Adult vasovagal syncope with abdominal pain diagnosed by head-up tilt combined with transcranial doppler: a preliminary study.

BACKGROUND: Syncope is a common condition that increases the risk of injury and reduces the quality of life. Abdominal pain as a precursor to vasovagal syncope (VVS) in adults is rarely reported and is often misdiagnosed.​. METHODS: We present three adult patients with VVS and presyncopal abdominal pain diagnosed by synchronous multimodal detection (transcranial Doppler [TCD] with head-up tilt [HUT]) and discuss the relevant literature. RESULTS: Case 1: A 52-year-old man presented with recurrent decreased consciousness preceded by six months of abdominal pain. Physical examinations were unremarkable. Dynamic electrocardiography, echocardiography, head and neck computed tomography angiography, magnetic resonance imaging (MRI), and video electroencephalogram showed no abnormalities. Case 2: A 57-year-old woman presented with recurrent syncope for 30 + years, accompanied by abdominal pain. Physical examination, electroencephalography, and MRI showed no abnormalities. Echocardiography showed large right-to-left shunts. Case 3: A 30-year-old woman presented with recurrent syncope for 10 + years, with abdominal pain as a precursor. Physical examination, laboratory analysis, head computed tomography, electrocardiography, and echocardiography showed no abnormalities. Syncope secondary to abdominal pain was reproduced during HUT. Further, HUT revealed vasovagal syncope, and synchronous TCD showed decreased cerebral blood flow; the final diagnosis was VVS in all cases. CONCLUSIONS: Abdominal pain may be a precursor of VVS in adults, and our findings enrich the clinical phenotypic spectrum of VVS. Prompt recognition of syncopal precursors is important to prevent incidents and assist in treatment decision-making. Abdominal pain in VVS may be a sign of sympathetic overdrive. Synchronous multimodal detection can help in diagnosing VVS and understanding hemodynamic mechanisms.

Molecular insights into gastric cancer: The impact of TGFBR2 and hsa-mir-107 revealed by microarray sequencing and bioinformatics.

BACKGROUND: Gastric carcinoma (GC) remains a significant therapeutic challenge, garnering widespread attention. Oxymatrine (OMT), an active component of the traditional Chinese medicine compound Kushen injection (CKI), has shown promising results in combination with chemotherapy for the treatment of GC. However, the molecular mechanisms underlying OMT's therapeutic effects in GC have yet to be elucidated. METHODS: The transcriptomic expression data of HGC-27 post-OMT intervention were obtained through microarray sequencing, while the miRNA and mRNA sequencing data for GC patients were sourced from the TCGA database. The mechanism of OMT intervention in GC is analyzed in multiple aspects, including Protein-Protein Interactions (PPI), Competitive Endogenous RNA (ceRNA) networks, correlation and co-expression analyses, immune infiltration, and clinical implications. RESULTS: By analyzing key modules, five critical mRNAs were identified, and their interacting miRNAs were predicted to construct a ceRNA network. Among these, TGFBR2 and hsa-miR-107 have correlations or co-expression relationships with other genes in the network. They are differentially expressed in most other cancers, associated with prognosis, and have diagnostic value. TGFBR2 also exhibits immune infiltration phenomena, and its high expression is linked to poor patient prognosis. Low expression of hsa-miR-107 is associated with poor patient prognosis. OMT may act on the TGFß/Smad signaling pathway or negatively regulate the WNT signaling pathway through the hsa-miR-107/BTRC axis, thereby inhibiting the onset and progression of GC. CONCLUSION: The mechanisms of OMT intervention in GC are diverse, TGFBR2 and hsa-miR-107 may serve as prognostic molecular biomarkers or potential therapeutic targets.

Graphene-based iron single-atom catalysts for electrocatalytic nitric oxide reduction: a first-principles study.

The electrocatalytic NO reduction reaction (NORR) emerges as an intriguing strategy to convert harmful NO into valuable NH3. Due to their unique intrinsic properties, graphene-based Fe single-atom catalysts (SACs) have gained considerable attention in electrocatalysis, while their potential for NORR and the underlying mechanism remain to be explored. Herein, using constant-potential density functional theory calculations, we systematically investigated the electrocatalytic NORR on the graphene-based Fe SACs. By changing the local coordination environment of Fe single atoms, 26 systems were constructed. Theoretical results show that, among these systems, the Fe SAC coordinated with four pyrrole N atoms and that co-coordinated with three pyridine N atoms and one O atom exhibit excellent NORR activity with low limiting potentials of -0.26 and -0.33 V, respectively, as well as have high selectivity toward NH3 by inhibiting the formation of byproducts, especially under applied potential. Furthermore, electronic structure analyses indicate that NO molecules can be effectively adsorbed and activated via the electron "donation-backdonation" mechanism. In particular, the d-band center of the Fe SACs was identified as an efficient catalytic activity descriptor for NORR. Our work could stimulate and guide the experimental exploration of graphene-based Fe SACs for efficient NORR toward NH3 under ambient conditions.

Microglial activation in spaceflight and microgravity: potential risk of cognitive dysfunction and poor neural health.

Due to the increased crewed spaceflights in recent years, it is vital to understand how the space environment affects human health. A lack of gravitational force is known to risk multiple physiological functions of astronauts, particularly damage to the central nervous system (CNS). As innate immune cells of the CNS, microglia can transition from a quiescent state to a pathological state, releasing pro-inflammatory cytokines that contribute to neuroinflammation. There are reports indicating that microglia can be activated by simulating microgravity or exposure to galactic cosmic rays (GCR). Consequently, microglia may play a role in the development of neuroinflammation during spaceflight. Prolonged spaceflight sessions raise concerns about the chronic activation of microglia, which could give rise to various neurological disorders, posing concealed risks to the neural health of astronauts. This review summarizes the risks associated with neural health owing to microglial activation and explores the stressors that trigger microglial activation in the space environment. These stressors include GCR, microgravity, and exposure to isolation and stress. Of particular focus is the activation of microglia under microgravity conditions, along with the proposal of a potential mechanism.

Exploring the mechanism of action of Shuangyang houbitong granules in the treatment of acute pharyngitis based on network pharmacology and molecular docking.

BACKGROUND: Acute pharyngitis (AP) refers to the acute inflammation of the pharynx, characterized by swelling and pain in the throat. Shuangyang houbitong granules (SHG), a traditional Chinese medicine compound, have been found to be effective in providing relief from symptoms associated with AP. METHODS: The chemical components of SHG were screened using Traditional Chinese Medicine Systems Pharmacology database, HERB database, and China National Knowledge Infrastructure. The targets of the granules were predicted using SwissTargetPrediction database. A network was constructed based on the targets of AP obtained from Genecards database, and protein-protein interaction analysis was performed on the intersection targets using STRING database. Key targets were screened for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and the binding activity of components and targets was predicted using AutoDockTools-1.5.7. RESULTS: A total of 65 components of SHG that met the screening criteria were retrieved, resulting in 867 corresponding targets. Additionally, 1086 AP target genes were retrieved, and 272 gene targets were obtained from the intersection as potential targets for SHG in the treatment of AP. Molecular docking results showed that the core components genkwanin, acacetin, apigenin, quercetin can stably bind to the core targets glyceraldehyde 3-phosphate dehydrogenase, interleukin 6, tumor necrosis factor, serine/threonine protein kinase, tumor protein 53, and epidermal growth factor receptor. CONCLUSION: The research results preliminarily predict and verify the mechanism of action of SHG in the treatment of AP, providing insights for further in-depth research.

Bioinformatics Analysis and Experimental Validation of Mitochondrial Autophagy Genes in Knee Osteoarthritis.

Background: Mitochondrial autophagy is closely related to the pathogenesis of osteoarthritis, In order to explore the role of mitochondrial autophagy related genes in knee osteoarthritis (KOA) and its molecular mechanism. Methods: KOA-related transcriptome data were extracted from the Gene Expression Omnibus (GEO) database. Differentially expressed mitochondrial autophagy gene (DEMGs) were screened in patients with KOA by differential expression analysis. The STRING website was used to construct a protein-protein interaction (PPI) network among DEMGs. Molecular complex detection (MCODE) method in Cytoscape software was performed to identify hub DEMGs. Support vector machine recursive feature elimination (SVM-RFE) method was used to construct the hub DEMG diagnosis model. Genes with diagnostic value were identified as biomarkers by plotting receiver operating characteristic (ROC) curves and Expression validation. CIBERSORT algorithm was used to calculate the proportion of 22 immune cells in each sample in the GSE114007 dataset. Finally, biomarker expression was verified by qPCR. Results: A total of 15 DEMGs were obtained and enrichment analyses showed that these DEMG strains were mainly enriched in the mitophagy-animal, shigellosis, autophagy-animal and FoxO signal pathways. The PPI network unveiled 13 DEMGs with interactions. In addition, 8 hub DEMGs (ULK1, CALCOCO2, MAP1LC3B, BNIP3L, GABARAPL1, BNIP3, FKBP8 and FOXO3) were obtained for KOA. And 5 model DEMGs (BNIP3L, BNIP3, MAP1LC3B, ULK1 and FOXO3) were screened. The ROC curves revealed that BNIP3 and FOXO3 has strong diagnostic value in these models of DEMG. Immune-infiltration and correlation analysis showed that BNIP3 and FOXO3 were significantly correlated with three different immune cells, including primary B cells, M0 macrophage and M2 macrophage. The cartilage tissue samples qPCR verification results show that FOXO3 and BNIP3 were all down-regulated in KOA (p < 0.01), and the validation results are consistent with the above analysis. Conclusion: BNIP3 and FOXO3 have been identified as biomarkers for the diagnosis of KOA, which might supply a new insight for the pathogenesis and treatment of KOA.

The efficacy and safety of diterpene ginkgolides meglumine injection for cerebral infarction: A meta-analysis of randomized controlled trials.

OBJECTIVE: To systemically evaluate the efficacy and safety of diterpene ginkgolides meglumine injection (DGMI) on cerebral infarction (CI). METHODS: Comprehensively collect randomized controlled trials of DGMI in the treatment of CI in 7 databases including Embase, PubMed, the Cochrane Library, the China National Knowledge Infrastructure Database, the WanFang Database, the China Science and Technology Journal Database, and the China Biology Medicinedisc as of January 2023. The studies were screened according to the inclusion and exclusion criteria and evaluated according to the criteria recommended by the Cochrane Handbook, then RevMan 5.3, Stata 12.0 software were used for Meta-analysis. RESULTS: A total of 22 randomized controlled trials with 2194 patients were included. Meta analysis showed that: the total effective rate of treatment (relative risk = 1.29, 95% confidence interval (1.21, 1.38), P < .001), National Institute of Health stroke scale score, Barthel index and Modified Rankin Scale were better in DGMI group than in Conventional Western Medicine Treatment group. The included studies reported 42 adverse events, 25 of which belonged to DGMI groups. CONCLUSION: Available evidence suggested that DGMI can significantly improve the clinical efficiency in the treatment of CI. DGMI is an ideal treatment for CI, which has high clinical application value.

What can molecular assembly learn from catalysed assembly in living organisms?

Molecular assembly is the process of organizing individual molecules into larger structures and complex systems. The self-assembly approach is predominantly utilized in creating artificial molecular assemblies, and was believed to be the primary mode of molecular assembly in living organisms as well. However, it has been shown that the assembly of many biological complexes is "catalysed" by other molecules, rather than relying solely on self-assembly. In this review, we summarize these catalysed-assembly (catassembly) phenomena in living organisms and systematically analyse their mechanisms. We then expand on these phenomena and discuss related concepts, including catalysed-disassembly and catalysed-reassembly. Catassembly proves to be an efficient and highly selective strategy for synergistically controlling and manipulating various noncovalent interactions, especially in hierarchical molecular assemblies. Overreliance on self-assembly may, to some extent, hinder the advancement of artificial molecular assembly with powerful features. Furthermore, inspired by the biological catassembly phenomena, we propose guidelines for designing artificial catassembly systems and developing characterization and theoretical methods, and review pioneering works along this new direction. Overall, this approach may broaden and deepen our understanding of molecular assembly, enabling the construction and control of intelligent assembly systems with advanced functionality.

Dissecting the pleiotropic roles of reactive oxygen species (ROS) in lung cancer: From carcinogenesis toward therapy.

Lung cancer is a major cause of morbidity and mortality. The specific pulmonary structure to directly connect with ambient air makes it more susceptible to damage from airborne toxins. External oxidative stimuli and endogenous reactive oxygen species (ROS) play a crucial role in promoting lung carcinogenesis and development. The biological properties of higher ROS levels in tumor cells than in normal cells make them more sensitive and vulnerable to ROS injury. Therefore, the strategy of targeting ROS has been proposed for cancer therapy for decades. However, it is embarrassing that countless attempts at ROS-based therapies have had very limited success, and no FDA approval in the anticancer list was mechanistically based on ROS manipulation. Even compared with the untargetable proteins, such as transcription factors, ROS are more difficult to be targeted due to their chemical properties. Thus, the pleiotropic roles of ROS provide therapeutic potential for anticancer drug discovery, while a better dissection of the mechanistic action and signaling pathways is a prerequisite for future breakthroughs. This review discusses the critical roles of ROS in cancer carcinogenesis, ROS-inspired signaling pathways, and ROS-based treatment, exemplified by lung cancer. In particular, an eight considerations rule is proposed for ROS-targeting strategies and drug design and development.

A deep learning system for predicting time to progression of diabetic retinopathy.

Diabetic retinopathy (DR) is the leading cause of preventable blindness worldwide. The risk of DR progression is highly variable among different individuals, making it difficult to predict risk and personalize screening intervals. We developed and validated a deep learning system (DeepDR Plus) to predict time to DR progression within 5 years solely from fundus images. First, we used 717,308 fundus images from 179,327 participants with diabetes to pretrain the system. Subsequently, we trained and validated the system with a multiethnic dataset comprising 118,868 images from 29,868 participants with diabetes. For predicting time to DR progression, the system achieved concordance indexes of 0.754-0.846 and integrated Brier scores of 0.153-0.241 for all times up to 5 years. Furthermore, we validated the system in real-world cohorts of participants with diabetes. The integration with clinical workflow could potentially extend the mean screening interval from 12 months to 31.97 months, and the percentage of participants recommended to be screened at 1-5 years was 30.62%, 20.00%, 19.63%, 11.85% and 17.89%, respectively, while delayed detection of progression to vision-threatening DR was 0.18%. Altogether, the DeepDR Plus system could predict individualized risk and time to DR progression over 5 years, potentially allowing personalized screening intervals.

An emerging biomarker for the diagnosis and treatment of esophageal squamous cell carcinoma - Aurora A.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a prominent form of esophageal cancer. Aurora A (AURKA), an enzyme that phosphorylates serine and threonine, has a vital function in controlling the process of separating chromosomes during cell division. The contribution of this entity has been documented in the advancement of malignant proliferations, including tumors occurring in the breast, stomach, and ovaries. METHODS: The potential molecular mechanism of AURKA is comprehensively examined through the analysis of bulk RNA-seq and single-cell RNA-seq data obtained from publicly available databases. This analysis encompasses various aspects such as expression levels, prognosis, and functional pathways, among others. RESULTS: The upregulation of AURKA in ESCC has been found to be correlated with the overall survival of patients. The functional annotation and pathway enrichment analysis conducted in this study lead to the conclusion that AURKA participates in the regulation of a number of malignant processes connected to cell proliferation, such as cell cycle control, apoptosis, and the p53 signaling pathway. Additionally, AURKA has been found to be associated with drug sensitivity and has an impact on the infiltration of tumor-infiltrating immune cells in ESCC. CONCLUSIONS: AURKA exhibits potential as a prognostic and therapeutic biomarker linked to the regulation of cell cycle and cell proliferation.

Systematic review and meta-analysis on the efficacy and safety of Injectable Lentinan combined with chemotherapy in the treatment of gastric cancer.

BACKGROUND: This study employed a meta-analysis to evaluate the efficacy and safety of adjunctive treatment with injectable Lentinan (LNT) in combination with chemotherapy for gastric cancer (GC). METHODS: Computer-based searches of 6 databases were performed to identify randomized controlled trials (RCTs) relevant to the treatment of GC with LNT through mid-March 2023. Two independent researchers performed risk of bias assessment and trial sequential analysis(TSA), extracted the data and used Revman 5.3 software for data analysis. The certainty of evidence was graded based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. RESULTS: A total of 31 RCTs with 2729 patients were included in the analysis. The results revealed that adjunctive therapy with LNT was associated with improved treatment efficacy (RR = 1.48, 95%CI: 1.36 ∼ 1.61, p < 0.00001), improvement in clusters of differentiation (CD3+, CD4+, and CD4+/CD8+), natural killer (NK) cells, and quality of life assessment (RR = 1.32, 95%CI: 1.20 ∼ 1.45, p < 0.00001) compared to using chemotherapy alone. In addition, there was a reduction in CD8+ levels, incidence of white blood cell decline, gastrointestinal reactions, and platelet decline. TSA results indicated that there was sufficient evidence to draw firm conclusions about these outcomes, and the GRADE scores showed 'high' or 'moderate' quality of evidence for these outcomes. CONCLUSION: The efficacy of treatment of GC with LNT in combination with chemotherapy was found to be better than chemotherapy alone. And no serious adverse effects were observed. However, further RCTs are needed to further validate the results of this study.

Identification of eight genomic protective alleles for mitochondrial diabetes by Kinship-graph convolutional network.

AIMS: Nearly 85% of maternally inherited diabetes and deafness (MIDD) are caused by the m.3243A>G mutation in the mitochondrial DNA. However, the clinical phenotypes of MIDD may also be influenced by the nuclear genome, this study aimed to investigate nuclear genome variants that influence clinical phenotypes associated with m.3243A>G mutation in MIDD based on whole-genome sequencing of the patients belonging to pedigrees. MATERIALS AND METHODS: We analyzed a whole-genome sequencing (WGS) dataset from blood samples of 38 MIDD patients with the m.3243A > G mutation belonging to 10 pedigrees, by developing a Kinship-graph convolutional network approach, called Ki-GCN, integrated with the conventional genome-wide association study (GWAS) methods. RESULTS: We identified eight protective alleles in the nuclear genome that have protective effects against the onset of MIDD, related deafness, and also type 2 diabetes. Based on these eight protective alleles, we constructed an effective logistic regression model to predict the early or late onset of MIDD patients. CONCLUSIONS: There are protective alleles in the nuclear genome that are associated with the onset-age of MIDD patients and might also provide protective effects on the deafness derived from MIDD patients.

Sex- and age-specific associations between abdominal fat and non-alcoholic fatty liver disease: a prospective cohort study.

Obesity is closely related to non-alcoholic fatty liver disease (NAFLD). Although sex differences in body fat distribution have been well demonstrated, little is known about the sex-specific associations between adipose tissue and the development of NAFLD. Using community-based cohort data, we evaluated the associations between magnetic resonance imaging-quantified areas of abdominal adipose tissue, including visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and incident NAFLD in 2830 participants (1205 males and 1625 females) aged 55-70 years. During a 4.6-year median follow-up, the cumulative incidence rates of NAFLD increased with areas of VAT and SAT both in males and females. Further analyses showed that the abovementioned positive associations were stronger in males than in females, especially in participants under 60 years old. In contrast, these sex differences disappeared in those over 60 years old. Furthermore, the risk of developing NAFLD increased nonlinearly with increasing fat area in a sex-specific pattern. Additionally, sex-specific potential mediators, such as insulin resistance, lipid metabolism, inflammation, and adipokines, may exist in the associations between adipose tissue and NAFLD. This study showed that the associations between abdominal fat and the risk of NAFLD were stratified by sex and age, highlighting the potential need for sex- and age-specific management of NAFLD.

A Bioorthogonal Decaging Chemistry of N-Oxide and Silylborane for Prodrug Activation both In Vitro and In Vivo.

Bioorthogonal decaging chemistry with both fast kinetics and high efficiency is highly demanded for in vivo applications but remains very sporadic. Herein, we describe a new bioorthogonal decaging chemistry between N-oxide and silylborane. A simple replacement of "C" in boronic acid with "Si" was able to substantially accelerate the N-oxide decaging kinetics by 106 fold (k2: up to 103 M-1 s-1). Moreover, a new N-oxide-masked self-immolative spacer was developed for the traceless release of various payloads upon clicking with silylborane with fast kinetics and high efficiency (>90%). Impressively, one such N-oxide-based self-assembled bioorthogonal nano-prodrug in combination with silylborane led to significantly enhanced tumor suppression effects as compared to the parent drug in a 4T1 mouse breast tumor model. In aggregate, this new bioorthogonal click-and-release chemistry is featured with fast kinetics and high efficiency and is perceived to find widespread applications in chemical biology and drug delivery.

A new strategy to identify ADAM12 and PDGFRB as a novel prognostic biomarker for matrine regulates gastric cancer via high throughput chip mining and computational verification.

BACKGROUND: Gastric cancer is a life-threatening disease that poses a serious risk to human health. Although there are numerous molecular targets for gastric cancer in clinical practice, they often exhibit low specificity and sensitivity. Consequently, this can result in a low early diagnosis rate, delayed treatment, and poor prognosis for patients with gastric cancer. Hence, it remains crucial to identify more precise diagnostic markers for this disease. METHODS: This study utilized ceRNA chips and bioinformatics methods to investigate the key genes and mechanisms involved in matrine intervention in gastric cancer cells. RESULTS: ADAM12 and PDGFRB are the key genes that are down-regulated after matrine intervention in gastric cancer cells. By conducting bioinformatics analysis, two ceRNA regulatory axes were identified, which are associated with the prognosis of gastric cancer. These axes are lncRNA DGCR5/hsa-miR-206/ADAM12 and circRNA ITGA3/hsa-miR-24-3p/PDGFRB. CONCLUSION: The low expression of ADAM12 may weaken the digestion of extracellular matrix (ECM) molecules, which can result in the invasion and metastasis of tumor cells. This occurs without the catalysis of ECM proteases, thereby impacting the invasion and metastasis of gastric cancer cells. Additionally, the analysis of immune infiltration suggests that ADAM12 and PDGFRB may influence changes in the tumor immune microenvironment, thereby affecting the occurrence and development of gastric cancer. This study contributes to a deeper understanding of the role of the matrine-related ceRNA network in gastric cancer, providing a reference for clinical diagnosis and treatment. It holds significant importance in discovering new drug treatment targets.

Aggregation, Transmission, and Toxicity of the Microtubule-Associated Protein Tau: A Complex Comprehension.

The microtubule-associated protein tau is an intrinsically disordered protein containing a few short and transient secondary structures. Tau physiologically associates with microtubules (MTs) for its stabilization and detaches from MTs to regulate its dynamics. Under pathological conditions, tau is abnormally modified, detaches from MTs, and forms protein aggregates in neuronal and glial cells. Tau protein aggregates can be found in a number of devastating neurodegenerative diseases known as "tauopathies", such as Alzheimer's disease (AD), frontotemporal dementia (FTD), corticobasal degeneration (CBD), etc. However, it is still unclear how the tau protein is compacted into ordered protein aggregates, and the toxicity of the aggregates is still debated. Fortunately, there has been considerable progress in the study of tau in recent years, particularly in the understanding of the intercellular transmission of pathological tau species, the structure of tau aggregates, and the conformational change events in the tau polymerization process. In this review, we summarize the concepts of tau protein aggregation and discuss the views on tau protein transmission and toxicity.

The Link between Trace Metal Elements and Glucose Metabolism: Evidence from Zinc, Copper, Iron, and Manganese-Mediated Metabolic Regulation.

Trace metal elements are of vital importance for fundamental biological processes. They function in various metabolic pathways after the long evolution of living organisms. Glucose is considered to be one of the main sources of biological energy that supports biological activities, and its metabolism is tightly regulated by trace metal elements such as iron, zinc, copper, and manganese. However, there is still a lack of understanding of the regulation of glucose metabolism by trace metal elements. In particular, the underlying mechanism of action remains to be elucidated. In this review, we summarize the current concepts and progress linking trace metal elements and glucose metabolism, particularly for the trace metal elements zinc, copper, manganese, and iron.

Investigation of the applicability of the zebrafish model for the evaluation of aristolochic acid-related nephrotoxicity.

BACKGROUND: The risk of compounds/drugs, including aristolochic acid-induced nephrotoxicity remains high and is a significant public health concern. Therefore, it is particularly important to select reasonable animal models for rapid screening and evaluation of different samples with complex chemical systems. The zebrafish (Danio rerio) has been used to study chemical-induced renal toxicity. However, most of the published literature was performed on individual components or drugs, and the key evidence confirming the applicability of zebrafish larvae for the evaluation of aristolochic acid-related nephrotoxicity in complex chemical systems, such as in traditional Chinese medicine (TCM), was insufficient. METHODS: High-performance liquid chromatography (HPLC) was used to determine the content of aristolochic acid (AA) in herbs and Chinese patent medicines. The zebrafish larvae at 4 days post-fertilization (dpf) were used to evaluate the nephrotoxicity of various samples, respectively, based on the phenotype of the kidney and histological, and biochemical. Transcriptome technology was used to investigate the related signaling pathways and potential mechanisms after treatment with AA, which was verified by RT-PCR technology. RESULTS: The results showed that the total amounts of AAI, AAII, and ALI ranged from 0.0004 to 0.1858 g·g-1( %) from different samples, including Aristolochia debilis, Fibraurea recisa, Asarum, Wantongjingu tablets, Jiuweiqianghuo granules, and Xiaoqinglong granules in descending order. Moreover, compared with the negative/blank control, substantial changes in phenotype, histomorphology and biochemical parameters of renal function were observed in the groups challenged with the sublethal concentration of drugs. The transcriptomics results showed the upregulation of most genes in PERK/ATF4/CHOP, ATM/Chk2/p53, Caspase/Bax/Bcl-2a, TGF/Smad/ERK, PI3K/Akt, induced by aristolochic acid analogues, which were essentially consistent with those of the q-RT-PCR experiments, highlighting the similar toxicity response to the previously published article with the other traditional evaluation model. CONCLUSION: The stability, accuracy and feasibility of the zebrafish larval model in screening and evaluating the nephrotoxicity of TCM were validated for the first time on the AAs-related drugs in a unified manner, confirming and promoting the applicability of zebrafish in assessing nephrotoxicity of samples with complex chemical character.