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.

Jiegengtang is a basic formula for treating sore throat and cough. By means of bibliometrics， this study conducted a textual research and analysis on the key information such as formula origin， decocting methods， and clinical application of Jiegengtang. After the research， it can be seen that Jiegengtang is firstly contained in Treatise on Febrile and Miscellaneous Disease， which is also known as Ganjietang， and it has been inherited and innovated by medical practitioners of various dynasties in later times. The origins of Chinese medicines in this formula is basically clear， Jiegeng is the dried roots of Platycodon grandiflorum， Gancao is the dried roots and rhizomes of Glycyrrhiza uralensis， the two medicines are selected raw products. The dosage is 27.60 g of Glycyrrhizae Radix et Rhizoma and 13.80 g of Platycodonis Radix， decocted with 600 mL of water to 200 mL， taken warmly after meals， twice a day， 100 mL for each time. In ancient times， Jiegengtang was mainly used for treating Shaoyin-heat invasion syndrome， with cough and sore throat as its core symptoms. In modern clinical practice， Jiegengtang is mainly used for respiratory diseases such as pharyngitis， esophagitis， tonsillitis and lung abscess， especially for pharyngitis and lung abscess with remarkable efficacy. This paper can provide literature reference basis for the modern clinical application and new drug development of Jiegengtang.

Jiegengtang is a basic formula for treating sore throat and cough. By means of bibliometrics， this study conducted a textual research and analysis on the key information such as formula origin， decocting methods， and clinical application of Jiegengtang. After the research， it can be seen that Jiegengtang is firstly contained in Treatise on Febrile and Miscellaneous Disease， which is also known as Ganjietang， and it has been inherited and innovated by medical practitioners of various dynasties in later times. The origins of Chinese medicines in this formula is basically clear， Jiegeng is the dried roots of Platycodon grandiflorum， Gancao is the dried roots and rhizomes of Glycyrrhiza uralensis， the two medicines are selected raw products. The dosage is 27.60 g of Glycyrrhizae Radix et Rhizoma and 13.80 g of Platycodonis Radix， decocted with 600 mL of water to 200 mL， taken warmly after meals， twice a day， 100 mL for each time. In ancient times， Jiegengtang was mainly used for treating Shaoyin-heat invasion syndrome， with cough and sore throat as its core symptoms. In modern clinical practice， Jiegengtang is mainly used for respiratory diseases such as pharyngitis， esophagitis， tonsillitis and lung abscess， especially for pharyngitis and lung abscess with remarkable efficacy. This paper can provide literature reference basis for the modern clinical application and new drug development of Jiegengtang.

Brain’s neural activities encompass both periodic rhythmic oscillations and aperiodic neural fluctuations. Rhythmic oscillations manifest as spectral peaks of neural signals, directly reflecting the synchronized activities of neural populations and closely tied to cognitive and behavioral states. In contrast, aperiodic fluctuations exhibit a power-law decaying spectral trend, revealing the multiscale dynamics of brain neural activity. In recent years, researchers have made notable progress in studying brain aperiodic dynamics. These studies demonstrate that aperiodic activity holds significant physiological relevance, correlating with various physiological states such as external stimuli, drug induction, sleep states, and aging. Aperiodic activity serves as a reflection of the brain’s sensory capacity, consciousness level, and cognitive ability. In clinical research, the aperiodic exponent has emerged as a significant potential biomarker, capable of reflecting the progression and trends of brain diseases while being intricately intertwined with the excitation-inhibition balance of neural system. The physiological mechanisms underlying aperiodic dynamics span multiple neural scales, with activities at the levels of individual neurons, neuronal ensembles, and neural networks collectively influencing the frequency, oscillatory patterns, and spatiotemporal characteristics of aperiodic signals. Aperiodic dynamics currently boasts broad application prospects. It not only provides a novel perspective for investigating brain neural dynamics but also holds immense potential as a neural marker in neuromodulation or brain-computer interface technologies. This paper summarizes methods for extracting characteristic parameters of aperiodic activity, analyzes its physiological relevance and potential as a biomarker in brain diseases, summarizes its physiological mechanisms, and based on these findings, elaborates on the research prospects of aperiodic dynamics.

Objective:To assess the impact of vaporized hydrogen peroxide (VHP) on the terminal decontamination effectiveness following the spillage of infectious materials in a BSL-3 laboratory.Methods:Within BSL-3 laboratories with volumes of 92.5 m 3 and 218 m 3, two types of Geobacillus stearothermophilus spore strips were used as biological indicators. ATCC7953 was affixed to stainless steel strips, while ATCC12980 was applied to paper strips. The strips were soaked in cell culture medium and chicken embryo egg fluid to simulate minor spill models. While strips continuously immersed in cell culture medium or chicken embryo egg fluid served as major spill models. These were compared against untreated biological indicator strips to evaluate the terminal decontamination efficacy of VHP. Results:After the completion of terminal disinfection, in laboratories of different volumes and at various sampling points, the culture result of both types of bacterial strips from the minor spill models and the untreated control strips were all negative. In the major spill models, the positivity rate of the two types of bacterial strips soaked in cell culture medium was 75%, while the positivity rate of the two types of bacterial strips soaked in chicken embryo egg fluid was 100%.Conclusions:In the event of a large spill of infectious materials in a laboratory, to ensure biosafety, it is recommended to first treat the spilled materials before initiating the terminal disinfection process. Additionally, under the same disinfection conditions, the material of the biological indicator strips does not affect the terminal disinfection outcomes.

Objective:To apply artificial intelligence（AI）in classifying ovarian tumors on ultrasound images，and compare the diagnostic results of several sonographers with varying seniority levels.Methods:A total of 645 patients diagnosed with adnexal masses via gynecological ultrasound examination at Qilu Hospital of Shandong University from January 2021 to December 2024 were enrolled. Three deep learning architectures，i.e.，Alexnet，Densenet121，and Resnet50 were developed and used to internally test the classification effectiveness of ovarian tumors，while the optimal model was selected for external testing. Two junior sonographers and two senior sonographers were recruited to independently diagnose ovarian tumors in the external test dataset. Subsequently，the benign and malignant results of the model's predictions were disclosed to each sonographer，and their revised diagnoses on the same external test data in combination with the best AI model were recorded.Results:The optimal model achieved an accuracy of 0.941，sensitivity of 0.936，and specificity of 0.944 on the internal test dataset，and maintained robust performance on the external test dataset with accuracy of 0.891，sensitivity of 0.880，and specificity of 0.907. Compared to junior sonographers，the optimal model demonstrated significantly higher sensitivity in discriminating benign from malignant ovarian tumors（0.880 vs. 0.723，0.602；all P<0.05）. No statistically significant difference was observed in diagnostic accuracy between the optimal model and senior sonographer 1（ P=0.05）. With assistance from the optimal model，junior sonographers achieved significant improvements in both sensitivity and specificity（sensitivity：0.723 vs. 0.843，0.602 vs. 0.819；specificity：0.778 vs. 0.833，0.685 vs. 0.741；all P<0.05）. Conclusions:The optimal model achieves comparable performance to that of senior sonographers in ovarian tumor classification. With model assistance，the diagnostic performance of junior sonographers is significantly improved.

Objective:To analyze the efficacy of the modified vertical superomedial five-flap reductive mammoplasty in patients with macromastia.Methods:A total of 31 female patients (62 breasts) with moderate-to-severe macromastia, aged 18-45 (36±6) years, were retrospectively included in the Department of Plastic Surgery, Sichuan Provincial People′s Hospital from October 2021 to October 2023. All patients underwent the modified vertical superomedial five-flap technique for breast reduction. Postoperative follow-up lasted for one year. Scar status was evaluated using the Vancouver scar scale (VSS), while patient satisfaction and breast morphology were assessed with the Chinese version of the Breast-Q questionnaire and the breast morphology score. Postoperative improvements in areolar diameter, nipple-to-inframammary fold midpoint distance, and nipple-to-suprasternal notch distance were compared with preoperative measurements. Adverse events, including sensory abnormalities and hypertrophic scarring, were recorded.Results:All patients were subject to follow-up, with restored breast fullness and natural contour. At the final follow-up, significant reductions were observed in bilateral areolar diameter, nipple-to-inframammary fold midpoint distance, and nipple-to-suprasternal notch distance compared to preoperative values (all P<0.001). The VSS score was (4.1±1.4) scores, and the breast morphology score was (79.9±2.5) scores. Scores from the Breast-Q questionnaire included satisfaction with breasts (81.6±2.5) scores, psychosocial well-being (83.6±5.2) scores, and sexual well-being (82.5±5.5) scores. Mild hypesthesia of the nipple-areola complex occurred in 2 patients and resolved spontaneously within 6 months postoperatively. Three patients developed mild hypertrophic scarring, which was effectively controlled with topical pharmacotherapy and physical therapy. Conclusion:The modified vertical superomedial five-flap technique is a safe and effective method for breast reduction in patients with macromastia.

OBJECTIVE To explore the potential mechanism of Cigu Xiaozhi Prescription(CGXP)in the treatment of non-alco-holic steatohepatitis(NASH)liver fibrosis.METHODS A NASH mouse model was established.The degree of liver enlargement was evaluated by calculating the liver index.Hematoxylin-eosin(HE)and Masson staining were used to observe the degree of liver fibro-sis.In addition,immunohistochemistry was employed to detect the expression of liver fibrosis-related proteins,including α-SMA,Collagen 1,MMP2,and MMP9.Western blot and qPCR techniques were used to detect the expression levels of HIF-1α,E-cadher-in,N-cadherin,Shh,Smo,Gli1,and Gli2 in the mouse liver.The alkaline hydrolysis method was used to measure the content of liv-er hydroxyproline.RESULTS CGXP could effectively reduce the liver index(P<0.001),alleviate liver enlargement and inflamma-tion,and significantly improve the pathological damage of liver tissue in mice with liver fibrosis.CGXP significantly decreased the ex-pression levels of liver fibrosis-related proteins α-SMA,Collagen 1,MMP2 and MMP9(P<0.01,P<0.000 1);reduced the levels of HIF-1α,E-cadherin,N-cadherin,Shh,Smo,Gli1,and Gli2,and the therapeutic effect of high-dose CGXP was particularly significant(P<0.05,P<0.01,P<0.001,P<0.000 1).CONCLUSION CGXP can relieve NASH liver fibrosis in mice by reducing the liver index,alleviating inflammation,and improving tissue pathological damage.The mechanism may be related to the inhibition of the Hedgehog signaling pathway,which alters the activation and proliferation of hepatic stellate cells and reduces the synthesis and dep-osition of extracellular matrix.

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for the treatment of ileocecal valve lipoma.Methods:A retrospective cohort study was performed on data of ileocecal lipoma patients who underwent ESD at the Endoscopy Center of Zhongshan Hospital, Fudan University from December 2013 to June 2023. According to the lesion location, the patients were divided into ileocecal valve group and cecum group. The operation time, operation speed, en bloc resection rate, complications, and follow-up outcomes between the two groups were compared.Results:A total of 59 patients with ileocecal lipoma were enrolled, including 31 patients in the ileocecal valve group and 28 patients in the cecum group.There were no significant differences in gender, age, specimen size, or lesion size between the two groups ( P>0.05). Lipomas in both the ileocecal valve group and the cecum group were successfully resected by ESD. The en bloc resection rates were 100.0% (31/31) and 92.9% (26/28) respectively, and the difference was not statistically significant ( χ2=0.033, P=0.133). Median operative duration significantly differed between the two groups ( ileocecal valve group 26 min VS cecum group 20 min, Z=-0.136, P=0.027), as did resection speed (ileocecal valve group 0.14 cm2/min VS cecum group 0.24 cm2/min, Z=-0.223, P=0.022). Adverse events included one postoperative fever in the ileocecal valve group and one delayed bleeding in the cecum group. During the median follow-up of 38 months (7-106 months), there was no case of residual tumor or recurrence. Conclusion:Despite technical challenges in ESD of ileocecal valve lipoma, it is still a safe, feasible and effective treatment method.