This study aims to compare multi-disciplinary team-based learning (MDTBL), problem-based learning (PBL) and lecture-based learning (LBL) on the learning outcomes and experiences of medical students. A randomized controlled study was designed to recruit 30 medical students with a minimum of one year of clinical experience and 45 with less than one year of clinical experience to take a course on clinical diagnosis and evaluation of pulmonary nodules from September 15, 2022, to December 31, 2023. The participants were randomly assigned to the MDTBL group, PBL group, and LBL group to complete a full-course curriculum. Before, during, and after the learning phases, all participants underwent identical theoretical assessments and received a score on their learning progress. In the MDTBL and PBL groups, group discussions were permitted. After the completion of the learning phase, self-evaluation and course satisfaction were assessed through a questionnaire. The authors collected basic information on participants to ensure comparability between groups. All groups showed significant improvement in their competence in the clinical diagnosis and evaluation of pulmonary nodules, with the MDTBL group demonstrating notably higher gains in theoretical knowledge and case analysis skills (P < 0.05). The learning participation scale indicated that student engagement in the MDTBL group was higher than in the other two groups (P < 0.05). Additionally, the MDTBL group perceived the course as more engaging and enjoyable. This study demonstrates that the MDTBL teaching model, as an innovative approach, excels in enhancing knowledge acquisition, collaborative skills, and clinical practice application skills in medical students. It positions itself as a valuable teaching model for future medical education, providing educators with a new toolkit for training specialists. This study was retrospectively registered in 2023 as No.JG2023-0203.

BackgroundLung ischemia-reperfusion injury (LIRI) is a principal cause of primary graft dysfunction (PGD) following lung transplantation, severely compromising recipient survival. However, effective therapies remain unavailable due to its complex pathophysiology. Pterostilbene (PTE) is a natural stilbene compound known for its well-documented anti-inflammatory, antioxidant, and antitumor properties. However, its effects and underlying mechanisms in LIRI remain unclear.MethodsPotential targets of PTE and LIRI were retrieved from multiple public databases, followed by network analysis and functional enrichment to identify core targets and pathways. Molecular docking and dynamics simulations were conducted to assess the binding affinity and stability between PTE and its core targets. Finally, a rat left hilar clamping model and an OGD/R model in BEAS-2B cells were employed to experimentally validate the protective effects and molecular mechanisms of PTE.ResultsA total of 104 intersecting targets were identified with ten core genes such as PIK3CB and MAPK8 highlighted. Gene Ontology and KEGG analyses revealed significant enrichment in apoptosis- and inflammation-related pathways, particularly PI3K/AKT and MAPK signaling. Docking and simulation results demonstrated stable binding of Pterostilbene to core targets (binding energy ≤−5.6 kcal/mol). In vivo, PTE alleviated IR-induced lung injury, reduced pulmonary edema, apoptosis, and pro-inflammatory cytokine release. In vitro, PTE enhanced cell viability, decreased the levels of pro-inflammatory cytokines, inhibited Caspase-3 activation and Bax expression, and increased Bcl-2 levels. Mechanistically, PTE promoted PI3K/AKT activation while suppressing JNK/c-Jun phosphorylation both in vivo and in vitro. Notably, LY294002 (a PI3K inhibitor) and Anisomycin (a JNK activator) partially reversed the anti-apoptotic and anti-inflammatory effects of PTE, respectively.ConclusionThis study provides the first integrated evidence combining network pharmacology and experimental validation that PTE protects against LIRI by modulating the PI3K/AKT and JNK/c-Jun signaling pathways, offering novel pharmacological insights into its translational potential in LIRI.

INTRODUCTION:Chronic heart failure (CHF) represents the end-stage progression of cardiac diseases, and its prognosis remains suboptimal. Poria Almond and Liquorice decoction(PALD), a traditional Chinese herbal formula, has demonstrated therapeutic efficacy in cardiovascular diseases, underscoring its promising potential for CHF management. Nevertheless, the underlying mechanisms of its action in CHF remain elusive. METHODS:First, a herb-component-target network was constructed to systematically identify the bioactive components of PALD and their potential protein targets. Concurrently, a protein-protein interaction (PPI) network was established to pinpoint key protein targets and core active ingredients in the CHF. Molecular docking was employed to validate the interactions between the primary active components of PALD and the predicted candidate targets. To further corroborate these findings, molecular docking was conducted. Furthermore, the R language was utilized for KEGG, GO, and DO enrichment analyses. RESULTS:Integrated bioinformatics and network pharmacology approaches predicted cerevisterol, licochalcone B, and hederagenin as core therapeutic candidates interacting with key signaling regulators such as SRC, PIK3CD, and PIK3CA. Molecular docking further validated potential binding of these compounds to inflammatory targets IL-6 and IL-1B, with cerevisterol showing binding energies of -6.227 kcal/mol (IL-6) and -6.607 kcal/mol (IL-1B), and hederagenin exhibiting -6.139 kcal/mol (IL-6) and -7.500 kcal/mol (IL-1B)-all values below the -6 kcal/mol threshold indicative of stable binding. These computational results suggest that PALD may exert multi-target effects against CHF-associated pathways, potentially through modulation of IL6/IL-1B-mediated inflammatory responses. DISCUSSION:By integrating network pharmacology, bioinformatics, and molecular docking, this study proposes a novel predictive framework suggesting that PALD may alleviate CHF by modulating the PI3K-AKT pathway and IL-6/IL-1B signaling to improve coronary artery function. While these findings are derived from computational models and require experimental confirmation, they provide a focused mechanistic hypothesis and a valuable roadmap for future in vitro and in vivo research into this traditional formula. CONCLUSION:PALD-derived bioactive constituents-cerevisterol, licochalcone B, and hederagenin- ameliorate coronary hemodynamics in chronic heart failure through coordinated inhibition of IL-6/IL-1Bmediated inflammatory responses and activation of PI3K/AKT signaling pathway. All proposed mechanisms are predictive and must be interpreted a.

Liver and lung transplantation are life-saving treatments for end-stage organ failure. While short-video platforms have become crucial health information sources, the educational quality and reliability of transplantation-related content remains uncertain. This cross-sectional study evaluated 416 liver (223) and lung (193) transplantation-related videos from TikTok and Bilibili in China (December 2025) using four validated instruments: Global Quality Score (GQS), modified DISCERN (mDISCERN), Medical Quality Video Evaluation Tool (MQ-VET), and Video Information and Quality Index (VIQI). Overall content quality was moderate to low. Videos by medical practitioners achieved statistically significantly higher quality scores than non-medical videos, though absolute differences were modest. TikTok videos achieved higher overall quality scores, while Bilibili videos showed better content reliability. Notably, user engagement metrics were inversely associated with medical professional quality scores in liver transplantation videos (a correlational observation that does not imply causation), with no such association in lung transplantation content. These findings, situated within the unique regulatory and content-governance environment of the Chinese digital ecosystem, highlight the need to optimize platform content governance and promote specialist-led educational content to improve the overall educational quality of transplantation-related short videos.

BACKGROUND:A rising trend in the incidence of hepatic trauma has been noted annually over recent years. Panax Notoginseng (PN) is renowned for its hemostatic and wound-healing properties, but its multicomponent mechanism against hepatic trauma remains unclear. OBJECTIVE:This study aimed to decipher the multi-component, multi-target mechanisms of PN in treating hepatic trauma by integrating network pharmacology, molecular docking, and in vivo experimental validation. METHODS:The bioactive constituents of PN and their corresponding protein targets were acquired from the TCMSP database. Hepatic trauma-associated genes were sourced from the GeneCards and OMIM databases. A comprehensive drug-component-target network and a protein-protein interaction (PPI) network were constructed to identify core compounds and hub targets. Functional enrichment analyses (GO and KEGG) were performed to delineate involved biological processes and signaling pathways. Molecular docking and Molecular Dynamics Simulations assessed the binding affinities between pivotal components and targets. Finally, the anti-inflammatory effect of PN was experimentally verified in a rat model of mechanical hepatic trauma. RESULTS:Our analysis identified seven primary bioactive compounds in PN. Among these, quercetin, β-sitosterol, and stigmasterol were discerned as the most influential based on network topology. PPI network analysis revealed AKT1, IL-6, and TNF as central hub targets. Enrichment analysis implicated several key pathways, most notably the PI3K-Akt, TNF, and IL-17 signaling pathways. Molecular docking and Molecular Dynamics Simulations confirmed stable binding conformations between the top compounds and the core targets, with favorable binding energies. Crucially, in vivo experimentation on mechanical hepatic trauma demonstrated that PN administration significantly suppressed the mRNA expression levels of pivotal proinflammatory cytokines (TNF-α, IL-6, and IL-1β) in injured liver tissue, thereby providing direct experimental corroboration for our computational predictions. DISCUSSION:This study fills the critical gap in understanding the multi-component mechanism of PN against hepatic trauma, which remains unclear despite its long-standing clinical use for hemostasis and wound healing. Unlike previous research focusing on single saponin components, our work reveals the synergistic hepato- protective effects of PN's core bioactive compounds via coordinated modulation of inflammatory cascades and pro-survival signaling pathways. Our integrated in silico and in vivo validation provides robust mechanistic support for PN's clinical repurposing and offers promising leads for developing novel adjuvant therapies for hepatic trauma. CONCLUSION:This study reveals that PN alleviates hepatic trauma through a multi-component synergy mechanism, primarily by targeting the PI3K-Akt pathway and inhibiting inflammation. Our findings provide a solid foundation for its future experimental confirmation and clinical application.

OBJECTIVES:Induction immunochemotherapy is the standard of care for resectable stage II and III non-small cell lung cancer. However, the comparative effectiveness of subsequent definitive surgery versus radiotherapy remains uncertain. We aimed to compare outcomes between these 2 strategies in routine clinical practice. METHODS:This multicenter, retrospective cohort study included patients with stage II and III non-small cell lung cancer who received induction immunochemotherapy followed by surgery or definitive radiotherapy across 12 centers in China. Propensity score matching (1:2) was used to balance clinicopathological characteristics. The primary end point was progression-free survival; secondary end points included overall survival and recurrence patterns. RESULTS:Among 967 patients (683 surgery; 284 radiotherapy), the matched intent-to-treat cohort included 548 patients (365 surgery; 183 radiotherapy). Compared with radiotherapy, surgery was associated with significantly longer progression-free survival (hazard ratio, 0.32; 95% CI, 0.23-0.44; P < .001) and overall survival (hazard ratio, 0.41; 95% CI, 0.26-0.66; P < .001). Surgery reduced overall recurrence (-21.3%; 95% CI, -31.1 to -11.3) and local recurrence (-17.5%; 95% CI, -25.0 to -9.9), but did not affect distant metastasis. In the subgroup of patients for whom pneumonectomy was indicated, surgery improved progression-free survival (hazard ratio, 0.47; 95% CI, 0.26-0.85; P = .013) but did not confer an overall survival benefit (hazard ratio, 1.14; 95% CI, 0.48-2.70; P = .76). Among patients who achieved a clinical complete response, outcomes were similar between the 2 groups. CONCLUSIONS:Definitive surgery after induction immunochemotherapy offers superior progression-free survival and overall survival compared with definitive radiotherapy, primarily driven by improved local control. For patients requiring pneumonectomy or achieving a clinical complete response, treatment should be individualized, and prospective trials are warranted.

Primary graft dysfunction (PGD) caused by ischemia-reperfusion injury (IRI) is a major complication after lung transplantation, yet its underlying mechanisms remain unclear. Triggering receptor expressed on myeloid cells 1 (Trem1) is an important mediator of inflammation, but its role in neutrophil function and metabolic reprogramming during lung IRI is not well understood. In this study, we used a murine orthotopic lung transplantation model with cold ischemia and reperfusion, and Trem1 knockout (Trem1-/-) and myeloid-specific Trem1 conditional knockout mice (LysmCreTrem1fl) to explore the role of Trem1 in neutrophil recruitment, neutrophil extracellular trap (NET) formation, and metabolism. Our results show that Trem1 expression increases in both mouse and human lungs after reperfusion and correlates with neutrophil infiltration and lung injury. Trem1 deficiency significantly reduced neutrophil and macrophage recruitment, NET formation, and tissue damage. Multi-omics analysis revealed that Trem1 deletion suppressed oxidative phosphorylation (OXPHOS) and induced a metabolic shift in neutrophils toward glycolysis. In clinical samples, the abundance of TREM1+ neutrophils was correlated with PGD severity and OXPHOS activity. These findings identify Trem1 as a key regulator of neutrophil metabolism and recruitment in lung IRI, and suggest that targeting Trem1 may provide a novel therapeutic strategy to mitigate PGD and improve lung transplant outcomes.

Autophagy is essential for mitigating excessive reactive oxygen species (ROS) to protect cells from ischemia-reperfusion injury (IRI), which often results in target organ damage and, consequently, lung transplant failure in clinical practice in thoracic surgery. However, excessive autophagy exacerbates IRI. Therefore, inducing or inhibiting autophagy is a paradoxical problem. Based on cell, rat and patient-derived organoid models, ROS accumulated as ischemia time increased. Moreover, ROS levels surged after a certain period of ischemia. Furthermore, autophagy is activated in response to IRI; however, with increased ischemia time, ferritinophagy is induced, leading to a ROS surge. Besides, we observed that ROS-induced DNA damage repair response was associated with ferritinophagy induction. Additionally, our results indicated that ROS-induced DNA damage induces NORAD expression to activate ferritinopahgy through regulating FOXO1-NCOA4 interaction. In this respect, we constructed siNORAD/LNP and NORAD knockout mice to further validate that NORAD is a candidate to suppress oxidative stress during lung ischemia-reperfusion by suppressing NCOA4 mediated ferritinophagy. In conclusion, understanding the interplay between ROS-induced DNA damage, mitophagy, and ferritinophagy is essential for deciphering IRI-associated cell death and for developing therapeutic candidates.

Background: Enhanced recovery after lung surgery is important as it impacts patient outcomes. Among Traditional Chinese Medicine (TCM) herbs, Panax Notoginseng (PN) has been studied for its remarkable properties, making it a promising candidate for accelerating postoperative healing. However, the mechanisms of PN in enhancing recovery after lung surgery remain incompletely understood. Methods: First, animal experiments were conducted to validate the efficacy of PN in postoperative recovery following lung surgery. Then, herb-component-target network and Protein-Protein Interaction (PPI) network were constructed to identify the bioactive components of PN and key protein targets. Molecular docking was employed to validate the interactions between the active components and candidate recovery targets. Results: Animal experiments demonstrated that PN significantly improved postoperative recovery by enhancing collagen deposition and reducing pulmonary edema around the wound. Eight active components from PN and 251 targets associated with its therapeutic effects were revealed; 650 targets were linked to postoperative recovery after lung surgery. Key protein targets, including SRC, PIK3R1, and EGFR, were identified, with Quercetin, Liquiritigenin, and Mandenol emerging as the core active ingredients. Molecular docking demonstrated that the core components exhibited favorable binding energies with target proteins. KEGG and GO enrichment analyses highlighted the PI3KAKT signaling pathway and epithelial cell proliferation as critical pathways and biological processes underlying PN’s efficacy. Discussion: PN may offer a novel strategy to enhance postoperative lung repair, as it may activate the PI3K/AKT pathway, which links traditional Chinese medicine with postoperative recovery. In this work, PN contributes to ERAS protocols in thoracic surgery, bridging molecular insights with clinical outcomes. Conclusion: The active components of PN, including Quercetin, Liquiritigenin, and Mandenol, can accelerate postoperative recovery after lung surgery by potentially activating the PI3K-AKT pathway and promoting collagen deposition processes.

Ischemia-reperfusion injury (IRI) remains a primary driver of primary graft dysfunction (PGD) following lung transplantation, yet effective therapeutic strategies are currently limited. Early IRI is driven by coordinated oxidative and inflammatory responses, highlighting the need for therapeutic strategies capable of targeting both processes simultaneously. Using integrated human multi-omics analysis, in silico target prediction, and experimental validation, we identified barbaloin as a dual-target lead compound acting on interleukin-6 (IL-6) and purine nucleoside phosphorylase (PNP). In vitro, barbaloin suppressed IL-6 and PNP expression, inhibited PNP activity, reduced reactive oxygen species (ROS) accumulation, and attenuated NF-κB/NLRP3 inflammatory signaling. Crucially, in vivo validation in a C57BL/6J mouse model demonstrated that barbaloin (15 mg/kg) attenuated pulmonary edema and histological injury, partially restored respiratory mechanics, and reduced IL-6 and PNP expression. Collectively, these findings support the IL-6/PNP axis as a critical mediator of early lung IRI and identify barbaloin as a promising dual-target therapeutic candidate for mitigating oxidative and inflammatory injury during lung transplantation.

Neoadjuvant chemoimmunotherapy (NCIT) has shown promising activity in locally advanced esophageal squamous cell carcinoma (ESCC), but comparative evidence against neoadjuvant chemotherapy (NCT) alone remains limited. This study aimed to compare the pathological response and perioperative safety of NCIT versus NCT in patients with locally advanced ESCC. This single-center retrospective cohort study included 199 patients with locally advanced ESCC who underwent neoadjuvant therapy followed by esophagectomy between 2017 and 2023. Among them, 131 patients received NCIT and 68 received NCT alone. Pathological response was assessed using major pathological response (MPR), pathological complete response (pCR), and tumor regression grade (TRG). Treatment-related adverse events (TRAEs) and postoperative outcomes, including 30-day and 90-day mortality, were evaluated. To reduce confounding from baseline imbalance, 1:1 propensity score matching (PSM) was performed as the primary adjusted analysis. In the overall cohort, MPR was achieved in 51 of 131 patients in the NCIT group and 17 of 68 patients in the NCT group (38.93

Background/Objectives: The aim of this study was to evaluate the performance of the Node-RADS scoring system for predicting lymph node metastasis in patients with non-small cell lung cancer (NSCLC) after neoadjuvant therapy and to assess its prognostic value for overall survival (OS) and event-free survival (EFS). Methods: A total of 247 patients with non-small cell lung cancer (NSCLC) from three centers who underwent surgery after neoadjuvant therapy were retrospectively enrolled. Post-treatment Node-RADS scores were reassessed by radiologists based on preoperative contrast-enhanced CT images. Logistic regression analysis was used to evaluate the predictive value of Node-RADS for postoperative pathological lymph node metastasis, while Cox regression analysis was performed to assess its associations with OS and EFS. Kaplan–Meier analysis was used to compare survival differences among different Node-RADS risk groups. Results: A total of 247 patients were included in this study, comprising 211 men and 36 women, with a mean age of 63.40 ± 7.58 years. Post-treatment Node-RADS score was significantly associated with both OS and EFS. In multivariable Cox regression analysis, Node-RADS remained independently associated with OS (HR = 1.79, 95% CI: 1.50–2.15, p < 0.001) and EFS (HR = 1.41, 95% CI: 1.23–1.62, p < 0.001). Using a Node-RADS score of 3 as the cutoff value, patients in the high-risk group had significantly worse OS and EFS than those in the low-risk group (both p < 0.01). For the prediction of lymph node metastasis, the inclusion of post-treatment Node-RADS markedly improved the discriminatory performance of the model, with an AUC of 0.769, a sensitivity of 46.2%, and a specificity of 87.6%. Conclusions: The Node-RADS score may provide useful imaging information for patient-level assessment of residual lymph node metastasis risk and survival stratification in patients with NSCLC after neoadjuvant therapy. These findings suggest that the scoring system may support patient-level post-treatment risk assessment.

Cisplatin resistance remains a significant obstacle in the treatment of esophageal squamous cell carcinoma (ESCC), yet its underlying molecular mechanisms are incompletely understood. This study examined whether METTL3-mediated m6A methylation and YTHDF2 SUMOylation collaboratively modulate SLC7A11 expression to drive cisplatin resistance in ESCC. Using cisplatin-resistant ESCC cell lines, clinical tissue samples, in vivo xenograft models, and functional assays, including CCK-8, ROS/GSH/MDA detection, RNA immunoprecipitation (RIP), MeRIP-qPCR, and SUMOylation analyses, we demonstrate that METTL3 exerts opposing, context-dependent effects on SLC7A11 mRNA stability. In cisplatin-sensitive cells, METTL3-mediated m6A modification promotes YTHDF2 binding to SLC7A11 mRNA, leading to its degradation and enhanced oxidative stress. In resistant cells, however, upregulation of the SUMO-specific protease Senp1 triggers YTHDF2 deSUMOylation, reducing its RNA-binding affinity and allowing YTHDF1 to instead stabilize SLC7A11 transcripts. This shift results in elevated SLC7A11 expression, enhanced antioxidant capacity, and cisplatin resistance. Importantly, restoring YTHDF2 SUMOylation via Senp1 knockdown reversed SLC7A11 overexpression and resensitized resistant cells to cisplatin both in vitro and in vivo. These findings reveal a SUMOylation-dependent switch in m6A reader function as a novel mechanism underlying chemoresistance, reconciling previously conflicting reports on the role of METTL3 in SLC7A11 regulation, and identify the METTL3-YTHDF1/2-SLC7A11 axis, particularly the Senp1-YTHDF2 node, as a potential target warranting further investigation for overcoming cisplatin resistance in ESCC.

Background: XueFu ZhuYu Decoction (XFZYD) is a classic herbal formula that shows promise in the treatment of malignant pleural effusion (MPE). However, its primary components and the underlying mechanisms of action remain unclear. Therefore, the objective of this study is to preliminarily elucidate the potential mechanisms by which XFZYD may treat MPE through network pharmacology and molecular docking. Methods: The effective components and their corresponding targets of XFZYD were identified using the traditional chinese medicine (TCM) systems Pharmacology database, and a related network was constructed utilizing Cytoscape. Subsequently, the targets associated with MPE were retrieved from the Online Mendelian Inheritance in Man (OMIM) and GeneCards databases. We then determined the intersection between compound targets and disease targets, constructing a protein–protein interaction (PPI) network by importing these into the STRING database. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses were performed through the Metascape database. Finally, molecular docking studies between core targets and effective compound molecules were conducted. Result: Quercetin, kaempferol, and luteolin were identified as the compounds with the highest values. The primary common targets of XFZYD in relation to MPE included STAT3, MAPK1, and MAPK3. Furthermore, GO and KEGG analyses indicated that XFZYD treatment for MPE was associated with responses to lipopolysaccharide, vesicle lumen dynamics, and protein kinase activity overall. The signaling pathways predominantly involved were the AGE‐RAGE pathway, IL‐17 signaling pathway, and P13K‐Akt signaling pathway. Molecular docking demonstrated high affinities between the lead compounds and their target proteins. Conclusions: The active ingredients Quercetin, kaempferol, and luteolin in XFZYD exert therapeutic effects against MPE via the PI3K‐Akt signaling pathway, with key targets involving STAT3, MAPK1, and MAPK3.

Due to constant stimulation by stomach acid and local bleeding, gastric tissue wounds tend to heal slowly and complications such as anastomotic leakage have a high incidence. Suturing is often used to treat gastric wounds in clinic, but it still faces risks such as bleeding, slow healing, and leakage. Recently, hydrogel have been widely used to treat various types of wounds. Although hydrogels have shown promising efficacy in wound healing, it is still a challenge in dealing with wounds in gastric tissue for the poor adaptability of traditional materials in acidic environments. Hence, a series of pH responsive and good tissue adhesive hydrogels (MA-HA/AA) based on methacryloyl hyaluronic acid (MA-HA) and acryloyl-6-aminocaproic acid (AA) via in situ photo-crosslinking were designed, and anti-inflammatory and pro-healing traditional Chinese medicines ginsenoside Rg1 was incorporated into the hydrogel to treat gastric tissue wound. These acid-responsive hydrogels could form effective acid-resistant barriers and could lead to hemostasis rapidly through its strong adhesion. Besides, the hydrogels contracted under an acidic environment, which could tighten the gastric tissue wounds and sustained release the loaded ginsenoside Rg1. In addition, the hydrogels showed excellent biocompatibility and in vivo degradability. In summary, the acid-responsive contractile hyaluronic acid hydrogel loaded with ginsenoside Rg1 had good properties for hemostasis and acid-resistance to facilitate the promotion of gastric wounds healing.

Di(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, has been implicated in various health risks, including tumorigenesis. Non-small cell lung cancer (NSCLC), accounting for over 80% of lung cancer cases, remains a leading cause of cancer-related mortality. This study employed network toxicology and molecular docking to explore the molecular mechanisms underlying DEHP's toxic effects on NSCLC. DEHP and NSCLC targets were retrieved from CTD, SwissTargetPrediction, and GeneCards, yielding 225 overlapping genes. Protein-protein interaction (PPI) network analysis identified five core targets: TP53, JUN, SRC, AKT1, and ESR1. Gene Ontology (GO) and KEGG pathway enrichment analyses revealed significant involvement of the PI3K/AKT signaling pathway and regulation of apoptotic signaling in DEHP-induced NSCLC pathogenesis. Molecular docking confirmed strong binding affinities between DEHP and the core targets, with binding energies ranging from - 4.611 to -7.535 kcal/mol. These findings suggest that DEHP promotes NSCLC progression, metastasis, and chemoresistance through PI3K/AKT signaling and apoptotic pathway dysregulation. This study provides mechanistic insights into DEHP's role in NSCLC and highlights the need for public health interventions to mitigate DEHP exposure. Further experimental validation is warranted to strengthen these findings and guide the development of targeted therapies.

Excessive blood loss is a key factor in death, while the control of bleeding is still a major clinical and emergency problem. Existing hemostatic materials usually have limited procoagulant properties, are either nondegradable or poorly degradable, and are prone to tissue adhesion. There are still challenges in developing hemostatic materials with efficient procoagulant effects, good degradability, and antitissue adhesion properties. Here, we design a hemostatic sponge adhesive made of polyphosphate-modified oxidized dextran (OD-P) and lauric acid-modified oxidized dextran (OD-L) by directly freeze-drying the mixture of OD-P and OD-L for hemostasis and postoperative antiadhesion. Polyphosphate and lauric acid significantly enhance the procoagulant property of the OD-P/OD-L sponge. The sponge has concentration-dependent mechanical strength and a good adhesion property to biological tissues. Besides, it has good biocompatibility and quick biodegradation without causing serious toxicity. Compared with commercial gelatin sponge, the optimized OD-P/OD-L sponge has much better hemostatic ability due to the combination of procoagulant property and wound sealing effect, showing less blood loss and shorter hemostasis time in animal bleeding models. In addition, the OD-P/OD-L sponge also demonstrates excellent antiadhesion properties in an abdomen-cecum adhesion model. This work provides a facile approach for designing hemostatic materials with integrated hemostasis and antiadhesion properties.

Hypoxia is a common feature of lung squamous cell carcinoma (LUSC), and hypoxia-inducible factor-1 (HIF-1) overexpression is associated with poor clinical outcome in LUSC. NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) is a recently identified target of HIF-1, but its roles in LUSC remain unclear. Herein, the expression and regulatory mechanisms of NDUFA4L2 were investigated in LUSC, and the influences on LUSC cell oxidative metabolism and survival of NDUFA4L2 were determined. The potential microRNA targeting to NDUFA4L2 was identified and its roles on LUSC cell were detected. We found that NDUFA4L2 were overexpressed in LUSC tissues, and that NDUFA4L2 expression correlated with shorter overall survival. NDUFA4L2 was regulated by HIF-1α under hypoxia, and NDUFA4L2 decreased mitochondrial reactive oxygen species (mitoROS) production through inhibiting mitochondrial complex I activity in LUSC cells. NDUFA4L2 silencing effectively suppressed LUSC cell growth and enhanced apoptosis by inducing mitoROS accumulation. Additionally, NDUFA4L2 was a target for miR-183-5p, and LUSC patients with high miR-183-5p levels had better prognoses. MiR-183-5p significantly induced mitoROS production and suppressed LUSC survival through negatively regulating NDUFA4L2 in vitro and in vivo. Our results suggested that regulation of NDUFA4L2 by HIF-1α is an important mechanism promoting LUSC progression under hypoxia. NDUFA4L2 inhibition using enforced miR-183-5p expression might be an effective strategy for LUSC treatment.

自21世纪以来,肺移植技术发展迅速,成为治疗各种终末期肺疾病患者的新策略.2020 年全球肺移植手术量已有2500例[1],我国接受肺移植手术的患者呈逐年增长趋势.截止2020年,我国双肺移植患者围术期生存率为80.5％,1年生存率为62.7％,仍低于其余器官移植水平[2].影响肺移植围术期生存率的原因包括感染、手术并发症、免疫排斥反应等,其中移植物的急性损伤直接影响患者术后短期生存率.移植器官的缺血/再灌注损伤(ischemia-reperfusion injury,IRI)是围术期移植物损伤的主要原因之一.导致和影响IRI的因素众多.近年来铁死亡作为一种新的细胞死亡方式,参与及影响了多种生物学行为,铁死亡被认为在越来越多的器官IRI过程中发挥作用[3-4].本综述旨在描述铁死亡在肺移植IRI中的研究进展,为提高肺移植术后患者短期生存率提供新思路.