategy from the perspective of donor loss
Zheng LIU ; Yamin SUN ; Xin PENG ; Yiqing KANG ; Ziqing WANG ; Jintong ZHU ; Juan DU ; Jianbin LI
Chinese Journal of Blood Transfusion 2025;38(2):238-243
[Objective] To analyze the loss rate of platelet donors and evaluate the strategies for establishing a platelet donor bank. [Methods] A total of 1 443 donors who joined the HLA and HPA gene donor bank for platelets in Henan Province from 2018 to 2020 were included in this study. Data on the total number of apheresis platelet donations, annual donation frequency, age at enrollment, donation habits (including the number of platelets donated per session and whether they had previously donated whole blood), and enrollment location were collected from the platelet donor information management system. Donor loss was determined based on the date of their last donation. The loss rates of different groups under various conditions were compared to assess the enrollment strategies. [Results] By the time the platelet bank was officially operational in 2022, 421 donors had been lost, resulting in an loss rate of 29% (421/1 443). By the end of 2023, the overall cumulative loss rate reached 52% (746/1 443). The loss rate was lower than the overall level in groups meeting any of the following conditions: total apheresis platelet donations exceeding 50, annual donation frequency of 10 or more, age at enrollment of 40 years or older, donation of more than a single therapeutic dose per session, or a history of whole blood donation two or more times. Additionally, loss rates varied across different enrollment locations, with higher enrollment numbers generally associated with higher loss rates. [Conclusion] Through a comprehensive analysis of donor loss, our center has adjusted its strategies for establishing the donor pool. These findings also provide valuable insights for other blood collection and supply institutions in building platelet donor banks.


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