Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

ObjectiveType I interferon (IFN-I) signaling is essential for antiviral innate immunity, yet its sustained or excessive activation contributes to the pathogenesis of several autoimmune diseases and interferonopathies, such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Current strategies targeting this pathway, exemplified by JAK inhibitors, act mainly on downstream signal transduction and provide limited direct control over upstream IFN-I production, while also carrying the risk of broad immunosuppression. Phyllanthus emblica L. has long been used in traditional medicine for inflammatory disorders, but the bioactive constituent responsible for its regulation of IFN-I signaling and the underlying molecular mechanism have not been clearly defined. This study aimed to identify the active anti-inflammatory component of P. emblica and to characterize its mechanism of action on the IFN-I pathway in macrophages. MethodsActive components ofP. emblica and their candidate targets were screened by network pharmacology using the TCMSP and DrugBank databases (oral bioavailability≥30%, drug-likeness≥0.18) and intersected with inflammation-related genes retrieved from public databases. The predicted interaction between EGCG and IFN-I pathway proteins (TBK1, IRF3, STAT1) was evaluated by molecular docking, with BX795 and GSK8612 used as reference TBK1 inhibitors. Mechanistic experiments were performed in THP-1-derived macrophages and primary bone marrow-derived macrophages (BMDM). Upstream signaling was activated by transfection of the nucleic acid analogs poly(I∶C) and poly(dA∶dT) or by lipopolysaccharide (LPS) stimulation, whereas downstream signaling was activated by exogenous IFN-β. An siRNA-mediated TREX1 knockdown model was used to mimic endogenous nucleic acid-driven interferonopathy. Expression of IFN-β1 and interferon-stimulated genes (ISGs) was measured by RT-qPCR, protein phosphorylation by Western blot, and IFN-β secretion by ELISA. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) were used to probe the interactionbetween EGCG and IRF3. ResultsNetwork pharmacology identified (-)-epigallocatechin-3-gallate (EGCG) as a candidate IFN-I-suppressive constituent of P. emblica, with predicted binding to TBK1, IRF3, and STAT1. Molecular docking yielded binding energies of -9.2, -7.2, and -8.2 kcal/mol for TBK1, IRF3, and STAT1, respectively, indicating an affinity for TBK1 comparable to that of the reference inhibitors BX795 (-5.7 kcal/mol) and GSK8612 (-6.4 kcal/mol). EGCG suppressed IFN-β1 and ISG mRNA expression under poly (I∶C), poly (dA∶dT), and LPS stimulation in both THP-1 macrophages and BMDM. At the protein level, EGCG reduced the phosphorylation of TBK1 and IRF3 without affecting the levels of the upstream sensors cGAS and RIG-I, and lowered IFN-β secretion in a concentration-dependent manner. CETSA and DARTS showed that EGCG did not enhance the thermal stability or protease resistance of IRF3, indicating that its effect on IRF3 is indirect. Following IFN-β stimulation, prolonged EGCG treatment reduced STAT1 phosphorylation in a time-dependent manner without an apparent change in IRF9, and partially attenuated ISG transcription; this effect was not monotonicly concentration-dependent, and CXCL10 showed the most consistent suppression. In TREX1-knockdown cells, the elevated mRNA levels of ISG15, ISG56, and CXCL10 were reduced by EGCG. ConclusionEGCG suppresses IFN-I responses by concurrently inhibiting TBK1-IRF3-dependent IFN‑β production and JAK-STAT1-mediated downstream transcription. These in vitro findings provide a mechanistic basis for the anti-inflammatory use of P. emblica in traditional medicine and identify EGCG as a candidate for further evaluation in interferon-driven autoimmune disease models.

Background and aims The mechanism of cholestatic liver injury (CLI) is unclear, and effective therapies are lacking. While peroxisome proliferator-activated receptor alpha (PPARα) agonists show potential hepatoprotective effect and pyroptosis is implicated in hepatocellular damage, how PPARα activation mitigates lithocholic acid (LCA)-induced pyroptosis remains unknown. Methods The hepatoprotective effect of PPARα agonists was evaluated in a mouse model of intrahepatic cholestasis induced by LCA. Liver injury was assessed via serum biochemistry, hematoxylin and eosin and TUNEL staining, and electron microscopy. Pyroptosis pathways were analyzed using real-time quantitative polymerase chain reaction, Western blot, and co-immunoprecipitation. Results Combined morphological, histopathological, and biochemical analyses confirmed that PPARα activation protects against CLI. Compared with LCA treatment alone, PPARα activation significantly attenuated the elevation of serum lactate dehydrogenase (LDH), the increased TUNEL-positive cells, and the formation of hepatocyte membrane pores. Mechanistically, PPARα activation suppressed both NOD-like receptor protein 3 (NLRP3) inflammasome-mediated pyroptosis and apoptosis protease-activating factor-1 (APAF-1)/CASPASE-3/GSDME-mediated pyroptosis. Furthermore, PPARα agonist pretreatment inhibited activation of the nuclear factor-kappa B (NF-κB) and forkhead box O1 (FOXO1) signaling pathways. Conclusions PPARα protects against LCA-induced CLI by inhibiting both NLRP3 inflammasome-mediated pyroptosis associated with NF-κB and APAF-1/CASPASE-3/GSDME-mediated pyroptosis associated with the FOXO1 signaling pathway.

RNA-binding proteins (RBPs) are ubiquitous components within cells, fulfilling essential functions in a myriad of biological processes. These proteins interact with RNA molecules to regulate gene expression at various levels, including transcription, splicing, transport, localization, translation, and degradation. Understanding the intricate network of RBP-RNA interactions is crucial for deciphering the complex regulatory mechanisms that govern cellular function and organismal development. Ultravidet (UV) cross-linking and immunoprecipitation (CLIP) stands out as a powerful approach designed to map the precise locations where RBPs bind to RNA. By using UV light to create covalent bonds between proteins and RNA, followed by immunoprecipitation to isolate the protein-RNA complexes, researchers can identify the direct targets of specific RBPs. The advent of high-throughput sequencing technologies has revolutionized CLIP, enabling the identification of not only the types but also the exact sequences of RNA bound by RBPs on a genome-wide scale. The evolution of CLIP has led to the development of specialized variants, each with unique features that address specific challenges and expand the scope of what can be studied. High-throughput sequencing CLIP (HITS-CLIP) was one of the first advancements, significantly increasing the throughput and resolution of RNA-protein interaction mapping. Photoactivatable-ribonucleoside-enhanced CLIP (PAR-CLIP) introduced the use of photoactivatable ribonucleosides to enhance cross-linking efficiency and specificity, reducing background noise and improving the detection of low-abundance RNA-protein interactions. Individual-nucleotide resolution CLIP (iCLIP) further refined the technique, achieving unprecedented precision by resolving individual nucleotides involved in RBP binding, which is particularly valuable for studying the fine details of RNA structure and function. Despite the remarkable progress, there remains room for improvement in CLIP technology. Researchers continue to seek methods to increase sensitivity, reduce technical variability, and improve the reproducibility of results. Advances in sample preparation, data analysis algorithms, and computational tools are critical for addressing these challenges. Moreover, the application of CLIP to more diverse biological systems, including non-model organisms and clinical samples, requires the development of tailored protocols and the optimization of existing ones. Looking forward, the field of RNA biology is poised to benefit greatly from ongoing innovations in CLIP technology. The exploration of non-canonical RNA-protein interactions, such as those involving long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), promises to reveal new layers of cellular regulation and may lead to the discovery of novel therapeutic targets. Furthermore, integrating CLIP data with other omics approaches, such as proteomics and metabolomics, will provide a more comprehensive understanding of the dynamic interplay between RNA and its binding partners within the cell. In conclusion, the continuous refinement and expansion of CLIP techniques have not only deepened our knowledge of RNA biology but have also opened up new avenues for investigating the molecular underpinnings of health and disease. As the technology matures, it is expected to play an increasingly pivotal role in both basic and applied research, contributing to the advancement of medical science and biotechnology.

Palliative care has become an important medical measure to provide professional healthcare and alleviate patients' suffering. Nurse-led palliative care models enable patients to access palliative care services in a timely manner and can be applied across various healthcare settings. This paper reviews the current status of nurse-led palliative care models in China and internationally, summarizes the summarizes the intervention settings, care forms, implementation contents, and effects of nurse-led palliative care models, and expounds on the existing barriers and improvement strategies of nurse-led palliative care models in China. The aim is to provide a reference for the implementation and development of palliative care.

On the occasion of the 110th Anniversary of the establishment of the Chinese Medical Association, the third conference of the Fourth Editorial Board of Chinese Journal of Digestive Surgery, and the Second Elite Group of Chinese Journal of Digestive Surgery, was successfully held in Kunming on July 4, 2025. This conference systematically summarizes the development experience of the journal over the past 20 years from three aspects: the role of ecological construction of thought in the discipline construction of digestive surgery, the display of the latest academic achievements in the field of digestive surgery, the development difficulties, and breakthrough paths of the discipline, and strategically plans the path of discipline construction in the new era.

Objective To collect and analyze outpatient prescription data for exogenous cough treatment from a hospital in Shenzhen,and to identify the characteristics and medication patterns of traditional Chinese medicine(TCM).Methods This study collected prescriptions from a hospital in Shenzhen for exogenous cough treatment in January 2024.R language for data mining were used to analyze the medication frequency,clustering patterns,and association rules in the treatment of exogenous cough by TCM and to explore the medication patterns and the usage of classic formulas in TCM for this condition.Results A total of 451 outpatient prescriptions for exogenous cough were include,the top ten most frequently used herbs were Licorice,Bitter almond,Bellflower,Ephedra,Tangerine peel,Stemonae radix,Tuckahoe,Pinellia ternata,Nepeta,Bulb of thunberg fritillary.Cluster analysis and association rules revealed that San'ao decoction,Kikyodon soup,and Zhisou powder were commonly prescribed,targeting lung function,dispersing wind,and resolving phlegm to effectively alleviate cough symptoms.Significant differences in medication usage were observed across different syndrome types.For the wind cold attacking lung pattern,the core herbs were warm in nature and focused on dispersing with acrid-warm properties.Conversely,the treatment of wind heat attacking the lung pattern typically involved cold-natured herbs,with a primary focus on clearing and draining lung heat.Stratification by age revealed that the pediatric group often used drugs with mild properties,such as Stemona and Shegan.The young adult group tended to be prescribed cold-natured drugs like Forsythia and Hogfonnel Root.The middle-aged and elderly group preferred warming and tonifying drugs such as Japanese Catnip and Perilla frutescens.Conclusion The TCM treatment of exogenous cough primarily focuses on releasing the exterior and dispersing the lung.Due to the region's subtropical monsoon climate and temperature fluctuations physicians flexibly modified classical formulas such as San'ao decoction and Zhisou powder according to individual constitutions and symptom patterns.This targeted,syndrome-based approach effectively disperses the lung qi,stops cough and transforms phlegm,and alleviates cough.

Objective To investigate the risk factors and clinical significance of layered plaques that were detected by optical coherence tomography(OCT)in patients with angiographically intermediate coronary lesions,and relationship with prognosis.Methods This was a signal-center retrospective study focusing on patients whom underwent coronary angiography and OCT.The layered plaque group and non-layered plaque group were divided according to the presence or absence of stratified plaque.Clinical data,laboratory indicators,angiography,and OCT results were collected and compared between the two groups.Using logistic regression to analyze the relationship between stratified plaques and clinical features;Cox regression analysis was used to investigate the influencing factors of cardiovascular adverse events in patients with critical coronary artery disease.Results A total of 172 patients were enrolled,including 96 patients in non-layered plaque group and 76 patients in layered plaque group.Male(OR 2.415,95％CI 1.162-5.020,P=0.018),diabetes(OR 2.505,95％CI 1.137-5.525,P=0.023)and history of hyperlipidemia(OR 3.590,95％CI 1.478-6.333,P=0.003)were independent risk factors for stratified plaque.In OCT analysis,the proportion of thin-cap fibroatheroma(TCFA)plaque,macrophage infiltration,microvascularization,thrombosis,plaque rupture,and intimal dissection,as well as lipid plaque length,lipid plaque arc,and lipid plaque index were higher in the layered plaque group.After adjusting for other risk factors,macrophage infiltration is independently associated with stratified plaques(OR 2.106,95％CI 1.019-4.353,P=0.044).Kaplan-Meier survival analysis showed that the target lesion revascularization rate in the layered plaque group was higher than that in the non-layered plaque group(Log-rank P=0.030).Cox regression analysis shows that it has both stratified plaque and thin fibrous membrane plaque characteristics was an independent predictor of cardiovascular adverse events(HR 5.165,95％CI 1.696-15.727,P=0.004).Conclusions In patients with angiographically intermediate coronary lesions,OCT detection of stratified lesions is often accompanied by other unstable plaque features,indicating an increased risk of adverse cardiovascular events.Simultaneously possessing features of stratified plaques and TCFA is an independent predictor of adverse cardiovascular events in patients with critical coronary artery disease.

Objective To analyze the diagnostic value of fat content measurement based on magnetic resonance multi-echo Dixon(ME-Dixon)technique combined with serological indicators for early liver fibrosis.Methods A total of 78 patients with early liver fibrosis who underwent liver biopsy at the First Affiliated Hospital of Army Medical University from August 2019 to October 2021 were included.According to the pathological results,the patients with early liver fibrosis were divided into the S0 group(n=21),the S1 group(n=32),and the S2 group(n=25).Meanwhile,the complete imaging examination results(including ME-Dixon sequence)and laboratory examination results[including hyaluronic acid(HA),procollagen Ⅲ(PCⅢ),collagen Ⅳ(CⅣ),laminin(LN),aspartate transaminase(AST),alanine amino-transferase(ALT),gamma-glutamyl transferase(GGT),alkaline phosphatase(ALP)]were collected.And the hepatic fat fraction(HFF)was measured by ME-Dixon technique.One-way ANOVA was used to analyze the differences in HFF and serological indicators among the three groups,and then factors with statistical differences in the univariate analysis were selected to draw receiver operating characteristic(ROC)curve,and the area under the curve(AUC)was calculated to evaluate their value in the diagnosis of liver fibrosis and the degree of early liver fibrosis.Results There was no statistically significant difference in the PCⅢ,LN,AST,or ALT among the S0,S1,and S2 groups(P>0.05),while there were statistically significant differences in the HFF,HA,CⅣ,GGT,and ALP(P<0.05),and the levels of HA,CⅣ,GGT,and ALP in the S2 group were significantly higher than those in the S0 and S1 groups(P<0.05).ROC curve analysis showed that the above indicators for diagnosing liver fibrosis and the degree of early liver fibrosis based on AUC values were in the following order:HFF+GGT(0.72)>HFF(0.68)>GGT(0.61)>CⅣ(0.54)>ALP(0.53)>HA(0.48)and HA+CⅣ(0.71)>CⅣ(0.68)>HA(0.66)>GGT(0.61)>ALP(0.59)>HFF(0.46).Conclusion The fat content measurement based on magnetic resonance ME-Dixon tech-nique combined with serological indicators has significant reference value for the diagnosis of early liver fibrosis,and it plays a certain guid-ing role in clinical diagnosis and treatment.

Hemodialysis patients exhibit compromised immune function and require long-term repeated vascular punctures as therapeutic approach,the risk of infection increases.Hospital-associated infection in hemodialysis de-partment(center)happens from time to time,which has already become a concern for the medical community,patients and social media.This paper outlines the task origin of China's"Standard for infection prevention and control in hemodialysis department(center)"(WS/T854-2025),the compilation basis and explanations for its key content,feasibility and implementation recommendations,as well as the clarifications on common issues encoun-tered during its promotion and enforcement.