Objective Although sequential treatment with doxorubicin (Dox) and trastuzumab (Trz) is initially effective in breast cancer patients, its efficacy is often transient due to severe cardiotoxicity. Tanshinone IIA (DST IIA), the active ingredient in the traditional Chinese medicine Salvia miltiorrhiza, is known for its cardiovascular benefits. However, its protective role when used alongside anticancer drugs remains unclear. This study aimed to investigate the cardioprotective effects of DST IIA in a Dox/Trz-mediated cardiotoxicity model and elucidate its potential mechanism. Methods A Dox/Trz-mediated cardiotoxicity rat model was established by sequential injection of Dox and Trz. The therapeutic effect of DST IIA on the cardiotoxicity model was first assessed by monitoring cardiac function parameters, biochemical indicators and pathological changes in heart tissues. Next, 16S rRNA sequencing and non-targeted metabolomics were used to identify the distinct gut microbiota and metabolites of the cardiotoxic rat following DST IIA intervention. Finally, the influence of DST IIA on the interactive functional information between microbial species, cardiac function indicators and altered metabolites associated with Dox/Trz-induced cardiotoxicity was assessed by Spearman correlation analysis. Results Tanshinone IIA significantly improves cardiac dysfunction and pathological alterations induced by Dox/Trz. It can also improve colonic pathological damage caused by Dox/Trz, and can modulate Dox/Trz-induced dysbiosis by increasing the proportion of beneficial bacteria (e.g. Bacteroides) and reducing the abundance of harmful bacteria (e.g. Ruminococcus and Oscillibacter). DST IIA also reversed Dox/Trz-induced alterations in metabolite levels by regulating tryptophan metabolites, such as 5-hydroxytryptophan, 5-methoxyindoleacetate, formylanthranilic acid, L-tryptophan, and tryptamine. Correlation studies suggested that DST IIA alleviated Dox/Trz-induced myocardial dysfunction by modulating the gut microbial community and associated metabolites. DST IIA demonstrated protection against Dox/Trz-induced cardiotoxicity in a gut microbiota-dependent manner. Conclusions This study highlights the potential of DST IIA from the traditional Chinese medicine Salvia miltiorrhiza Bge. to attenuate Dox/Trz-induced cardiotoxicity through the regulation of metabolic function and gut microbiota composition, providing new insights into the treatment of cardiotoxicity associated with anti-tumor drugs and other metabolic disorders by natural compounds.

Sequential treatment with anthracyclines and trastuzumab is highly effective for HER-2 positive breast cancer but poses a significant risk of cardiotoxicity. Qizaobaoxin Decoction (QZBXD), a modified Chinese herbal formula, has shown promise in protecting against antineoplastic drug-induced cardiotoxicity. This study aimed to investigate the chemical composition, efficacy, and mechanisms of QZBXD in mitigating doxorubicin/trastuzumab (DOX/TRZ)-induced cardiotoxicity. Using UPLC-Q-TOF-MS/MS, 83 compounds in QZBXD were identified, including flavonoids, organic acids, and phthalides. In DOX/TRZ-induced cardiotoxicity model, QZBXD treatment improved cardiac function (increased left ventricular ejection fraction and left ventricular fractional shortening), reduced biomarkers of myocardial injury (cTnI, BNP, LDH, CK-MB, α-HBDH), and alleviated histopathological damage. Mechanistically, 16S rDNA sequencing revealed that QZBXD restored gut microbiota diversity, reducing harmful bacteria (Ruminococcus, Oscillibacter) and increasing beneficial bacteria (Bacteroides). Untargeted metabolomics showed that QZBXD modulated tryptophan and arachidonic acid metabolism, affecting key metabolites (e.g., decreasing tryptamine and 8,9-epoxyeicosatrienoic acid, and increasing 4-hydroxy-L-tryptophan and L-formylkynurenine). Integrated analysis revealed that QZBXD confers cardioprotective effects against DOX/TRZ-induced cardiotoxicity by modulating gut microbiota composition, which subsequently influences tryptophan and arachidonic acid metabolism. This study provides a pharmacological basis for the clinical application of QZBXD in mitigating DOX/TRZ-induced cardiotoxicity.

Liver cancer treatment remains challenging, and the anti-liver cancer mechanism of the “Psoralea corylifolia Linn.-Epimedium brevicornu Maxim.” herb pair is unclear. This study aims to elucidate its synergistic mechanism based on network pharmacology. Network pharmacology was used to screen the active components and targets of the herb pair, construct protein–protein interaction (PPI) and “herbs-components-targets-disease” networks, perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and validate findings via molecular docking. A total of 221 overlapping core targets between the “Psoralea corylifolia Linn.-Epimedium brevicornu Maxim.” herb pair and liver cancer were identified, among which TP53, AKT1, CYP1A1, UGT1A7, and UGT1A1 were the five key nodes crucial for the synergistic effects of the herb pair. KEGG enrichment analysis showed that “Chemical carcinogenesis - receptor activation” and “Lipid and atherosclerosis” are the core pathways through which this herb pair exerts its effects. Molecular docking confirmed stable binding between core components like kaempferol and key targets such as CYP1A1, supporting the potential for this herb pair to intervene in liver cancer progression via multiple targets and pathways. This study systematically elucidates how the “Psoralea corylifolia Linn.-Epimedium brevicornu Maxim.” herb pair exerts anti-liver cancer effects through a multi-target and multi-pathway network, establishing a molecular mechanism framework for the synergistic intervention of liver cancer using traditional Chinese medicine herb pairs.

INTRODUCTION:Trastuzumab and its antibody-drug conjugates (ADCs) are pivotal in treating human epidermal growth factor receptor 2(HER2)-positive cancers. With the growing scope of clinical use, an increasing body of evidence from studies and case reports suggests that these agents can induce hepatotoxicity of varying severity. AREAS COVERED:This review synthesizes evidence from published clinical trials, preclinical studies, pharmacovigilance data, drug labeling information, meta-analyses and clinical guidelines to comprehensively evaluate the potential mechanisms, risk factors, potential predictive methods, and preventive strategies associated with liver injury induced by trastuzumab and its ADCs. EXPERT OPINION:Trastuzumab-related liver injury is uncommon but occurs more frequently with its antibody-drug conjugates, particularly trastuzumab emtansine (T-DM1), which can cause hepatopulmonary syndrome (HPS), nodular regenerative hyperplasia (NRH), and sinusoidal obstruction syndrome (SOS). Risk factors include dosage, treatment duration, and drug interactions. T-DM1 shows dose-dependent hepatotoxicity, while cytochrome P450 3A4 (CYP3A4) inhibitors may increase hepatic accumulation of trastuzumab deruxtecan (T-DXd). Trastuzumab mainly induces hepatocellular and cholestatic injury, whereas T-DM1 involves both HER2-dependent and independent pathways. Diagnosis relies on causality assessment, and most cases are reversible with liver function monitoring and timely dose adjustment.

Ligusticum Chuanxiong (Chuanxiong Rhizoma) is used in Traditional Chinese medicine (TCM) and has cardioprotective effects. Trastuzumab improves outcomes in HER2-positive breast cancer, but acquired resistance and cardiotoxicity limit its utility. Current quality-control methods rarely integrate composition with functional efficacy, hindering rational standardization. We developed an efficacy-oriented quality-control strategy that couples HPLC profiling with in vitro bioassays. HPLC profiling of 12 commercial batches identified ten common constituents: tetramethylpyrazine, chlorogenic acid, ferulic acid, senkyunolide I, senkyunolide H, 6″-feruloylspinosin, senkyunolide A, n-butylbenzene, ligustilide, and butenylbenzene. All constituents were evaluated by CCK-8 assay to identify those with both cytotoxic activity against a trastuzumab-resistant HER2-positive breast cancer cell line and protective effects against trastuzumab-induced cardiomyocyte injury. We constructed two Effect-Constituent Indexes (ECIJ for cytotoxicity; ECIH for cardioprotection) by weighting abundances by measured bioactivities. Both indices correlated with experimentally determined potency (ECIJ vs 1/IC50: rJ = 0.727, **P < 0.01; ECIH vs 1/EC50: rH = 0.592, *P < 0.05) and discriminated batches better than single markers. Batch S10 exhibited the strongest dual efficacy (IC50 = 0.6553 mg/mL; EC50 = 0.00288 mg/mL). Molecular docking indicated that bioactive constituents may modulate ferroptosis via interactions with SLC7A11 and FSP1. The integrated ECI framework offers an efficacy-driven quality control approach for Chuanxiong Rhizoma and supports its dual application to enhance antitumor activity while mitigating trastuzumab-induced cardiotoxicity.

Purpose To investigate the active components and mechanisms of Qizao Baoxin Formula (QBF) in improving trastuzumab-induced cardiotoxicity (TIC) via ferroptosis regulation using network pharmacology and molecular docking. Methods The components of QBF were got from TCMSP 2.0, Herb 2.0, SymMap 2.0, ETCM 2.0, and BATMAN-TCM 2.0 five traditional Chinese medicine databases and screened using SwissADME. Targets were obtained from TCMSP and SwissTargetPrediction. Targets related to TIC were got from GeneCards, PubMed, and the Gene Expression Omnibus (GSE264120). Targets related to ferroptosis were obtained from FerrDb. Venny was applied to obtain the intersection targets.The Protein-Protein Interaction was constucted to investigate protein interactions and identify core targets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were made to explore functions and pathways. A "Chinese Medicine-Component-Target" network was made to identify core components. Molecular docking was performed to validate interactions. Results A total of 1,690 QBF-related targets, 856 TIC-related targets, and 969 targets related to ferroptosis were identified, yielding 52 intersection targets. PPI network analysis identified 25 core targets, including BCL2, HIF1A, NFE2L2, and more. Enrichment analysis revealed significant involvement in oxidative stress, the FoxO signaling pathway, and more. The "Chinese Medicine-Component-Target" network analysis identified 268 core components, six main components of which exhibited strong binding affinity to BCL2, HIF1A, and NFE2L2. Conclusion QBF may target BCL2, HIF1A, and NFE2L2 via its core components to regulate oxidative stress, modulate ferroptosis, and alleviate TIC. These findings provide a scientific basis for further experimentation investigating QBF-mediated modulation of ferroptosis in TIC treatment.

Background:Immune checkpoint inhibitor (ICIs)-associated cardiotoxicity is a significant cause of immune-related adverse events and mortality in cancer immunotherapy, lacking effective preventative or therapeutic strategies. Xihuang Pill (XHW), a traditional Chinese medicine with established anti-inflammatory properties and clinical use in cancer treatment and adverse event mitigation, merits investigation for its efficacy against ICIs-induced cardiac toxicity. Purpose:To investigate XHW's therapeutic effects on Immune checkpoint inhibitors (ICIs)-associated cardiotoxicity and its underlying mechanisms. Methods:This study utilized mass spectrometry technology to identify the chemical components in XHW. The experimental model for ICIs-associated myocarditis was generated in BALB/c mice by immunizing them with murine cardiac troponin I (cTnI) peptide and administering anti-programmed death 1 (PD-1) antibodies to mice. Mice received varying XHW dosages (0.39, 0.78, and 1.56 mg/kg). Myocardial contractility and plasma cardiac injury markers (CK, CK-MB) were assessed. Metabolomics and transcriptomics identified key signaling pathways modulated by XHW, validated via real-time quantitative PCR (QT-PCR). In addition, a correlation analysis was conducted between key genes and differential metabolites. Results:Mass spectrometry identified 171 components in XHW. Pharmacological studies demonstrated that XHW improved cardiac contractility, reduced plasma cardiac injury biomarkers, and attenuated myocardial injury in the myocarditis model. Integrated metabolomic and transcriptomic analyses revealed that XHW primarily modulates the HIF-1 signaling pathway, significantly upregulating HIF-1 mRNA expression and downregulating the mRNA expression of Nppa, Angpt1, Angpt2, and Trf. Correlation analysis identified significant associations between 16 metabolites, including 13-tetradecynoic acid, 1-pentadecanoylglycerol, and arginyl-glycyl-aspartic acid, and these genes. Conclusion:These findings suggest that XHW may alleviate ICIs-associated myocarditis via HIF-1 signaling pathway, offering a promising therapeutic approach for ICIs-related cardiotoxicity.

This study aimed to assess the removal efficiency and mechanism by which microalgae remove sulfamethoxazole (SMX). As a sustainable and environmentally friendly method, microalgae-based biotechnology to remove antibiotics has received increasing attention. However, the mechanism of sulfamethoxazole removal by microalgae is still unclear. This study investigated the ecological toxicity of sulfamethoxazole and its removal by Chlorella vulgaris. The results showed that the removal efficiency was from 6.4 % to 49.9 % at different initial antibiotic concentrations. Biodegradation contributed 5.04 %-44.6 % to SMX removal, while abiotic degradation contributed 1.35 %-5.25 %. Low concentrations (1 and 10 mg/L) of SMX promoted the growth and total protein content of microalgae, while high concentrations (20, 40, 70, and 100 mg/L) had inhibitory effects. High concentrations of antibiotics also significantly inhibited the photosynthetic pigments of microalgae. After 96 h of exposure, the content of exopolysaccharides and lipids in microalgae increased compared to the control group. As the initial concentration of SMX increased, the superoxide dismutase, catalase, and malondialdehyde content increased, which indicated that SMX caused oxidative stress in microalgae. Throughout the entire exposure period, 14 TPs (transformation products) were identified. The risk assessment of TPs indicated that SMX treatment using microalgae tends to produce less toxic TPs.

Flavonoids, the key active compounds in Epimedii Folium, have both protective and toxic effects on the liver. Their hepatoprotective effects are associated with reducing lipid accumulation and oxidative stress, which contribute to the management of various liver conditions. In contrast, the mechanisms driving Epimedii Folium-induced hepatotoxicity are less understood but likely involve oxidative stress and pyroptosis. Pharmacokinetic studies, especially on icaritin, indicate that it undergoes isopentenyl dehydrogenation, glycosylation, and glucuronidation in vivo, contributing to its pharmacological effects. However, intermediate metabolites of icaritin may interact with biomolecules, potentially leading to liver toxicity. This review offers a detailed examination of the dual effects of Epimedii Folium flavonoids on liver function, emphasizing recent discoveries in their hepatoprotective and hepatotoxic pathways. We also summarize and discuss the pharmacokinetics of these flavonoids, highlighting how their metabolism affects therapeutic efficacy and toxicity. Lastly, we propose strategies to mitigate liver injury, providing new perspectives on the safe use of Epimedii Folium.

ETHNOPHARMACOLOGICAL RELEVANCE:Despite the initial efficacy of trastuzumab (TRZ) in breast cancer treatment, its use is hampered by cardiotoxicity. Salvia miltiorrhiza Bunge (DS) has demonstrated potential in treating cardiovascular diseases, but its role in mitigating TRZ-induced cardiotoxicity remains unclear. MATERIALS AND METHODS:We established both in vitro and in vivo models of TRZ-induced cardiotoxicity. Cell viability was measured using the CCK-8 assay following intervention with DS extract. The efficacy of varying doses of DS extract was assessed in the in vivo rat model. Cardiac function was determined via echocardiography, myocardial injury via biochemical markers, and tissue damage via hematoxylin and eosin (H&E) staining. Multi-omics integration (metabolomics, transcriptomics and network pharmacology) was used to identify potential therapeutic targets and bioactive compounds. We employed Western blot analysis and immunofluorescence to confirm that DS extract modulates ferroptosis-related proteins. We used transmission electron microscopy (TEM) to observe the mitochondrial morphology in rat myocardial tissue. Then we employed molecular docking and dynamics simulations to validate the binding affinities of compounds to their targets. RESULTS:DS was found to exert cytotoxic effects on JIMT-1 breast cancer cells, as well as significantly ameliorating TRZ-induced myocardial injury in H9c2 rat cardiomyocytes in a dose-dependent manner. DS extract significantly improved cardiac function and reduced markers of myocardial injury in TRZ treated rats, while also attenuating histopathological damage. A combined analysis of transcriptomics, metabolomics and network pharmacology identified potential bioactive compounds and targets. Further validation revealed that DS extract treatment increased the expression of GPX4 and decreased the expression of ACSL4, thereby inhibiting lipid peroxidation and oxidative stress. TEM observations revealed that DS extract alleviates mitochondrial damage induced by TRZ. Tanshinone I, tanshinone II A, and tanshinone II B demonstrated a strong binding affinity for ACSL4 and GPX4 in molecular docking and dynamic simulations. CONCLUSION:DS extract alleviates TRZ-induced cardiotoxicity, manifested by improved cardiac function, reduced myocardial injury markers, and mitigated tissue and mitochondrial damage. Its mechanism of action is associated with regulating proteins in the ferroptosis pathway (upregulating GPX4 and downregulating ACSL4). Additionally, tanshinone I, IIA, and IIB have been identified as potential active components.

OBJECTIVE:To elucidate the therapeutic effect and mechanism of Compound Danshen Dripping Pill (CDDP) on cardiotoxicity caused by doxorubicin (DOX) and trastuzumab (TRZ) METHODS: Eighteen Sprague-Dawley (SD) rats were randomly divided into the normal group (normal saline), the model group (DOX/TRZ), and CDDP administration group (DOX/TRZ+CDDP), by a random number table, with 6 rats in each group. Rats' were administered either DOX or saline via tail vein injection 6 times over an 11-day period. One week later, they received either TRZ or saline via intraperitoneal injection 6 times over another 11-day period. All rats received CDDP or saline via oral gavage continuously for 36 days. Then, echocardiography was performed on the rats, and biochemical parameters of blood and heart samples were determined. Rats' feces were taken for intestinal flora testing and plasma metabolites were analyzed using untargeted metabolomics. RESULTS:Echocardiographic assessment in rats demonstrated that DOX/TRZ induced cardiac dysfunction, whereas CDDP significantly ameliorated this impairment (P<0.05 or P<0.01). Furthermore, results revealed that DOX/TRZ elevated cardiac injury indicators (left ventricular ejection fraction, fractional shortening, cardiac troponin I, creatine kinase, creatine kinase-MB), while CDDP treatment significantly reduced these levels (P<0.05 or P<0.01). Plasma metabolite analysis revealed enrichment in tryptophan metabolism, tricarboxylic acid cycle, and phenylalanine metabolism. Intestinal microbiota analysis showed increased richness and altered abundance of certain bacteria (Clostridia_UCG-014 and Lactobacillus) with CDDP treatment. CONCLUSIONS:CDDP can prevent and protect against DOX/TRZ-induced cardiac injury. It influences tryptophan metabolism by modulating Clostridia_UCG-014 abundance, inhibits indole-3-carboxylic acid levels, increases kynurenine levels, thereby exerting anti-cardiotoxic effects.

The application of immune checkpoint inhibitors (ICIs) has made extraordinary achievements in tumor treatment. Among them, programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors can improve the prognosis of advanced tumors, and have been widely used in clinical practice to treat many types of cancers. However, excessive immune response can also induce immune-related adverse events (irAEs) involving many organs. Of these, immune-related liver injury is the relatively common and carries the highest morbidity, which has attracted the attention of hepatologists all over the world. The incidence of this type of liver injury depends specifically on factors such as the type of drug being combined, viral infection, type of cancer and liver transplantation. Although there is no unanimity on the mechanism of PD-1/PD-L1 inhibitor-induced liver injury, in this review, we also summarize the current evidence that provides insights into the pathogenesis of PD-1/PD-L1 inhibitor-induced liver injury, including the fact that PD-1/PD-L1 inhibitors cause reactivation of CTLs, aberrant presentation of autoantigens, hepatic immune tolerance environment is disrupted, and cytokine secretion, among other effects. Patients usually develop liver injury after the use of PD-1/PD-L1 inhibitors, and clinical symptoms mainly include weakness, muscle pain, nausea and vomiting, and jaundice. Histologically, the main manifestation is lobular hepatitis with lobular inflammatory infiltration. Since the specific biomarkers for PD-1/PD-L1 inhibitor-associated liver injury have not been identified yet, alpha-fetoprotein, IL-6, and IL-33 have the potential to be biomarkers for predicting this type of liver injury in the future, but this requires further research. We also describe the examination and treatment of this type of liver injury, which usually includes eliminating related influencing factors, regularly monitoring liver function, temporarily retaining or permanently stopping ICIs treatment according to the severity of toxicity, and using corticosteroids. This review may provide useful information for the future clinical practice of PD-1/PD-L1 inhibitors.

ObjectiveA typical case of Xianling Gubao (XLGB) Tablets-induced liver injury was systematically studied in the clinic and the laboratory.MethodsA patient with herb-induced liver injury (HILI) and a history of taking XLGB Tablets before disease onset was engaged as the study subject, and the case was diagnosed according to the updated Roussel Uclaf Causality Assessment Method (RUCAM) and the integrated evidence chain (iEC) method recommended by the Guidelines for Diagnosis and Treatment of Herb-induced Liver Injury (HILI Guidelines).ResultsClinical history, biochemical indexes and imaging tests were used to exclude the influence of fundamental diseases and confusing liver diseases such as viral, alcoholic and autoimmune liver diseases on the diagnosis. Based on an investigation of the patient’s medication history, she was suspected to have HILI caused by XLGB Tablets, as the patient was only taking an oral preparation of XLGB Tablets, and the influence of other drugs on the diagnosis was excluded. This patient with alanine aminotransferase (ALT) ≥ 3 × upper limit of normal (ULN) and a calculated R of 6 was diagnosed with possible acute drug-induced hepatocellular injury. The relationship was considered “highly probable” (score of 9) using the updated RUCAM of 2016. Moreover, the fingerprint similarity between the preparation taken by the patient and a commercially available preparation was 0.99, suggesting that the patient was consuming XLGB Tablets rather than another drug. LC-MS technology and the Agilent Fake TCM-Drugs database were used to investigate the drug, and no chemical additions were found. Examination of the drug for pesticide residues, heavy metals, aflatoxins and other exogenous substances indicated compliance with the content limits of the Chinese Pharmacopoeia.ConclusionIn summary, the final diagnosis of XLGB-induced liver injury reached the clinical diagnosis of HILI and was acute severe hepatocellular injury type by the updated RUCAM and iEC. Therefore, this study provides scientific evidence regarding the causality evaluation of compound preparations of traditional Chinese medicines-induced liver injury.

Objective: Xianling gubao (XLGB), a widely used Chinese patent medicine for osteoporosis, has garnered significant attention due to its potential to cause liver injury. The constituents Psoraleae Fructus (PF, the dried ripe seeds of Psoralea corylifolia L.) and Epimedii Folium (EF, the dried leaves of various Epimedium species) present in XLGB have been implicated in causing idiosyncratic drug-induced liver injury (IDILI). However, the specific components and mechanisms underlying liver injury related to these tonics remain elusive. This study aims to establish that the combination of bavachin (the primary active compound in PF, and icariside II, the main active compound in EF) induces IDILI in a tumor necrosis factor-α (TNF-α)-mediated mouse model. Methods: To assess the impact of bavachin and icariside II on the liver in the presence of TNF-α immune stress, an animal model was developed. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics technology was employed to identify biomarkers associated with TNF-α-induced IDILI and the combination of bavachin and icariside II. Additionally, 16S rRNA high-throughput sequencing technology was utilized to explore changes in the species composition and relative abundance of gut microbiota. Spearman correlation analysis was conducted to unveil the relationship between gut microbiota and in vivo metabolites. Results: The study observed that the combined administration of bavachin and icariside II induced liver injury in the TNF-α mediated susceptibility mouse model of IDILI. Under TNF-α stimulation, there was an elevation in levels in mouse livers following bavachin and icariside II administration, while Gly-Tyr, Leu-Gly, and Trp-Ser levels decreased. These differentially expressed metabolites associated with liver injury were predominantly enriched in metabolic pathways such as sphingolipid metabolism, sphingolipid signaling pathway, and necroptosis. it is noteworthy that the gut of mice with liver injury induced by the bavachin and icariside II combination exhibited a significant increase in Bacteroides and Desulfovibrionaceae abundance. Correlation analysis revealed a positive association between Bacteroidaceae and Desulfovibrionaceae with methylcarbamoyl PAF and methyl Indole-3-acetate, while a negative correlation was observed with Gly-Tyr, Leu-Gly, and Trp-Ser. Conclusions: These findings demonstrated that the combination of bavachin and icariside II increased the risk of IDILI in vivo, providing a promising scientific basis for understanding the component basis of IDILI resulting from the compatibility of EF and PF.

Immunotherapy has emerged as a powerful tool in cancer treatment, achieving remarkable success in combating various cancers. However, it also raises concerns due to its potential adverse effects, with immune-associated pneumonia being one of the most significant. The clinical symptoms of this condition primarily include dyspnea, persistent cough, and fever. Diagnosis requires knowledge of the patient's medication history and diagnostic tools like chest CT and bronchoalveolar lavage bronchoscopy to differentiate immune-associated pneumonia from other lung diseases. Studies suggest that the pathogenesis of CIP involves an immune response characterized by overexpression of T-lymphocyte subsets and elevated levels of inflammatory factors. The prevalence of CIP generally ranges between 2 % and 6 %, though it can vary depending on factors like the patient's individual characteristics, tumor type, and treatment strategy. Corticosteroids are the first-line treatment for CIP, with dosage adjustments based on clinical response. Additionally, traditional Chinese medicine is being explored as an adjuvant therapy to potentially enhance therapeutic outcomes.

Sanqi (SQ), as a health food, is clinically used as an effective complementary therapy for treating multiple cancers with the advantages of immunomodulatory potential. Nevertheless, the efficacy and the underlying mechanism of combining SQ and PD-1 inhibitors remain inconclusive. In this study, we examined the anti-lung cancer effects of SQ in combination with PD-1 inhibitors in tumor-bearing mice. We found that PD-1 inhibitors and SQ combinedtreatment significantly inhibited tumor growthin tumor-bearing mice. Following the administration of SQ combined with PD-1 inhibitors, there was an increase in the levels of Glycolaldehyde and N-Acetyl-D-glucosamine in the plasma of mice, while the levels of 1,4-Dihydro-1-methyl-4-oxo-3-pyridinecarboxamide decreased. Specifically, SQ supplementation increased the abundance of beneficial bacteria, such as Aerococcus, while reducing the levels of pathogenic bacteria, including norank_f_norank_o_Clostridia_UCG-014, Candidatus_Saccharimonas, and Bilophila. Our data suggested that a combination of PD-1 inhibitors and SQ treatment may be a novel therapeutic strategy for lung cancer patients.

Objectives: Reports of traditional Chinese medicine (TCM)-related liver injury have increased over recent years; however, identifying susceptibility-related components and biomarkers remains challenging due to the heterogeneous nature of TCM and idiosyncratic drug-induced liver injury (IDILI). Psoraleae Fructus (PF) and Epimedii Folium (EF), commonly found in TCM prescriptions, have been implicated in IDILI, but their constituents and underlying mechanisms are poorly understood.Methods: In this study, we identified bavachin (Bav) and icariin (Ica) as susceptibility components for IDILI in PF and EF using a TNF-alpha-mediated mouse model. Lipidomics and transcriptomics were used to investigate their related mechanism.Results: Liver biochemistry and histopathology analyses revealed that co-exposure to Bav, Ica, and a non-toxic dose of TNF-alpha prestimulation induced significant liver injury, while Bav and Ica alone did not. Lipidomics identified seven differentially abundant metabolites in the Bav/Ica/TNF-alpha group compared to the Ica/TNF-alpha or Bav/TNF-alpha groups, mainly enriched in alpha-linolenic acid (ALA), arachidonic acid (AA), and linoleic acid (LA) metabolic pathways. Additionally, transcriptomics revealed 49 differentially expressed genes (DEGs) in the Bav/TNF-alpha vs Bav/Ica/TNF-alpha and Ica/TNF-alpha vs Bav/Ica/TNF-alpha groups, primarily associated with the PI3K/AKT/mTOR signaling pathway and sphingolipid metabolism. Integrative lipidomics and transcriptomics analyses identified significant positive correlations between five differential metabolites (DMs) - PC (O-16:0_14:1), PG (22:1_20:3), PI (16:0_14:1), PS (18:0_19:2), and TG (17:0_18:2_22:5) - and ten DEGs - Nr0b2, Btbd19, Btg2, Fam222a, Fam83f, Gtse1, Anln, Gja4, Srrm4, and Zfp13.Conslusions: Collectively, these results suggest that alterations in intracellular metabolism and gene expression levels may contribute to the synergistic induction of IDILI by the incompatible pair Bav and Ica in the presence of TNF-alpha.

Polygoni Multiflori Radix (He Shou Wu) is a Chinese medicine widely used in clinical treatment and preventive healthcare. However, recently there have been frequent reports of liver injury caused by Polygoni Multiflori Radix and its related preparations, and some patients have serious adverse outcomes, attracting wide attention worldwide. The risk of liver damage caused by preparations containing Polygoni Multiflori Radix or Polygoni Multiflori Caulis has been repeatedly reported by the Chinese Food and Drug Administration. Fortunately, substantial progress has recently been made in revealing the basic properties, main causes, material basis, and molecular mechanism of Polygoni Multiflori Radix-related liver injury. The basic characteristics and biomarkers of susceptible people have been identified, indicating that Polygoni Multiflori Radix has the risk of inducing liver injury only in a few specific populations and is safe for most populations. This study provides a scientific basis for a correct and objective understanding of liver injury caused by Polygoni Multiflori Radix, and a reasonable formulation of safe medication measures for Polygoni Multiflori Radix and related preparations. The China Association of Chinese Medicine organized experts in relevant fields across the country to draft and formulate the “Guidelines for Safe Use of Polygoni Multiflori Radix” with the aim of helping the public and relevant institutions at home and abroad to scientifically understand, evaluate, and avoid the risk of liver injury; guide the rational use; protect the health rights and interests of consumers; and promote the healthy and sustainable development of Polygoni Multiflori Radix and related preparations. These guidelines were issued by the China Association of Chinese Medicine (No. T/CACM 1328-2019).

目的 以挥发油成分为油相、水煎液为水相制备升清解毒微乳凝胶,并对其进行处方优化和质量评价.方法 采用伪三元相图法优选微乳处方,再采用D-最优混料设计优化处方,通过单因素法筛选凝胶基质及用量,并对升清解毒微乳凝胶进行质量评价.结果 优化后的升清解毒微乳凝胶呈金黄色、半透明、均一稳定的黏稠状半固体,有轻微花椒油气味,均匀细腻,易于涂展,pH值为(6.54±0.08),黏度为(15.33±0.15)Pa·s.处方组成:水相3.49 g,油相0.11 g,EL-35 0.27 g,1,2-丙二醇0.13 g,卡波姆940 0.4 g,三乙醇胺0.5 g.结论 优化后的微乳凝胶制备工艺稳定可行,初步质量评价符合皮肤外用制剂的要求.