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.Compilation Instructions for Expert Consensus on Clinical Application of Dieda Huoxue Capsules
Yuhang MENG ; Jinghua GAO ; Minshan FENG ; Quan JI ; Jin JIN ; Ting CHENG ; Yongyao LI ; Yuanyuan LI ; Xin CUI ; Yanming XIE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):177-183
The Compilation Instructions for Expert Consensus on Clinical Application of Dieda Huoxue capsules systematically expound the development methods and evidence-based basis of this consensus. In view of the weak clinical application evidence and ambiguous indications of Dieda Huoxue capsules, the Institute of Basic Research in Clinical Medicine of the China Academy of Chinese Medical Sciences and Wangjing Hospital took the lead and collaborated with 33 experts from 28 medical institutions nationwide. They strictly followed the World Health Organization (WHO) guideline-making norms and the Grading of Recommendations Assessment, Development and Evaluations (GRADE) evidence-grading system and completed the compilation through multidisciplinary cooperation. The workflow included constructing clinical questions (19 items were screened by the nominal group technique), retrieving evidence (from Chinese and English databases and grey literature), assessing safety (integrating drug monitoring data and clinical investigations), and forming recommendations and consensus suggestions (3 recommendations were reached via the GRADE grid method, and 16 consensus suggestions were reached by the majority vote rule). The results indicate that the consensus clearly states that this medicine (Dieda Huoxue capsules) is applicable to conditions like traumatic injury, blood stasis-induced pain, and sudden lumbar sprains. The recommended dose is 6 capsules each time, twice a day. Combining oral administration with external application can enhance the efficacy, and elderly patients should take the medicine at intervals. Safety monitoring suggests that it should be used with caution in people with a bleeding tendency and those with an allergic constitution. The compilation process involved three rounds of reviews by internal and external experts. Literature analysis, the Delphi method, and clinical applicability tests were employed to ensure methodological rigor. The compilation instructions comprehensively present key aspects such as project approval and registration, conflict-of-interest statements, and evidence evaluation through 12 appendices, providing methodological support for the clinical translation of the consensus. In the future, it will be continuously improved through a dynamic revision mechanism.
4.Assessment of the implementation of Radiation shielding requirements for radiotherapy room—Part 4: Radiotherapy room of 252Cf neutron afterloading (GBZ/T 201.4-2015)
Yuze YANG ; Hongfang WANG ; Haoxian YANG ; Quan WU ; Mingsheng LI ; Bala HARI ; Yongzhong MA ; Zechen FENG ; Bin BAI ; Jie GAO ; Wei ZHOU ; Weixu HUANG ; Zhengjie SHI ; Hezheng ZHAI
Chinese Journal of Radiological Health 2025;34(5):660-665
Objective To track and evaluate the implementation and application of the occupational health standard Radiation shielding requirements for radiotherapy room—Part 4: Radiotherapy room of 252Cf neutron afterloading (GBZ/T 201.4-2015) by radiation health technical service agencies, medical institutions, health supervision agencies, and radiotherapy facility design units, and to provide a scientific basis for the further revision and implementation of this standard. Methods Following the Guideline for health standards tracking evaluation (WS/T 536-2017) and the project implementation plan, relevant practitioners were randomly selected for a questionnaire survey. The survey primarily focused on their awareness, standard training, application, and revision suggestions of GBZ/T 201.4-2015. The results were summarized and analyzed. Results A total of 168 evaluation questionnaires were collected from relevant practitioners in 28 provinces. Only 31.6% of the respondents reported being “well familiar” or “ familiar” with the standard, 27.4% of the respondents believed that the standard was widely used, and 45.2% of the respondents believed that the standard could meet the needs of their work. Only 14.9% of the respondents had received relevant training on the standard, more than half of the respondents had not applied the standard within the past 10 years, and 45.2% of the respondents believed that the standard "needs to be revised". Conclusion Due to the small number of californium-252 neutron afterloading radiotherapy devices in operation on the market, the overall awareness of the standard is low, suggesting that relevant authorities need to strengthen training and publicity of the standard, and that certain sections of the standard need to be revised or merged.
5.Development of a shark single-domain antibody targeting a unique B cell epitope in the SARS-CoV-2 spike protein
Yue WANG ; Li-jun SHEN ; Quan FANG ; Feng ZHANG ; Yong-neng LUO
Chinese Journal of Zoonoses 2025;41(1):32-39
The purpose of this study is to develop a shark single domain antibody(SdAb)targeting a unique B cell epitope in the SARS-CoV-2 spike protein,and explore its role in the immunological detection targeting SARS-CoV-2 spike protein S.A u-nique peptide S9 was artificially synthesized based on the sequence of a unique B cell epitope of SARS-CoV-2 spike protein,then it was conjugated to the carrier protein KLH.It was used as an immunogen for subcutaneous injection into shark back and boosted according to the standard immunization protocol.Blood collected from shark tail vein and peripheral blood lymphocytes(PBL)were isolated.Total RNA was purified from PBL and transcribed to cDNA by reverse transcription.Shark vNAR frag-ments were amplified from cDNA templates and cloned into pComb3XSS vector to obtain phage library.A positive clone named T01 was obtained through screening the phage library by indirect ELISA.Then its gene was cloned into the expression vector pET-28a.The SdAb T01 was then prokaryotically expressed and purified,and its specific recognition of the SARS-CoV-2 spike protein S was indentified by Western-blot(WB),indirect ELISA and IF A.T01 binds well with peptide S9 at EC50 value of 2.050±0.064 nmol/L.The purified SdAb T01 was proven by WB to be able to selectively detect recombinant spike protein sub-unit 1(S1)of SARS-CoV-2,with no cross-reactive to recombinant spike protein subunit 1 of other six human coronavirus.It was showed by ELISA that SdAb T01 can sensitively detect the recombinant N terminal domain(NTD)of SARS-CoV-2 pro-tein.Moreover,it also specifically recognizes the spike protein of SARS-CoV-2 that was transiently expressed in transfected HEK293 cells by IFA.Therefore,a shark single domain antibody targeting a unique B cell epitope in the spike protein of SARS-CoV-2 was successfully developed,and has shown potential immunodiagnostic value by WB,ELISA and IFA.Thus,it provides an effective tool for unique antigen detection of SARS-CoV-2.
6.Troubleshooting of Siemens SOMATOM Force Dual Source CT:Three case reports
Feng LIU ; Jin-quan LIN ; Yu-sheng LI
Chinese Medical Equipment Journal 2025;46(9):114-117
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]
7.The changes of serum histone deacetylase 2,lonely G protein-coupled receptor ligand and B-type brain natriuretic peptide in patients with chronic obstructive pulmonary disease and the predictive value for prognosis
Yingbin HU ; Quan LI ; Qi FENG ; Xinting XIA ; Zhanliang YIN
Chinese Journal of Postgraduates of Medicine 2025;48(12):1069-1073
Objective:To explore the changes of serum histone deacetylase 2 (HDAC2), lonely G protein-coupled receptor ligand (Apelin) and B-type brain natriuretic peptide (BNP) in patients with chronic obstructive pulmonary disease (COPD) and the predictive value for prognosis.Methods:A retrospective selection was made of 100 COPD patients (COPD group) admitted to the Fourth People's Hospital of Langfang from May 2022 to May 2023 and 50 healthy individuals who underwent physical examinations during the same period (healthy control group) as the research subjects. The levels of serum HDAC2, Apelin and BNP in the two groups were compared. The levels of HDAC2, Apelin and BNP in COPD patients with different clinical characteristics were compared. The correlation among serum HDAC2, Apelin and BNP in COPD patients were analyzed by Spearman test. The predictive value of serum HDAC2, Apelin and BNP for the prognosis of patients with COPD was analyzed by the receiver operating characteristic (ROC) curve.Results:The level of HDAC2 in the COPD group was lower than that in the healthy control group, the levels of Apelin and BNP were higher than those in the healthy control group: (2.38 ± 0.56) U/L vs. (7.51 ± 1.33) U/L, (491.62 ± 53.82) ng/L vs. (337.19 ± 46.52) ng/L, (211.05 ± 23.46) ng/L vs. (37.52 ± 4.32) ng/L, there were statistical differences ( P<0.05). COPD patients with different clinical characteristics, including those in acute exacerbation and stable stages, mild, moderate and severe cases, COPD patients with pulmonary function grades Ⅱ, Ⅲ and Ⅳ, COPD patients with and without pulmonary hypertension, and patients with poor prognosis and good prognosis, there were statistically significant differences in the levels of HDAC2, Apelin and BNP ( P<0.05). The Spearman test results indicated that in COPD patients, serum HDAC2 was negatively correlated with Apelin ( r = - 0.469, P = 0.001), HDAC2 was negatively correlated with BNP ( r = - 0.435, P = 0.001), and Apelin was positively correlated with BNP ( r = 0.418, P = 0.001). The results of ROC curve analysis indicated that the combined detection of HDAC2, Apelin and BNP had the highest area under the curve for predicting the prognosis of COPD patients (0.954), with a sensitivity of 81.66%. Conclusions:COPD patients have lower HDAC2 and higher Apelin and BNP levels. The three indicators are correlated to a certain extent, and their levels are closely related to the clinical characteristics of patients. The combined detection of the three indicators can be used as important predictive indicators for the prognosis of COPD patients.
8.Maintenance of MAQUET ROTAFLOW ECMO system:Four case reports
Zeng-qiang FANG ; Bin-quan WANG ; Li-gang LOU ; Jing-yi FENG
Chinese Medical Equipment Journal 2025;46(5):116-120
The composition and working principle of MAQUET ROTAFLOW ECMO system were introduced.Four cases of common failures of ROTAFLOW ECMO systems were analyzed in terms of the cause and elimination method.The methods for the maintenance and quality control of ECMO system were put forward.References were provided for engineering technicians to treat similar faults.[Chinese Medical Equipment Journal,2025,46(5):116-120]
9.The Construction and Empirical Research of the Operation and Management Capability Evaluation Indicator System in Tertiary Public Hospital
Hao DING ; Aolun XU ; Jing FENG ; Yan LI ; Quan WAN ; GULIDANNA·ASIHAER ; Tiemin ZHAI
Chinese Health Economics 2025;44(5):53-57
Objective:To construct an evaluation index system for the operational management capability in tertiary public hospitals and validate its feasibility,providing a reference for accurately assessing the operational management capability of public hospitals.Methods:A literature review and Delphi method were employed to construct the index system.The Analytic Hierarchy Process was used to calculate weights,and a weighted comprehensive index method was applied to evaluate the operational management capability of sample hospitals.Results:A hierarchical indicator system was established,comprising 6 first-level indicators,16 second-level indicators,and 40 third-level indicators,covering the dimensions of resource allocation,service efficiency,economic operation,risk prevention and control,development capacity,and social benefits.Empirical results indicated that the composite score of the sample hospital decreased from 71.5 in 2019 to 53.8 in 2020 and rebounded to 57.9 by 2023.Conclusions:The empirical outcomes align well with the operational capacity as understood by the operational management personnel of the sample hospital,demonstrating that the indicator system is scientifically sound and rational,possessing a high evaluative capability.
10.Self-made reverse leveling device for assisting CT-guided puncture:Phantom experiment
Feng WANG ; Jianyuan QUAN ; Jun LI ; Junjie ZHANG ; Liqin ZHANG ; Liye LIU
Chinese Journal of Interventional Imaging and Therapy 2025;22(7):477-480
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.

Result Analysis
Print
Save
E-mail