Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

Objective To evaluate the efficacy and safety of the antibody-drug conjugate(ADC)vedotinumab combined with programmed cell death protein 1(PD-1)inhibitors as neoadjuvant therapy in patients with bladder cancer.Methods This retrospective study included 54 patients with bladder cancer who underwent neoadjuvant therapy at the Department of Urology,Peking University First Hospital,between Jun.2023 and Jun.2025.Among them,26 patients received vedotinumab combined with a PD-1 inhibitors,and 28 patients received gemcitabine plus cisplatin(GC).Clinical data,pathological complete response(pCR)rates,and pathological downstaging rates were collected.Treatment-related adverse events(TRAEs)were also assessed in both groups.Results There were no statistically significant differences between the two groups in terms of age,sex,smoking history,tumor grade and stage,depth of invasion,or human epidermal growth factor receptor 2(HER2)expression,indicating good baseline comparability(P＞0.05).The pCR rate in the vedotinumab plus PD-1 inhibitor group was 57.69％(15/26),significantly higher than that of the GC group at 25.00％(7/28)(P＜0.05).Pathological downstaging occurred in 5 patients in either group,with no statistically significant difference(P＞0.05).The main TRAEs in the vedotinumab plus PD-1 inhibitor group were peripheral sensory neuropathy and rash,and no grade 3-4 severe adverse events were observed.In contrast,the GC group predominantly experienced bone marrow suppression,with 4 cases of grade 3-4 adverse events.Conclusion Vedotinumab combined with PD-1 inhibitors demonstrated significantly superior efficacy and favorable safety compared with the conventional GC regimen as neoadjuvant therapy for bladder cancer.

Objective To evaluate the efficacy and safety of the antibody-drug conjugate(ADC)vedotinumab combined with programmed cell death protein 1(PD-1)inhibitors as neoadjuvant therapy in patients with bladder cancer.Methods This retrospective study included 54 patients with bladder cancer who underwent neoadjuvant therapy at the Department of Urology,Peking University First Hospital,between Jun.2023 and Jun.2025.Among them,26 patients received vedotinumab combined with a PD-1 inhibitors,and 28 patients received gemcitabine plus cisplatin(GC).Clinical data,pathological complete response(pCR)rates,and pathological downstaging rates were collected.Treatment-related adverse events(TRAEs)were also assessed in both groups.Results There were no statistically significant differences between the two groups in terms of age,sex,smoking history,tumor grade and stage,depth of invasion,or human epidermal growth factor receptor 2(HER2)expression,indicating good baseline comparability(P＞0.05).The pCR rate in the vedotinumab plus PD-1 inhibitor group was 57.69％(15/26),significantly higher than that of the GC group at 25.00％(7/28)(P＜0.05).Pathological downstaging occurred in 5 patients in either group,with no statistically significant difference(P＞0.05).The main TRAEs in the vedotinumab plus PD-1 inhibitor group were peripheral sensory neuropathy and rash,and no grade 3-4 severe adverse events were observed.In contrast,the GC group predominantly experienced bone marrow suppression,with 4 cases of grade 3-4 adverse events.Conclusion Vedotinumab combined with PD-1 inhibitors demonstrated significantly superior efficacy and favorable safety compared with the conventional GC regimen as neoadjuvant therapy for bladder cancer.

Objective:To investigate the current status of clinical leadership among Interventional Operating Room nurses in Shandong Province and to analyze its influencing factors.Methods:In December 2024, 220 Interventional Operating Room nurses from 46 ClassⅢ Grade A general hospitals in Shandong Province were selected for a cross-sectional survey using convenience sampling. General Information Questionnaire, Clinical Leadership Survey, Chinese version of Wong and Law Emotional Intelligence Scale (WLEIS-C) , and Jefferson Scale of Empathy-Health Professionals (JSE-HP) were used as survey instruments. Multiple linear regression was used to analyze the factors influencing clinical leadership among Interventional Operating Room nurses. Pearson correlation analysis was used to explore the relationship between emotional intelligence, empathy, and clinical leadership.Results:A total of 220 questionnaires were distributed and 204 valid questionnaires were recovered, with a valid recovery rate of 92.73% (204/220) . The clinical leadership scores of the 204 Interventional Operating Room nurses were (66.35±8.74) , and the dimensions scored, in descending order, as encouraging the heart, enabling others to act, modeling the way, inspiring a shared vision, and challenging the process. The mean scores of WLEIS-C and JSE-HP items were (5.88±0.90) and (4.61±0.63) , respectively. Multiple linear regression analysis showed that the nature of employment and whether or not they participated in leadership training were influencing factors for clinical leadership among Interventional Operating Room nurses (partial regression coefficients of -2.831 and -2.999, respectively; P<0.05) . Emotional intelligence and empathy ability among Interventional Operating Room nurses were positively correlated with clinical leadership ( P<0.05) . Conclusions:Clinical leadership of nurses in the Interventional Operating Room of ClassⅢ Grade A general hospitals in Shandong Province is at a moderate to high level. Nurses who participate in leadership training, have staffing, have greater empathy, and have higher emotional intelligence have greater clinical leadership. It is recommended that nursing administrators add leadership-related courses to the training of nurses in the Interventional Operating Room, and take steps to improve nurses' emotional intelligence and empathy ability, thereby promoting clinical leadership among Interventional Operating Room nurses.

Objective:To investigate the current status of clinical leadership among Interventional Operating Room nurses in Shandong Province and to analyze its influencing factors.Methods:In December 2024, 220 Interventional Operating Room nurses from 46 ClassⅢ Grade A general hospitals in Shandong Province were selected for a cross-sectional survey using convenience sampling. General Information Questionnaire, Clinical Leadership Survey, Chinese version of Wong and Law Emotional Intelligence Scale (WLEIS-C) , and Jefferson Scale of Empathy-Health Professionals (JSE-HP) were used as survey instruments. Multiple linear regression was used to analyze the factors influencing clinical leadership among Interventional Operating Room nurses. Pearson correlation analysis was used to explore the relationship between emotional intelligence, empathy, and clinical leadership.Results:A total of 220 questionnaires were distributed and 204 valid questionnaires were recovered, with a valid recovery rate of 92.73% (204/220) . The clinical leadership scores of the 204 Interventional Operating Room nurses were (66.35±8.74) , and the dimensions scored, in descending order, as encouraging the heart, enabling others to act, modeling the way, inspiring a shared vision, and challenging the process. The mean scores of WLEIS-C and JSE-HP items were (5.88±0.90) and (4.61±0.63) , respectively. Multiple linear regression analysis showed that the nature of employment and whether or not they participated in leadership training were influencing factors for clinical leadership among Interventional Operating Room nurses (partial regression coefficients of -2.831 and -2.999, respectively; P<0.05) . Emotional intelligence and empathy ability among Interventional Operating Room nurses were positively correlated with clinical leadership ( P<0.05) . Conclusions:Clinical leadership of nurses in the Interventional Operating Room of ClassⅢ Grade A general hospitals in Shandong Province is at a moderate to high level. Nurses who participate in leadership training, have staffing, have greater empathy, and have higher emotional intelligence have greater clinical leadership. It is recommended that nursing administrators add leadership-related courses to the training of nurses in the Interventional Operating Room, and take steps to improve nurses' emotional intelligence and empathy ability, thereby promoting clinical leadership among Interventional Operating Room nurses.

Objective To observe the value of 80 kVp combined with artificial intelligence iterative reconstruction(AIIR)in lower extremity CT angiography(CTA)of diabetic foot.Methods Sixty patients with diabetic foot were prospectively enrolled and divided into experimental group and control group(each n=30).Lower extremity CTA was performed using 80 kVp combined with AIIR in experimental group,while using 120 kVp combined with hybrid iterative reconstruction(HIR)in control group.The subjective and objective evaluation results of imaging quality,as well as the radiation dose of scanning were compared between groups.Results Compared with control group,images in experimental group showed higher subjective scores(5[5,5]vs.4[4,4]),displayed more branches of lower limb arteries(both P＜0.05),while the radiation dose decreased by 59.76％ ([8.29±0.53]mSv vs.[20.60±2.42]mSv).CT values,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of each lower extremity artery segments were higher,while the noise of each lower extremity artery segments in experimental group were lower than those in control group(all P＜0.05).Conclusion 80 kVp combined with AIIR could reduce radiation dose and improve imaging quality of lower extremity CTA of diabetic foot,hence being helpful to displaying small arteries of lower extremity,such as dorsalis pedis arteries and common plantar metatarsal arteries.

Objective To observe the value of 80 kVp combined with artificial intelligence iterative reconstruction(AIIR)in lower extremity CT angiography(CTA)of diabetic foot.Methods Sixty patients with diabetic foot were prospectively enrolled and divided into experimental group and control group(each n=30).Lower extremity CTA was performed using 80 kVp combined with AIIR in experimental group,while using 120 kVp combined with hybrid iterative reconstruction(HIR)in control group.The subjective and objective evaluation results of imaging quality,as well as the radiation dose of scanning were compared between groups.Results Compared with control group,images in experimental group showed higher subjective scores(5[5,5]vs.4[4,4]),displayed more branches of lower limb arteries(both P＜0.05),while the radiation dose decreased by 59.76％ ([8.29±0.53]mSv vs.[20.60±2.42]mSv).CT values,signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of each lower extremity artery segments were higher,while the noise of each lower extremity artery segments in experimental group were lower than those in control group(all P＜0.05).Conclusion 80 kVp combined with AIIR could reduce radiation dose and improve imaging quality of lower extremity CTA of diabetic foot,hence being helpful to displaying small arteries of lower extremity,such as dorsalis pedis arteries and common plantar metatarsal arteries.

Objective: To prospectively compare single-shot (SS) echo-planar imaging (EPI) and field-of-view optimized and constrained undistorted single-shot multiplexed sensitivity-encoding (FOCUS MUSE) for diffusion-weighted imaging (DWI) in evaluating thyroid-associated ophthalmopathy (TAO). Materials and Methods: SS EPI and FOCUS MUSE DWIs were obtained from 39 patients with TAO (18 male; mean ± standard deviation: 48.3 ± 13.3 years) and 26 healthy controls (9 male; mean ± standard deviation: 43.0 ± 18.5 years). Two radiologists scored the visual image quality using a 4-point Likert scale. The image quality score, signal-to-noise ratio (SNR), contrast-tonoise ratio (CNR), and apparent diffusion coefficient (ADC) of extraocular muscles (EOMs) were compared between the two DWIs. Differences in the ADC of EOMs were also evaluated. The performance of discriminating active from inactive TAO was assessed using receiver operating characteristic curves. The correlation between ADC and clinical activity score (CAS) was analyzed using Spearman correlation. Results: Compared with SS EPI DWI, FOCUS MUSE DWI demonstrated significantly higher image quality scores (P < 0.001), a higher SNR and CNR on the lateral rectus muscle (LRM) and medial rectus muscle (MRM) (P < 0.05), and a non-significant difference in the ADC of the LRM and MRM. Active TAO showed higher ADC than inactive TAO and healthy controls with both SS EPI and FOCUS MUSE DWIs (P < 0.001). Inactive TAO and healthy controls did not show a significant ADC difference with both DWIs. Compared with SS EPI DWI, FOCUS MUSE DWI demonstrated better discrimination of active from inactive TAO (AUC:0.925 vs. 0.779; P = 0.007). The ADC was significantly correlated with CAS in SS EPI DWI (r = 0.391, P < 0.001) and FOCUS MUSE DWI (r = 0.645, P < 0.001). Conclusion FOCUS MUSE DWI provides better images for evaluating EOMs and better performance in diagnosing active TAO than SS EPI DWI. The application of FOCUS MUSE will facilitate the DWI evaluation of TAO.

Objective:To investigate the relationship between the LAMA2 gene expression and the survival time of cancer patients, tumor microenvironment, tumor immune cell infiltration, and the immunotherapy responsiveness in pan-cancer. Methods:Download the expression data matrix and the clinical data from TCGA and IMvigor210, furthermore analyze the correlation between the expression level of LAMA2 and survival time, tumor microenvironment, and immunotherapy responsiveness by R and perform the gene set enrichment analysis of LAMA2 in pan-cancer to explore the related pathways. The Wilcoxon test was used to compare the expression difference of LAMA2 between tumor tissues and normal tissues. Kaplan-Meier method was used for survival analysis, and univariate COX regression analysis was used to evaluate the risk ratio relationship of LAMA2 in various tumors. Spearman correlation analysis was used to evaluate the correlation between the expression level of LAMA2 and tumor microenvironment immune score, as well as immune cell infiltration. Pearson correlation analysis was used to evaluate the correlation between the immunotherapy responsiveness and the expression level of LAMA2. Results:Compared with normal tissues, the expression level of LAMA2 was significantly decreased in most cancer types. In addition, the up-regulation or down-regulationand of LAMA2 expression may indicate the prognosis of patients. Univariate COX regression analysis showed that LAMA2 was significantly associated with prognosis in bladder cancer, renal papillary cell carcinoma, adrenocortical carcinoma, and so on. LAMA2 expression level was also significantly correlated with tumor microenvironment score, immune score and stromal score. Furthermore, the expression level of LAMA2 was correlated with the infiltration of tumor immune cells, including B cell, CD8 + T cell, regulatory T cell, mast cell, and so on. The results of gene set enrichment analysis show that the LAMA2 was mostly involved in the biological process of ion channels, gene expression, and skeletal muscle movement. LAMA2 expression was also associated with tumor mutation burden, microsatellite instability, and cell programmed death-ligand 1 immunotherapy responsiveness. Conclusions:LAMA2 has predictive value for survival and prognosis of patients in tumors, and is significantly correlated with tumor microenvironment, immune cell infiltration, tumor microenvironment, immunotherapy responsiveness, etc. As a potential tumor marker, LAMA2 provides a new direction for tumor prognosis judgment and treatment selection.

Objective To investigate the value of radiomics nomogram model based on enhanced CT for predicting postoperative pancreatic fistula(POPF)in patients undergoing pancreaticoduodenectomy(PD).Methods The clinical and abdominal imaging data of 82 patients who underwent PD were analyzed retrospectively.They were divided into training set and validation set at a ratio of 3∶2.In the venous phase of CT,the maximum slice of the pancreatic duct was selected to delineate the region of interest(ROI),and the features were extracted and screened to construct the radiomics model.The independent risk factors associated with POPF were screened by univariate and multivariable logistic regression analyses to construct the clinical model.A nomogram model was created by combining Radiomics score(Radscore)and clinical risk factors.The diagnostic performance of the model was verified by the vali-dation set.Results The nomogram model demonstrated significant predictive power,with an area under the curve(AUC)of 0.862 and 0.806 in the training set and validation set,respectively.Conclusion The nomogram model exhibits excellent predictive performance and outperforms the clinical model and radiomics model in predicting POPF,which can provide important guidance for clinical deci-sion-making.