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.

Three common faults of Siemens SOMATOM Force Dual Source CT were investigated in terms of phenomenon,cause,troubleshooting measure and maintenance experience.References were provided for treating similar faults.[Chinese Medical Equipment Journal,2025,46(9):114-117]

Objective:To explore the influence of value orientation brief therapy (VBT) on anxiety and depression symptoms, social function, coping style and self-acceptance level of major depressive disorder adolescents with anxious distress.Methods:From June 2021 to June 2022, seventy adolescent major depressive disorder patients with anxious distress were included in the study, who were randomly divided into study group(35 people, 31 people completed)and control group (35 people, 30 people completed). The study group was given routine treatment combined with VBT, while the control group was given routine treatment only. Before and after treatment, Hamilton anxiety scale(HAMA), Hamilton depression scale (HAMD), social disability screening schedule (SDSS), coping style questionnaire(CSQ) and self-acceptance questionnaire (SAQ) were used to evaluate the two groups, and SPSS 26.0 software was used to statistically analyze the data of the two groups. Paired sample t-test was used for intra-group comparison, and independent sample t-test was used for inter-group comparison. Results:After 6 weeks of treatment, the scores of HAMA((6.03±3.58) vs (14.03±7.06), t=5.55, P<0.01), HAMD((8.77±5.52 ) vs (16.50±7.59), t=4.56, P<0.01)and SDSS((4.23±1.50) vs (6.63±0.96), t=7.43, P<0.01)in the study group were significantly lower than those in the control group, the differences were statistically significant. The scores of self-acceptance((19.23±1.33) vs (13.47±1.46), t=-16.12, P<0.01)and self-evaluation ((19.87±2.87) vs (12.77±1.68), t=-11.75, P<0.01) in the SAQ scale and the scores of problem-solving((8.71±2.30) vs (6.23±3.45), t=3.31, P<0.05) and rationalization ((6.20±3.11) vs (4.67±2.43), t=2.13, P<0.05) in the CSQ questionnaire were significantly higher than those in the control group, the differences were statistically significant. The total effective rate of the study group(90.3%(28/31) vs 66.7%(20/30), χ2=5.09, P<0.05) was significantly higher than that of the control group, the difference was statistically significant. Conclusion:The effect of routine treatment combined with VBT is better, which can effectively improve anxiety and depression symptoms, social function and coping style, and enhance self-acceptance and self-evaluation in adolescent major depressive disorder patients, which is worthy of clinical application.

Objective To observe the effect of the self-made reverse leveling device for assisting CT-guided puncture of phantom.Methods The reverse leveling device was made using protractor base,leveling bubble,puncture needle fixator,protractor and protractor pointer,and a puncture phantom was self-made with 18K foam plastic.Using a random function to set the puncture angle,3 physicians performed each 50 punctures at different angles respectively on the puncture phantom without assistance(control group)or under assistance of the self-made reverse leveling device(experimental group),and the absolute values of the errors in angles of puncture needle at head-foot and left-right directions measured on CT among 3 physicians were observed and compared between groups.Taken the absolute values of puncture angle errors at head-foot and left-right directions both≤3° as criteria of qualified puncture,the puncture qualification rates were calculated and compared between groups.Results There was no significant difference of the absolute values of puncture angle error at head-foot or left-right direction with or without assistance among 3 physicians(all P＞0.05).In experimental group,the absolute values of puncture angle error at head-foot and left-right directions were all lower than(both P＜0.001),while the puncture qualification rate was higher than those in control group(52.00%[78/150]vs.4.67%[7/150],χ2=82.752,P＜0.001).Conclusion The self-made reverse leveling device could improve the accuracy of CT-guided puncture of phantom.

In recent years,organs-on-chips(OOCs)technology has gradually matured and been recognized by regulatory agencies,playing a key role in the construction of pathophysiological models,pharmacodynamic screening,toxicological evaluation and other fields,providing guidance for the research and development of innovative drugs of Chinese materia medica and the clinical application of classic prescriptions.This article reviewed the application progress of OOCs technology in the research of Chinese materia medica from four dimensions:pharmacodynamic and toxicological evaluation,quality control,active component analysis and innovative drug research and development,in order to provide a reference for the precise application of this technology in the field of Chinese materia medica.

BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

BACKGROUND: Neoadjuvant chemoradiotherapy followed by radical surgery has been a common practice for patients with locally advanced rectal cancer, but the response rate varies among patients. This study aimed to develop a ResNet-Vision Transformer based magnetic resonance imaging (MRI)-endoscopy fusion model to precisely predict treatment response and provide personalized treatment. METHODS: In this multicenter study, 366 eligible patients who had undergone neoadjuvant chemoradiotherapy followed by radical surgery at eight Chinese tertiary hospitals between January 2017 and June 2024 were recruited, with 2928 pretreatment colonic endoscopic images and 366 pelvic MRI images. An MRI-endoscopy fusion model was constructed based on the ResNet backbone and Transformer network using pretreatment MRI and endoscopic images. Treatment response was defined as good response or non-good response based on the tumor regression grade. The Delong test and the Hanley-McNeil test were utilized to compare prediction performance among different models and different subgroups, respectively. The predictive performance of the MRI-endoscopy fusion model was comprehensively validated in the test sets and was further compared to that of the single-modal MRI model and single-modal endoscopy model. RESULTS: The MRI-endoscopy fusion model demonstrated favorable prediction performance. In the internal validation set, the area under the curve (AUC) and accuracy were 0.852 (95% confidence interval [CI]: 0.744-0.940) and 0.737 (95% CI: 0.712-0.844), respectively. Moreover, the AUC and accuracy reached 0.769 (95% CI: 0.678-0.861) and 0.729 (95% CI: 0.628-0.821), respectively, in the external test set. In addition, the MRI-endoscopy fusion model outperformed the single-modal MRI model (AUC: 0.692 [95% CI: 0.609-0.783], accuracy: 0.659 [95% CI: 0.565-0.775]) and the single-modal endoscopy model (AUC: 0.720 [95% CI: 0.617-0.823], accuracy: 0.713 [95% CI: 0.612-0.809]) in the external test set. CONCLUSION The MRI-endoscopy fusion model based on ResNet-Vision Transformer achieved favorable performance in predicting treatment response to neoadjuvant chemoradiotherapy and holds tremendous potential for enabling personalized treatment regimens for locally advanced rectal cancer patients.
Humans ; Rectal Neoplasms/diagnostic imaging* ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Middle Aged ; Neoadjuvant Therapy/methods* ; Aged ; Adult ; Chemoradiotherapy/methods* ; Endoscopy/methods* ; Treatment Outcome

Purpose: This study aimed to assess the impact of aerobic exercise at different intensities over an eight-week period on the expression and activation of cortical synaptic proteins, with the potential to reduce anxiety and improve memory in young mice. Methods: Seven-week-old C57BL/6 mice were subjected to treadmill exercises at low (n = 10), moderate (n = 10), and high intensity (n = 10) for eight weeks. Behavioral assessments were conducted to evaluate anxiety and cognitive function. To explore the underlying mechanisms, we measured the phosphorylated levels of extracellular signal-regulated kinase (ERK), cyclic adenosine monophosphate response-binding protein (CREB), protein kinase (AKT), adenosine monophosphate activated protein kinase (AMPK), synapsin (S9, S549, S609), and PSD-95 in the cortex, as these are associated with synaptic strength. Additionally, the expression of doublecortin (DCX), a neurogenic factor, was analyzed in the hippocampus. Results: Exercise led to reductions in depressive and anxiety-related behaviors and elevated the levels of phosphorylated ERK, CREB, AKT, AMPK, synapsin (S9, S549, S609), and PSD-95 in the cortex of young mice. Furthermore, exercise increased DCX expression in the hippocampus. Moderate-intensity exercise yielded more pronounced effects than other intensities. Conclusion The findings of this research indicate that consistent moderate-intensity exercise increases synaptic strength and reduces depression and anxiety in young mice by activating multiple factors.

Purpose: This study aimed to assess the impact of aerobic exercise at different intensities over an eight-week period on the expression and activation of cortical synaptic proteins, with the potential to reduce anxiety and improve memory in young mice. Methods: Seven-week-old C57BL/6 mice were subjected to treadmill exercises at low (n = 10), moderate (n = 10), and high intensity (n = 10) for eight weeks. Behavioral assessments were conducted to evaluate anxiety and cognitive function. To explore the underlying mechanisms, we measured the phosphorylated levels of extracellular signal-regulated kinase (ERK), cyclic adenosine monophosphate response-binding protein (CREB), protein kinase (AKT), adenosine monophosphate activated protein kinase (AMPK), synapsin (S9, S549, S609), and PSD-95 in the cortex, as these are associated with synaptic strength. Additionally, the expression of doublecortin (DCX), a neurogenic factor, was analyzed in the hippocampus. Results: Exercise led to reductions in depressive and anxiety-related behaviors and elevated the levels of phosphorylated ERK, CREB, AKT, AMPK, synapsin (S9, S549, S609), and PSD-95 in the cortex of young mice. Furthermore, exercise increased DCX expression in the hippocampus. Moderate-intensity exercise yielded more pronounced effects than other intensities. Conclusion The findings of this research indicate that consistent moderate-intensity exercise increases synaptic strength and reduces depression and anxiety in young mice by activating multiple factors.