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 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.

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 study the in vitro cytotoxicity of HRZ (isoniazid + rifampin + pyrazinamide) / transforming growth factor (TGF) β1 siRNA nanoliposomes on human macrophages and the underlying mechanism. Methods Self-made nanoliposomes were used to study with the cultured human macrophages in vitro. MTT assay was used to detect cell proliferation. Flow cytometry was used to analyze apoptosis and cell cycle. Electron microscopy was used to observe autophagy. RT-PCR and Western blot were employed to analyze the silenced expression of target gene TGF-β1. Results HRZ/TGF-β1 siRNA nanoliposomes (triple liposome) inhibited macrophage proliferation within certain range of concentration, and cell cycle was captured in G2 phase. The HRZ / TGF-β1 SiRNA nanoliposomes could significantly inhibit the expression of target gene TGF-β1 in human macrophages. Conclusions The self-made triple liposome has evident effect in silencing the target gene. It is a promising biomaterial, which meets the required specifications in terms of cytotoxicity.

Objective:To determine the clinical efficacy of posterior intervertebral surgery for single-segment thoracolumbar spinal tuberculosis.Methods:Clinical data were retrospectively analyzed in 62 patients with thoracolumbar spinal tuberculosis who underwent posterior intervertebral surgery (A group) or posterior and anterior combined intervertebral surgery (B group) from January 2010 to January 2015 in Department of Spinal Surgery,General Hospital,Ningxia Medical University.The operative time,blood loss,length of hospital stay,erythrocyte sedimentation rate (ESR),C-reactive protein (CRP) level,neurological function,VAS score,vertebral Cobb angle,bone healing,and postoperative complications were compared between the 2 groups.Results:All patients were followed up for 10 to 30 (average 22) months after the operation.In the A group,operative time,blood loss,and hospital stay were less than those in the B group (P＜0.05).In the follow-up,the pain of patients was alleviated and nervous function was improved obviously in the 2 groups compared with pre-operation.The ESR and CRP at the 6 months after operation returned to the normal range in patients of the 2 groups.There were significant differences in the ESR and CRP among the pre-operation,the 6 months after operation,and the end of follow-up within the group (P＜0.05),while there were no significant differences in ESR and CRP between the 6 months after operation and the end of follow-up (P＞0.05).There were no significant differences in the ESR and CRP among the pre-operation,the 6 months after operation,and the end of follow-up in the 2 group (P＞0.05).The Cobb angles after the operation and the end of follow-up were significanthy smaller than those before the operation (P＜0.01),while there were no significant differences in Cobb angle before operation,after the operation,and the end of follow-up between the 2 groups (P＞0.05).There were no significant differences in the bone healing rate at 6 months or 1 year after operation between the A group and B group (P＞0.05) and the complication rate of the A group was lower than the B group (P＜0.01).Conclusion:Clinical efficacy of posterior intervertebral surgery is satisfatory in treating single-segment thoracolumbar spinal tuberculosis with less complications.

Objective To evaluate the efficacy and safety of minor endoscopic sphincterotomy (EST)with endoscopic papillary large balloon dilation(EPLBD)for common bile duct stones(CBDS)in elderly patients and to study the influence of the periampullary diverticula on efficacy. Methods Data of 209 patients with CBD stones(more than 1. 0 cm)over the age of 70 were retrospectively analyzed. The pa-tients were divided into EST group(103 cases)and the EST with EPLBD group(106 cases),which was further divided into two subgroups with and without periampullary diverticula.Operation time,complete stone removal rate in the first session,mechanical lithotripsy usage rate and complications were compared between the two groups. Results Compared with EST group,the EST with EPLBD group had shorter operation time [(25. 65±8. 76)min VS(35±6. 67)min,P= 0. 000],a higher success rate of the complete stone removal in the first session( 90. 57% VS 83. 50%,P = 0. 030),lower rate of mechanical lithotripsy( 8. 50% VS 55. 34%,P= 0. 000),but with a higher incidence of hyperamylemia(18/ 106 VS 7/ 103,P = 0. 044).The o-verall stone removal rates showed no difference(96. 23% VS 95. 14%,P= 0. 700).In the EPLBD group,di-verticulum had no effects on the results and complications of ERCP( P> 0. 05). Conclusion EST with EPLBD is a safe and effective method for CBDS in elderly patients. Periampullary diverticula does not affect the therapeutic effects of this method.