Objective To construct a targeted drug delivery system, Ang-BEVs@Dox, based on Angiopep-2 peptide-modified bacterial extracellular vesicles （BEVs） loaded with doxorubicin （Dox）, overcome the challenges of blood-brain barrier （BBB） penetration and systemic toxicity in chemotherapy for glioblastoma （GBM）, enhance drug targeting to brain tumors and reduce its toxic side effects. Methods BEVs derived from Escherichia coli were isolated using ultracentrifugation. The targeting ligand Angiopep-2, specific for the LRP-1 receptor, was conjugated onto the surface of BEVs to construct the targeted carrier （Ang-BEVs）. Dox was loaded into Ang-BEVs using low-frequency sonication to form Ang-BEVs@Dox. The physicochemical properties （morphology and size） of the carriers were characterized by transmission electron microscopy （TEM） and dynamic light scattering （DLS）. The BBB-penetrating capability, in vitro/in vivo anti-tumor efficacy, and biosafety of the system were evaluated using cellular uptake assays, 3D tumor spheroid models, and orthotopic tumor-bearing mouse models. Results ① Carrier characterization and in vitro efficacy: Ang-BEVs@Dox exhibited a particle size of approximately 100 nm and maintained structural stability after Dox loading. It significantly enhanced cellular uptake efficiency in U87MG cells and achieved deep penetration within 3D tumor spheroids. Cytotoxicity assays demonstrated synergistic anti-tumor effects between the BEVs and Dox in the Ang-BEVs@Dox system. ② In vivo targeting and anti-tumor efficacy: In orthotopic tumor-bearing mouse models, Ang-BEVs@Dox effectively penetrated the BBB and significantly inhibited tumor growth, extending the median survival time of tumor-bearing mice to 33.5 days （compared to 23.5 days in the blank control group, P<0.001）. Immunohistochemical analysis revealed significant suppression of the tumor cell proliferation marker Ki-67 and enhancement of the apoptosis marker TUNEL staining signals. ③ Biosafety: Major organs from mice in the Ang-BEVs@Dox treatment group showed no observable pathological damage, indicating good biosafety. Conclusion This study successfully constructed an Angiopep-2 peptide-modified engineered BEVs delivery system （Ang-BEVs@Dox）. Through Angiopep-2-mediated BBB penetration and tumor targeting, it significantly enhanced the accumulation and therapeutic efficacy of BEVs at the GBM site. This method combined efficient delivery, low systemic toxicity, and clinical translation potential, which provided an innovative solution to overcome the therapeutic bottleneck in GBM treatment.

Abstract In recent years, digital exercise games based on motion capture and body sensing interaction technologies have gradually emerged and become a new trend in sports. Due to the ingenious integration of physical activity and electronic games, digital exercise games have demonstrated significant advantages in improving the health of children and adolescents. The paper aims to systematically analyze the intervention effects of digital exercise games on children and adolescents body composition, motor ability, muscle strength and bone density, cardiovascular health, executive function as well asemotions, aiming to explore new approaches and methods to improve the health status of children and adolescents in China.

Abstract To explore the mechanism of the impact of small games (SSG) on the physical health of children and adolescents and the reasonable application strategies, the study reviewes the multi-dimensional effects of SSG on the body composition, motor ability, cardiovascular health, musculoskeletal health and metabolic health of children and adolescents, and proposes the strategies for the reasonable application of SSG, which include scientifically designing training programs, emphasizing individualized differences, and strengthening monitoring and feedback. It can provide theoretical support and practical suggestions for the application of SSG in promoting the physical health of children and adolescents.

Objective To establish and verify a mature and stable glioblastoma(GBM)organoid model,so as to provide an accurate and personalized preclinical model for the research and treatment of GBM.Methods Fresh GBM tissues obtained through surgical procedures were initially processed,and then GBM stem cells(GSCs)were isolated using stem cell culture medium and were identified.Subsequently,GSCs were cultured in organoid culture medium for 3D cultivation,and GBM organoids were successfully obtained.The histological morphology of GBM organoids was observed by hematoxylin-eosin(H-E)staining;the stemness and similarity to the parental tumor were identified by immunofluorescence staining;and the in vivo tumorigenic ability of GBM organoids was identified by orthotopic tumorigenesis experiments in nude mice.Results A total of 7 GBM organoids were constructed from 9 human GBM samples,with a morphology resembling"neurosphere",and the average duration for organoid formation was 1 week.H-E staining results showed that the histological morphology of GBM organoids under high-power microscope was very similar to that of GBM tumor tissues;immunofluorescence staining results indicated that the GBM organoids possessed stemness characteristics and histological cellular similarity;and GBM organoids had a stronger tumorigenic ability compared to ordinary GBM cells in nude mice.Conclusion This study presents a stable and reliable method for constructing GBM organoids retaining the histological characteristics of the original GBM tissue,which providing new insights for future GBM research and clinical practice.

In recent years, organ transplantation has developed rapidly in China, whereas the proportion of supply and demand of organs for donation is severely unbalanced. To resolve the shortage of donor livers, repairing extended criteria donor liver and improving the quality of donor liver are critical research directions. Mesenchymal stem cell (MSC) is a category of stem cells with self-renewal and differentiation potential, which possess the functions of immunomodulation and tissue repair. The derivatives of MSC have the advantages of low immunogenicity and high biocompatibility, which have been widely applied in the treatment of multiple diseases. In this article, research progress on the role of MSC, exosomes and extracellular vesicles in alleviating liver steatosis, repairing ischemia-reperfusion injury and promoting the regeneration of small-for-size liver allograft was reviewed, and the feasibility and safety of MSC and the derivatives in repairing donor liver were summarized, aiming provide novel ideas for repairing marginal donor liver and enhancing the quality of liver allograft.

Objective:To investigate the effect of curriculum on the awareness and attitude on the rural-oriented medical education among medical students.Methods:The grade 2019 and 2020 medical students of rural-oriented program in Hebei Medical University were enrolled. Two different curricula were adopted in the first year, for students of grade 2020 more courses in general medicine, humanities and social sciences were added, and not for those of grade 2019. A questionnaire survey was conducted at the end of their first academic year. The questionnaire contained the basic information of students, opinions and satisfaction with curriculum design, understanding of policies about rural-oriented medical education, and the sense of career identity; each item in the questionnaire was scored by 5-point Likert scale.Results:A total of 173 questionnaires were distributed and 161 valid questionnaires were recovered, with a recovery rate of 93.1%; there were 55 responders (15 males and 40 females) from grade 2019, and 106 from grade 2020 (52 males and 54 females). The main reasons for choosing rural-oriented program were job security (60.0% (33/55) in 2019 and 58.5% (62/106) in 2020), the main way to know the relevant policies of the program was through the internet (54.5% (30/55) in 2019 and 66.0% (70/106) in 2020); 34.5% (19/55) of grade 2019 students were willing to continue working in rural areas after contracted period of service, while the percentage was 47.2% (50/106) for grade 2020. Students in grade 2020 had a higher satisfaction scores on the content and quality of teaching courses, as well as teaching satisfaction compared to those in grade 2019( t=2.34 and 3.00, P<0.05). The awareness of relevant policies before enrollment and policies related to contract violations among grade 2020 students was higher than that of grade 2019( t=2.70 and 5.08, P<0.05); the scores of all questions about general practice answered by students in grade 2020 were higher than those in grade 2019( t=3.96, 3.37, 3.55, 2.85, 3.84, 5.26 and 5.10,all P<0.05). There were no statistically significant differences in the scores of cognitive, emotional, behavioral, and adaptive aspects of career identity between students of two grades( t=0.70, 0.78, 0.74 and 1.37,all P>0.05). Conclusions:The reformed curriculum has positive effect on the satisfaction and awareness of rural-oriented medical education program and relevant policies among medical students in the program; however, it has less effect on the sense of career identity and willingness to continue to work in rural areas after the contracted period of serve.

Objective:To study the effect of Long non-coding RNA(LncRNA)small nucleolar RNA host gene 12(SNHG12)regulating miR-138-5p/hypoxia inducible factor-1(HIF-1α)axis on improving the damage of hypoxia/reoxygenation(H/R)human vas-cular endothelial cells.Methods:Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and randomly divided into control group,H/R model group,H/R+LncRNA SNHG12 overexpression group,H/R+miR-138-5p mimics group,H/R+co-transfec-tion group and H/R+co-transfection negative control group,each transfection group was transfected separately,and except for control group,the remaining groups were given hypoxia for 5 hours and then reoxygenated for 1 hour to induce the cell models,and then the cell viability of each group was detected by CCK-8 experiment;the cell apoptosis in each group was detected by flow cytometry experi-ment,and the apoptosis rate of each group was compared;the levels of reactive oxygen species(ROS),lactate dehydrogenase(LDH)and inflammatory factors IL-6,IL-17 and IL-18 in each group were measured by the kit;the expressions of miR-138-5p and HIF-1α mRNA in cells of each group were measured by real-time quantitative PCR(qRT-PCR)experiment;the expressions of apoptotic pro-teins caspase-9,Bcl-2-associated X protein(Bax)and HIF-1α in each group were evaluated by Western blot.Results:Compared with control group,the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular HIF-1α mRNA and protein levels,cellular caspase-9,Bax and HIF-1α protein levels were increased in H/R model group(P<0.05),the cell viability and miR-138-5p level were decreased(P<0.05).Compared with H/R model group and H/R+co-transfection group,the cell viability,cell HIF-1αmRNA and protein levels were increased in H/R+LncRNA SNHG12 overexpression group(P<0.05),the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular caspase-9 and Bax protein levels,and miR-138-5p level were decreased(P<0.05);the cell viability,cellular HIF-1α mRNA and protein levels were decreased in H/R+miR-138-5p mimics group(P<0.05),the apoptosis rate,cellular ROS,LDH,IL-6,IL-17 and IL-18 levels,cellular caspase-9 and Bax protein levels were increased(P<0.05).Com-pared with H/R model group,there was no significant difference in cell index levels between the H/R+co-transfection negative control group and the H/R+co-transfection group(P>0.05).Conclusion:LncRNA SNHG12 can upregulate HIF-1α expression by downregulat-ing miR-138-5p expression,inhibit H/R-induced inflammation and oxidative stress in HUVECs,and reduce cell damage and apoptosis.

This paper discussed "people-centered" view on the epidemic prevention and control in the new era from three aspects: theoretical origin, value implication and practical orientation. This view originates not only from the thought of people subject in Marxist historical materialism and people’s view in the important discourse on epidemic prevention and control of successive leaders of Communist Party of China, but also from the people-oriented thought of eliminating epidemic diseases in the traditional Chinese culture. Its value implication mainly manifested as the people’s stand of the prevention and control concept, the people’s orientation of the prevention and control work, and the people’s sharing of the prevention and control achievements. Its practical orientation is reflected in the prevention and control work relies on the people’s promotion, the prevention and control process relies on the people’s supervision, and the effectiveness of prevention and control depends on the people’s test.

Objective:To investigate the role of advanced oxidation protein products (AOPPs) in epithelial - mesenchymal transition (EMT) of small intestinal epithelial cells, and provide basis for the study of mechanism of intestinal fibrosis (IF) in intestinal bowel disease (IBD) .Methods:The small intestinal crypt epithelial cells IEC-6 were cultured in vitro. AOPPs was made by hypochlorous acid oxidation of rat serum albumin (RSA) in vitro. IEC-6 cells were divided into blank control group, AOPPs group and RSA group. The different concentrations (50, 100, 200, 400 μg/ml) of AOPPs were used to interfere with IEC-6 cells respectively in AOPPs group, 50, 100, 200, 400 μg/ml RSA were used to interfere with IEC-6 cells respectively in RSA group and no intervention in blank control group. The morphological changes of IEC-6 cells were observed and apoptosis was detected by flow cytometry in 3 groups 24 h after intervention. When the apoptosis rate was highest, the concentration of AOPPs were analyzed statistically and used to interfere IEC-6 for 48 and 72 h. The difference of apoptosis rate were analyzed between the different times. The mRNA expression of E-cadherin, Fibronectin, Snail, Slug and Collagen Ⅰ were detected in blank control group, AOPPs group and RSA group by fluorescence quantitative PCR.Results:AOPPs could induce the apoptosis of IEC-6 cells with time- and concentration-dependent effects ( P<0.05) . The apoptosis rate was (17.30 ± 1.03) %, which reached the peak by the intervention of 400 μg/ml AOPPs for 72 h. AOPPs significantly decreased the mRNA expression of E-cadherin in IEC-6 cells, significantly increased the mRNA expression of Fibronectin and CollagenⅠ, and significantly increased the mRNA expression of transcription factor Snail and Slug (all P<0.05) . Conclusions:AOPPs can promote the ECT of small intestinal epithelial cells and play a role in IF of IBD by inducing the apoptosis of IEC-6 cells, inhibiting of the transcription of E-cadherin, up-regulating the gene expression of the transcription factors Snail and Slug, while increasing the gene expression of Fibronectin and CollagenⅠ.

Objective:To investigate the role of advanced oxidation protein products (AOPPs) in epithelial - mesenchymal transition (EMT) of small intestinal epithelial cells, and provide basis for the study of mechanism of intestinal fibrosis (IF) in intestinal bowel disease (IBD) .Methods:The small intestinal crypt epithelial cells IEC-6 were cultured in vitro. AOPPs was made by hypochlorous acid oxidation of rat serum albumin (RSA) in vitro. IEC-6 cells were divided into blank control group, AOPPs group and RSA group. The different concentrations (50, 100, 200, 400 μg/ml) of AOPPs were used to interfere with IEC-6 cells respectively in AOPPs group, 50, 100, 200, 400 μg/ml RSA were used to interfere with IEC-6 cells respectively in RSA group and no intervention in blank control group. The morphological changes of IEC-6 cells were observed and apoptosis was detected by flow cytometry in 3 groups 24 h after intervention. When the apoptosis rate was highest, the concentration of AOPPs were analyzed statistically and used to interfere IEC-6 for 48 and 72 h. The difference of apoptosis rate were analyzed between the different times. The mRNA expression of E-cadherin, Fibronectin, Snail, Slug and Collagen Ⅰ were detected in blank control group, AOPPs group and RSA group by fluorescence quantitative PCR.Results:AOPPs could induce the apoptosis of IEC-6 cells with time- and concentration-dependent effects ( P<0.05) . The apoptosis rate was (17.30 ± 1.03) %, which reached the peak by the intervention of 400 μg/ml AOPPs for 72 h. AOPPs significantly decreased the mRNA expression of E-cadherin in IEC-6 cells, significantly increased the mRNA expression of Fibronectin and CollagenⅠ, and significantly increased the mRNA expression of transcription factor Snail and Slug (all P<0.05) . Conclusions:AOPPs can promote the ECT of small intestinal epithelial cells and play a role in IF of IBD by inducing the apoptosis of IEC-6 cells, inhibiting of the transcription of E-cadherin, up-regulating the gene expression of the transcription factors Snail and Slug, while increasing the gene expression of Fibronectin and CollagenⅠ.