BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.

Objective:To investigate the predictive value of neutrophil extracellular traps (NETs) on the prognosis of patients with epidermal growth factor receptor (EGFR) wild-type lung adenocarcinoma.Methods:A total of 132 surgical paraffin specimens of EGFR wild-type lung adenocarcinoma diagnosed at the Tumor Hospital Affiliated to Xinjiang Medical University from January 2016 to December 2023 and 12 pairs of cancer and paracancerous fresh tissues from patients with EGFR wild-type lung adenocarcinoma diagnosed in March-July 2024 were collected with their clinical information. Western blotting and immunofluorescence were used to detect the expression levels of citrullinated histone H3 (CitH3) and myeloperoxidase (MPO) in cancerous and paraneoplastic tissues. Immunohistochemistry was used to detect the infiltration of PD-L1, CD4 + T cells and CD8 + T cells in the tumors. The clinical and prognostic correlations between NETs and EGFR wild-type lung adenocarcinoma patients were analyzed. Results:The expression of MPO ( P＜0.001) and CitH3 ( P=0.009) was significantly increased in the tumors compared with the paracancerous tissues. The rate of high expression of NETs in cancer tissues was higher in patients with EGFR wild-type lung adenocarcinoma who were in stage Ⅲ and Ⅳ, with lymph node metastasis, distant metastasis, pleural invasion, high expression of Ki-67, low expression of CD8 + T, and lowered lymphocyte counts when compared to paraneoplastic tissues ( P＜0.05). Patients were stratified based on TNM stage Ⅱb for prognostic analysis. Kaplan-Meier univariate analysis showed that the median overall survival (OS) (stage Ⅰ to Ⅱb: 47 vs 87 months; stage Ⅲ to Ⅳ: 27 months vs not reach) and the median disease-free survival (DFS) (stage Ⅰ to Ⅱb: 42 vs 78 months; stage Ⅲ to Ⅳ: 18 vs 39 months) of patients with high expression of NETs in stage Ⅰ to II b and stage Ⅲ to Ⅳ were lower than those with low expression (stage Ⅰ to Ⅱb: OS, P＜0.001; DFS, P＜0.001; stage Ⅲ to Ⅳ: OS, P=0.001; DFS, P=0.022). The OS (stage Ⅰ to Ⅱb: HR=3.513, 95% CI: 1.966-6.277, P＜0.001; stage Ⅲ to Ⅳ: HR=3.215, 95% CI: 1.324-7.806, P=0.010) and the DFS (stage Ⅰ to Ⅱb: HR=2.478 ,95% CI: 1.396-4.400, P=0.002; stage Ⅲ to Ⅳ: HR=2.248, 95% CI: 1.089-4.638, P=0.028) in the group with high expression of NETs in either stage Ⅰ to Ⅱb or stage Ⅲ to Ⅳ were significantly shorter than those in the group with low expression. Conclusion:The EGFR wild-type lung adenocarcinoma patients with high expression of NETs have relatively shorter DFS and OS, which are independent risk factors for the prognosis of patients with EGFR wild-type lung adenocarcinoma, and are likely to be the potential biomarkers for the diagnosis and treatment of EGFR wild-type lung adenocarcinoma.

Objective To provide reference for future basic research and clinical research,the research status and trend of podophyllotoxin were explored.Methods Based on Citespace and R software,the co-occurrence map,keyword clustering and burst analysis of the English literature on podophyllotoxin in the Scientific Core Collection(WoSCC)were carried out to explore the research hotspots and analyze the frontier progress.Results A total of 1220 papers on podophyllotoxin published by 531 institutions from 77 countries and regions were retrieved.The number of published papers showed an overall upward trend.The analysis of the author 's cooperation network map showed that there was cooperation and communication between the authors,but it was relatively scattered,and the cooperation was not close.This phenomenon also existed in the relationship between research institutions.The country with the largest number of papers was China,and the institution was Lanzhou University.869 authors participated in the research in this field,and 422 academic journals published papers on podophyllotoxin.Among them,podophyllotoxin,derivatives,analogues,biological evaluation and etoposide had a high frequency of occurrence,indicating that these fields had high attention and great research potential.Conclusion In recent years,the research on podophyllotoxin and its derivatives in the treatment of tumors has developed rapidly.In addition,the pharmacological effects and gene regulation of podophyllotoxin are also new research trends.The research hotspots show a trend of diversification,which provides strong evidence for further exploring the molecular mechanism of podophyllotoxin in the treatment of various diseases.However,the lack of relatively in-depth basic research has limited the development of clinical research.

eIF3a is a N ⁶-methyladenosine (m⁶A) reader that regulates mRNA translation by recognizing m⁶A modifications of these mRNAs. It has been suggested that eIF3a may play an important role in regulating translation initiation via m⁶A during infection when canonical cap-dependent initiation is inhibited. However, the death of animal model studies impedes our understanding of the functional significance of eIF3a in immunity and regulation in vivo. In this study, we investigated the in vivo function of eIF3a using eIF3a knockout and knockdown mouse models and found that eIF3a deficiency resulted in splenic tissue structural disruption and multi-organ damage, which contributed to severe sepsis induced by Lipopolysaccharide (LPS). Ectopic eIF3a overexpression in the eIF3a knockdown mice rescued mice from LPS-induced severe sepsis. We further showed that eIF3a maintains a functional and healthy immune system by regulating B cell function and quantity through m⁶A modification of mRNAs. These findings unveil a novel mechanism underlying sepsis, implicating the pivotal role of B cells in this complex disease process regulated by eIF3a. Furthermore, eIF3a may be used to develop a potential strategy for treating sepsis.

Objective: To systematically review the development and changes in mental health policies within the National Outline for Children s Development in China from 1992 to 2030, providing a reference basis for future formulation of mental health policies among children and adolescent in China. Methods: Based on the four editions of the National Outline for Children s Development in China across different periods from 1992 to 2030, word frequency analysis was used to reveal shifts in policy priorities, and an internationally recognized framework for adolescent health policy analysis was applied to conduct a textual review. Results: Word frequency analysis revealed that the term "psychological" appeared 6 times in the National Outline for Children s Development in China (2001-2010) but increased to 20 times in the National Outline for Children s Development in China (2021-2030) (abbreviated as the National Outline of 2021), while the term "health" rose from 4 times in the National Outline for Children s Development Plan in China in the 1990s to 68 times in the National Outline of 2021. The scope of mental health policy interventions expanded to encompass five key areas:health, safety, education, welfare and legal protection. Textual analysis highlighted that the policies of the National Outline for Children s Development in China were demand driven, prioritized vulnerable groups and continuously broadened their coverage, emphasizing sustainability and appropriateness, and monitoring/evaluation mechanisms. By 2023, 42.3% of primary schools and 64.8% of secondary schools employed full time mental health education teachers. However, the National Outline for Children s Development in China lacked direct evidence of children and adolescents participation in policy formulation, and publicly available mental health data disaggregated by age and gender remained limited. Conclusion Mental health policies of children and adolescents in China have evolved from nonexistence to gradual refinement, yet institutionalized channels for youth involvement in policy development and evaluation remain insufficient, and transparency in age and gender specific mental health data needs improvement.

Objective:To explore the correlation between weekend moderate-to-vigorous physical activity(MVPA), weekday sedentary behavior(SB)and the risk of frailty in the elderly population monitored by wearable devices, and to provide a scientific basis for lifestyle interventions for frailty in the elderly.Methods:This study was based on the data of the UK Biobank from 2013 to 2015.A cross-sectional study design was adopted, and 33, 212 elderly people aged 60 and above with complete physical activity monitoring data were selected.The Frailty Index(FI)constructed by the deficit accumulation method was used to assess the frailty status.The correlation between the combined effect of weekday SB and weekend MVPA and the frailty status was analyzed, and the differences between genders were explored.Results:There were significant differences in physical activity indicators among the elderly with different frailty statuses.As the degree of frailty increased, the MVPA-related indicators showed a downward trend, while the weekday SB time gradually increased.There were sex differences in physical activity patterns and frailties.Compared with women, men had longer SB time on weekdays, lower metabolic equivalent of weekly MVPA consumption, and higher MVPA time on weekends, but the frailties index of women was slightly higher than that of men.After adjusting for confounding factors, the frailty risks for men and women in the subgroup with the lowest weekday SB and the highest weekend MVPA duration decreased by 46.9% and 59.8%, respectively( P<0.001)when compared to the highest-risk group. Conclusions:Based on the monitoring data from wearable devices, elderly individuals who reduced their SB time during weekdays and increased their MVPA time on weekends were associated with a lower risk of frailty, especially among women; which providing a new perspective for lifestyle-based intervention strategies for frailty among the elderly.

Objective To provide reference for future basic research and clinical research,the research status and trend of podophyllotoxin were explored.Methods Based on Citespace and R software,the co-occurrence map,keyword clustering and burst analysis of the English literature on podophyllotoxin in the Scientific Core Collection(WoSCC)were carried out to explore the research hotspots and analyze the frontier progress.Results A total of 1220 papers on podophyllotoxin published by 531 institutions from 77 countries and regions were retrieved.The number of published papers showed an overall upward trend.The analysis of the author 's cooperation network map showed that there was cooperation and communication between the authors,but it was relatively scattered,and the cooperation was not close.This phenomenon also existed in the relationship between research institutions.The country with the largest number of papers was China,and the institution was Lanzhou University.869 authors participated in the research in this field,and 422 academic journals published papers on podophyllotoxin.Among them,podophyllotoxin,derivatives,analogues,biological evaluation and etoposide had a high frequency of occurrence,indicating that these fields had high attention and great research potential.Conclusion In recent years,the research on podophyllotoxin and its derivatives in the treatment of tumors has developed rapidly.In addition,the pharmacological effects and gene regulation of podophyllotoxin are also new research trends.The research hotspots show a trend of diversification,which provides strong evidence for further exploring the molecular mechanism of podophyllotoxin in the treatment of various diseases.However,the lack of relatively in-depth basic research has limited the development of clinical research.

Objective:To explore the correlation between weekend moderate-to-vigorous physical activity(MVPA), weekday sedentary behavior(SB)and the risk of frailty in the elderly population monitored by wearable devices, and to provide a scientific basis for lifestyle interventions for frailty in the elderly.Methods:This study was based on the data of the UK Biobank from 2013 to 2015.A cross-sectional study design was adopted, and 33, 212 elderly people aged 60 and above with complete physical activity monitoring data were selected.The Frailty Index(FI)constructed by the deficit accumulation method was used to assess the frailty status.The correlation between the combined effect of weekday SB and weekend MVPA and the frailty status was analyzed, and the differences between genders were explored.Results:There were significant differences in physical activity indicators among the elderly with different frailty statuses.As the degree of frailty increased, the MVPA-related indicators showed a downward trend, while the weekday SB time gradually increased.There were sex differences in physical activity patterns and frailties.Compared with women, men had longer SB time on weekdays, lower metabolic equivalent of weekly MVPA consumption, and higher MVPA time on weekends, but the frailties index of women was slightly higher than that of men.After adjusting for confounding factors, the frailty risks for men and women in the subgroup with the lowest weekday SB and the highest weekend MVPA duration decreased by 46.9% and 59.8%, respectively( P<0.001)when compared to the highest-risk group. Conclusions:Based on the monitoring data from wearable devices, elderly individuals who reduced their SB time during weekdays and increased their MVPA time on weekends were associated with a lower risk of frailty, especially among women; which providing a new perspective for lifestyle-based intervention strategies for frailty among the elderly.

Objective:To investigate the predictive value of neutrophil extracellular traps (NETs) on the prognosis of patients with epidermal growth factor receptor (EGFR) wild-type lung adenocarcinoma.Methods:A total of 132 surgical paraffin specimens of EGFR wild-type lung adenocarcinoma diagnosed at the Tumor Hospital Affiliated to Xinjiang Medical University from January 2016 to December 2023 and 12 pairs of cancer and paracancerous fresh tissues from patients with EGFR wild-type lung adenocarcinoma diagnosed in March-July 2024 were collected with their clinical information. Western blotting and immunofluorescence were used to detect the expression levels of citrullinated histone H3 (CitH3) and myeloperoxidase (MPO) in cancerous and paraneoplastic tissues. Immunohistochemistry was used to detect the infiltration of PD-L1, CD4 + T cells and CD8 + T cells in the tumors. The clinical and prognostic correlations between NETs and EGFR wild-type lung adenocarcinoma patients were analyzed. Results:The expression of MPO ( P＜0.001) and CitH3 ( P=0.009) was significantly increased in the tumors compared with the paracancerous tissues. The rate of high expression of NETs in cancer tissues was higher in patients with EGFR wild-type lung adenocarcinoma who were in stage Ⅲ and Ⅳ, with lymph node metastasis, distant metastasis, pleural invasion, high expression of Ki-67, low expression of CD8 + T, and lowered lymphocyte counts when compared to paraneoplastic tissues ( P＜0.05). Patients were stratified based on TNM stage Ⅱb for prognostic analysis. Kaplan-Meier univariate analysis showed that the median overall survival (OS) (stage Ⅰ to Ⅱb: 47 vs 87 months; stage Ⅲ to Ⅳ: 27 months vs not reach) and the median disease-free survival (DFS) (stage Ⅰ to Ⅱb: 42 vs 78 months; stage Ⅲ to Ⅳ: 18 vs 39 months) of patients with high expression of NETs in stage Ⅰ to II b and stage Ⅲ to Ⅳ were lower than those with low expression (stage Ⅰ to Ⅱb: OS, P＜0.001; DFS, P＜0.001; stage Ⅲ to Ⅳ: OS, P=0.001; DFS, P=0.022). The OS (stage Ⅰ to Ⅱb: HR=3.513, 95% CI: 1.966-6.277, P＜0.001; stage Ⅲ to Ⅳ: HR=3.215, 95% CI: 1.324-7.806, P=0.010) and the DFS (stage Ⅰ to Ⅱb: HR=2.478 ,95% CI: 1.396-4.400, P=0.002; stage Ⅲ to Ⅳ: HR=2.248, 95% CI: 1.089-4.638, P=0.028) in the group with high expression of NETs in either stage Ⅰ to Ⅱb or stage Ⅲ to Ⅳ were significantly shorter than those in the group with low expression. Conclusion:The EGFR wild-type lung adenocarcinoma patients with high expression of NETs have relatively shorter DFS and OS, which are independent risk factors for the prognosis of patients with EGFR wild-type lung adenocarcinoma, and are likely to be the potential biomarkers for the diagnosis and treatment of EGFR wild-type lung adenocarcinoma.

Objective To improve the efficiency of induced differentiation of primitive neural epithelial cells derived from human induced pluripotent stem cells(hiPSCs-NECs)into functional midbrain dopaminergic progenitor cells(DAPs).Methods HiPSCs were cultured in mTeSRTM medium containing DMH1(10 μmol/L),SB431542(10 μmol/L),SHH(200 ng/mL),FGF8(100 ng/mL),purmorphamine(2 μmol/L),CHIR99021(3 μmol/L),and N2(1%)for 12 days to induce their differentiation into primitive neuroepithelial cells(NECs).The hiPSCs-NECs were digested with collagenase IV and then cultured in neurobasal medium supplemented with 1%N2,2%B27-A,BDNF(10 ng/mL),GDNF(10 ng/mL),AA,TGF-β,cAMP,and 1%GlutaMax in the presence of different concentrations of Rho kinase inhibitor Y27632,and the culture medium was changed the next day to remove Y27632.Continuous induction was performed until day 28 to obtain DAPs.Results Human iPSCs expressed the pluripotency markers OCT4,SOX2,Nanog,and SSEA1 and were positive for alkaline phosphatase staining.The hiPSCs-NECs were obtained on day 13 in the form of neural rosettes expressing neuroepithelial markers SOX2,nestin,and PAX6.In digested hiPSCs-NECs,the addition of 5 μmol/L Y27632 significantly promoted survival of the adherent cells,increased cell viability and the proportion of S-phase cells(P<0.01),and reduced the rate of apoptotic cells(P<0.05).On day 28 of induction,the obtained cells highly expressed the specific markers of DAPS(TH,FOXA2,NURR1,and Tuj1).Conclusion Treatment with Y27632(5 μmol/L)for 24 h significantly promotes the survival of human iPSCs-NECs during their differentiation into DPAs without affecting the cell differentiation,which indirectly enhances the efficiency of cell differentiation.