OBJECTIVE To focus on the classic NOD-like receptor protein 3 （NLRP3）/Caspase-1/gasdermin D （GSDMD） pyroptosis pathway and explore the mechanism by which Huatan qushi huoxue formula （HQHF） inhibits macrophage pyroptosis to ameliorate metabolic dysfunction-associated steatohepatitis （MASH）. METHODS RAW264.7 cells were divided into 5 groups： Control group （10% blank serum）， Model group [10% blank serum+5 μg/mL lipopolysaccharide （LPS）]， HQHF-L group （2.5% drug-containing serum+7.5% blank serum+5 μg/mL LPS）， HQHF-M group （5% drug-containing serum+5% blank serum+5 μg/mL LPS）， and HQHF-H group （10% drug-containing serum+5 μg/mL LPS）. After 24 h of routine culture post-administration， cells and supernatants were collected for assays. Cell morphology was observed via scanning electron microscopy and phase-contrast microscopy； localization and expression of gasdermin D-N （GSDMD-N） were observed by immunofluorescence. Interleukin-1β （IL-1β） and IL-18 contents in supernatants were detected by ELISA； mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD were measured using real-time PCR and Western blot. RESULTS Compared with the Control group， the Model group showed typical pyroptotic morphology （cell membrane bulging and pore formation）， increased aggregation and fluorescence intensity of GSDMD-N on the cell membrane （ P ＜0.05）， significantly increased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly up-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. Compared with the Model group， the HQHF-L， HQHF-M and HQHF-H groups showed improved pyroptotic morphology， reduced membrane localization and significantly weakened fluorescence intensity of GSDMD-N （ P ＜0.05）， significantly decreased the contents of IL-1β and IL-18 in cell supernatants （ P ＜0.05）， and significantly down-regulated mRNA and protein expressions of NLRP3， Caspase-1， and GSDMD in cells （ P ＜0.05）. CONCLUSIONS HQHF inhibits LPS-induced macrophage pyroptosis， and its mechanism of improving MASH may be associated with the suppression of the activation of the classical NLRP3/Caspase-1/GSDMD pyroptosis pathway.

For patients with advanced non-small cell lung cancer (NSCLC) harboring sensitive epidermal growth factor receptor (EGFR) mutations, guidelines prioritize the use of third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), which offer higher objective response rate (ORR), longer progression-free survival (PFS), and better quality of life. However, due to the low proportion of elderly patients enrolled in clinical trials, the existing evidence is insufficient to fully guide clinical practice. This review examines the efficacy and safety differences of third-generation EGFR-TKIs as monotherapy or in combination in the elderly NSCLC by integrating subgroup analyses or pre-specified research objectives from prospective and retrospective studies. The results show that third-generation EGFR-TKIs have comparable efficacy in elderly patients to younger populations and are well-tolerated. Although combination therapies may extend survival time, the associated increased toxicity necessitates careful risk-benefit assessment.
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Humans ; Carcinoma, Non-Small-Cell Lung/enzymology* ; Lung Neoplasms/enzymology* ; ErbB Receptors/metabolism* ; Protein Kinase Inhibitors/adverse effects* ; Aged ; Antineoplastic Agents/adverse effects*

Perineural invasion (PNI) by tumor cells is a key phenotype of highly-invasive oral squamous cell carcinoma (OSCC). Since Schwann cells (SCs) and fibroblasts maintain the physiological homeostasis of the peripheral nervous system, and we have focused on cancer-associated fibroblasts (CAFs) for decades, it's imperative to elucidate the impact of CAFs on SCs in PNI⁺ OSCCs. We describe a disease progression-driven shift of PNI^- towards PNI⁺ during the progression of early-stage OSCC (31%, n = 125) to late-stage OSCC (53%, n = 97), characterized by abundant CAFs and nerve demyelination. CAFs inhibited SC proliferation/migration and reduced neurotrophic factors and myelin in vitro, and this involved up-regulated ER stress and decreased MAPK signals. Moreover, CAFs also aggravated the paralysis of the hind limb and PNI in vivo. Unexpectedly, leukemia inhibitory factor (LIF) was exclusively expressed on CAFs and up-regulated in metastatic OSCC. The LIF inhibitor EC330 restored CAF-induced SC inactivation. Thus, OSCC-derived CAFs inactivate SCs to aggravate nerve injury and PNI development.
Schwann Cells/metabolism* ; Mouth Neoplasms/metabolism* ; Humans ; Cancer-Associated Fibroblasts/metabolism* ; Animals ; Carcinoma, Squamous Cell/metabolism* ; Neoplasm Invasiveness/pathology* ; Male ; Female ; Mice ; Cell Movement/physiology* ; Cell Proliferation/physiology* ; Cell Line, Tumor ; Leukemia Inhibitory Factor/metabolism* ; Middle Aged

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Objective:To analyze the experiences of implementing coverage with evidence development for cell and gene therapy products in the UK.to provide references for the future access of cell and gene therapy products in China.Methods:By systematically combing the strategies of coverage with evidence development adopted by National Health Service(NHS)in the UK.,and summarizing the four links of assessment,payment,further evidence collection and final decision-making,the implementation experience of coverage with evidence development of cell and gene therapy products was analyzed by taking the reimbursement of four typical cell gene therapy products as an example,and suggestions were made for the access of this type of products in China.Results:Access to cell and gene therapy products in the UK.is cautious,with assessment focused on clinical utility.Management access agreement is used to control the risk of overspending during specialized fund reimbursement,while a unified data collection system has been established.Conclusion:China could learn from the experience of the UK.and promote the admission of cell gene therapy products from three aspects:exploring the evidence-based reimbursement model for universal commercial medical insurance;developing a targeted data collection framework based on actual data needs;establishing a unified data collection platform to provide the support for product access decision.

Objective:To investigate the underlying mechanism behind the significant reduction in intracellular virus loads after respiratory syncytial virus (RSV) and influenza viruses infect respiratory epithelial cells overexpressing the chemokine (C-C motif) receptor 1 (CCR1).Methods:A549 cells were infected with respiratory syncytial virus (RSV), influenza A viruses (H1N1, H3N2), or influenza B virus (FluB), and the expression of chemokine (C-C motif) ligand 5 (CCL5) and CCR1 were detected by qRT-PCR, ELISA, and Western blot. After overexpressing or knocking down CCR1 in A549 cells, these cells were infected with RSV, H1N1, H3N2, or FluB, and the expression of CCR1, heat shock protein 90 (HSP90), cyclin-dependent kinase 1 (CDK1), and viral proteins were detected by qRT-PCR and Western blot. After stimulating CCR1-overexpressed A549 cells with CCL5, Western blot was used to detect the expression of HSP90 and CDK1, and co-immunoprecipitation was used to detect the interaction between HSP90 and CCR1. CCR1 -/- mice were infected with RSV, H1N1, or H3N2 to observe the changes in the expression of HSP90, CDK1, and viral proteins with Western blot, and the inflammation in lung tissues with HE staining. One-way analysis of variance and t test were used for statistical analysis. Results:RSV, H1N1, H3N2, and FluB infections induced high expression of CCL5 in A549 cells ( P<0.05), but the expression of CCR1 showed an overall downward trend. After activating its receptor CCR1, CCL5 inhibited the replication of RSV and influenza viruses by suppressing the activity of HSP90 ( P<0.05). The experiments conducted on CCR1 -/- mice confirmed that the enhanced activity of HSP90 facilitated the replication of RSV and influenza viruses. Conclusion:RSV and influenza viruses may reduce the binding of CCL5 to CCR1 by downregulating the expression of CCR1 in respiratory epithelial cells, thereby weakening the inhibitory effect of CCR1 on HSP90 activity, which enables them to evade host immune defense.

Congenital portosystemic shunts（CPSS）are vascular malformations caused by developmental anomalies that create abnormal shunts between the portal and systemic veins.This anomaly permits partial or complete bypass of portal blood flow from the liver，leading it directly into the systemic circulation without hepatic filtration.If untreated，CPSS can lead to multisystem complications，with pulmonary vascular complications being the most severe outcome.These complications are complex in mechanism，often insidious in onset，and present with nonspecific symptoms，increasing the risk of delayed diagnosis and significantly impacting the quality of children lives.Pulmonary vascular complications associated with CPSS primarily include portopulmonary hypertension，characterized by pulmonary vascular remodeling，and hepatopulmonary syndrome，distinguished by intrapulmonary vascular dilatation and abnormal arterial oxygenation.This article aims to review the anatomical classifications of CPSS，along with the pathophysiology，clinical presentation，diagnosis，and treatment of its pulmonary vascular complications，with the goal of enhancing clinical awareness and providing a reference for diagnosis and management.

Objective To analyze the current occupational health literacy (OHL) level and its influencing factors among manufacturing workers in Bao'an District, Shenzhen City. Methods The front-line workers of manufacturing enterprises from seven key industries in two streets of Bao'an District were selected as the research subjects using a stratified cluster random sampling method. The Occupational Health Literacy Questionnaire of National Key Populations was used to online investigate their OHL level. Multivariable logistic regression analysis was used to screen the influencing factors of OHL. Results A total of 633 front-line workers of manufacturing enterprises were surveyed, and 283 had OHL, with an overall OHL level of 44.7%. The levels of literacy across different dimensions, from high to low, were basic knowledge of occupational health protection (84.5%), legal knowledge of occupational health (41.5%), health behaviors and practices (41.2%), and basic skills for occupational health protection (22.0%). The results of the multivariable logistic regression analysis showed that younger age, higher educational level, and higher personal monthly income, were related to higher OHL level among the workers (all P<0.05). Conclusion The OHL level of manufacturing workers in Bao'an District, Shenzhen City still has room for improvement. Efforts should focus on workers with low education levels, low incomes, and older ages, with targeted training in theoretical knowledge to improve the practical application of basic skills for occupational health protection, to improve their OHL.

Successful cloning through somatic cell nuclear transfer (SCNT) faces significant challenges due to epigenetic obstacles. Recent studies have highlighted the roles of H3K4me3 and H3K27me3 as potential contributors to these obstacles. However, the underlying mechanisms remain largely unclear. In this study, we generated genome-wide maps of H3K4me3 and H3K27me3 in mouse pre-implantation NT embryos. Our analysis revealed that aberrantly over-represented broad H3K4me3 domain and H3K27me3 signal lead to increased bivalent marks at gene promoters in NT embryos compared with naturally fertilized (NF) embryos at the 2-cell stage, which may link to relatively low levels of H3K36me3 in NT 2-cell embryos. Notably, the overexpression of Setd2, a H3K36me3 methyltransferase, successfully restored multiple epigenetic marks, including H3K36me3, H3K4me3, and H3K27me3. In addition, it reinstated the expression levels of ZGA-related genes by reestablishing H3K36me3 at gene body regions, which excluded H3K27me3 from bivalent promoters, ultimately improving cloning efficiency. These findings highlight the excessive bivalent state at gene promoters as a potent barrier and emphasize the removal of these barriers as a promising approach for achieving higher cloning efficiency.
Animals ; Mice ; Histone-Lysine N-Methyltransferase/biosynthesis* ; Histones/genetics* ; Nuclear Transfer Techniques ; Female ; Gene Expression Regulation, Developmental ; Promoter Regions, Genetic ; Epigenesis, Genetic ; Embryo, Mammalian/metabolism*

Objective:To analyze the assessment tools for quality of life of children with autism spectrum disorder (ASD) at home and abroad, so as to provide a basis for healthcare professionals to select and revise the assessment tools suitable for the quality of life of children with ASD in China.Methods:A scoping review method was used to systematically search the literature on quality of life assessment tools for children with ASD included in PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Data, China Biology Medicine disc and VIP. The search period was from the establishment of the database to March 12, 2025. Literature that met the inclusion criteria was screened, basic information about the assessment tools was extracted, and the search results were reported in a normalized manner.Results:A total of 3 905 articles were retrieved and 29 articles were finally included. Eleven quality of life assessment scales for children with ASD were included, including two scales developed to characterize children with ASD.Conclusions:There is a wide variety of quality of life assessment tools for children with ASD, with good overall reliability and validity, but no standardized indigenous scales are developed in China. Existing quality of life assessment tools for children with ASD should be sinicized and improved, and localized assessment tools should be developed.