1.Coronary CT Angiography-Derived Fractional Flow Reserve in Asia and the United States: 2025 Status Update
Woo Jin AHN ; Maros FERENCIK ; Ming-Yen NG ; Liang ZHONG ; Mona BHATIA ; Akira KURATA ; Pannipa SUWANNASOM ; Yung-Liang WAN ; Trang Ngoc NGUYEN ; Suyon CHANG ; Sung Mok KIM ; Hwan Seok YONG ; Cherry KIM
Korean Journal of Radiology 2026;27(1):27-33
Coronary CT-derived fractional flow reserve (CT-FFR) is a noninvasive alternative to invasive FFR for assessing the hemodynamic significance of coronary artery stenosis. CT-FFR uses routinely acquired coronary CT angiography (CCTA) with artificial intelligence and computational fluid dynamics to estimate pressure gradients, thereby supporting clinical decisionmaking without procedural risk. Adoption and implementation vary widely across regions. In Asia, South Korea exclusively uses HeartMedi+, which enables rapid analysis, streamlined workflow integration, and high user satisfaction. Japan relies primarily on FFR CT, which has national reimbursement and significantly influences treatment strategies, reducing unnecessary invasive procedures. Hong Kong, Singapore, Taiwan, Thailand, and Vietnam remain in early or exploratory phases due to cost, reimbursement, and infrastructure barriers. In the United States, CT-FFR is guideline-endorsed and reimbursed, where HeartFlow is the most widely used, supported by robust clinical validation and outcome data. Despite regional variability, CTFFR offers a noninvasive solution that enhances patient management, reduces unnecessary invasive testing, and is poised for broader clinical integration as technology and validation advance.
2.The Neural Circuit Characteristics of Repetitive Transcranial Magnetic Stimulation Over The Dorsolateral Prefrontal Cortex for The Treatment of Migraine
Chen-Xia JIN ; Bo-Lin TAN ; Yang YE ; Ji-Qing HE ; Ling-Yan WANG ; Zhong-Ming GAO ; Yu-Jun WANG ; Hui-Li LIU ; Yong-Xing YAN ; Xian-Wei CHE
Progress in Biochemistry and Biophysics 2026;53(7):1953-1968
ObjectiveMigraine is a leading neurological disorder and the fourth most common cause of years lived with disability worldwide, affecting nearly 116 million individuals. Although pharmacological treatments are available, their efficacy is often limited by side effects and variable response rates. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) offers a safe, non-invasive alternative for migraine management. However, the neurophysiological mechanisms, particularly how rTMS modulates local cortical excitability and distributed pain-related circuits, remain poorly understood. Elucidating these mechanisms is essential for optimizing treatment protocols and improving clinical outcomes. MethodsThis study employed concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to investigate neuroplastic and neurocircuitry mechanisms of DLPFC-rTMS in migraine. Study 1 compared 30 migraineurs and 28 healthy controls to identify abnormalities in TMS-evoked potentials (TEPs) and significant current density (SCD) within sensory-discriminative regions including the primary somatosensory cortex (S1) and posterior insula (pINS), cognitive-affective regions including the anterior insula (aINS) and midcingulate cortex (MCC), and a descending modulatory region, the periaqueductal gray (PAG). Study 2 used a single-blind, crossover, sham-controlled design in 34 healthy participants. Each participant received both active (10 Hz, 80% RMT, 1 500 pulses) and sham DLPFC-rTMS in counterbalanced order. TMS-EEG and cold pain tolerance were assessed before and after each session. ResultsIn Study 1, migraineurs showed a significantly less negative N120 amplitude compared to healthy controls (P=0.027, Cohen’s d=0.60), indicating local intracortical disinhibition. No group differences were observed for N40, P60, or P180 components. At the source level, migraineurs exhibited significantly higher SCD in the S1, pINS, aINS, and MCC (allQ<0.05), but not in the ventroposterior thalamus (vpTHAL), mediodorsal thalamus (mdTHAL), or PAG. In Study 2, active rTMS significantly reduced SCD from pre- to post-stimulation in the S1, aINS, and MCC (all Q<0.05). Sham stimulation also reduced SCD in the S1 (Q<0.05) but not in the aINS or MCC. Although no significant group-level analgesic effect was observed between active and sham conditions (P=0.107), correlation analyses revealed that greater SCD reductions in the S1 and MCC were significantly associated with higher post-rTMS pain tolerance (R=-0.487 and -0.495, both Q<0.01) and larger improvements in pain tolerance(R=-0.487 and -0.451, both Q<0.05). No such correlations were found following sham stimulation, suggesting that the behavioural relevance of neural changes is specific to active rTMS. ConclusionThis study provides novel evidence that migraineurs exhibit both local neuroplastic abnormalities (reduced N120 amplitude) and hyperactivity in key pain-processing regions (S1, pINS, aINS, MCC). A single session of DLPFC-rTMS reduced hyperactivity in the aINS, MCC, and S1. Notably, greater reductions in the S1 and MCC were associated with improved pain tolerance. These findings identify distinct cortical circuitries, particularly within the cognitive-affective pain network, that may serve as potential biomarkers for optimizing rTMS treatment in migraine and other chronic pain conditions. Future studies should validate these results in patient populations experiencing spontaneous migraine attacks and explore multi-session or accelerated rTMS protocols.
3.Investigation on prevalence of pinworm infection among kindergarten children and knowledge of prevention and control among teachers and parents in Gaoyou City from 2023 to 2025
Wei WANG ; Yuhui XU ; Fang TIAN ; Jinbin GAO ; Zhong WAN ; Yong HE
Chinese Journal of Schistosomiasis Control 2026;38(3):309-313
Objective To investigate the prevalence of pinworm infections among kindergarten children and the effectiveness of health interventions among teachers and parents in Gaoyou City, so as to provide insights into optimization of enterobiasis control strategies. Methods From September to November each year from 2023 to 2025, Gaoyou City’s 57 kindergartens were divided into five zones based on the five cardinal directions: east, west, south, north, and center. At least one kindergarten was randomly selected as a survey site in each zone, with a minimum of 200 children surveyed per site. The transparent adhesive tape anal swab method was used to detect pinworm infection in the surveyed children, while the transparent adhesive tape sticking method was employed to assess pinworm egg contamination in the children’s home and classroom environments. Concurrently, health education interventions were conducted for kindergarten teachers and parents. Additionally, self-administered questionnaires were administered to teachers and parents to evaluate children’s hygiene behaviors and the awareness rates of pinworm prevention knowledge among teachers and parents before and after the health education interventions. Results From 2023 to 2025, a total of 1 939 children from nine kindergartens in Gaoyou City were tested for pinworm infection, with two cases detected, resulting in an overall infection rate of 0.10% (2/1 939). No pinworm eggs were found in the samples from the children’s families or classroom environments. In public kindergartens, the proportions of children practicing the four hygiene habits, namely “handwashing after defecation” [96.10% (1 305/1 358) vs. 74.65% (212/284); χ2 = 153.646, P < 0.05], “regular nail trimming” [92.93% (1 262/1 358) vs. 77.82% (221/284); χ2 = 61.349, P < 0.05], “not biting toys or pencils” [88.14% (1 197/1 358) vs. 76.76% (218/284); χ2 = 25.549, P < 0.05], and “showering twice or more per week” [89.03% (1 209/1 358) vs. 74.65% (212/284); χ2 = 41.699, P < 0.05], were all higher than those in private kindergartens. Before health education intervention, the awareness rates of pinworm prevention knowledge among teachers in public and private kindergartens were 86.89% (53/61) and 75.00% (21/28), respectively, with no statistically significant difference (χ2 = 1.935, P > 0.05). The awareness rates among parents of children in public and private kindergartens were 64.73% (879/1 358) and 57.39% (163/284), respectively, showing a statistically significant difference (χ2 = 5.447, P < 0.05). After the intervention, the awareness rates among teachers in public and private kindergartens increased to 96.72% (59/61) and 82.14% (23/28), respectively, while those among parents rose to 88.95% (1 208/1 358) and 77.81% (221/284), both with statistically significant differences (χ2 = 5.628 and 25.808, both P < 0.05). Among the questionnaire items, teachers [32.58% (29/89)] and parents [26.00% (427/1 642)] had the lowest overall awareness rate regarding the “main reasons for the difficulty in preventing and controlling pinworm disease”. After the intervention, these rates increased to 77.53% (69/89) and 70.77% (1 162/1 642), respectively. Conclusions The prevalence of pinworm infection in kindergarten children in Gaoyou City is at a low level. Health intervention can effectively improve the knowledge level of teachers and parents on the prevention and treatment of pinworm disease, but further efforts are needed to strengthen the health education and management of pinworm disease in private kindergartens.
4.Study on quality standard of ethnic medicine Diplazium lanceum
Liyuan HU ; Chuhui ZHOU ; Limei LIANG ; Yong CHEN ; Jiajia ZHONG ; Jiangcun WEI
China Pharmacy 2026;37(15):1986-1991
OBJECTIVE To study the quality standard of the ethnic medicine Diplazium lanceum, and to provide reference for its quality control.METHODS The medicinal material of D. lanceum was identified by properties, microscopy, and thin-layer chromatography(TLC), and its moisture, ash, and extract contents were determined. The contents of chlorogenic acid and rutin in 10 batches of D. lanceum were determined by high-performance liquid chromatography . RESULTS The rhizome of D. lanceum is slender and creeping, the leaf is leathery and shriveled, and yellow sporangia are borne on the abaxial surface of the leaf. The transverse section of the leaf shows inclusions, sclerenchyma, phloem cells, etc.; the transverse section of the petiole shows ground tissue, sclerenchyma, endodermis, etc.; the transverse section of the rhizome shows ground tissue, tracheids, vascular bundles, etc.; and the powder shows spiral vessels and brown inclusions. The TLC identification results showed that the chromatogram of the test sample exhibited spots of the same color at the corresponding positions as the chromatogram of the chlorogenic acid reference substance. The content ranges of moisture, total ash, acid-insoluble ash, extract, chlorogenic acid, and rutin in the 10 batches of samples were 10.18%-12.43%, 7.08%-19.12%, 0.95%-10.62%, 14.13%-26.05%, 0.113 1-1.015 9 mg/g, and 0.009 9-0.208 9 mg/g, respectively. CONCLUSIONS In the quality standard of D. lanceum, the moisture content should be ≤12.5%, total ash content should be ≤20.0%, acid-insoluble ash content should be ≤11.0%, extract content should be ≥14.0%, and chlorogenic acid content should be ≥0.11 mg/g. The established method is simple, specific, and reproducible, and can provide a scientific basis for the quality control of D. lanceum.
5.Exploring Mechanism of Luoshi Neiyi Prescription in Treating Endometriosis Based on Ferroptosis and Serum Metabolomics
Haixia PAN ; Yingqiao ZHONG ; Ting MAO ; Ziyi DENG ; Meilin WU ; Lei HUANG ; Siyang CHEN ; Yong GUO ; Ying ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):201-212
ObjectiveThis study aimed to investigate the mechanism by which Luoshi Neiyi prescription treats endometriosis (EMs) through regulating ferroptosis, and to screen key metabolites and analyze their association with ferroptosis. MethodsClinical samples of normal endometrium from patients without EMs and eutopic and ectopic endometrium from EMs patients (10 cases each) were collected and divided into control group, eutopic group, and EMs group. Hematoxylin-eosin (HE) staining was performed to observe ectopic lesions of EMs. Immunohistochemistry was used to detect the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). Enzyme-linked immunosorbent assay (ELISA) was adopted to determine the levels of malondialdehyde (MDA), ferrous ion (Fe2+), GPX4 and glutathione (GSH) in endometrial tissues, as well as serum levels of Fe2+, GPX4 and GSH. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of SLC7A11, GPX4, transferrin receptor (TFR) and ferritin heavy chain 1 (FTH1). In the in vitro experiment, primary stromal cells were isolated from ectopic lesions of EMs patients. Cell counting kit-8 (CCK-8) was used to determine the optimal concentration of drug-containing serum for intervention. The level of reactive oxygen species (ROS) was measured, and Real-time PCR was applied to detect ferroptosis-related indicators. In the animal experiments, an EM rat model was established, and the rats were randomly assigned to the sham operation group, EMs group, low-dose Luoshi Neiyi Formula group (7.87 g·kg-1), high-dose Luoshi Neiyi prescription group (15.74 g·kg-1), and danazol group (42 mg·kg-1). Untargeted metabolomics detection and pathway enrichment analysis were conducted on serum samples from patients and rats. Spearman correlation analysis was performed to assess the relationship between differential metabolites and ferroptosis indicators. The correlations between differential metabolites in patient endometrium and serum and key ferroptosis indicators (GPX4, Fe2+, MDA, GSH) as well as ferroptosis-related mRNAs (GPX4, SLC7A11, FTH1) were analyzed, and correlation heatmaps were generated accordingly. ResultsCompared with normal eutopic endometrium, ectopic lesions in EMs patients showed glandular disorganization and stromal fibrosis. In ectopic endometrium, the contents of MDA, ROS, and Fe2+ decreased, while GPX4 level increased, and the mRNA expression of SLC7A11 and GPX4 was upregulated (P<0.05, P<0.01). In serum, the levels of GPX4 and Fe2+ were elevated, whereas the GSH level declined, suggesting abnormalities in ferroptosis-related pathways in ectopic lesions (P<0.05, P<0.01). After intervention with Luoshi Neiyi prescription-containing serum, the intracellular ROS level in ectopic endometrial stromal cells was elevated, the mRNA expression of SLC7A11 and GPX4 was downregulated, and TFR mRNA expression was upregulated (P<0.05, P<0.01). Metabolomics analysis revealed 1104 and 198 differential metabolites in EMs patients and EMs rats, respectively, compared with their corresponding control groups, and both low-dose and high-dose Luoshi Neiyi prescription were found to regulate this metabolic disturbance, with the core regulatory pathways mainly involving arginine and proline metabolism. Correlation analysis showed that the glycerophospholipids including PI(16∶0/17∶0) and PI[18∶2(9Z,12Z)] were negatively correlated with GPX4 and positively correlated with MDA, while 17α-hydroxyprogesterone was positively correlated with GPX4, SLC7A11, and FTH1 q<0.05). ConclusionLuoshi Neiyi prescription may systematically ameliorate disease-associated metabolic dysregulation via modulation of the serum arginine and proline metabolism pathway, and may regulate ferroptosis in ectopic lesions through a mechanism potentially linked to the serum glycerophospholipid and steroid metabolism pathways. Collectively, these findings provide experimental evidence for the clinical application of Luoshi Neiyi prescription.
6.Exploring Mechanism of Luoshi Neiyi Prescription in Treating Endometriosis Based on Ferroptosis and Serum Metabolomics
Haixia PAN ; Yingqiao ZHONG ; Ting MAO ; Ziyi DENG ; Meilin WU ; Lei HUANG ; Siyang CHEN ; Yong GUO ; Ying ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(20):201-212
ObjectiveThis study aimed to investigate the mechanism by which Luoshi Neiyi prescription treats endometriosis (EMs) through regulating ferroptosis, and to screen key metabolites and analyze their association with ferroptosis. MethodsClinical samples of normal endometrium from patients without EMs and eutopic and ectopic endometrium from EMs patients (10 cases each) were collected and divided into control group, eutopic group, and EMs group. Hematoxylin-eosin (HE) staining was performed to observe ectopic lesions of EMs. Immunohistochemistry was used to detect the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). Enzyme-linked immunosorbent assay (ELISA) was adopted to determine the levels of malondialdehyde (MDA), ferrous ion (Fe2+), GPX4 and glutathione (GSH) in endometrial tissues, as well as serum levels of Fe2+, GPX4 and GSH. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of SLC7A11, GPX4, transferrin receptor (TFR) and ferritin heavy chain 1 (FTH1). In the in vitro experiment, primary stromal cells were isolated from ectopic lesions of EMs patients. Cell counting kit-8 (CCK-8) was used to determine the optimal concentration of drug-containing serum for intervention. The level of reactive oxygen species (ROS) was measured, and Real-time PCR was applied to detect ferroptosis-related indicators. In the animal experiments, an EM rat model was established, and the rats were randomly assigned to the sham operation group, EMs group, low-dose Luoshi Neiyi Formula group (7.87 g·kg-1), high-dose Luoshi Neiyi prescription group (15.74 g·kg-1), and danazol group (42 mg·kg-1). Untargeted metabolomics detection and pathway enrichment analysis were conducted on serum samples from patients and rats. Spearman correlation analysis was performed to assess the relationship between differential metabolites and ferroptosis indicators. The correlations between differential metabolites in patient endometrium and serum and key ferroptosis indicators (GPX4, Fe2+, MDA, GSH) as well as ferroptosis-related mRNAs (GPX4, SLC7A11, FTH1) were analyzed, and correlation heatmaps were generated accordingly. ResultsCompared with normal eutopic endometrium, ectopic lesions in EMs patients showed glandular disorganization and stromal fibrosis. In ectopic endometrium, the contents of MDA, ROS, and Fe2+ decreased, while GPX4 level increased, and the mRNA expression of SLC7A11 and GPX4 was upregulated (P<0.05, P<0.01). In serum, the levels of GPX4 and Fe2+ were elevated, whereas the GSH level declined, suggesting abnormalities in ferroptosis-related pathways in ectopic lesions (P<0.05, P<0.01). After intervention with Luoshi Neiyi prescription-containing serum, the intracellular ROS level in ectopic endometrial stromal cells was elevated, the mRNA expression of SLC7A11 and GPX4 was downregulated, and TFR mRNA expression was upregulated (P<0.05, P<0.01). Metabolomics analysis revealed 1104 and 198 differential metabolites in EMs patients and EMs rats, respectively, compared with their corresponding control groups, and both low-dose and high-dose Luoshi Neiyi prescription were found to regulate this metabolic disturbance, with the core regulatory pathways mainly involving arginine and proline metabolism. Correlation analysis showed that the glycerophospholipids including PI(16∶0/17∶0) and PI[18∶2(9Z,12Z)] were negatively correlated with GPX4 and positively correlated with MDA, while 17α-hydroxyprogesterone was positively correlated with GPX4, SLC7A11, and FTH1 q<0.05). ConclusionLuoshi Neiyi prescription may systematically ameliorate disease-associated metabolic dysregulation via modulation of the serum arginine and proline metabolism pathway, and may regulate ferroptosis in ectopic lesions through a mechanism potentially linked to the serum glycerophospholipid and steroid metabolism pathways. Collectively, these findings provide experimental evidence for the clinical application of Luoshi Neiyi prescription.
7.Risk prediction of Reduning Injection batches by near-infrared spectroscopy combined with multiple machine learning algorithms.
Wen-Yu JIA ; Feng TONG ; Heng-Xu LIU ; Shu-Qin JIN ; Yong-Chao ZHANG ; Chen-Feng ZHANG ; Zhen-Zhong WANG ; Xin ZHANG ; Wei XIAO
China Journal of Chinese Materia Medica 2025;50(2):430-438
In this paper, near-infrared spectroscopy(NIRS) was employed to analyze 129 batches of commercial products of Reduning Injection. The batch reporting rate was estimated according to the report of Reduning Injection in the direct adverse drug reaction(ADR) reporting system of the drug marketing authorization holder of the Center for Drug Reevaluation of the National Medical Products Administration(National Center for ADR Monitoring) from August 2021 to August 2022. According to the batch reporting rate, the samples of Reduning Injection were classified into those with potential risks and those being safe. No processing, random oversampling(ROS), random undersampling(RUS), and synthetic minority over-sampling technique(SMOTE) were then employed to balance the unbalanced data. After the samples were classified according to appropriate sampling methods, competitive adaptive reweighted sampling(CARS), successive projections algorithm(SPA), uninformative variables elimination(UVE), and genetic algorithm(GA) were respectively adopted to screen the features of spectral data. Then, support vector machine(SVM), logistic regression(LR), k-nearest neighbors(KNN), naive bayes(NB), random forest(RF), and artificial neural network(ANN) were adopted to establish the risk prediction models. The effects of the four feature extraction methods on the accuracy of the models were compared. The optimal method was selected, and bayesian optimization was performned to optimize the model parameters to improve the accuracy and robustness of model prediction. To explore the correlations between potential risks of clinical use and quality test data, TreeNet was employed to identify potential quality parameters affecting the clinical safety of Reduning Injection. The results showed that the models established with the SVM, LR, KNN, NB, RF, and ANN algorithms had the F1 scores of 0.85, 0.85, 0.86, 0.80, 0.88, and 0.85 and the accuracy of 88%, 88%, 88%, 85%, 91%, and 88%, respectively, and the prediction time was less than 5 s. The results indicated that the established models were accurate and efficient. Therefore, near infrared spectroscopy combined with machine learning algorithms can quickly predict the potential risks of clinical use of Reduning Injection in batches. Three key quality parameters that may affect clinical safety were identified by TreeNet, which provided a scientific basis for improving the safety standards of Reduning Injection.
Spectroscopy, Near-Infrared/methods*
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Drugs, Chinese Herbal/administration & dosage*
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Machine Learning
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Algorithms
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Humans
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Quality Control
8.Correlation between differences in starch gelatinization, water distribution, and terpenoid content during steaming process of Curcuma kwangsiensis root tubers by multivariate statistical analysis.
Yan LIANG ; Meng-Na YANG ; Xiao-Li QIN ; Zhi-Yong ZHANG ; Zhong-Nan SU ; Hou-Kang CAO ; Ke-Feng ZHANG ; Ming-Wei WANG ; Bo LI ; Shuo LI
China Journal of Chinese Materia Medica 2025;50(10):2684-2694
To elucidate the mechanism by which steaming affects the quality of Curcuma kwangsiensis root tubers, methods such as LSCM, RVA, dual-wavelength spectrophotometry, LF-NMR, and LC-MS were employed to qualitatively and quantitatively detect changes in starch gelatinization characteristics, water distribution, and material composition of C. kwangsiensis root tubers under different steaming durations. Based on multivariate statistical analysis, the correlation between differences in gelatinization parameters, water distribution, and terpenoid material composition was investigated. The results indicate that steaming affects both starch gelatinization and water distribution in C. kwangsiensis. During the steaming process, transformations occur between amylose and amylopectin, as well as between semi-bound water and free water. After 60 min of steaming, starch gelatinization and water distribution reached an equilibrium state. The content of amylopectin, the amylose-to-amylopectin ratio, and parameters such as gelatinization temperature, viscosity, breakdown value, and setback value were significantly correlated(P≤0.05). Additionally, the amylose-to-amylopectin ratio was significantly correlated with total free water and total water content(P≤0.05). Steaming induced differences in the material composition of C. kwangsiensis root tubers. Clustering of primary metabolites in the OPLS-DA model was distinct, while secondary metabolites were classified into 9 clusters using the K-means clustering algorithm. Differential terpenoid metabolites such as(-)-α-curcumene were significantly correlated with zerumbone, retinal, and all-trans-retinoic acid(P<0.05). Curcumenol was significantly correlated with isoalantolactone and ursolic acid(P<0.05), while all-trans-retinoic acid was significantly correlated with both zerumbone and retinal(P<0.05). Alpha-tocotrienol exhibited a significant correlation with retinal and all-trans-retinoic acid(P<0.05). Amylose was extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and α-tocotrienol(P<0.05). Amylopectin was significantly correlated with zerumbone(P<0.05) and extremely significantly correlated with(-)-α-curcumene, curcumenol, zerumbone, retinal, all-trans-retinoic acid, and 9-cis-retinoic acid(P<0.01). The results provide scientific evidence for elucidating the mechanism of quality formation of steamed C. kwangsiensis root tubers as a medicinal material.
Curcuma/chemistry*
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Starch/chemistry*
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Multivariate Analysis
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Water/chemistry*
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Terpenes/analysis*
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Plant Roots/chemistry*
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Plant Tubers/chemistry*
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Drugs, Chinese Herbal/chemistry*
9.Mechanism related to bile acids metabolism of liver injury induced by long-term administration of emodin.
Jing-Zhuo TIAN ; Lian-Mei WANG ; Yan YI ; Zhong XIAN ; Nuo DENG ; Yong ZHAO ; Chun-Ying LI ; Yu-Shi ZHANG ; Su-Yan LIU ; Jia-Yin HAN ; Chen PAN ; Chen-Yue LIU ; Jing MENG ; Ai-Hua LIANG
China Journal of Chinese Materia Medica 2025;50(11):3079-3087
Emodin is a hydroxyanthraquinone compound that is widely distributed and has multiple pharmacological activities, including anti-diarrheal, anti-inflammatory, and liver-protective effects. Research indicates that emodin may be one of the main components responsible for inducing hepatotoxicity. However, studies on the mechanisms of liver injury are relatively limited, particularly those related to bile acids(BAs) metabolism. This study aims to systematically investigate the effects of different dosages of emodin on BAs metabolism, providing a basis for the safe clinical use of traditional Chinese medicine(TCM)containing emodin. First, this study evaluated the safety of repeated administration of different dosages of emodin over a 5-week period, with a particular focus on its impact on the liver. Next, the composition and content of BAs in serum and liver were analyzed. Subsequently, qRT-PCR was used to detect the mRNA expression of nuclear receptors and transporters related to BAs metabolism. The results showed that 1 g·kg~(-1) emodin induced hepatic damage, with bile duct hyperplasia as the primary pathological manifestation. It significantly increased the levels of various BAs in the serum and primary BAs(including taurine-conjugated and free BAs) in the liver. Additionally, it downregulated the mRNA expression of farnesoid X receptor(FXR), retinoid X receptor(RXR), and sodium taurocholate cotransporting polypeptide(NTCP), and upregulated the mRNA expression of cholesterol 7α-hydroxylase(CYP7A1) in the liver. Although 0.01 g·kg~(-1) and 0.03 g·kg~(-1) emodin did not induce obvious liver injury, they significantly increased the level of taurine-conjugated BAs in the liver, suggesting a potential interference with BAs homeostasis. In conclusion, 1 g·kg~(-1) emodin may promote the production of primary BAs in the liver by affecting the FXR-RXR-CYP7A1 pathway, inhibit NTCP expression, and reduce BA reabsorption in the liver, resulting in BA accumulation in the peripheral blood. This disruption of BA homeostasis leads to liver injury. Even doses of emodin close to the clinical dose can also have a certain effect on the homeostasis of BAs. Therefore, when using traditional Chinese medicine or formulas containing emodin in clinical practice, it is necessary to regularly monitor liver function indicators and closely monitor the risk of drug-induced liver injury.
Emodin/administration & dosage*
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Bile Acids and Salts/metabolism*
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Animals
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Male
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Liver/injuries*
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Chemical and Drug Induced Liver Injury/genetics*
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Drugs, Chinese Herbal/adverse effects*
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Humans
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Rats, Sprague-Dawley
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Mice
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Rats
10.Coptidis Rhizoma-Scutellariae Radix alleviates CpG1826-induced cytokine storm secondary lung injury in mice by inhibiting mPTP/NLRP3 pyroptosis pathway.
Qing-Rui ZHONG ; Hong-Kai HUANG ; Yue-Jia LAN ; Huan WANG ; Yong ZENG ; Jia-Si WU
China Journal of Chinese Materia Medica 2025;50(15):4141-4152
This study aims to investigate the therapeutic effects of the Coptidis Rhizoma-Scutellariae Radix on cytokine storm secondary lung injury(CSSLI) induced by CpG1826 in mice, and to elucidate the potential molecular mechanisms by which its major active components, i.e., coptisine and wogonin, alleviate CSSLI by inhibiting the mitochondrial permeability transition pore(mPTP)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3) inflammasome pyroptosis pathway. In vivo, a mouse model of CSSLI was established by CpG1826 induction. Pulmonary edema was assessed by lung wet-to-dry weight ratio(W/D), lung injury was evaluated by hematoxylin-eosin(HE) staining, and ultrastructural changes in lung tissue were observed by transmission electron microscopy(TEM). The levels of interleukin(IL)-1β, high mobility group box 1 protein(HMGB1), IL-18, and IL-1α in bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay(ELISA). The results showed that the decoction of the Coptidis Rhizoma-Scutellariae Radix significantly reduced pulmonary edema, alleviated lung injury, and decreased the concentrations of related cytokines in BALF more effectively than either single herb alone, thereby improving CSSLI. In vitro, a CpG1826-induced CSSLI model was established in mouse alveolar macrophage MH-S cells. Calcein-AM quenching was used to screen for the most effective monomer components from the herb pair in inhibiting mPTP opening. Coptisine(5, 10, 20 μmol·L~(-1)) and wogonin(10, 20, 40 μmol·L~(-1)) markedly inhibited mPTP opening, with optimal effects and a clear dose-dependent pattern. These components suppressed mPTP opening, thereby reducing the release of mitochondrial DNA(mtDNA) and the accumulation of reactive oxygen species(ROS), effectively reversing the CpG1826-induced decrease in mitochondrial membrane potential(MMP). Further studies revealed that both coptisine and wogonin inhibited pyroptosis and downregulated the expression of key proteins in the NLRP3/Caspase-1/gasdermin D(GSDMD) pathway. In conclusion, the Coptidis Rhizoma-Scutellariae Radix improves CpG1826-induced CSSLI in mice, and this effect is associated with the inhibition of the mPTP/NLRP3 pyroptosis pathway, providing scientific evidence for its clinical application and further development.
Animals
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Mice
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Drugs, Chinese Herbal/administration & dosage*
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Pyroptosis/drug effects*
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NLR Family, Pyrin Domain-Containing 3 Protein/immunology*
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Male
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Lung Injury/immunology*
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Cytokines/immunology*
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Scutellaria baicalensis/chemistry*
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Oligodeoxyribonucleotides/adverse effects*
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Mice, Inbred C57BL
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Coptis chinensis

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