ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectiveThe present study aimed to investigate alterations in white matter microstructure and spontaneous neural activity in male college smokers, and to further explore their associations with nicotine dependence. Given that adolescence and early adulthood represent critical periods for brain maturation, particularly for white matter development, understanding the neural correlates of smoking behavior during this stage is of substantial importance for both neuroscience and public health. MethodsA total of 115 male undergraduate students were initially recruited for this study. After quality control and exclusion procedures, 52 male college smokers and 42 demographically matched healthy non-smokers were included in the final analysis. All participants underwent multimodal magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI) and resting-state functional MRI (rs-fMRI). White matter fiber tracts were reconstructed using the automated fiber quantification (AFQ) method, which enables precise identification and quantification of major fiber bundles. Eighteen major white matter tracts were segmented for each participant. Along the core trajectory of each tract, 100 equidistant nodes were sampled. Fractional anisotropy (FA) was calculated at each node to assess white matter microstructural integrity, while amplitude of low-frequency fluctuation (ALFF) was computed to evaluate spontaneous neural activity within white matter tracts. Between-group differences in FA and ALFF were assessed using two-sample t-tests, with appropriate corrections applied for multiple comparisons. Furthermore, Pearson correlation analyses were conducted to examine the relationships between imaging-derived metrics (FA and ALFF values in regions showing significant group differences) and nicotine dependence severity, as measured by the Fagerström test for nicotine dependence (FTND). ResultsCompared with healthy non-smokers, male college smokers exhibited significantly increased FA values in several white matter tracts, including the left thalamic radiation, right corticospinal tract, forceps major of the corpus callosum, left uncinate fasciculus, and right arcuate fasciculus. These findings suggest altered microstructural organization or increased directional coherence within these pathways. In addition, smokers demonstrated significantly elevated ALFF values in the forceps major, right uncinate fasciculus, and left arcuate fasciculus, indicating enhanced spontaneous neural activity in these white matter regions. Correlation analyses revealed that FA values in the left thalamic radiation and right corticospinal tract were negatively correlated with FTND scores, suggesting that higher levels of nicotine dependence were associated with reduced microstructural integrity or altered fiber organization in these regions. In contrast, ALFF values in the forceps major and right uncinate fasciculus were positively correlated with FTND scores, indicating that greater nicotine dependence was associated with increased spontaneous neural activity in specific white matter pathways. ConclusionThe present study provides evidence that male college smokers exhibit distinct alterations in both white matter microstructure and functional activity. These abnormalities are not uniformly distributed but rather localized to specific fiber tracts implicated in sensorimotor processing, interhemispheric communication, and higher-order cognitive and emotional regulation. Importantly, the observed associations between imaging metrics and nicotine dependence severity suggest that these structural and functional alterations may reflect neurobiological mechanisms underlying addiction. The combination of AFQ-based tract profiling and multimodal MRI offers a sensitive approach for detecting subtle changes along white matter pathways, highlighting its potential utility in identifying neuroimaging biomarkers of nicotine dependence. Overall, these findings indicate that smoking during early adulthood may disrupt ongoing white matter maturation, potentially leading to long-term consequences for brain function. This study provides novel insights into the neural basis of nicotine dependence and underscores the importance of early intervention and prevention strategies targeting young smokers.

Objective To investigate the risk factors for ICU-acquired weakness (ICU-AW) in patients with sepsis, and to construct a nomogram prediction model. Methods A total of 360 patients with sepsis admitted from January 2020 to December 2025 were enrolled as study subjects. The risk factors for ICU-AW were identified by logistic regression analysis. A nomogram prediction model was constructed, and the model was validated. Results Multivariate logistic regression analysis indicated that age, APACHE II score, duration of mechanical ventilation, duration of immobilization, duration of sedation, and NLR were risk factors for the occurrence of ICU-AW (P<0.05), while ALB was a protective factor (P<0.05). A nomogram model was constructed based on these seven variables. After validation via Bootstrap resampling, ROC curve showed an AUC of 0.949 (0.929–0.969) and a corrected AUC of 0.942 (0.940–0.948), indicating good discrimination degree of the model. Hosmer-Lemeshow test for calibration curve revealed a chi-square value of 10.188 (P=0.252), suggesting that the predicted value of fitting was generally consistent with the actual value. Decision curve analysis demonstrated that when the threshold was in the range of 0.05–0.9, the model had a good net benefit. Conclusion The nomogram prediction model for sepsis ICU-AW based on seven indicators including age, APACHE II score, NLR, ALB, and the durations of mechanical ventilation, immobilization, and sedation exhibits good predictive efficiency and stability. This nomogram prediction model is helpful for the clinical rapid screening of ICU-AW high-risk groups in patients with sepsis, and meets clinical needs for early warning and precise prevention and control.

Objective: To analyze the epidemiological characteristics of infectious diseases among children and adolescents in Lanshan District, Linyi City, 2014-2023,so as to provide a scientific basis for prevention and control strategies in schools. Methods: The surveillance data were obtained from the China Information System for Disease Control and Prevention (CISDCP). Data on reported infectious disease cases and related demographic information among school children and kindergarteners in the study area from 2014 to 2023 were collected. Rate comparison was performed by using the χ 2 test. Trend analysis was conducted by using Joinpoint Regression Progrom, and the annual percent change (APC) and average annual percent change (AAPC) were calculated. Results: A total of 10 222 cases of infectious diseases among children and adolescents were reported from 2014 to 2023, with an average annual incidence rate of 273.32 per 100 000. The overall incidence trend remained stable from 2014 to 2023 (AAPC=12.33%, 95%CI=-2.63%-29.59%, P >0.05). Whereas a significant upward trend was observed from 2014 to 2019 (AAPC=37.08%, 95% CI =12.92%-66.41%, P <0.05), followed by a stable trend from 2019 to 2023 (AAPC=-0.31%, 95%CI=-39.70%-64.83%, P>0.05). Seasonal distribution exhibited dual peaks in summer and winter. The incidence rate in urban areas(707.29/100 000) was significantly higher than that in rural areas(257.50/100 000), and the incidence rate among kindergarteners (325.49/100 000) was higher than that among school children (257.07/100 000) (χ2=1 518.60, 116.36, both P<0.01). The reported infectious diseases among children and adolescents were predominantly respiratory and intestinal infectious diseases, with incidence rates of 156.13/100 000 and 108.51/100 000, respectively. Hand, foot, and mouth disease (HFMD) was the predominant infectious disease among kindergarteners, accounting for 47.51%. Influenza was the leading condition in the primary school group, accounting for 38.64%, and other infectious diarrheal diseases were most common in junior and senior high school group, accounting for 53.34%. The top six diseases by incidence rate were other infectious diarrheal diseases(65.22/100 000), influenza(63.24/100 000), varicella(46.34/100 000), HFMD(41.07/100 000), mumps(23.42/100 000), and scarlet fever(10.56/100 000). Among them, the incidence of other infectious diarrheal diseases rose significantly (AAPC=35.31%, 95% CI =14.32%-60.14%, P <0.01). The trend transitioned from a rapid escalation during 2014-2019 (APC=69.98%, 95% CI =17.58%-145.74%, P =0.01) to a stable phase during 2019-2023 (APC=1.74%, 95% CI =-15.61%- 22.66%, P >0.05). Conclusions In Lanshan, urban educational institutions should prioritize the prevention and control of infectious diseases, with particular emphasis on other infectious diarrheal diseases, influenza and varicella. Targeted interventions should be implemented in accordance with seasonal patterns and the specific characteristics of the school age populations.

Lung cancer has the highest incidence and mortality among malignant tumors in China.Persistent subsolid nodules(SSNs)are closely associated with early-stage lung adenocarcinoma.Artificial intelligence(AI),as an emerging technology,is capable of performing in-depth analysis of large-scale imaging data through autonomous learning and possesses the ability to predict outcomes from new data,demonstrating great potential and application prospects in the assessment of SSNs.AI can not only effectively assist radiologists in diagnosis and treatment,but also improve work efficiency while reducing misdiagnosis and missed diagnosis rates.This review summarizes the recent applications and research progress of AI in the assessment of SSNs,to provide new insights for the diagnosis and treatment of SSNs.

Objective To propose a high-precision deep learning-based image assessment method of osteosarcoma chemotherapy efficacy for clinical treatment,as existing methos have low accuracy of osteosarcoma assessment.Methods The low incidence of osteosarcoma led to the small scale of its imaging data and the problem of imbalance in data categories.This study combined deep learning with clinical medical information,combined the bone sarcoma generation module of BoneGAN and the scale lesion information capture module,and proposed OMLA-Net,a deep learning assessment network for chemotherapy effect of bone sarcoma based on multi-scale lesion attention network,which achieved computer-aided bone tumor assessment with integrated data augmentation and focused lesion information through pre-training and generalized loss training.Results In this study,40 cases of osteosarcoma MRI data were used as the basis for the comparison test on the generated dataset,and the OMLA-Net assessment outperformed the SOTA method Conv-LSTM-GAN in terms of the assessment effects such as accuracy and F1 scores,and the difference was statistically significant(Bootstrap statistical method P＜0.05);the subsequent K-fold cross-validation ablation experiments further demonstrated the effectiveness of each module proposed by OMLA-Net.Conclusion OMLA-Net can effectively perform the impact assessment of chemotherapy effect on osteosarcoma,which provides a new idea for subsequent clinical application.

Objective To discuss the causes and the therapeutic strategy of acute cardiac tamponade(ACT)occurring as a complication of transcatheter aortic valve replacement(TAVR)so as to improve the success rate of the surgery and to make a further understanding of this complication.Methods The general clinical data,surgical procedures,and postoperative follow-up results of five patients,who received TAVR at the Affiliated Northern Jiangsu People's Hospital of Yangzhou University of China and developed ACT from March 2018 to September 2024,were retrospectively analyzed.Results After developing ACT,all the 5 patients received pericardiocentesis together with other adjuvant therapies including blood volume expansion with infusion,vasopressors,heparin neutralization,and blood transfusion.However,due to no obvious reduction in drainage volume and unstable hemodynamics all the 5 patients had eventually to receive open-chest surgery to identify the source of bleeding and to make hemostasis.Surgical exploration revealed that the perforation or rupture of cardiac structures caused by the temporary pacemaker lead or a super-stiff guide wire during the procedure was the main cause of ACT.Finally,after active treatment four patients recovered and discharged,and one patient died.The discharged patients were followed up for 3-12 months,and no procedure-related complications such as acute coronary artery occlusion,severe arrhythmia,exacerbation of heart failure symptoms,valve displacement,or stroke occurred.Conclusion As a severe complication occurring during the TAVR procedure,ACT requires to get a rapid diagnosis and management.Improvement of surgical techniques and operative methods,comprehensive preoperative assessment,and close intraoperative monitoring are crucial points for the prevention of ACT.

Catheter-based percutaneous coronary intervention has become a crucial approach for treating obstructive coronary artery disease and is widely applied in clinical practice.Although the new generation of drug-eluting stents(DES)has significantly reduced the incidence of post-procedur-al restenosis and improved long-term clinical outcomes,in-stent restenosis(ISR)remains one of the key challenges affecting the long-term efficacy of percutaneous coronary intervention.Recent studies have demonstrated that DES still have certain inherent limitations.From the metallic stent platform,drug coating to the polymer carrier,each component may exert varying degrees of biological effects on the vascular intima.Optical coherence tomography(OCT),as a high-resolution intravascular imaging technique,has shown significant value in the mechanism research,etiological diagnosis,and clinical classification of ISR.It can clearly identify the tissue composition and morphological characteristics of ISR,providing a precise basis for the formulation of individualized treatment strategies.This review aimed to systematically search the existing literature,comprehensively review the clinical and patho-logical features of ISR after DES implantation,focus on the OCT-based ISR classification system,and summarize the current treatment strategies and latest advances for ISR.

Objective:To explore the changes in nutritional status and body composition of cervical cancer patients during concurrent chemoradiotherapy (CCRT) and their correlation with CCRT toxicities.Methods:In this prospective and observational clinical study, eligible treatment -na?ve patients with stage IB-IV primary cervical cancer were consecutively enrolled in the Department of Radiotherapy of Peking Union Medical College Hospital from September 2022 to August 2023. The patients were screened for nutritional risks, received dietary assessment, and were measured for body composition using multi-frequency bioelectrical impedance at baseline (prior to treatment), 4 weeks, and 8 weeks since treatment initiation. Insufficient muscle mass was diagnosed ccording to the Asian Working Group for Sarcopenia 2019 criteria. The severity of nausea, vomiting, abdominal pain, diarrhea, and hematological toxicity was assessed by the U.S. National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).Results:A total of 109 patients were included. At baseline, there were 11 (10.1%) patients who were lean, 17 (15.6%) patients with insufficient muscle mass, and 28 patients (25.7%) at nutritional risk; at Week 8 of CCRT, patients at nutritional risk increased to 61 (56.0%). Compared to baseline, weight [(59.34±9.67) kg vs. (61.30±9.64) kg, P<0.001], skeletal muscle index [SMI, (6.15±0.74) kg/m 2vs. (6.39±0.74) kg/m 2, P<0.001], body fat percentage [(31.13±7.67) % vs. (32.07±7.70) %, P=0.004] were significantly decreased at Week 8 of CCRT. Besides, ≥10% SMI loss was only related to baseline body fat percentage ( HR=0.216, 95% CI: 0.001-0.724, P=0.038), but not related to age, nutritional status, or muscle mass (all P>0.05). At baseline and 8 weeks since CCRT, 8 (28.6%) and 40 (65.6%) patients at nutritional risk received nutritional support, respectively. During CCRT, the rates of grade ≥2 nausea and vomiting, diarrhea, and grade 3/4 hematological toxicity were 37.6%, 28.4% and 44.0%, respectively. Baseline nutritional risk was a risk factor for diarrhea ( HR=2.447, 95% CI: 1.017-6.068, P=0.047), and an advanced International Federation of Gynecology and Obstetrics (FIGO) stage was a risk factor for severe nausea and vomiting ( HR=1.735, 95% CI: 1.005-2.995, P=0.048). Patients presenting with severe nausea and vomiting had more significant reductions in body mass index [(-1.44±1.29) kg/m 2vs. (-0.59±0.84) kg/m 2, P<0.001] and SMI [(-0.37±0.41) kg/m 2vs. (-0.12±0.27) kg/m 2, P=0.013] compared to those without nausea and vomiting, while there was no significant difference in visceral fat area between these two groups [(-9.95±19.48) cm 2vs. (-5.12±15.79) cm 2, P=0.161]. Conclusions:Patients with cervical cancer have increased nutritional risk and more loss of body weight and muscle mass during CCRT. The presence of nutritional risk at baseline is a risk factor for diarrhea, while nausea and vomiting exacerbate the losses of body weight, muscle, and fat. Close monitoring, intensive symptomatic therapy, and appropriate nutritional interventions should be performed in the clinical setting to improve patients' tolerance of treatment and maintenance of body weight.