The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting was held in Chicago. At the meeting, researches on the treatment of epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) once again took the spotlight. Combination therapy strategies have demonstrated the potential to overcome resistance to EGFR tyrosine kinase inhibitor (EGFR-TKI) and prolong survival. Meanwhile, progress has also been made in individualized treatment strategies for young patients and those with fibrotic interstitial lung disease. However, the complexity of resistance mechanisms, special treatment considerations for different populations, and the impact of socioeconomic factors on treatment accessibility remain challenges in the field of EGFR-mutant NSCLC treatment. In the future, it is necessary to further explore more effective treatment regimens and expand the accessibility of precision medicine to maximize patient benefits.

The 26th World Conference on Lung Cancer (WCLC) was held in Barcelona during September 6-9, 2025. As the world's largest and most influential academic meeting in the field of lung cancer, this year's congress unveiled long-term follow-up data from several pivotal studies and significant advances in novel therapeutic strategies. In the realm of targeted therapy, a next-generation combination strategy has been established as the new standard of care for the first-line treatment of patients with advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), demonstrating a significant improvement in overall survival. In immunotherapy, novel combination regimens have not only addressed the therapeutic challenge of acquired resistance to EGFR targeted therapies, but also shown clear long-term survival benefits in both the perioperative and locally advanced settings. These findings pave the way for shifting the treatment paradigm to earlier stages for patients with NSCLC. Antibody-drug conjugates have made remarkable strides in this field. They have shown outstanding efficacy in patients with specific resistance mutations and those with brain metastases, and have also demonstrated immense potential in treating patients with HER2-aberrant lung cancer and broader NSCLC populations. This offers new therapeutic options for patients with refractory lung cancer.However, significant challenges remain, including the heterogeneity of resistance mechanisms, the selection of optimal treatment regimens, and management strategies for special populations. Future research should focus on identifying novel precision biomarkers and optimizing therapeutic strategies to ultimately improve clinical outcomes for all patients with lung cancer.

ObjectiveTo establish an ultra-performance liquid fingerprint and multi-components determination method for Naomaili granules. To evaluate the quality of different batches by chemometrics， and the anti-neuroinflammatory effects of water extract and main components of Naomaili granules were tested in vitro. MethodsThe similarity and common peaks of 27 batches of Naomaili granules were evaluated by using Ultra performance liquid chromatography （UPLC） fingerprint detection. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） technology was used to determine the content of the index components in Naomaili granules and to evaluate the quality of different batches of Naomaili granules by chemometrics. LPS-induced BV-2 cell inflammation model was used to investigate the anti-neuroinflammatory effects of the water extract and main components of Naomaili granules. ResultsThe similarity of fingerprints of 27 batches of samples was > 0.90. A total of 32 common peaks were calibrated， and 23 of them were identified and assigned. In 27 batches of Naomaili granules， the mass fractions of 14 components that were stachydrine hydrochloride， leonurine hydrochloride， calycosin-7-O-glucoside， calycosin，tanshinoneⅠ， cryptotanshinone， tanshinoneⅡ_A， ginsenoside Rb₁， notoginsenoside R₁， ginsenoside Rg₁， paeoniflorin， albiflorin， lactiflorin， and salvianolic acid B were found to be 2.902-3.498， 0.233-0.343， 0.111-0.301， 0.07-0.152， 0.136-0.228， 0.195-0.390， 0.324-0.482， 1.056-1.435， 0.271-0.397， 1.318-1.649， 3.038-4.059， 2.263-3.455， 0.152-0.232， 2.931-3.991 mg∙g^-1， respectively. Multivariate statistical analysis showed that paeoniflorin， ginsenoside Rg₁， ginsenoside Rb₁ and staphylline hydrochloride were quality difference markers to control the stability of the preparation. The results of bioactive experiment showed that the water extract of Naomaili granules and the eight main components with high content in the prescription had a dose-dependent inhibitory effect on the release of NO in the cell supernatant. Among them， salvianolic acid B and ginsenoside Rb₁ had strong anti-inflammatory activity， with IC₅₀ values of （36.11±0.15） mg∙L^-1 and （27.24±0.54） mg∙L^-1， respectively. ConclusionThe quality evaluation method of Naomaili granules established in this study was accurate and reproducible. Four quality difference markers were screened out， and eight key pharmacodynamic substances of Naomaili granules against neuroinflammation were screened out by in vitro cell experiments.

ObjectiveProtein-protein interactions (PPIs) are fundamental to the execution of biological functions within living cells. However, traditional biochemical methods, such as co-immunoprecipitation (Co-IP), often fail to capture transient, weak, or membrane-associated interactions due to the stringent detergent requirements for cell lysis. Proximity labeling (PL) has emerged in recent years as a transformative technology for mapping the proteomes of specific subcellular compartments and identifying dynamic interactomes in situ. Golgi protein 73 (GP73, also known as GOLPH2), a resident type II Golgi transmembrane protein, is a well-recognized clinical biomarker for liver diseases, including hepatocellular carcinoma (HCC). Despite its clinical significance, the comprehensive physiological and pathological functions of GP73 remain partially understood. This study aims to establish an APEX2-mediated proximity labeling system specifically targeting GP73 to map its interactome in a living cellular environment, thereby providing new insights into its molecular roles and regulatory mechanisms. MethodsTo achieve spatial specificity, we first constructed a stable cell line expressing a fusion protein consisting of GP73 and the engineered soybean peroxidase APEX2. The localization of the GP73-APEX2 fusion protein was validated to ensure it correctly targeted the Golgi apparatus. The proximity labeling reaction was initiated by incubating the cells with biotin-phenol (BP) for 30 min, followed by a brief (1 min) treatment with1 mmol/L hydrogen peroxide (H₂O₂). This catalytic reaction converts BP into highly reactive, short-lived biotin-phenoxyl radicals that covalently attach to endogenous proteins within a small labeling radius of the GP73-APEX2 enzyme. Subsequently, the cells were quenched, and biotinylated proteins were enriched using high-affinity streptavidin-coated magnetic beads. The captured “neighbor” proteins were subjected to on-bead digestion and analyzed via liquid chromatography-tandem mass spectrometry (LC-MS/MS) for high-throughput identification. Rigorous bioinformatics analysis, including Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction network mapping, was performed to interpret the biological significance of the identified candidates. ResultsOur results demonstrate the successful establishment of a robust and sensitive APEX2-based proximity labeling system for GP73. We identified a total of 95 high-confidence interacting proteins that were significantly enriched in the GP73 proximity proteome compared to control groups. Bioinformatics analysis revealed that these interactors were predominantly associated with biological processes such as vesicular transport, protein localization, and, most notably, molecular functions related to “ribosome binding” and “translation regulation”. This suggested an unexpected role for the Golgi-resident GP73 in the cellular translation machinery. To validate these findings, we performed targeted biochemical assays which confirmed a direct interaction between GP73 and the subunits of the eukaryotic translation initiation factor 3 (eIF3) complex, specifically EIF3G and EIF3I. Furthermore, functional validation using the surface sensing of translation (SUnSET) assay—a non-radioactive method to monitor protein synthesis—revealed that the overexpression of GP73 significantly promoted global protein translation levels in the cell, whereas its depletion or inhibition resulted in reduced translation efficiency. ConclusionThis study successfully utilized APEX2-mediated proximity labeling to provide the first systematic map of GP73 interactome in living cells. Our findings uncover a novel, unconventional function of GP73 as a regulator of cellular protein translation, likely mediated through its interaction with the eIF3 complex. This discovery significantly broadens our understanding of the biological roles of GP73 beyond its traditional function in the Golgi apparatus and suggests that it may act as a bridge between Golgi-related trafficking and the protein synthesis machinery. Furthermore, the technical framework established in this study provides a valuable template for investigating other complex organelle-associated protein networks and resolving transient macromolecular interactions in various physiological and pathological contexts.

ObjectiveTo combine metabolomics， proteomics， and transcriptomics to analyze the biological characteristics of damp-heat toxin accumulation syndrome and damp-heat accumulation syndrome in acute gout. MethodsBlood samples were collected from 15 patients with damp-heat toxin accumulation syndrome and 15 patients with damp-heat accumulation syndrome in acute gout in clinical practice. Metabolomics technology was applied to detect serum metabolites， and an orthogonal partial sample least squares discriminant analysis model was constructed to screen for metabolites with significant intergroup changes， and enrichment pathway analysis and receiver operating characteristic （ROC） curve analysis were performed. Astral data independence acquisition （DIA） was used to detect serum proteins， perform principal component analysis and screen differential proteins， demonstrate differential ploidy by radargram， apply subcellular localisation to analyse protein sources， and finally apply weighted gene co-expression network analysis （WGCNA） to find key proteins. Transcriptome sequencing technology was also applied to detect whole blood mRNA， screen differential genes and perform WGCNA， and construct machine learning models to screen key genes. ResultsMetabolome differential analysis revealed 62 differential metabolites in positive ion mode and 26 in negative ion mode. These differential metabolites were mainly enriched in the mTOR signaling pathway and FoxO signaling pathway， with trans-3,5-dimethoxy-4-hydroxycinnamaldehyde， guanabenz， 4-aminophenyl-1-thio-beta-d-galactopyranoside showing the highest diagnostic efficacy. The proteome differential analysis found that 55 proteins up-regulated and 20 proteins down-regulated in the samples of damp-heat toxin accumulation syndrome. Notably， myelin basic protein （MBP）， transferrin （TF）， DKFZp686N02209， and apolipoprotein B （APOB） showed the most significant differences in expression. Differential proteins were mainly enriched in pathways related to fat digestion and absorption， lipid and atherosclerosis， and cholesterol metabolism. WGCNA showed the highest correlation between damp-heat toxin accumulation syndrome and the brown module， with proteins in this module primarily enriched in the hypoxia-inducible factor 1 （HIF-1） signaling pathway and lipid and atherosclerosis. Transcriptomic differential analysis identified 252 differentially expressed genes， with WGCNA indicating the highest correlation between damp-heat toxin accumulation syndrome and the midnight blue module. The random forest （RF） model was identified as the optimal machine learning model， predicting apolipoprotein B receptor （APOBR）， far upstream element-binding protein 2 （KHSRP）， POU domain class 2 transcription factor 2 （POU2F2）， EH domain-containing protein 1 （EHD1）， and family with sequence similarity 110A （FAM110A） as key genes. Integrated multi-omics analysis suggested that damp-heat toxin accumulation syndrome in the acute phase of gout is closely associated with lipid metabolism， particularly APOB. ConclusionCompared to damp-heat accumulation syndrome in the acute phase of gout， damp-heat toxin accumulation syndrome is more closely associated with lipid metabolism， particularly APOB， and lipid metabolism disorders contribute to the development of damp-heat toxin accumulation syndrome in patients with acute gout.

The 2025 European Lung Cancer Congress (ELCC) convened in Paris, France, centering on the optimization and innovation of immunotherapy for non-small cell lung cancer (NSCLC). Key topics at the congress included the application strategies for perioperative immunotherapy, breakthroughs in combination therapy models for advanced NSCLC, and the emerging roles of biomarkers in predicting diverse treatment outcomes. This paper integrates data from several key pivotal studies to systematically analyze the clinical value of neoadjuvant therapy within the perioperative setting, the potential of targeted combination regimens, and the challenges of managing drug resistance, thus offering new directions for clinical practice.

OBJECTIVE: To observe the clinical efficacy of acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux for gastroesophageal reflux cough (GERC). METHODS: A total of 120 GERC patients were randomly assigned to an observation group (60 cases, 1 case dropped out) and a control group (60 cases, 1 case was eliminated). The observation group received acupoint thread-embedding treatment at positive response points of governor vessel. If no such points were detected, the following acupoints were used: Dazhui (GV14), Fenghu (Extra), Shendao (GV11), Lingtai (GV10), and Zhiyang (GV9). Treatment was administered once every two weeks. The control group received oral rabeprazole enteric capsules at 20 mg twice daily. All the treatment was given for 6 weeks. Clinical outcomes were assessed using cough symptom score, reflux disease questionnaire (RDQ) score, and Leicester cough questionnaire (LCQ) score before and after treatment in the two groups. Clinical efficacy was also compared between the two groups. RESULTS: After treatment, both groups showed decreased cough symptom scores and the each item scores and total scores of RDQ (P<0.001), and increased LCQ scores (P<0.001) compare with those before treatment. The observation group exhibited lower cough symptom score and chest pain, reflux and total score of RDQ, and higher LCQ score compared to those in the control group (P<0.05). The total effective rate in the observation group was 94.9% (56/59), which was higher than 84.7% (50/59) in the control group (P<0.05). CONCLUSION Acupoint thread-embedding therapy of regulating governor vessel, dispersing lung, and suppressing reflux could effectively alleviate cough and reflux symptoms in patients with GERC and improve their quality of life.
Humans ; Acupuncture Points ; Gastroesophageal Reflux/physiopathology* ; Male ; Female ; Cough/physiopathology* ; Middle Aged ; Aged ; Acupuncture Therapy ; Adult ; Treatment Outcome ; Lung/physiopathology* ; Meridians

The study aims to examine the effects and potential mechanisms of disulfiram (DSF) on cardiac hypertrophic injury, focusing on the role of transforming growth factor-β-activated kinase 1 (TAK1)-mediated pan-apoptosis (PANoptosis). H9C2 cardiomyocytes were treated with angiotensin II (Ang II, 1 µmol/L) to establish an in vitro model of myocardial hypertrophy. DSF (40 µmol/L) was used to treat cardiomyocyte hypertrophic injury models, either along or in combination with the TAK1 inhibitor, 5z-7-oxozeaenol (5z-7, 0.1 µmol/L). We assessed cell damage using propidium iodide (PI) staining, measured cell viability with CCK8 assay, quantified inflammatory factor levels in cell culture media via ELISA, detected TAK1 and RIPK1 binding rates using immunoprecipitation, and analyzed the protein expression levels of key proteins in the TAK1-mediated PANoptosis pathway using Western blot. In addition, the surface area of cardiomyocytes was measured with Phalloidin staining. The results showed that Ang II significantly reduced the cellular viability of H9C2 cardiomyocytes and the binding rate of TAK1 and RIPK1, significantly increased the surface area of H9C2 cardiomyocytes, PI staining positive rate, levels of inflammatory factors [interleukin-1β (IL-1β), IL-18, and tumor necrosis factor α (TNF-α)] in cell culture media and p-TAK1/TAK1 ratio, and significantly up-regulated key proteins in the PANoptosis pathway [pyroptosis-related proteins NLRP3, Caspase-1 (p20), and GSDMD-N (p30), apoptosis-related proteins Caspase-3 (p17), Caspase-7 (p20), and Caspase-8 (p18), as well as necroptosis-related proteins p-MLKL, RIPK1, and RIPK3]. DSF significantly reversed the above changes induced by Ang II. Both 5z-7 and exogenous IL-1β weakened these cardioprotective effects of DSF. These results suggest that DSF may alleviate cardiac hypertrophic injury by inhibiting TAK1-mediated PANoptosis.
Animals ; MAP Kinase Kinase Kinases/physiology* ; Rats ; Myocytes, Cardiac/pathology* ; Disulfiram/pharmacology* ; Cardiomegaly ; Apoptosis/drug effects* ; Cell Line ; Angiotensin II ; Necroptosis/drug effects* ; Interleukin-1beta/metabolism* ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Lactones ; Resorcinols ; Zearalenone/administration & dosage*

In a healthy human, the airway mucus forms a thin, protective liquid layer covering the surface of the respiratory tract. It comprises a complex blend of mucin, multiple antibacterial proteins, metabolic substances, water, and electrolytes. This mucus plays a pivotal role in the lungs' innate immune system by maintaining airway hydration and capturing airborne particles and pathogens. However, heightened mucus secretion in the airway can compromise ciliary clearance, obstruct the respiratory tract, and increase the risk of pathogen colonization and recurrent infections. Consequently, a thorough exploration of the mechanisms driving excessive airway mucus secretion is crucial for establishing a theoretical foundation for the eventual development of targeted drugs designed to reduce mucus production. Across a range of lung diseases, excessive airway mucus secretion manifests with unique characteristics and regulatory mechanisms, all intricately linked to mucin. This article provides a comprehensive overview of the characteristics and regulatory mechanisms associated with excessive airway mucus secretion in several prevalent lung diseases.
Humans ; Mucus/metabolism* ; Mucins/physiology* ; Lung Diseases/metabolism* ; Respiratory Mucosa/metabolism* ; Pulmonary Disease, Chronic Obstructive/physiopathology* ; Asthma/physiopathology* ; Cystic Fibrosis/physiopathology* ; Mucociliary Clearance/physiology*