OBJECTIVE To systematically evaluate the quality of the Heat-clearing and symptom-relieving formula and screen potential marker components that influence the quality of the formula. METHODS The contents of 11 components （calycosin-7- O - β -D-glucoside， ononin， hyperoside， isoquercitrin， baicalin， baicalein， cryptotanshinone， tanshinone Ⅱ A ， tanshinone Ⅰ， senkyunolide A， ferulic acid） in the Heat-clearing and symptom-relieving formula were determined by high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）. Using the contents of the aforementioned components as variables， cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） were conducted using OriginPro 2024 software and SIMCA 14.1 software； marker components affecting the quality of the Heat-clearing and symptom-relieving formula were then screened based on the criteria of variable importance in the projection （VIP） value＞1 and P ＜0.05. The comprehensive evaluation of 20 batches of samples was carried out using the entropy weight-technique for order preference by similarity to ideal solution（TOPSIS） and grey correlation analysis （GCA） methods. RESULTS The contents of the above 11 components were 7.993-72.866， 4.542-31.228， 727.666-1 901.884， 496.846-1 293.279， 1 995.501-6 779.150， 54.500-241.280， 150.302-304.339， 79.698-189.206， 257.118-682.418， 5.498-21.687， 7.524-26.935 μg/g. CA， PCA and OPLS-DA results showed that 20 batches of samples were grouped into 2 categories. Q1， Q3， Q4， Q7-Q9， Q12， Q15， Q16 were grouped into one category， and the rest were grouped into another category； VIP values of ferulic acid， tanshinone Ⅱ A ， baicalin， cryptotanshinone， calycosin-7- O - β -D-glucoside and ononin were all greater than 1 （ P ＜0.05）. Both the entropy weight-TOPSIS and GCA methods showed that the samples ranked in the top 11 according to the euclidean distance and relative correlation degree were Q2， Q5， Q6， Q10， Q11， Q13， Q14， Q17-Q20. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate and highly sens itive. Combined with chemical pattern recognition analysis， entropy weight-TOPSIS and GCA methods， this method can be used to evaluate the quality of the Heat-clearing and symptom-relieving formula. Ferulic acid， tanshinone Ⅱ A ， baicalin， cryptotanshinone， calycosin-7- O - β -D-glucoside and ononin may be the marker components that affect the quality of this formula. The overall quality of 11 batches of the Heat-clearing and symptom-relieving formula， including Q17， is relatively superior.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a major cause of chronic kidney disease and kidney failure. IgAN exhibits marked heterogeneity in clinical presentation, histopathology, and pathogenic mechanisms, contributing to variable treatment responses and prognosisamong patients. Precise risk assessment and individualized intervention are therefore of critical importance. This review systematically traces the evolution of IgAN management from traditional risk stratification toward biomarker-driven precision medicine. We first review the clinical utility and limitations of established risk stratification tools, including the KDIGO guidelines, the Oxford MEST-C classification, and the International IgAN Prediction Tool. We then discuss emerging biomarkers closely linked to disease pathogenesis, including galactose-deficient IgA1 (Gd-IgA1), anti-Gd-IgA1 autoantibodies, B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), and complement components, as well as the targeted therapies they have informed. In addition, urinary biomarkers and multi-omics approaches show promise for dynamic disease monitoring and individualized risk stratification.

ObjectiveTo evaluate the antitumor activity of Periplaneta americana extract（PAE） against human-derived lung adenocarcinoma organoids（LUAD-PDOs） and to elucidate its potential mechanism based on transcriptomics. MethodsFresh tumor and adjacent normal tissues from patients with LUAD were collected to construct LUAD-PDOs and normal lung organoid（Nor-PDOs） models using 3D organoid culture technology. The effective intervention concentration of PAE was determined using the cell counting kit-8（CCK-8） assay. Experimental groups included the model group（LUAD-PDOs）， normal group， model administration group（LUAD-PDOs+PAE）， and normal administration group（Nor-PDOs+PAE）. Hematoxylin-eosin（HE） staining was used to observe the pathological structures of PDOs， immunohistochemistry（IHC） was performed to detect the expressions of the proliferation marker Ki-67 and lung adenocarcinoma differentiation markers cytokeratin-7（CK-7） and Napsin A， TUNEL staining was applied to detect cell apoptosis. RNA sequencing（RNA-Seq） was conducted to identify differentially expressed genes（DEGs）， followed by Gene Ontology（GO）， Kyoto Encyclopedia of Genes and Genomes（KEGG）， and Gene Set Enrichment Analysis（GSEA）， alongside protein-protein interaction（PPI） network analysis to screen core mechanisms. Finally， key targets were validated by integrating external database analysis with immunofluorescence（IF）. ResultsNor-PDOs and LUAD-PDOs that highly recapitulated the pathological characteristics of the primary tissues were successfully established. The CCK-8 assay determined that the effective intervention concentration of PAE was 16 g·L^-1. Morphological observation showed that Nor-PDOs exhibited lumen-forming structures， whereas LUAD-PDOs displayed dense， solid structures. CCK-8 and TUNEL assays revealed that， compared with the model group， PAE intervention inhibited the proliferation of LUAD-PDOs and promoted apoptosis in LUAD cells， while showing no significant effect on the viability of Nor-PDOs. Transcriptomic analysis identified 719 DEGs that were significantly reversed after PAE intervention（347 up-regulated and 372 down-regulated）（P<0.05）. GO enrichment analysis indicated that DEGs in the model administration group were significantly enriched in biological processes related to cell cycle regulation compared to the model group. KEGG pathway analysis revealed that PAE affected pathways related to proliferation and metabolism， including pathways in cancer and the p53 signaling pathway. GSEA further confirmed that PAE significantly enhanced the activity of the p53 signaling pathway（P<0.05）. PPI network analysis indicated that breast cancer type 1 susceptibility protein（BRCA1） and checkpoint kinase 1（CHEK1） were the core down-regulated targets in the p53 pathway. IF verified the high expression of BRCA1 and CHEK1 in LUAD-PDOs and their significant downregulation after PAE intervention（P<0.05）. Furthermore， survival analysis based on The Cancer Genome Atlas（TCGA） database indicated that low expression of BRCA1 and CHEK1 was significantly associated with prolonged overall survival in patients with LUAD（P<0.05）. ConclusionPAE effectively inhibits proliferation of LUAD-PDOs and promotes their apoptosis， its anti-tumor mechanism is potentially associated with the activation of the p53 signaling pathway， with BRCA1 and CHEK1 genes likely serving as key downstream targets for the effects of PAE.

This article reports the diagnosis and treatment of one patient with fascioliasis of the common bile duct, aiming to provide reference for the clinical diagnosis and treatment of this disease. The patient sought medical attention due to long-term symptoms such as abdominal pain, abdominal distension, nausea, and vomiting. Imaging examinations displayed dilatation of the common bile duct and intrahepatic bile ducts, and the patient was admitted to the hospital with a diagnosis of “common bile duct stone”. Through endoscopic retrograde cholangiopancreatography and choledochoscopy, two worms were collected from the common bile duct, which were identified as Fasciola hepatica by high-throughput sequencing.

Purpose: Due to the preservation of the entire stomach after endoscopic resection, the occurrence of metachronous gastric cancer (MGC) remains a possibility. In this study, we investigated the incidence and risk factors for MGC in patients with early gastric cancer who underwent endoscopic submucosal dissection (ESD) and successfully eradicatedHelicobacter pylori. Materials and Methods: A retrospective analysis was conducted of 1,191 patients who underwent ESD and successfully eradicated H. pylori at the Affiliated Drum Tower Hospital of Nanjing University. Endoscopic surveillance was performed at 3, 6, and 12 months post-resection, and annually thereafter. MGC was defined as the development of a new cancer at a site other than the primary gastric cancer site, at least 1 year after the initial endoscopic resection. Results: A total of 77 patients were diagnosed with MGC during a median follow-up of 41.5 months. Kaplan-Meier analysis showed a 5-year cumulative incidence of MGC of 9.4% after successful H. pylori eradication. Multivariate analysis of the training set using Cox proportional hazards models identified male sex, severe atrophic gastritis, multiple gastric cancers before H. pylori eradication, and smoking history as independent risk factors for MGC.The nomogram exhibited favorable discrimination, with area under the curves of 0.767 and 0.822 in the training set and 0.724 and 0.745 in the testing set at 3 and 5 years, respectively. Conclusions Patients with gastric cancer who undergo endoscopic resection, even after successful H. pylori eradication, should undergo annual and continuous endoscopic surveillance for MGC.

Background/Aims: Non-pharmacological treatments are crucial for managing irritable bowel syndrome (IBS), yet patient engagement remains a challenge. Understanding patients' knowledge, attitudes, and practices regarding these treatments is essential for improving care. Methods: A cross-sectional study was conducted across 5 hospitals, from October 2023 to February 2024. A self-designed knowledge, attitudes, and practices questionnaire along with the IBS quality of life and IBS severity scoring system was administered, and 496 valid responses were analyzed. Statistical analyses included correlation tests, multivariate linear regression, and mediation effect analysis. Results: The median scores for knowledge, attitude, and practice were 28, 25.5, and 21, respectively. Significant positive correlations were found between knowledge-attitude (r = 0.195), knowledge-practice (r = 0.364), and attitude-practice (r = 0.151). The multivariate linear regression analysis further indicated that knowledge (β = 0.399, P < 0.001) and attitude (β = 0.219, P = 0.022) positively correlated with the practical performance. SEM revealed that knowledge had a significant direct effect on both attitude (β = 0.186, P = 0.013) and practice (β = 0.356, P = 0.006). However, the direct effect of attitude on practice was not significant, and attitude did not mediate the relationship between knowledge and practice. Conclusions IBS patients exhibit a significant gap between their positive attitudes and their actual practices concerning non-pharmacological treatments. Knowledge is a direct driver of practice, but positive attitudes alone are insufficient to translate into behavior. Healthcare providers must move beyond simply fostering positive attitudes and focus on targeted educational interventions that provide actionable knowledge and skills to improve patient outcomes.

Mitochondrial biogenesis represents a promising therapeutic target in triple-negative breast cancer (TNBC) due to its essential role in cancer cell metabolism and survival. The natural compound γ-Elemene exhibits potent anti-tumor activity, but its effects on mitochondrial regulation in TNBC remain unclear. In this study, we demonstrate that γ-Elemene induces dose-dependent cytotoxicity in MDA-MB-468 and HCC1806 TNBC cells while significantly impairing mitochondrial function, as shown by reduced membrane potential, oxidative phosphorylation capacity, and ATP production. γ-Elemene treatment markedly suppressed mitochondrial biogenesis, decreasing mitochondrial DNA content and downregulating key mitochondrial genes and proteins. These effects were associated with reduced expression of the master regulators NRF1 and TFAM, but independent of PGC-1α expression levels.Mechanistically, γ-Elemene upregulated the acetyltransferase GCN5, leading to enhanced PGC-1α acetylation. This upregulation occurs primarily through increased GCN5 transcription. Genetic ablation of GCN5 completely reversed γ-Elemene-induced PGC-1α acetylation and restored mitochondrial biogenesis and cell viability, establishing a critical role for GCN5 in mediating these effects. Our findings reveal a novel mechanism whereby γ-Elemene disrupts mitochondrial function in TNBC through GCN5-mediated PGC-1α acetylation, providing new insights into its anti-cancer properties and potential therapeutic applications against TNBC.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.

Objective:Explore the protective effect and mechanism of methyl badosolone (CDDO-Me) on rats with traumatic brain injury (TBI).Methods:A total of 72 SPF-grade SD rats aged 8 weeks were randomly (random number) divided into 4 groups ( n=18) using the random number table method: Sham, TBI, TBI+Vehicle, and TBI+CDDO-Me. The rat TBI model was established using the hydraulic impact head injury method. The TBI+CDDO-Me group was administered CDDO-Me (dissolved in 1% DMSO, at a dose of 10 mg/kg) via intraperitoneal injection 30 minutes after modeling, twice a day for a total of 3 days. On the third day after modeling, brain tissue was collected for pathological and water content detection after mNSS scoring. Immunofluorescence double staining was used to detect the expression of nuclear factor erythroid2 related factor 2 (Nrf2); immunohistochemical staining was used to detect the expression of ionized calcium binding adapter molecule-1(Iba-1); ELISA was used to detect the levels of tumor necrosis factor-α(TNF-α), interleukin (IL)-1β, and IL-18 in serum; kits were used to detect the levels of malondialdehyde (MDA) and reactive oxygen species (ROS); Western blot was used to detect the expression of the Nrf2 pathway, B-cell lymphoma-2 (BCL-2), and BCL-2 associated X protein (BAX). Results:(1) Compared with the Sham group, the mNSS scores and water content in the injured cortex of the TBI group rats were significantly increased (both P<0.05), and both significantly decreased after CDDO-Me intervention (both P<0.05). (2) Compared with the Sham group, the proportion of Nissl-stained injured neurons and apoptotic positive cells in the TBI group rats were significantly increased (both P<0.05), and both significantly decreased after CDDO-Me intervention (both P<0.05), accompanied by a decrease in BAX protein expression and upregulation of BCL-2 protein expression (both P<0.05). (3) Immunofluorescence and Western blot results showed that compared with the Sham group, the expression of total Nrf2, nuclear Nrf2, HO-1, and NQO1 proteins in the TBI group were all increased (all P<0.05), and the increase was more significant after CDDO-Me intervention (all P<0.05). (4) Immunohistochemistry and ELISA results showed that compared with the Sham group, the levels of MDA, ROS, Iba-1 in brain tissue and the levels of TNF-α, IL-1β, and IL-18 in serum in the TBI group rats were all significantly increased (all P<0.05), and all significantly decreased after CDDO-Me intervention (all P<0.05). Conclusion:CDDO-Me helps to reduce oxidative stress and inflammatory responses in TBI rats, and the mechanism may be related to the activation of the Nrf2/HO-1 antioxidant stress pathway.

Background: Obesity and chronic pain are related in both directions, according to earlier observational research.This research aimed to analyze the causal association between obesity and chronic pain at the genetic level, as well as to assess whether common factors mediate this relationship. Methods: This study used bidirectional two sample Mendelian randomization (MR) technique to analyze the association between obesity and chronic pain. Obesity's summary genome-wide association data were obtained from European ancestry groups, as measured by body mass index (BMI), waist-to-hip ratio, waist circumference (WC), and hip circumference (HC), genome-wide association study data for chronic pain also came from the UK population, including chronic pain at three different sites (back, hip, and headache), chronic widespread pain (CWP), and multisite chronic pain (MCP). Secondly, a two-step MR and multivariate MR investigation was performed to evaluate the mediating effects of several proposed confounders. Results: The authors discovered a link between chronic pain and obesity. More specifically, a sensitivity analysis was done to confirm the associations between greater BMI, WC, and HC with an increased risk of CWP and MCP.Importantly, the intermediate MR results suggest that education levels and smoking initiation may mediate the causal relationship between BMI on CWP, with a mediation effect of 23.08% and 15.38%, respectively. Conclusions The authors’ findings demonstrate that the importance of education and smoking in understanding chronic pain’s pathogenesis, which is important for the primary prevention and prognosis of chronic pain.