1.Polypeptide-based Nanocarriers for Oral Targeted Delivery of CAR Genes to Pancreatic Cancer
Feng XIN ; Jian REN ; Zhao-Zhen LI ; Quan FANG ; Rui-Jing LIANG ; Lan-Lan LIU ; Lin-Tao CAI
Progress in Biochemistry and Biophysics 2026;53(2):431-441
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.
2.Polypeptide-based Nanocarriers for Oral Targeted Delivery of CAR Genes to Pancreatic Cancer
Feng XIN ; Jian REN ; Zhao-Zhen LI ; Quan FANG ; Rui-Jing LIANG ; Lan-Lan LIU ; Lin-Tao CAI
Progress in Biochemistry and Biophysics 2026;53(2):431-441
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.
3.Intra-abdominal Hernia with Bowel Obstruction Triggering Multi-organ Failure: The Role of Preoperative Enteritis
Yue-zhen Wang ; Ben-yi Tian ; Jian-hui Qin ; Hao Liang
Journal of Surgical Academia 2026;16(1):1-4
Intra-abdominal Hernia with Bowel Obstruction Triggering Multi-organ Failure: The Role of Preoperative Enteritis
This report details the clinical course of a 41-year-old male who developed fulminant multiple organ dysfunction syndrome following emergency surgery for a strangulated intra-abdominal hernia. Preoperative manifestations, including diarrhea and marked leukocytosis, pointed towards an underlying infectious enteritis. We posited that surgical release of the obstructed, ischemic bowel segment precipitated a massive systemic influx of endotoxins and inflammatory mediators, triggering septic shock and rapid sequential organ failure. This case underscored the critical need to suspect concomitant gastrointestinal infection in patients presenting with mechanical bowel obstruction accompanied by infectious signs. Aggressive perioperative sepsis management encompassing early empiric antimicrobial therapy, vigilant hemodynamic monitoring, and preparedness for advanced organ support is essential to mitigate this severe complication.
4.Self-Supervised Multi-Organ Segmentation in Pediatric Abdominal CT Based on Vision Foundation Models
Qinghua ZHANG ; Ming LI ; Zhedian ZHOU ; Jian ZHENG ; Huadan XUE ; Qiuxia WANG ; Yu DU ; Zhen LI
Medical Journal of Peking Union Medical College Hospital 2026;17(4):954-962
To address the scarcity of annotated data for pediatric abdominal CT imaging and the insufficient generalization capability of existing models, we constructed a self-supervised pretraining architecture tailored for pediatric CT domain adaptation based on the visual foundation model DINOv3, and validated its performance in the task of pediatric abdominal multi-organ segmentation. We built a general-purpose radiological visual representation using the large-scale adult CT dataset CT-3M, and introduced a Gram-anchoring mechanism that employs a frozen adult pretrained model as a structural teacher to guide domain alignment of local topological structures on unlabeled pediatric CT data. Combined with a multi-scale feature aggregation strategy and a lightweight Primus decoder, downstream segmentation tasks were evaluated on a public pediatric CT dataset. Based on case-wise paired results, we compared the mean Dice similarity coefficient (DSC) and mean intersection over union (IoU) between our model and the baseline nnU-Net using the Wilcoxon signed-rank test, and computed the relative performance improvements. A total of 867 abdominal CT imaging cases were collected, constituting a pretraining dataset comprising 367 588 two-dimensional CT slices. On the public Pediatric-CT-SEG dataset (359 cases), our model achieved a mean DSC of (71.38±1.08)% and a mean IoU of (63.73±1.01)%, representing improvements of 3.22% and 3.59% over the baseline nnU-Net, respectively, with statistically significant differences ( The self-supervised pretraining framework proposed in this study effectively alleviates the domain shift between adult and pediatric abdominal CT images, significantly enhances segmentation accuracy for pediatric abdominal multi-organs-particularly small organs and structures with complex boundaries-and provides a reliable technical solution for intelligent pediatric imaging analysis in scenarios with limited annotated data.
5.Clinical characteristics and treatment strategies for thyroid carcinoma combined with cervical vagus nerve schwannoma
Weihua JIAN ; Zhen CHEN ; Jianhua FENG ; Wensong CAI ; Bo XU
Chinese Journal of Endocrine Surgery 2025;19(4):547-551
Objective:To investigate the diagnostic and surgical strategies in managing patients with coexisting thyroid carcinoma and cervical vagal schwannoma.Methods:We retrospectively analyzed three cases treated at Guangzhou First People’s Hospital between Jun. 2019 and Dec. 2024.Results:All patients presented with neck masses or thyroid nodules. Ultrasonography identified suspicious malignant thyroid nodules and lateral neck lesions—interpreted as metastatic lymphadenopathy in two cases and as a possible nerve sheath tumor in one. Fine-needle aspiration cytology (FNAC) of thyroid nodules yielded Bethesda VI results in all cases. FNAC of the lateral neck lesions revealed no evidence of malignancy in all cases; in one case, a core needle biopsy confirmed a vagal schwannoma. Two patients underwent MRI, which supported the diagnosis of vagal schwannoma. Surgical management included single-stage resection in two patients and staged surgery in one. Postoperative histopathology confirmed papillary thyroid carcinoma and schwannoma in all cases. Transient postoperative hoarseness occurred in two patients, with recovery within 3-6 months.Conclusions:When thyroid carcinoma is complicated by cervical vagal schwannoma, the schwannoma may be misdiagnosed as metastatic cervical lymph nodes, potentially leading to iatrogenic vagus nerve injury during neck dissection. Although cervical vagal schwannoma can be diagnosed preoperatively, simultaneous surgical treatment of both conditions may increase the risk of vocal cord paralysis, and in severe cases, result in airway compromise. Therefore, comprehensive preoperative evaluation is important. It is recommended to classify cases based on the anatomical locations of the thyroid carcinoma and vagal schwannoma to guide surgical planning, and to use intraoperative nerve monitoring to enhance surgical safety and avoid serious complications.
6.Research progress on iron metabolism and neurodevelopment in premature infants
Jia-wen ZHOU ; Shu-jian CHEN ; Bo-xin WU ; Zuan-zhen MAI
Journal of Regional Anatomy and Operative Surgery 2025;34(4):363-367
Iron is one of the essential trace elements for the human body,which is crucial for the growth and development of newborns,especially premature infants.It participates in the generation of hemoglobin,affects the activity of various enzymes,and subsequently affects neurometabolism,neurochemistry,neuroanatomy,and gene/protein composition,thereby having a lasting impact on the development of the central nervous system.This article reviews the research progress on the relationship between iron metabolism and neurodevelopment in premature infants in recent years,aiming to provide scientific basis for clinical management and preventive intervention of premature infants.
7.Progress in anti-cancer target PARP7 and its inhibitors
Zhen-yu ZHAO ; Xiao-lu LU ; Jian LI
Chinese Pharmacological Bulletin 2025;41(4):620-625
PARP7 is a mono-ADP ribotransferase belonging to the PARP family that acts as a specific amino acid to catalyze the transfer of ADP ribose from NAD+to itself and other sub-strate proteins.PARP7 is overactive in many tumors and can in-terfere with interferon signaling pathways to enable cancer cells to achieve immune escape.Inhibition of PARP7 can restore IFN-β expression in tumor cells,thereby activating T cell-mediated anti-tumor immunity in vivo,so PARP7 is considered as a new immunomodulatory target for cancer therapy.At present,only one selective inhibitor of PARP7,RBN-2397,has entered phaseⅠ clinical studies.This article focuses on the structure and bio-logical function of PARP7,the correlation between PARP7 and cancer occurrence,and the research progress of PARP7-related inhibitors,in order to provide theoretical basis and new ideas for the research and development of new PARP7 inhibitors and the structural optimization of RBN-2397.
8.Key technology and equipment development status of first-aid robotics
Zhen-bao WANG ; Zi-jian WANG ; Xin-xi XU ; Xin LIU ; Tao CHENG ; Pei-peng LIU ; Xiu-guo ZHAO ; Chen SU
Chinese Medical Equipment Journal 2025;46(3):96-114
The development status of the key technologies of first-aid robotics was introduced in autonomous system,embo-died intelligence,digital twins,large artificial intelligence model and autonomous unmanned medical treatment.The present situation in first-aid robotics equipment was reviewed for first-aid diagnosis,treatment,assistance and transportation.The development trends of the key technology and equipment of first-aid robotics were analyzed.It was pointed out the involve-ment of big model-based embodied intelligence technology and digital twins technology in first aid might provide new pers-pectives for the application and advancement of specialized first-aid robotics.[Chinese Medical Equipment Journal,2025,46(3):96-114]
9.The Mechanism by Which Maternal Metabolites Mediate Histone Modification to Regulate the Occurrence of Neural Tube Defects
Zeng-Li LIU ; Jian-Ting LI ; Zhi-Zhen LIU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(7):956-966
Neural tube defects(NTDs)are a category of severe congenital birth defects that seriously af-fect the life and health of the fetus.The occurrence mechanism is very complex,involving the complex interaction between genetic factors and environmental factors.In recent years,the increasingly wide-spread application of proteomics has revealed the key role of histone modifications in epigenetic regula-tion,especially in the pathogenesis of NTDs.Histone modifications include various types such as histone methylation,acetylation,ubiquitination,homocysteinylation,malonylation,and crotonylation.These modifications affect the expression of key proteins involved in neural tube closure and are crucial for ge-nomic stability during neural tube closure,participating in the occurrence and development of NTDs.Ab-normal regulation of these regulations is closely related to the occurrence of NTDs.In addition,during embryonic brain development,histone modifications are easily affected by environmental factors such as maternal metabolite levels and exposure to teratogenic substances.Abnormal maternal metabolite levels can cause abnormal regulation of key gene expression,which affects histone modifications and thereby regulates the abnormal expression of downstream related genes,including genes related to neural tube de-velopment,leading to the occurrence of NTDs and other neurodevelopmental diseases.Although there have been numerous studies on the mechanism of NTDs,the exact pathogenesis of NTDs has not yet been fully elucidated.In-depth research on the pathogenic factors and occurrence mechanism of NTDs is of great significance for improving the quality of the birth population and reducing neonatal mortality.This article reviews the research progress in recent years on the occurrence of fetal NTDs caused by abnormal histone modifications mediated by maternal metabolites and provides a prospect for the future research di-rection.With the aim of revealing the key regulatory function of histone modifications in neural tube de-velopment,this review also provides a theoretical basis for further research on the relationship between histone modifications and the occurrence of NTDs,and for the future prevention and treatment strategies of NTDs.
10.Construction and evaluation of a deep learning-based intelligent diagnosis model for temporomandibular joint osteoarthritis imaging
Dandan WU ; Pei WANG ; Yang JING ; Zhen JIA ; Jian YANG
Journal of Practical Stomatology 2025;41(4):519-524
Objective:To develop an automatic diagnostic model for temporomandibular joint osteoarthritis(TMJOA)imaging based on deep learning technology,and to assist clinical diagnosis and improve the efficiency and accuracy of TMJOA diagnosis.Methods:CBCT data of 220 patients were collected,and 2 052 sagittal images were exported.Regions of interest were delineated according to the imaging analysis criteria for temporomandibular joint disorders,and the images were classified into TMJOA-free,TMJOA-uncer-tain and TMJOA.The data were randomly divided into a training set and a validation set according to 8∶2 ratio,and the training set data were used to train a TMJOA detection model based on three lightweight YOLOV5 deep learning frameworks,and the models' performance was evaluated on the validation set.Results:The Yolov5N model demonstrated the best performance,achieving a de-tection accuracy,recall,and precision of 92.5%,90.1%and 85.7%on the validation set,respectively.Conclusion:The auto-matic detection model for TMJOA imaging developed in this study can effectively identify arthritic lesions.Artificial intelligence tools are expected to become a powerful auxiliary tool for the clinical diagnosis of TMJOA.


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