1.Efficacy Analysis of RCT of Arsenic-containing TCM Compound in Treatment of Myelodysplastic Syndrome Based on MMRM and Win Ratio
Daxiang SUN ; Peizhen JIANG ; Haixia DI ; Bing WU ; Qifeng LIU ; Jian LIU ; Jiahe LIANG ; Xudong TANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):251-259
ObjectiveThis paper aims to conduct a secondary analysis of a randomized controlled trial on the treatment of myelodysplastic syndrome (MDS) with deficiency of both the spleen and kidney and blockage of toxin and blood stasis with an arsenic-containing traditional Chinese medicine compound, by applying the mixed model for repeated measure (MMRM) and the method of stratified composite outcome with win ratio. The analysis includes the assessment of hematological efficacy and the composite outcome evaluation of adverse reactions, so as to more comprehensively assess the therapy of this regimen. MethodsThe MMRM and win ratio methods were used to evaluate the efficacy of a prospective,multi-center,double-blind,randomized controlled study. The blood routine (hemoglobin concentration,neutrophil count, and platelet count) and biochemical indexes (aspartate aminotransferase,alanine aminotransferase,serum creatinine,and serum ferritin) of the patients were detected at the time of enrollment and at the end of each course of treatment in the laboratory department of Xiyuan Hospital. The patients' syndromes at the time of enrollment and after treatment were recorded and scored according to the therapy standard of traditional Chinese medicine for diseases and syndromes. MMRM was used to analyze the blood routine indexes of the experimental group and the control group. This method has the advantages of high data reliability and dynamic efficacy under intervention and time. The win ratio method was used to evaluate the composite outcome of traditional Chinese medicine syndrome scores and biochemical indexes according to the priority and to verify the clinical safety of arsenic-containing traditional Chinese medicine compound. ResultsThe results of MMRM analysis showed that the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly compared with that before treatment in the group,while that in the placebo group decreased significantly (P<0.01). When compared with that after treatment in the placebo group,the hemoglobin concentration of patients in the group with arsenic-containing traditional Chinese medicine compound increased significantly,and the mean difference of least squares (LS) was statistically significant (P<0.01). When compared with those before treatment in the group,there were no statistically significant differences in the neutrophil count and platelet count in both groups. After treatment,there were no statistically significant differences in the neutrophil count, platelet count, and the mean difference of LS between the two groups. The analysis results of win ratio showed that the group with arsenic-containing traditional Chinese medicine compound had a significant advantage in the comparison of composite outcomes,with a win ratio (95% CI) of 2.01 (1.24-3.27) (P<0.01),and that the possibility of "winning" in terms of safety was 2.01 times that of the placebo group. The safety advantage of the group with arsenic-containing traditional Chinese medicine compound mainly came from the traditional Chinese medicine syndrome scores,renal function indexes, and iron reserve capacity indexes,and the number of winning times was less than that of losing times in the comparison of liver function outcomes. ConclusionThe MMRM analysis proves that the arsenic-containing traditional Chinese medicine compound can significantly improve the hemoglobin concentration of patients with myelodysplastic syndrome with refractory cytopenia and multilineage dysplasia (MDS-RCMD) of the type of deficiency of both the spleen and kidney and blockage of toxin and blood stasis. This conclusion is not interfered with by time trends and individual relationships and methodologically improves the credibility of the therapy of the arsenic-containing traditional Chinese medicine compound in treating MDS. Four outcomes are evaluated by the win ratio method,namely traditional Chinese medicine syndromes,liver function,renal function, and iron reserve capacity,proving that the arsenic-containing traditional Chinese medicine compound has the comprehensive advantages of improving the survival quality of the patients and reducing adverse reactions. The win ratio outcome provides clear comparative indexes for the evaluation of adverse reactions,making it easier for regulatory authorities,medical staff, and patients to understand the safety of the arsenic-containing traditional Chinese medicine compound in clinical application.
2.Influence of CYP2C19 gene polymorphism on platelet function and inflammatory cytokines and analysis of factors associated with poor prognosis in elderly patients with ischemic stroke
Hai LIANG ; Hong ZHANG ; Runan XIA ; Huijuan CHEN ; Mengyu JIANG ; Fanqin LI ; Panpan DI ; Miao YANG
China Pharmacy 2026;37(6):782-787
OBJECTIVE To investigate the influence of CYP2C19 gene polymorphism on platelet function and inflammatory cytokines in elderly patients with ischemic stroke, and to analyze potential factors associated with poor prognosis. METHODS A retrospective study was conducted on elderly patients with ischemic stroke admitted to our hospital from June 2024 to June 2025, wh o underwent CYP2C19 genotype testing and received antiplatelet therapy with clopidogrel. The levels of platelet function indicators and inflammatory cytokines before and after treatment were compared among patients with different metabolic phenotypes. Based on the prognosis at 6 months post-treatment, patients were divided into poor prognosis group and good prognosis group. Univariate analysis was performed on general data, metabolic phenotype, the levels of platelet function indicators and inflammatory cytokines. Variables with P <0.05 and the levels of inflammatory cytokines before treatment were included in a multivariate Logistic regression analysis to identify independent risk factors for poor prognosis. Multiple linear regression was used to further analyze the relationship between metabolic phenotypes and inflammatory cytokines. RESULTS A total of 448 elderly patients with ischemic stroke were included; among them, 162 cases were normal metabolic phenotype, 218 were intermediate metabolic phenotype, and 68 were poor metabolic phenotype. No rapid or ultrarapid metabolic phenotypes were observed. After treatment, platelet aggregation rate, the levels of P-selectin and platelet activated complex-1 (PAC-1), high-sensitivity C-reactive Protein (hs-CRP), interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α) in the normal metabolic phenotype group, intermediate metabolic phenotype group, and poor metabolic phenotype group (except for platelet aggregation rate, and the levels of P-selectin and PAC-1 in the poor metabolic phenotype group) were significantly lower than those before treatment in the same group. Moreover, the above indicators in the normal metabolic phenotype group were significantly lower than those in the intermediate and poor metabolic phenotype groups at the corresponding time, and the levels of platelet function indicators in the intermediate metabolic phenotype group were significantly lower than those in the poor metabol ic phenotype group at the corresponding time ( P <0.05). Univariate and multivariate Logistic regression analyses showed that combined with hypertension, combined with diabetes mellitus, and intermediate or poor metabolic genotypes were independent risk factors for poor prognosis in elderly patients with ischemic stroke ( P <0.05). Multiple linear regression analysis showed that serum levels of hs-CRP, IL-1β, IL-6 and TNF-α before treatment were significantly higher in patients with intermediate and poor metabolic genotypes compared to those with normal metabolic genotype ( P <0.05), with a greater magnitude of increase in inflammatory cytokines observed in the patients with poor metabolic genotype. CONCLUSIONS The elderly ischemic stroke patients with CYP2C19 intermediate and poor metabolic genotypes have poor inhibition effect on platelet and higher levels of inflammatory cytokines than normal metabolic genotype; CYP2C19 gene polymorphism, and in combination with hypertension and diabetes, can be used as independent predictors of poor prognosis.
3.Material Basis of Anti-Inflammatory Efficacy and Mechanism of Action of Bushen Tongdu Prescription Based on UPLC-LTQ-Orbitrap-MS and Network Pharmacology
Yan RONG ; Lulu JING ; Hongping HOU ; Huijun WANG ; Lihua CHEN ; Yunxin CHEN ; Liang LI ; Li LIN ; Xiaoqin LUO ; Haiyu ZHAO ; Xiaolu WEI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):152-161
ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription (BSTDP). MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry (UPLC-LIT-Orbitrap-MS). Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction (PPI) network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg (mpx: GFP). At three days post-fertilization (3 dpf), larvae of zebrafish were randomly assigned to blank group, model group, positive drug dexamethasone acetate group (75 μmol·L-1), and BSTDP groups with low, medium, and high doses (500, 1 000, and 2 000 mg·L-1). The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) signaling pathway and inflammatory factors including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) were detected by Real-time quantitative polymerase chain reaction (Real-time PCR). ResultsA total of 120 chemical components were identified in BSTDP, among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis (RA) and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine, vomicine, sinapine, rehmannioside, cinnamyl alcohol glycoside, and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 (Akt1), signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor (TNF), TLR4, mitogen-activated protein kinase 14 (MAPK14), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA), thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L-1. Compared to those in the blank group, zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region (P<0.01) and rising mRNA levels of TLR4, MyD88, NF-κB, TNF-α, IL-6, and IL-1β (P<0.01). Compared to that in the model group, the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses, as well as the dexamethasone acetate group (P<0.05, P<0.01). There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4, MyD88, NF-κB, TNF-α, IL-6, and IL-1β were significantly down-regulated (P<0.05, P<0.01). ConclusionThis paper identifies the material basis of the efficacy of BSTDP, demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.
4.Material Basis of Anti-Inflammatory Efficacy and Mechanism of Action of Bushen Tongdu Prescription Based on UPLC-LTQ-Orbitrap-MS and Network Pharmacology
Yan RONG ; Lulu JING ; Hongping HOU ; Huijun WANG ; Lihua CHEN ; Yunxin CHEN ; Liang LI ; Li LIN ; Xiaoqin LUO ; Haiyu ZHAO ; Xiaolu WEI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):152-161
ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription (BSTDP). MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry (UPLC-LIT-Orbitrap-MS). Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction (PPI) network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg (mpx: GFP). At three days post-fertilization (3 dpf), larvae of zebrafish were randomly assigned to blank group, model group, positive drug dexamethasone acetate group (75 μmol·L-1), and BSTDP groups with low, medium, and high doses (500, 1 000, and 2 000 mg·L-1). The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) signaling pathway and inflammatory factors including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) were detected by Real-time quantitative polymerase chain reaction (Real-time PCR). ResultsA total of 120 chemical components were identified in BSTDP, among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis (RA) and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine, vomicine, sinapine, rehmannioside, cinnamyl alcohol glycoside, and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 (Akt1), signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor (TNF), TLR4, mitogen-activated protein kinase 14 (MAPK14), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA), thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L-1. Compared to those in the blank group, zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region (P<0.01) and rising mRNA levels of TLR4, MyD88, NF-κB, TNF-α, IL-6, and IL-1β (P<0.01). Compared to that in the model group, the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses, as well as the dexamethasone acetate group (P<0.05, P<0.01). There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4, MyD88, NF-κB, TNF-α, IL-6, and IL-1β were significantly down-regulated (P<0.05, P<0.01). ConclusionThis paper identifies the material basis of the efficacy of BSTDP, demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.
5.Rationality and economic evaluation of Compound amino acid injection (14AA-SF) in the perioperative period of neurosurgery
Hai LIANG ; Jingjing WANG ; Huijuan CHEN ; Runan XIA ; Panpan DI ; Mengyu JIANG ; Fanqin LI ; Jinghe MA
China Pharmacy 2026;37(17):2303-2309
OBJECTIVE To establish standards for the rational use of Compound amino acid injection (14AA-SF) (hereinafter referred to as “14AA-SF”), and evaluate its rationality and cost-effectiveness.METHODS The standards for the rational use of 14AA-SF were established based on the Delphi method. Archived medical records of patients who used 14AA-SF in the Dept. of Neurosurgery of People’s Hospital of Bozhou from January 2024 to December 2025 were randomly selected. On the basis of the established standards for the rational use, the attribute hierarchical model was applied to evaluate the use rationality of 14AA-SF in the included medical records. The decision tree model was applied to calculate the incremental cost-effectiveness ratio (ICER), so as to evaluate the cost-effectiveness of 14AA-SF administered via single-bottle infusion versus “all-in-one” infusion, and the robustness of the cost-effectiveness evaluation results was verified through sensitivity analysis.RESULTS A total of 205 medical records were collected, among which 163 records (79.51%) were qualified with medical record score (MRS) ≥90, and 42 records (20.49%) were unqualified with MRS <90. The main irrational types of 14AA-SF use included unreasonable infusion method (67 case-times, accounting for 32.68%), unreasonable amino acid dosage (62 case-times, accounting for 30.24%) and unreasonable non-protein calorie-nitrogen ratio (55 case-times, accounting for 26.83%). Compared wtih single-bottle infusion, the incremental cost of “all-in-one” infusion for each 1% increase in effective rate was 165.40 yuan. The one-way sensitivity analysis showed that the effective rate of single-bottle infusion had the greatest impact on ICER. The probabilistic sensitivity analysis showed that under the willingness-to-pay (WTP) threshold (89 358 yuan) set in this study, the cost-effectiveness probability of “all-in-one” infusion relative to single-bottle infusion was 89.9%. When the WTP threshold exceeds 17 871.60 yuan, the “all-in-one” infusion is more cost-effective than the single-bottle infusion.CONCLUSIONS The established standards for the rational use of 14AA-SF are practical and feasible. There are phenomena of irrational use of 14AA-SF in Dept. of Neurosurgery of the hospital in terms of indications, nutritional risk screening, infusion methods and other aspects, which need to be further standardized. The “all-in-one” infusion is more cost-effective than the single-bottle infusion.
6.Trends in Oncomelania hupensis distribution in Yixing City, Jiangsu Province from 2008 to 2024
Jing LIANG ; Zhi-qiang XUE ; Xue-bing LI ; Di WU ; Han WANG
Acta Parasitologica et Medica Entomologica Sinica 2026;33(3):168-172
Objective To investigate changes in the distribution of Oncomelania hupensis snails in Yixing City, Jiangsu Province, from 2008 to 2024, and to provide insights to guide formulation of O. hupensis snail investigation and surveillance programs. Methods Data from O. hupensis snail surveys in Yixing City from 2008 to 2024 were collected. Trends in snail habitat site numbers, snail-infested areas, proportion of total area with snail habitats, occurrence of frames with living snails, and density of living snails in snail habitats in hilly regions of Yixing City were evaluated from 2008 to 2024 by applying a Joinpoint regression model to collect annual percent change (APC) and average annual percent change (AAPC) data. Results From 2008 to 2024, a total of 193.815 hm2 of snail-infested area was found within Yixing City, of which 191.765 hm2 (accounting for 98.94%) was distributed in hilly regions. A total of 344 snail infestation sites in hilly regions were identified. The average occurrence rate of living snail frames in snail habitats was 8.650% and the average living snail density in snail habitats was 0.246 per 0.1 m2. No Oncomelania snails were positively identified. The number of snail habitat sites in hilly regions of Yixing City showed no significant decreasing trend (AAPC=-2.8%, P=0.527). Similarly, no significant increasing trend in snail-infested area (APC=AAPC=5.7%, P=0.328) was found. The occurrence rate of living snail frames in snail habitats showed no significant increasing trend (APC=AAPC=5.1%, P=0.583). Living snail density in snail habitats also showed no significant increasing trend (APC=AAPC=3.2%, P=0.598). Conclusions From 2008 to 2024, snail infestation has persisted in the hilly areas of Yixing City with an unclear variation trend. The quality of snail investigation and snail surveillance system should be strengthened to permit timely identification of hidden dangers and rapid risk responses, thereby preventing schistosomiasis outbreaks.
7.Value of 18F-FDG PET/CT in differentiating primary intestinal diffuse large B-cell lymphoma from colon cancer in the ileocecal region
Qiaoliang CHEN ; Di LIANG ; Jing CHEN ; Jian HE
Journal of International Oncology 2025;52(10):628-632
Objective:To investigate the value of 18F-fluorodeoxyglucose ( 18F-FDG) PET/CT in the differential diagnosis of primary intestinal diffuse large B-cell lymphoma (PIDLBCL) and colon cancer in the ileocecal region. Methods:A total of 42 patients with ileocecal tumors admitted to Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from June 2013 to December 2023 were selected as the study objects, including 17 cases of PIDLBCL and 25 cases of colon cancer. General data and 18F-FDG PET/CT parameters were compared between patients with PIDLBCL and colon cancer in the ileocecal region. Binary logistic regression was used to analyze the independent influencing factors for the differential diagnosis of PIDLBCL and colon cancer in the ileocecal region. The receiver operator characteristic (ROC) curve was used to evaluate the diagnostic efficacy of independent influencing factors. Results:There were statistically significant differences in tumor length diameter ( Z=-2.63, P=0.009), maximum thickness ( Z=-3.26, P=0.001), ileal involvement ( χ2=6.04, P=0.014), intestinal dilation ( χ2=10.38, P=0.001), maximum standardized uptake value (SUV max) ( Z=-3.73, P<0.001), SUV mean ( Z=-3.40, P<0.001), metabolic tumor volume ( Z=-2.37, P=0.018) and total lesion glycolysis ( Z=-2.93, P=0.003) between patients with PIDLBCL and colon cancer in the ileocecal region. Multivariate analysis showed that SUV max ( OR=1.16, 95% CI: 1.04-1.31, P=0.011) and intestinal dilation ( OR=6.64, 95% CI: 1.13-39.10, P=0.036) were both independent influencing factors for the differential diagnosis of PIDLBCL and colon cancer in the ileocecal region. ROC curve analysis showed that, the areas under the curve of SUV max and intestinal dilation for the differential diagnosis of PIDLBCL and colon cancer in the ileocecal region were 0.84 (95% CI: 0.70-0.94) and 0.73 (95% CI: 0.58-0.86), respectively. The optimal cut-off value for SUV max was determined to be 19.14, with a sensitivity of 70.6% and a specificity of 88.0%, while intestinal dilation exhibited a sensitivity of 58.8% and a specificity of 88.0%. Conclusions:18F-FDG PET/CT can be used for the differential diagnosis of PIDLBCL and colon cancer in the ileocecal region, and SUV max and intestinal dilation have high diagnostic efficacy.
8.Application of tenecteplase combined with tirofiban in interventional treatment for acute myocardial infarction
Tao DI ; Kai SHAO ; Jie LIANG ; Xiaozhao WANG
Basic & Clinical Medicine 2025;45(9):1215-1219
Objective To analyze the therapeutic effect of the combination of tenecteplase and tirofiban in percuta-neous coronary intervention(PCI)for acute myocardial infarction(AMI).Methods A total of 120 AMI patients who underwent PCI in Shijiazhuang People's Hospital from June 2023 to January 2024 were collected and randomly separated into a tenecteplase group(tenecteplase during surgery as control)and a test group(tenecteplase in combined with tirofiban during surgery)with 60 patients in each.Two groups were compared for thrombolysis in myocardial infarction(TIMI)blood flow grading,TIMI myocardial perfusion grade(TMPG),myocardial injury markers[creatine kinase isoenzyme MB(CK-MB),cardiac troponinⅠ(cTnⅠ)],peak time,incidence of related bleeding events,echocardiography results[left ventricular end systolic diameter(LVESD),left ventricularend diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF)]and incidence of major adverse cardiac events(MACEs).Results The proportion of immediate TIMI blood flow grade 3 and TMPG grade 3 in the test group was higher than that in control group(P<0.05).The proportion of ST segment regression>50%in test group(93.33%vs.80.00%)was higher than that in the control group(P<0.05).The peak time of CK-MB and cTnⅠin test group was shorter than that in the control group(P<0.05).Three months after surgery,the LVESD and LVEDD of the test group were lower than those before surgery and those of control group(P<0.05),and the LVEF was higher than that before surgery and that of contemporaneous control group(P<0.05).The incidence of MACEs at 3 months after surgery was lower in the test group(6.67%compared to 21.67%,P<0.05).Conclusions The application of tenecteplase combined with tirofiban during PCI for AMI can effectively promote myocardial perfusion recovery and ST segment regression,significantly shorten the peak time of myocardial injury markers and improve heart function and reduce MACEs.
9.Administration of Psoralea corylifolia L. (Buguzhi) during pregnancy causes mild liver injury in mouse mothers and weaned offspring
Chenyue LIU ; Jingzhuo TIAN ; Yan YI ; Chunying LI ; Yong ZHAO ; Jiayin HAN ; Lianmei WANG ; Suyan LIU ; Yushi ZHANG ; Chen PAN ; Shasha QIN ; Jing MENG ; Sulakkana NOIPRASERT ; Aihua LIANG
Science of Traditional Chinese Medicine 2025;3(2):168-177
Background: Psoralea corylifolia L. (Buguzhi, BGZ), known for its efficacy in supporting pregnancy and preventing miscarriage, has been used in China for over 1000 years. Recently, BGZ has been identified as a potential cause of drug-induced liver injury. However, its safety during pregnancy remains unclear, which significantly hinders its routine clinical application. Objective: To investigate the effects of BGZ administration during pregnancy on the liver of mouse mothers and their weaned 21-day-old offspring. Methods: Mice were orally administered BGZ at doses of 2.5 and 10 g/kg during pregnancy, with BGZ withdrawal during the lactation period. Liver histopathology (hematoxylin-eosin staining), biochemical analysis, and evaluation of liver bile acid metabolism were performed after the lactation period. Results: BGZ administration at doses of 2.5 and 10 g/kg during pregnancy, followed by withdrawal during the lactation period, caused mild liver damage in both mothers and their 21-day-old offspring. Serum total bile acid (TBA) levels were elevated compared with those in the control group. Additionally, changes were observed in the levels and proportions of various bile acids (BAs) in the liver, suggesting mild effects on BA metabolism. Conclusion: BGZ administration during pregnancy caused mild liver damage and increased serum TBA levels in both mouse mothers and their 21-day-old offspring. This phenomenon may be associated with imbalanced BA metabolism in the liver. Based on the present study and the limited toxicological research on BGZ, pregnant women should avoid prolonged use of BGZ. If BGZ is administered during pregnancy, serum TBA levels should be monitored, and if elevated, BGZ should be discontinued.
10.Toxicological evaluation of aristolochic acid II following single and repeated oral administration over a 24-week period
Yan YI ; Chunying LI ; Yong ZHAO ; Jingzhuo TIAN ; Yuan WANG ; Yushi ZHANG ; Suyan LIU ; Chen PAN ; Lianmei WANG ; Shuangrong GAO ; Jianyin HAN ; Zhong XIAN ; Chenyue LIU ; Dunfang WANG ; Jing MENG ; Meiting LIU ; Aihua LIANG
Science of Traditional Chinese Medicine 2025;3(4):366-377
Background: Aristolochic acid II (AAII), a major nephrotoxic and carcinogenic component of aristolochic acids (AAs), has been less studied compared with its well-characterized analog, aristolochic acid I (AAI). Although AAs are known to induce carcinogenesis via DNA adduct formation, the toxicity mechanisms, environmental prevalence, and long-term health impacts of AAII remain poorly understood. Objective: This study aimed to systematically evaluate AAII’s acute and chronic toxicity, carcinogenic mechanisms, and environmental exposure patterns using integrated murine models and phytochemical analyses to clarify its toxicological profile and associated health risks. Methods: C57BL/6J mice were used in the following experiments: (1) determination of AAII content in 3 commonly used Aristolochia medicinal materials via liquid chromatography-mass spectrometry/mass spectrometry; (2) acute toxicity testing with single doses of 10, 20, or 40 mg/kg; and (3) chronic exposure with 1 or 10 mg/kg administered every other day for 24 weeks, followed by 21 to 40 weeks of postexposure monitoring. Histopathological examination, whole-exome sequencing, biochemical assays, and micronucleus tests were performed to assess multi-organ damage, tumorigenesis, genomic mutation signatures, and direct clastogenicity. Phytochemical analyses were used to evaluate environmental distribution. Results: (1) A single 40 mg/kg dose of AAII induced dose-dependent renal tubular degeneration without hepatotoxicity; (2) the 10 mg/kg group showed significant mortality (20%), tumor incidence (33.3%, primarily forestomach and bladder transitional cell carcinomas), persistent renal interstitial fibrosis, and subclinical hepatic injury. Chronic exposure to 1 mg/kg still induced 13.3% mortality and 15.5% tumor incidence over a 64-week period; (3) whole-exome sequencing revealed a predominance of C>T mutations and pathway enrichment in chemical carcinogenesis and cytochrome P450-mediated metabolism, indicating reactive metabolite-driven mechanisms distinct from classical AA-DNA adducts; and (4) no histopathological changes were observed in nontarget organs (brain, heart, and testes), and micronucleus assays confirmed the absence of direct clastogenicity. Conclusion: This study highlights the delayed carcinogenic risks of low-dose chronic AAII exposure and emphasizes the need to update regulatory frameworks to ensure the safe use of aristolochiaceae-containing herbal products.


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