1.Long-term survival outcomes and prognostic factors following radical resection of pancreatic body and tail cancer:a retrospective analysis of 992 patients
Dong XU ; Yang WU ; Kai ZHANG ; Nan LYU ; Qianqian WANG ; Pengfei WU ; Jie YIN ; Baobao CAI ; Guodong SHI ; Jianzhen LIN ; Yazhou WANG ; Lingdi YIN ; Zipeng LU ; Min TU ; Jianmin CHEN ; Feng GUO ; Jishu WEI ; Junli WU ; Wentao GAO ; Cuncai DAI ; Yi MIAO ; Kuirong JIANG
Chinese Journal of Surgery 2026;64(1):46-54
Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.
2.Trends in incidence and mortality of thyroid cancer in Nantong City from 2013 to 2022
HAN Yarong ; HAN Yingying ; CAI Bo ; LIN Ling
Journal of Preventive Medicine 2026;38(1):20-25
Objective:
To investigate the trends in incidence and mortality of thyroid cancer in Nantong City, Jiangsu Province from 2013 to 2022, so as to provide a basis for optimizing comprehensive regional prevention and control strategies.
Methods:
Data on incidence and mortality of thyroid cancer in Nantong City from 2013 to 2022 were collected via the Nantong Cancer Registration Reporting System. Crude incidence and mortality were calculated. The Chinese population-standardized incidence and Chinese population-standardized mortality were calculated using the standard age structure from the Fifth National Population Census in 2000. The average annual percent change (AAPC) was used to analyze the trends in incidence and mortality of thyroid cancer across different genders, age groups, and urban-rural areas from 2013 to 2022.
Results:
The crude incidence and Chinese population-standardized incidence in Nantong City rose from 5.79/100 000 and 4.36/100 000 in 2013 to 34.87/100 000 and 30.40/100 000 in 2022, respectively (AAPC=22.226%, 24.139%, both P<0.05). The crude mortality increased from 0.39/100 000 to 1.07/100 000 (AAPC=10.469%, P<0.05), while the trend for Chinese population-standardized mortality was not statistically significant (P>0.05). The Chinese population-standardized incidence and Chinese population-standardized mortality for females were 20.41/100 000 and 0.30/100 000, respectively, which were 3.28 times and 1.50 times those of males. The Chinese population-standardized incidence showed upward trends for both males and females (AAPC=22.840%, 24.592%, both P<0.05), while the trends for Chinese population-standardized mortality were not statistically significant (both P>0.05). From 2013 to 2022, the crude incidence in the age groups of 15-<45, 45-<65, and 65-<85 years, and the crude mortality in the age group of 65-<85 years showed upward trends (AAPC=27.808%, 21.756%, 13.365%, and 8.030%, all P<0.05), while trends in other age groups were not statistically significant (all P>0.05). The Chinese population-standardized incidence in urban areas was 16.96/105, which was 1.40 times that of rural areas. The Chinese population-standardized mortality in rural areas was 0.27/105, which was 1.29 times that of urban areas. From 2013 to 2022, the Chinese population-standardized incidence in both urban and rural areas and Chinese population-standardized mortality in rural areas showed upward trends (AAPC=17.264%, 27.758%, 6.387%, all P<0.05), while trend in Chinese population-standardized mortality in urban areas was not statistically significant (P>0.05).
Conclusions
From 2013 to 2022, the crude incidence, Chinese population-standardized incidence, and crude mortality of thyroid cancer in Nantong City all showed upward trends in the total population, males, and females, while the trend in Chinese population-standardized mortality was stable. There were differences in mortality trends between urban and rural areas: the trend in urban areas was stable, whereas the trend in rural areas was upward.
3.Assessment of health exposure risks from preservatives in beverages sold near primary schools in Anshun
XU Lin, QU Guangsheng, DAI Qian, LU Shunhua, CAI Guixiang, ZHANG Jialin, WEI Gang
Chinese Journal of School Health 2026;47(1):129-133
Objective:
To quantitatively assess the health risk of preservatives from beverages around primary schools in Anshun City, and to provide scientific basis for precise food safety supervision.
Methods:
From December 2023 to July 2024, 602 beverage samples were randomly collected from within 100 meters of 19 primary schools in Anshun City. The content of benzoic acid, sorbic acid, and dehydroacetic acid was detected according to GB 5009 series standards. Combined with children s physiological parameters (body weight 30 kg, daily intake 0.15 L), the Hazard Quotient (HQ) and Hazard Index (HI) models were used to evaluate health risks.
Results:
The total detection rate of preservatives from beverages around primary schools was 63.0%, and the total over limit rate was 9.0%. The detection rate of preservatives in flavored beverages was the highest (72.6%), and the highest over limit rate of preservatives in special purpose beverages was the highest (17.2%). The single preservative HQ (benzoic acid up to 0.47 ) and mixed HI (up to 0.55) of all samples were below 1(safety threshold). However, the HQ value of benzoic acid in flavored beverages (0.47) was 2.9 times that of sorbic acid (0.16), contributing significantly to health risk. Sensitivity analysis showed that if the daily consumption increased to 0.3 L, the HI value of flavored beverages would rise to 1.11, exceeding the safety threshold. Enterprise scale analysis showed that the exceedance rate of special purpose beverages in large enterprises reached 30.0%, while micro enterprises, accounting for a dominant market share (52.2%), constituted the main source of children s daily exposure to their products.
Conclusions
The overall health risk of perservatives in beverages sold near primary schools in Anshun City is controllable, but there is a noticeable risk of gradient. The risk of children’s exposure to preservatives through beverage consumption should not be ignored.
4.Expert Consensus on Neurocritical Care Monitoring and Management in Beijing and Tibet(2025)
Drolma PHURBU ; Wenjin CHEN ; Heng ZHANG ; Jian ZHANG ; Xiaomeng WANG ; Guoying LIN ; Wenjun PAN ; Xiying GUI ; Xin CAI ; Chodron TENZIN ; Jianlei FU ; Qianwei LI ; TSEYANG ; Yijun LIU ; Bo LIU ; Tsering DROLMA ; Yudron SONAM ; KYILV ; Samdrup TSERING ; Wa DA ; Juan GUO ; Cheng QIU ; Huan CHEN ; Xiaoting WANG ; Yangong CHAO ; Dawei LIU ; Wenzhao CHAI ; Chenggong HU ; Wanhong YIN ; Shihong ZHU
Medical Journal of Peking Union Medical College Hospital 2026;17(1):59-72
Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.
5.Influencing Factors of Urate Crystal Deposition in Patients with Hyperuricemia and Prediction Model of TCM Syndrome Types-inflammatory Indicators
Jiaqi XU ; Bin AI ; Chao LIN ; Qiaoxuan LIN ; Changning LI ; Jing CAI ; Yan XIAO ; Jiemei GUO ; Youxin SU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):66-73
ObjectiveTo identify potential influencing factors of urate crystal deposition at ankle/foot in patients with hyperuricemia (HUA), and to analyze the predictive value of inflammatory indicators for urate crystal deposition in patients with different traditional Chinese medicine (TCM) syndromes, so as to provide potential reference for clinical risk assessment and individualized TCM intervention. MethodsA retrospective study was carried out with the enrollment of 231 HUA patients from The Third Affiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2021 and December 2024. The enrolled patients were further divided into a crystal deposition-positive group (143 cases) and a crystal deposition-negative group (88 cases) according to the results of dual-energy computed tomography (CT). Sociodemographic data, living habits, serum uric acid levels, and inflammatory indicators of the enrolled patients were collcted, and TCM syndrome differentiation was performed. Furthermore, univariate analysis was used to compare inter-group differences in clinical characteristics. MMultivariate Logistic regression was applied to identify the influencing factors of urate crystal deposition. In addition, the receiver operating characteristic (ROC) curves were plotted to evaluate the predictive efficacy of inflammatory indicators for crystal deposition across different TCM syndromes. ResultsThere were statistically significant inter-group differences in the proportion of males, age, body mass index, proportion of mental labor, rate of low water intake, and rate of high-sugar beverage consumption (P<0.05),whereas no significant difference in low exercise intensity was found between the two groups. Furthermore, compared with the negative group, the positive group had higher serum uric acid level, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), but lower systemic immune-inflammation index (SIRI) (P<0.05). Regarding the distribution of TCM syndromes, the positive group was dominated by the dampness-heat accumulation syndrome (55/143,38.46%), while the negative group was mainly characterized by the phlegm-turbidity obstruction syndrome (44/88,50.00%). Multivariate Logistic regression analysis revealed that high-sugar beverage consumption, elevated NLR, and elevated PLR were risk factors for urate crystal deposition [odd ratio (OR) = 8.002, 5.377, 1.034, respectively; 95% CI 1.572-40.732, 2.179-13.270, 1.013-1.054,all P<0.05], while SIRI was a protective factor (OR = 0.869, 95% CI 0.778-0.971, P<0.05). In the positive group, patients with the dampness-heat accumulation syndrome exhibited the highest NLR, while the lowest PLR and SIRI, showing statistically significant differences with those of other syndromes (all P<0.05). In addition, ROC curve analysis indicated that for the dampness-heat accumulation syndrome, the combined "NLR + PLR" model had an area under the curve (AUC) of 0.901 (95% CI 0.850-0.951, P<0.01), with a sensitivity of 89.1% and a specificity of 79.5%; for the blood stasis-heat obstruction syndrome, the combined "NLR + PLR" model had an AUC of 0.880 (95% CI 0.825-0.934, P<0.01), with a sensitivity of 100.0% and a specificity of 67.3%; for the liver-kidney Yin-deficiency syndrome, the single PLR model had an AUC of 0.842 (95% CI 0.731-0.952, P<0.01), with a sensitivity of 83.3% and a specificity of 84.0%. ConclusionUrate crystal deposition in HUA patients exhibits intimate associations with high-sugar beverage consumption as well as elevated NLR and PLR levels. Meanwhile, TCM syndrome differentiation has potential correlation with inflammatory characteristics. The inflammatory indicator-based prediction model constructed based on TCM syndromes exhibits good predictive value.
6.Mechanisms of Traditional Chinese Medicine in Treatment of Ulcerative Colitis Based on AMPK Signaling Pathway: A Review
Keqiu YAN ; Xiaoyu ZHANG ; Yifan CAI ; Wenjie XIAO ; Xinkun BAO ; Guangjun SUN ; Aizhen LIN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):341-351
Ulcerative colitis (UC), a chronic relapsing inflammatory bowel disease, involves multifaceted pathological mechanisms such as intestinal barrier dysfunction, immune dysregulation, and oxidative stress. Current therapeutic strategies remain limited in efficacy and safety. In recent years, the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway has emerged as a pivotal therapeutic target for UC due to its central role in energy metabolism, inflammatory regulation, and intestinal homeostasis. This article systematically reviewed the mechanisms by which traditional Chinese medicine (TCM) prevented and treated UC through the regulation of the AMPK signaling pathway, with a focus on elucidating AMPK's multidimensional regulatory network in inflammatory signaling crosstalk, alleviating oxidative stress, restoring intestinal immune balance, repairing the intestinal barrier, and modulating gut microbiota. Leveraging its unique advantages of multi-target engagement and low toxicity, TCM demonstrates promising potential in UC treatment and has become a focal area of research. By systematically summarizing and synthesizing the existing literature on TCM-mediated AMPK pathway modulation in UC, this review aims to provide a theoretical foundation for advancing mechanistic research and clinical interventions in UC.
7.Prevalence of Clonorchis sinensis human infections in Congjiang County of Guizhou Province in 2023
Danya SHE ; Shan CAI ; Songping LI ; Guangchu LIN ; Zhangjing SHI ; Chunyan WU ; Lan HE ; Lidan LU
Chinese Journal of Schistosomiasis Control 2026;38(1):92-95
Objective To investigate the prevalence of Clonorchis sinensis human infections in Congjiang County, Guizhou Province in 2023, so as to provide insights into formulation of the clonorchiasis control strategy. Methods Congjiang County was divided into eastern, western, southern, northern and central areas according to the geographical locations, and one township was randomly sampled from each area. Then, each administrative village was randomly sampled from each township, and 200 permanent residents over 3 years of age were randomly sampled from each village. Participants’ stool samples were collected for detection of C. sinensis eggs with the Kato-Katz technique (two slides for each stool sample), and the prevalence and intensity of C. sinensis infections were calculated. In addition, the risk factors of clonorchiasis were identified among participants using a questionnaire survey. Results A total of 1 001 residents were included, and the prevalence of C. sinensis infections was 16.28% (163/1 001), with mild infections as the predominant category of infection intensity [73.01% (119/163)]. The prevalence rates of C. sinensis human infections were 30.50% (61/200), 1.50% (3/200), 30.35% (61/201), 12.50% (25/200), and 6.50% (13/200) at five survey sites, respectively (χ2 = 107.03, P < 0.05), and there was a significant difference in the prevalence of C. sinensis infections between men [22.44% (112/499)] and women [10.16% (51/502)] (χ2 = 27.71, P < 0.05). The prevalence of C. sinensis infections was relatively high among participants at ages of 60 to 70 years [26.14% (23/88)], public servants [46.15% (6/13)], and Han ethnic participants [33.33% (5/15)]. The prevalence of C. sinensis infections was higher among participants with a habit of consuming raw or un-dercooked freshwater fish and shrimp [22.06% (90/408)] than among those without the habit [12.31% (73/593)] (χ2 = 16.85, P < 0.05), and there was no significant difference in the prevalence of C. sinensis infections between participants with [13.99% (41/293)] and without separation of raw and cooked chopping boards [17.23% (122/708)] (χ2 = 1.59, P > 0.05). In addition, the prevalence of C. sinensis infections was 8.70% (2/23) and 16.46% (161/978) among participants with and without fever complicated by discomfort in the right upper abdomen during the past half year (χ2 = 0.99, P > 0.05). Conclusions The prevalence of C. sinensis human infections was high in Congjiang County, Guizhou Province in 2023, and infections predominantly occurred among young and middle-aged men. Intensified health education among high-risk residents and alteration of dietary habits of consuming raw or undercooked freshwater fish or shrimp are recommended to reduce the prevalence of C. sinensis human infections.
8.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.
9.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.
10.TGF-β1-engineered Biomimetic Platelet Nanoparticles for Targeted Therapy of Ischemic Stroke
Li-Qi CHEN ; Tian-Fang KANG ; Guo-Jun HUANG ; Ting YIN ; Ai-Qing MA ; Lin-Tao CAI ; Hong PAN
Progress in Biochemistry and Biophysics 2026;53(3):697-710
ObjectivePost-ischemic acute inflammation and the subsequent persistent dysregulation of the immune microenvironment represent major pathological drivers that aggravate neuronal injury and severely restrict functional recovery following ischemic stroke. Although current reperfusion therapies partially restore blood flow, they fail to effectively modulate the secondary inflammatory cascade and oxidative stress, which remain critical barriers to neurological restoration. To address this challenge, this study aimed to engineer and systematically evaluate a biomimetic nanosystem composed of transforming growth factor-β1 (TGF-β1)-loaded platelet membrane-camouflaged lipid nanoparticles (PLP). This nanosystem was designed to achieve dual lesion-targeted delivery and immune microenvironment remodeling. By verifying its spatiotemporal accumulation, anti-inflammatory activity, and neuroprotective efficacy, we sought to establish an integrated therapeutic strategy that simultaneously enables lesion targeting, immune regulation, and functional recovery after ischemic injury. MethodsThe physicochemical properties of PLP, including hydrodynamic particle size, zeta potential, structural stability, and morphology, were characterized using dynamic light scattering, zeta potential analysis, and transmission electron microscopy. The preservation of platelet membrane-derived adhesion and immunoregulatory proteins was confirmed by SDS-PAGE through comparative analysis of protein band profiles between PLP and native platelet membranes. The in vitro biological activities of PLP were evaluated using two complementary cellular models. LPS-induced M1-polarized RAW264.7 macrophages were employed to assess inflammatory modulation, while oxygen glucose deprivation/reperfusion (OGD/R)-induced BV2 microglial cells and SH-SY5Y neuronal cells were utilized to investigate neuroinflammatory regulation and neuronal protection. For in vivo validation, a transient middle cerebral artery occlusion (tMCAO) mouse model was established to mimic ischemia-reperfusion injury. The spatiotemporal biodistribution and lesion-targeting capability of the PLP were monitored through live fluorescence imaging. Therapeutic efficacy was comprehensively evaluated by triphenyltetrazolium chloride (TTC) staining, glial fibrillary acidic protein (GFAP) immunofluorescence analysis, body weight monitoring, and neurological severity score (NSS) assessment. ResultsPLP nanoparticles displayed a uniform spherical morphology, nanoscale particle size distribution, and stable negative surface charge, indicating favorable colloidal stability and circulation potential. SDS-PAGE results confirmed the effective retention of key platelet membrane proteins associated with endothelial adhesion, immune evasion, and inflammatory regulation, demonstrating the successful biomimetic construction. Optimal therapeutic concentrations were determined in OGD/R-induced BV2 cells, where PLP exhibited excellent cytocompatibility and anti-inflammatory activity.In vitro experiments demonstrated that PLP significantly inhibited the polarization of RAW264.7 macrophages toward the pro-inflammatory M1 phenotype and markedly reduced neuronal apoptosis under ischemia-reperfusion conditions. In vivo fluorescence imaging revealed that PLP rapidly accumulated in the ischemic brain hemisphere and maintained prolonged retention for up to 7 d, suggesting enhanced lesion-specific targeting and sustained drug release. Compared with control group, PLP treatment significantly reduced cerebral infarct volume, attenuated reactive astrogliosis, improved weight recovery, and accelerated neurological functional restoration, as reflected by significantly improved NSS scores. ConclusionThis study establishes a multifunctional biomimetic nanoplatform that integrates platelet membrane-mediated active targeting with the anti-inflammatory, antioxidative, and neuroprotective properties of TGF-β1. The PLP system enables rapid lesion homing and long-term retention while synergistically regulating the post-stroke inflammatory microenvironment by suppressing pro-inflammatory immune activation, reducing neuronal apoptosis, and limiting excessive astrocyte reactivity. Importantly, this study proposes a conceptually therapeutic paradigm that combines targeted delivery with immune microenvironment remodeling to achieve comprehensive neurovascular protection. These findings provide strong experimental evidence supporting the translational potential of biomimetic nanotherapeutics as next-generation precision interventions for ischemic stroke.


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