ObjectiveThis study aimed to elucidate the mechanistic role of Staphylococcus aureus in the pathogenesis of atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by pruritus and barrier dysfunction. A key focus was screening traditional Chinese medicine (TCM) active components with dual antibacterial and antipruritic efficacy, followed by systematic evaluation of their in vitro antibacterial activity. Additionally, a novel drug delivery system was constructed to enable localized efficient drug delivery, inhibiting S. aureus proliferation and alleviating its induced pruritus, thereby providing new strategies for targeted AD therapy. MethodsMale C57BL/6J mice aged 6-8 weeks (body weight 18-22 g) were used to establish an AD model via repeated oxazolone sensitization. On day 14, microbial samples were collected from the lesional area (1 cm²) using sterile cotton swabs, followed by vortex mixing, serial dilution, and plating on 5% sheep blood agar plates (incubated at 37°C for 24 h). Single colonies with complete transparent β-hemolytic zones were isolated and identified as vancomycin-intermediate S. aureus (VISA) via 16S rRNA sequencing. An S. aureus mono-infection animal model was then established by applying gauze saturated with bacterial suspension (McFarland turbidity 0.1) to the nape and back skin of mice. The pruritic phenotype and inflammatory cell infiltration induced by S. aureus were evaluated using comprehensive approaches including behavioral assays (e.g., scratching frequency recording), hematoxylin-eosin (HE) staining, and toluidine blue staining. The in vitro antibacterial efficacy of the TCM monomer pseudolaric acid B (PAB) and double network hydrogel (DN) was separately assessed by disk diffusion assay, while the minimum inhibitory concentration (MIC) of PAB was determined via broth dilution method. Further validation of the pharmacodynamic characteristics of the composite system (PAB@DN, composed of PAB and DN) was conducted through behavioral assays, HE staining, and dermatitis scoring, with its drug release profile evaluated by mass spectrometry analysis. Based on scratching behavioral analysis and dermatitis scoring, the optimal ratio and concentration of PAB@DN were optimized. ResultsThe S. aureus load in AD lesional tissues was significantly higher than in normal skin ((5.3±0.33)×10⁶ CFU vs. (3.6±0.26)×10⁷ CFU, P<0.001). In the S. aureus mono-infection group, mice exhibited a 6.7-fold increase in scratching frequency compared to the control group. HE staining revealed marked epidermal thickening ((10.4±2.39) μm vs. (85.6±1.95) μm, P<0.000 1), and toluidine blue staining showed a 23-fold increase in mast cell degranulation. Pseudolaric acid B exhibited a significant concentration-dependent inhibitory effect onS. aureus growth, with its in vitro antibacterial effect being 57% that of the antibiotic cefepime (inhibition zone diameter: PAB (1.885±0.036) cm vs. cefepime (3.636±0.005) cm, P<0.000 1) and a minimum inhibitory concentration (MIC) of 1 g/L. The carrier double network hydrogel (DN) itself lacked direct antibacterial activity (no significant difference in inhibition zone diameter compared to the control) but effectively ameliorated the dry symptoms of AD-like lesions. The PAB@DN composite system demonstrated a synergistic effect compared to individual components, resulting in a 50% reduction in scratching behavior, an 86% decrease in dermatitis score, and a 60% reduction in epidermal thickening. It also reduced the S. aureus load in mouse skin by approximately 34%, with the optimal effective formulation being PAB at 1 g/L loaded onto DN. ConclusionS. aureus colonization plays a critical driving role in the onset and progression of AD. Using an S. aureus infection model, this study confirmed that the pseudolaric acidB-hydrogel composite delivery system (PAB@DN) can effectively alleviate S. aureus-induced pruritus and skin damage, providing experimental evidence for microbiota-targeted therapy of AD.

Objective To investigate the expression characteristics of the transcription factor E2F2 in clear cell renal cell carcinoma (ccRCC), its impact on patient prognosis, and its potential role in the tumor immune microenvironment, with validation using clinical samples and functional assays. Methods RNA sequencing data and clinical information of ccRCC patients were obtained from the TCGA database; GSE53757 and GSE66272 datasets were downloaded from the GEO database as external validation cohorts. The expression difference of E2F2 between ccRCC tissue and normal tissue was compared, and the relationship between E2F2 expression and clinical pathological characteristics was analyzed. Kaplan-Meier (KM) survival analysis with log-rank test was performed to evaluate the effects of E2F2 on overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS). The prognostic efficacy of E2F2 in predicting 1-, 3- and 5-year survival was evaluated using receiver operating characteristic (ROC) curve. GSEA was performed to identify E2F2-related signaling pathways, and the ESTIMATE and CIBERSORT algorithms were used to assess the relationship between E2F2 expression level and tumor immune cell infiltration and immune microenvironment. Twenty pairs of surgically resected and pathologically confirmed ccRCC tissues and matched adjacent non-tumor tissues were collected from our hospital, and immunohistochemistry (IHC) was performed to detect the protein expression of E2F2. Human ccRCC cell line 786-O was used for functional assays;shRNA was used to knock down E2F2 expression (constructing stable shE2F2#1 and shE2F2#2 cell lines), and qRT-PCR and Western blot were performed to verify knockdown efficiency, followed by MTT, colony formation, and Transwell migration assays to evaluate the effects of E2F2 on the biological behaviors of ccRCC cells. Results E2F2 was significantly upregulated in ccRCC tissues (the same results in the verification set). Higher E2F2 expression was associated with advanced histological grade, clinical stage and higher TNM classification (P＜0.05). KM analysis showed that patients in the E2F2 high-expression group had worse OS, PFS, and DSS (P=0.019, 0.036, ＜0.001); the ROC curves showed area under the curve (AUC) of E2F2 of predicting 1-, 3- and 5- year survival of ccRCC patients were 0.844, 0.851 and 0.815, respectively. GSEA revealed that the E2F2 low-expression group was enriched in multiple metabolism-related pathways, whereas the E2F2 high-expression group was associated with immune-related pathways. Immune analysis demonstrated that high E2F2 expression was associated with increased immune scores, increased proportion of immune cells, higher tumor mutation burden, and potentially stronger immunotherapy response. IHC results showed that the E2F2 immunoreactivity score in ccRCC tissues was significantly higher than that in adjacent non-tumor tissues (P＜0.05). Functional assays indicated that E2F2 knockdown significantly inhibited the proliferation, colony formation, and migration of ccRCC cells. Conclusion E2F2 is highly expressed in ccRCC and may be involved in tumorigenesis and progression through modulation of the immune microenvironment. Its expression level is closely associated with patient prognosis, and E2F2 has the potential to serve as a prognostic biomarker and immunotherapeutic target in ccRCC.

Objective To analyze the status of teaching occupational health and occupational medicine course under the background of new medical science, and to construct a semantic knowledge graph to realize the digital teaching reform of the course. Methods i) The literature on teaching research of occupational health and occupational medicine courses published between January 1, 2005 to December 31, 2025 was retrieved through the China National Knowledge Infrastructure. CiteSpace 6.4.R2 and VOSviewer 1.6.20 were used for bibliometric visualization. ii) A knowledge graph system based on Web front-end was constructed using the textbook of Occupational Health and Occupational Medicine (9th ed.), published by People's Medicine Publishing House, as the core data source. Results i) A total of 240 publications related to the teaching in occupational health and occupational medicine courses were included. The overall number of publications showed an upward trend. The research focused on curriculum teaching reform, curriculum-based political education, and digital technology-empowered teaching, forming an interdisciplinary and multi-dimensional research system. The evolution of keywords included three stages: the foundation period (2005-2015), the growth period (2016-2020), and the innovation period (2021-2025). ii) The constructed semantic knowledge graph realizes structural visualization and a dual-mode intelligent question answering agent. A total of four independent navigation modules, including chapter overview, core concept exploration, learning progress details, and relationship network visualization, were used to achieve multidimensional learning pathways. The system requires no installation and supports cross-platform operation, meeting the needs of both teachers and students. It effectively helps students establish systematic knowledge frameworks and enhances interdisciplinary integration ability and learning initiative. Conclusion In the context of new medical science, research on teaching in occupational health and occupational medicine has evolved from a niche field into a research hotspot and entered a stage of high-quality development. The constructed semantic knowledge graph for the Occupational Health and Occupational Medicine course facilitates digital teaching reform in this field and lays a solid foundation for cultivating high-level interdisciplinary occupational health professionals.

ObjectiveType 2 diabetes mellitus (T2DM) often causes severe hepatic metabolic complications, dominated by metabolic associated fatty liver disease (MAFLD). Persistent hepatic steatosis and oxidative stress further trigger steatohepatitis and progressive liver damage, increasing the mortality risk of diabetic patients. Aerobic exercise effectively improves hepatic lipid metabolism and antioxidant capacity, but poor patient adherence restricts its long-term clinical application. Mitochondrial-derived mitochondrial open reading frame of the 12S rRNA type-c (MOTS-c) is a key peptide regulating insulin sensitivity and hepatic redox homeostasis. This study aimed to explore the protective mechanism of MOTS-c against T2DM-related liver injury and its combined beneficial effect with aerobic exercise via the NRF2/PPARγ signaling axis. This study aimed to investigate whether MOTS-c cooperates with aerobic exercise to alleviate T2DM-associated hepatic oxidative stress and metabolic dysfunction by activating the NRF2/PPARγ axis, and to clarify the molecular and transcriptomic characteristics of their combined intervention. MethodsStable MOTS-c overexpression and knockdown HepG2 cell lines were constructed using lentiviral transfection. An oleic acid-induced cellular lipid accumulation model and NRF2-knockout cell model were applied to verify the NRF2-dependent mechanism ofMOTS-c. Intracellular lipid deposition, triglyceride levels, antioxidant enzyme activities, and the expression of NRF2/PPARγ pathway-related genes and proteins were detected. In vivo, a T2DM rat model with obvious hepatic steatosis was established via a high-fat and high-sucrose diet combined with streptozotocin injection. Model rats received aerobic exercise, MOTS-c intraperitoneal injection, or combined intervention. We detected systemic glycolipid metabolic indicators, hepatic histopathological changes, and the expression of core proteins in the hepatic NRF2/PPARγ axis. Hepatic transcriptomic sequencing was performed to screen differentially expressed genes (DEGs) and enrich key pathways co-regulated by MOTS-c and aerobic exercise. ResultsCellular results showed that MOTS-c overexpression significantly reduced oleic acid-induced lipid deposition, enhanced antioxidant enzyme activity, and upregulated NRF2 and PPARγ expression. Conversely, MOTS-c knockdown aggravated hepatic lipid accumulation and oxidative damage and inhibited NRF2/PPARγ pathway activation. NRF2 knockout completely eliminated the protective effects of MOTS-c on lipid metabolism and redox balance, confirming its NRF2-dependent regulatory mechanism. In T2DM rats, both MOTS-c supplementation and aerobic exercise effectively improved insulin resistance, corrected glycolipid metabolic disorders, and alleviated hepatic steatosis, while consistently activating the hepatic NRF2/PPARγ axis. Compared with single intervention, the combined treatment showed a better improvement trend in hepatic metabolic and oxidative injury, without definitive synergistic effects. Transcriptomic analysis revealed that the co-regulated DEGs of MOTS-c and aerobic exercise were primarily enriched in lipid metabolism and PPAR signaling pathways, with multiple antioxidant and lipid-regulating genes significantly modulated by combined intervention. ConclusionMOTS-c exhibits obvious exercise-mimetic hepatoprotective effects in T2DM. It activates the hepatic NRF2/PPARγ axis to strengthen antioxidant defense, stabilize lipid metabolism, and relieve T2DM-associated hepatic steatosis and oxidative damage. Furthermore, MOTS-c produces additive beneficial effects with aerobic exercise, showing a superior intervention trend on diabetic liver dysfunction. This study identifies the NRF2/PPARγ axis as the core mechanism of MOTS-c-regulated hepatic protection, elucidates the transcriptomic basis of combined intervention, and provides a reliable theoretical basis and potential therapeutic target for clinical intervention in T2DM-complicated MAFLD.

ObjectiveTo summarize the research results on the toxic mechanism and the relevant regulatory policies at home and abroad of pyrrolizidine alkaloids （PAs）， the main toxic components， in Senecionis Scandentis Herba， thereby providing insights into the clinical use and scientific regulation of Senecionis Scandentis Herba. MethodsMultiple Chinese and English databases including PubMed， ScienceDirect， Elsevier， China national knowledge infrastructure （CNKI）， Wanfang Data， and VIP were searched， with "Senecio，" "PSenecio scandens，" and "pyrrolizidine alkaloids" as search terms. The relevant articles published from 1959 to 2025 were retrieved and analyzed， and 79 articles were finally selected for review. ResultsThe chemical components of Senecionis Scandentis Herba include alkaloids， flavonoids， volatile oils， sesquiterpenes， jacaranone derivatives， and organic acids， among which alkaloids are the most toxic components， followed by jacaranone derivatives. PAs are metabolized into highly active pyrrole derivatives in the liver， which can cause serious adverse reactions such as sinusoidal obstruction syndrome and DNA damage. The content of PAs varies significantly due to the origin， harvest period， and medicinal parts. There have been reports of clinical liver injury caused by preparations containing Senecionis Scandentis Herba， and some preparations have a daily intake of PAs exceeding the international safety threshold. Currently， international organizations have set limited standards for PAs， while China only controls the content of adonifoline， and the supervision is not yet perfect. ConclusionAlthough Senecionis Scandentis Herba has medicinal value， its PAs have significant toxicological properties. This is a problem that cannot be ignored and needs to be overcome in the use of Senecionis Scandentis Herba. Therefore， it is necessary to strengthen the quality control of raw materials， establish a more comprehensive limited standard for PAs， and optimize the medication strategy in combination with traditional Chinese medicine theory to ensure the safety of clinical medication.

ObjectiveTo summarize the research results on the toxic mechanism and the relevant regulatory policies at home and abroad of pyrrolizidine alkaloids （PAs）， the main toxic components， in Senecionis Scandentis Herba， thereby providing insights into the clinical use and scientific regulation of Senecionis Scandentis Herba. MethodsMultiple Chinese and English databases including PubMed， ScienceDirect， Elsevier， China national knowledge infrastructure （CNKI）， Wanfang Data， and VIP were searched， with "Senecio，" "PSenecio scandens，" and "pyrrolizidine alkaloids" as search terms. The relevant articles published from 1959 to 2025 were retrieved and analyzed， and 79 articles were finally selected for review. ResultsThe chemical components of Senecionis Scandentis Herba include alkaloids， flavonoids， volatile oils， sesquiterpenes， jacaranone derivatives， and organic acids， among which alkaloids are the most toxic components， followed by jacaranone derivatives. PAs are metabolized into highly active pyrrole derivatives in the liver， which can cause serious adverse reactions such as sinusoidal obstruction syndrome and DNA damage. The content of PAs varies significantly due to the origin， harvest period， and medicinal parts. There have been reports of clinical liver injury caused by preparations containing Senecionis Scandentis Herba， and some preparations have a daily intake of PAs exceeding the international safety threshold. Currently， international organizations have set limited standards for PAs， while China only controls the content of adonifoline， and the supervision is not yet perfect. ConclusionAlthough Senecionis Scandentis Herba has medicinal value， its PAs have significant toxicological properties. This is a problem that cannot be ignored and needs to be overcome in the use of Senecionis Scandentis Herba. Therefore， it is necessary to strengthen the quality control of raw materials， establish a more comprehensive limited standard for PAs， and optimize the medication strategy in combination with traditional Chinese medicine theory to ensure the safety of clinical medication.

6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.

Background: s/Aims: Sarcomatoid hepatocellular carcinoma (HCC) is a rare histological subtype of HCC characterized by extremely poor prognosis; however, its molecular characterization has not been elucidated. Methods: In this study, we conducted an integrated multiomics study of whole-exome sequencing, RNA-seq, spatial transcriptome, and immunohistochemical analyses of 28 paired sarcomatoid tumor components and conventional HCC components from 10 patients with sarcomatoid HCC, in order to identify frequently altered genes, infer the tumor subclonal architectures, track the genomic evolution, and delineate the transcriptional characteristics of sarcomatoid HCCs. Results: Our results showed that the sarcomatoid HCCs had poor prognosis. The sarcomatoid tumor components and the conventional HCC components were derived from common ancestors, mostly accessing similar mutational processes. Clonal phylogenies demonstrated branched tumor evolution during sarcomatoid HCC development and progression. TP53 mutation commonly occurred at tumor initiation, whereas ARID2 mutation often occurred later. Transcriptome analyses revealed the epithelial–mesenchymal transition (EMT) and hypoxic phenotype in sarcomatoid tumor components, which were confirmed by immunohistochemical staining. Moreover, we identified ARID2 mutations in 70% (7/10) of patients with sarcomatoid HCC but only 1–5% of patients with non-sarcomatoid HCC. Biofunctional investigations revealed that inactivating mutation of ARID2 contributes to HCC growth and metastasis and induces EMT in a hypoxic microenvironment. Conclusions We offer a comprehensive description of the molecular basis for sarcomatoid HCC, and identify genomic alteration (ARID2 mutation) together with the tumor microenvironment (hypoxic microenvironment), that may contribute to the formation of the sarcomatoid tumor component through EMT, leading to sarcomatoid HCC development and progression.

Objective: This study aims to investigate the anatomical relationship among the nerve roots, intervertebral space, pedicles, and intradural rootlets of the cervical spine for improving operative outcomes and exploring neuroventral decompression approach in posterior endoscopic cervical discectomy (PECD). Methods: Cervical computed tomography myelography imaging data from January 2021 to May 2023 were collected, and the RadiAnt DICOM Viewer Software was employed to conduct multiplane reconstruction. The following parameters were recorded: width of nerve root (WN), nerve root-superior pedicle distance (NSPD), nerve root-inferior pedicle distance (NIPD), and the relationship between the intervertebral space and the nerve root (shoulder, anterior, and axillary). Additionally, the descending angles between the spinal cord and the ventral (VRA) and dorsal (DRA) rootlets were measured. Results: The WN showed a gradual increase from C4 to C7, with measurements notably larger in men compared to women. The NSPD decreased gradually from the C2–3 to the C5–6 levels. However, the NIPD showed an opposite level-related change, notably larger than the NSPD at the C4–5, C5–6, and C7–T1 levels. Furthermore, significant differences in NIPD were observed between different age groups and genders. The incidence of the anterior type exhibited a gradual decrease from the C2–3 to the C5–6 levels. Conversely, the axillary type exhibited an opposite level-related change. Additionally, the VRA and DRA decreased as the level descended, with measurements significantly larger in females. Conclusion A prediction of the positional relationship between the intervertebral space and the nerve root is essential for the direct neuroventral decompression in PECD to avoid damaging the neural structures. The axillary route of the nerve root offers a safer and more effective pathway for performing direct neuroventral decompression compared to the shoulder approach.