ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol（Chol） in conventional liposomes with saikosaponin D（SSD） and modifying with poloxamer 407（P407） for co-delivery of curcumin（Cur）. The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes， and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes（P407-DiR-Chol-LPs， PDCL） and novel SSD-based liposomes（P407-DiR-SSD-LPs， PDSL） were prepared by the optimized formulation process， and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups， including blank group， model group， free doxorubicin（DOX） group（2 mg·kg^-1）， free Cur group（8 mg·kg^-1）， free SSD group（10 mg·kg^-1）， P407-Cur-Chol-LPs（PCCL） group， P407-SSD-LPs（PSL） group， and P407-Cur-SSD-Lps（PCSL） group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change， organ indices， tumor volume and mass， relative tumor proliferation rate（T/C）， and tumor growth inhibition rate（TGI）. Histopathological analysis of liver， kidney， and tumor tissues was performed using hematoxylin-eosin（HE） staining. Serum levels of aspartate aminotransferase（AST）， alanine aminotransferase （ALT）， blood urea nitrogen（BUN）， and creatinine（Crea）in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur， SSD， and P407 to soybean phosphatidylcholine（SPC） as 1∶25， 1∶20， and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm， a Zeta potential of -47.25 mV， and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics， demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group（P<0.05， P<0.01）. Among the treatment groups， PCSL group showed superior efficacy over free Cur group， free SSD group， PCCL group， and PSL group， with TGI>40% and T/C<60%， indicating pronounced anti-hepatocellular carcinoma effects（P<0.05， P<0.01）. Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy， achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma， providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.

Objective: To explore the association between mental health and muscle strength among Chinese adolescents aged 13- 18, providing a theoretical foundation and intervention strategies for mental health promotion. Methods: Data were obtained from the 2019 Chinese National Survey on Students Constitution and Health, including 98 631 Chinese adolescents aged 13- 18. Psychological distress was assessed by using the Kessler Psychological Distress Scale (K10), and mental well being was measured with the Warwick-Edinburgh Mental Well being Scale (WEMWBS). Based on the gender and age specific Z scores of various test items [grip strength, standing long jump, pull ups (for males), and sit ups (for females)], muscle strength index (MSI) was constructed to evaluate the comprehensive level of muscle strength in adolescents. According to the Dual factor Model (DFM) of mental health, participants were categorized into four groups:troubled, symptomatic but content, vulnerable, and complete mental health. Gender differences were analyzed by using Chi-square tests, trends were tested with Cochran-Armitage tests, and multinomial Logistic regression models were applied to assess associations between muscle strength and mental health among adolescents. Results: In 2019, 37.4% of Chinese adolescents aged 13-18 were reported of high mental distress, and 59.9% were reported of low mental well being. Boys had significantly lower rates of high mental distress (35.3%) and low mental well being (55.6%) compared to girls (39.4%, 64.3%), and the differences were of statistical significance ( χ 2=176.13, 780.42, both P <0.05). In 2019, the rate of complete mental health among adolescents showed a downward trend with increasing age ( χ 2 trend = 258.47) and a gradual upward trend with increasing muscle strength levels ( χ 2 trend =123.14)，and both boys and girls exhibited similar trends ( χ 2 trend =103.83, 168.46; 57.00 , 67.34) (all P <0.05). The results of the unordered multiclass Logistic regression model showed that after controlling for confounding factors such as age and gender, when the completely pathological group as a reference, for every 1 unit increase in MSI in adolescents, the likelihood of being in a completely mental health state increased by 29% ( OR = 1.29); for every unit increase in the Z-score for pull ups, the likelihood of being in a completely mental health state increased by 6% ( OR =1.06) among boys; for every 1 unit increase in sit up Z score, the likelihood of being in a completely mental health state increased by 19% ( OR =1.19) among girls (all P <0.05). Conclusions The mental health status of Chinese adolescents is not good enough. Muscle strength is positively associated with mental health.

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 analyze the changes in the prevalence characteristics of multimorbidity among adolescents aged 13-18 in Inner Mongolia Autonomous Region from 2019 to 2022 and to explore the association between multimorbidity and moderate to high-intensity physical activity among them.Methods:A stratified random cluster sampling method was used to select students aged 13-18 in Inner Mongolia Autonomous Region every September from 2019 to 2022. Physical examinations, demographic characteristics, and depression-related surveys were conducted to analyze the multimorbidity of overweight, obesity, high blood pressure, myopia, spinal curvature abnormality, and depression. A logistic regression model was used to analyze the association between multimorbidity and moderate to high-intensity physical activity.Results:From 2019 to 2022, 70 972, 62 923, 80 254, and 78 288 study subjects were included, with the rates of multimorbidity being 56.4%, 55.4%, 57.2%, and 55.8%, respectively. The rates of multimorbidity remained relatively stable from 2019 to 2022 ( χ2=0.06, P=0.950). The incidence of multimorbidity among girls was significantly higher than that among boys ( P<0.001). The incidence of multimorbidity among urban students was significantly higher than that among suburban students ( P<0.001). The incidence of multimorbidity among high school students was higher than that among middle school students ( P<0.001). The top three multimorbidity combinations were myopia and overweight/obesity (26.4%), myopia and high blood pressure (24.4%), and myopia and depression (19.8%), while the least common combination was depression and spinal curvature abnormality (1.1%). The multimorbidity patterns showed no significant differences between years ( χ2=0.03, P=0.999). The multimorbidity status was significantly associated with the status of meeting the standard of moderate to high-intensity physical activity ( OR=0.83, 95% CI: 0.80-0.86). The association was stronger in boys ( OR=0.77, 95% CI: 0.73-0.81) compared with girls ( OR=0.90, 95% CI: 0.85-0.96), with a significant interaction term ( P<0.001). Conclusion:From 2019 to 2022, the incidence of multimorbidity among adolescents aged 13 to 18 in Inner Mongolia Autonomous Region is relatively high, mainly due to the co-occurrence of myopia and other health problems. Adequate physical activity is an important factor in reducing multimorbidity.

Objective:To study the risk factors and dosiomics-based prediction model of bone marrow suppression in patients with esophageal cancer during radiotherapy.Methods:Clinic data and radiotherapy planning documents of 107 patients with oesophageal cancer who underwent radiotherapy at the First Affiliated Hospital of Nanjing Medical University from January 2021 to May 2024 were retrospectively analyzed. Blood test results before and during radiotherapy were collected, and patients were classified into myelosuppressive groups (≤grade 1 and ≥grade 2). Clinical features, traditional dosimetric features and dosiomics features were collected, respectively. According to the stratified randomization grouping method, all patients were divided into the training and test sets in a 7 vs. 3 ratio. The region of interest was obtained by automatically outlining the thoracic skeleton (including the sternum, thoracic vertebrae and ribs) by AccuContour software. Dosiomics features were extracted from the dose distribution of the thoracic skeleton, and these features were screened using the independent samples t-test, the muse selector and the least absolute shrinkage operator. Subsequently, the dosiomic scores were calculated. Statistically significant clinical characteristics were screened using univariate and multivariate logistic regression analyses. Support vector machine method was used to construct a clinical model and a clinical combined with dosiomic model. Subsequently, nomogram was drawn for clinical prediction. The clinical efficacy and clinical benefit of predictive model were assessed by plotting the receiver operating characteristic (ROC) curve and evaluating its performance through the area under the ROC curve (AUC), the calibration curve and decision curve analysis (DCA). Results:Thirteen dosiomic features associated with bone marrow suppression were screened. Based on both univariate and multivariate logistic regression analyses, simultaneous chemotherapy, V 35 Gy and the average dose to bone were identified as statistically significant clinical predictors (all P<0.05). The AUC values of the combined model in the training and test sets were 0.800 and 0.776, higher than 0.709 and 0.650 of the clinical model. The calibration curves showed good agreement between the predicted and actual probabilities of the combined model. The DCA results showed that the net clinical benefit of the combined model was higher than that of the clinical model. Conclusions:The combined dosiomics-based model is effective in improving the predictive performance of bone marrow suppression occurring after radiotherapy for esophageal cancer.

Objective:This study aims to investigate the alterations in m 6A methylation associated with age-related idiopathic pulmonary fibrosis(IPF). Methods:By collecting peripheral blood samples from IPF patients, we investigated the changes in m6A modification levels of total RNA and key regulatory factors in elderly IPF patients.Then, the pulmonary fibrosis models of young and old mice were constructed for verification.A total of 10 IPF patients and 10 healthy controls were selected for this study.The m 6A methylation quantitative kit was employed to assess the m 6A modification levels of total RNA.The expression levels of key m 6A methylation regulators, METTL3, METTL14, and FTO, were quantified using qRT-PCR.Additionally, thirty-two healthy male C57BL/6 mice, comprising 16 mice aged 10-12 weeks and 16 mice aged 6-7 months, were divided into four groups: young control(A), young pulmonary fibrosis(B), aged control(C), and aged pulmonary fibrosis(D), with 8 mice in each group.Mice in groups B and D were intratracheally administered bleomycin to establish a pulmonary fibrosis model, while those in groups A and C received normal saline.Twenty-eight days post-model establishment, the mice were euthanized, and lung tissues were collected for analysis.Histological evaluations were performed using hematoxylin and eosin(HE)staining, Masson staining, hydroxyproline content determination, and immunohistochemistry to assess the extent of pulmonary fibrosis.The m 6A methylation quantification kit was also utilized to measure the m 6A modification levels of total RNA in lung tissue.Furthermore, the mRNA and protein expression levels of the methyltransferase METTL3 were assessed by qRT-PCR and Western blot experiments. Results:The level of m 6A modification was significantly elevated in the aged IPF patient group(0.36±0.03)compared to the control group t=4.882( P<0.05).Furthermore, the expression of METTL3 was markedly higher in the aged IPF patients( t=6.082), while the expression of METTL14 was significantly lower t=17.58( P<0.05).In contrast, the expression level of FTO did not exhibit a significant difference.It is hypothesized that the increased m 6A modification of total RNA in aged IPF patients is closely associated with METTL3.Furthermore, the degree of lung fibrosis in aged mice was more severe than that in young mice.Immunohistochemistry results indicated that TGF-β1 expression was elevated in the lung fibrosis group, with higher levels observed in group D compared to group B( t=5.891, P<0.05), and in group C compared to group A t=4.135( P<0.05).The percentage of positive area for α-SMA was significantly greater in the lung fibrosis mouse model than in the control group t=20.08( P<0.05).The level of m 6A modification was increased in both lung fibrosis groups relative to the normal control group( P<0.05), although no significant difference was found between group D and group B. Overall, METTL3 mRNA and protein expression were upregulated in the lung fibrosis group, with expression in group D being lower than in group B( P<0.05). Conclusions:The level of m 6A modification is elevated in pulmonary fibrosis, and the expression of METTL3 is upregulated in this condition.The downregulation of METTL3 may be associated with the extent of aging, which subsequently exacerbates the progression of pulmonary fibrosis.

Objective:To analyze the changes in the prevalence characteristics of multimorbidity among adolescents aged 13-18 in Inner Mongolia Autonomous Region from 2019 to 2022 and to explore the association between multimorbidity and moderate to high-intensity physical activity among them.Methods:A stratified random cluster sampling method was used to select students aged 13-18 in Inner Mongolia Autonomous Region every September from 2019 to 2022. Physical examinations, demographic characteristics, and depression-related surveys were conducted to analyze the multimorbidity of overweight, obesity, high blood pressure, myopia, spinal curvature abnormality, and depression. A logistic regression model was used to analyze the association between multimorbidity and moderate to high-intensity physical activity.Results:From 2019 to 2022, 70 972, 62 923, 80 254, and 78 288 study subjects were included, with the rates of multimorbidity being 56.4%, 55.4%, 57.2%, and 55.8%, respectively. The rates of multimorbidity remained relatively stable from 2019 to 2022 ( χ2=0.06, P=0.950). The incidence of multimorbidity among girls was significantly higher than that among boys ( P<0.001). The incidence of multimorbidity among urban students was significantly higher than that among suburban students ( P<0.001). The incidence of multimorbidity among high school students was higher than that among middle school students ( P<0.001). The top three multimorbidity combinations were myopia and overweight/obesity (26.4%), myopia and high blood pressure (24.4%), and myopia and depression (19.8%), while the least common combination was depression and spinal curvature abnormality (1.1%). The multimorbidity patterns showed no significant differences between years ( χ2=0.03, P=0.999). The multimorbidity status was significantly associated with the status of meeting the standard of moderate to high-intensity physical activity ( OR=0.83, 95% CI: 0.80-0.86). The association was stronger in boys ( OR=0.77, 95% CI: 0.73-0.81) compared with girls ( OR=0.90, 95% CI: 0.85-0.96), with a significant interaction term ( P<0.001). Conclusion:From 2019 to 2022, the incidence of multimorbidity among adolescents aged 13 to 18 in Inner Mongolia Autonomous Region is relatively high, mainly due to the co-occurrence of myopia and other health problems. Adequate physical activity is an important factor in reducing multimorbidity.

Objective:This study aims to investigate the alterations in m 6A methylation associated with age-related idiopathic pulmonary fibrosis(IPF). Methods:By collecting peripheral blood samples from IPF patients, we investigated the changes in m6A modification levels of total RNA and key regulatory factors in elderly IPF patients.Then, the pulmonary fibrosis models of young and old mice were constructed for verification.A total of 10 IPF patients and 10 healthy controls were selected for this study.The m 6A methylation quantitative kit was employed to assess the m 6A modification levels of total RNA.The expression levels of key m 6A methylation regulators, METTL3, METTL14, and FTO, were quantified using qRT-PCR.Additionally, thirty-two healthy male C57BL/6 mice, comprising 16 mice aged 10-12 weeks and 16 mice aged 6-7 months, were divided into four groups: young control(A), young pulmonary fibrosis(B), aged control(C), and aged pulmonary fibrosis(D), with 8 mice in each group.Mice in groups B and D were intratracheally administered bleomycin to establish a pulmonary fibrosis model, while those in groups A and C received normal saline.Twenty-eight days post-model establishment, the mice were euthanized, and lung tissues were collected for analysis.Histological evaluations were performed using hematoxylin and eosin(HE)staining, Masson staining, hydroxyproline content determination, and immunohistochemistry to assess the extent of pulmonary fibrosis.The m 6A methylation quantification kit was also utilized to measure the m 6A modification levels of total RNA in lung tissue.Furthermore, the mRNA and protein expression levels of the methyltransferase METTL3 were assessed by qRT-PCR and Western blot experiments. Results:The level of m 6A modification was significantly elevated in the aged IPF patient group(0.36±0.03)compared to the control group t=4.882( P<0.05).Furthermore, the expression of METTL3 was markedly higher in the aged IPF patients( t=6.082), while the expression of METTL14 was significantly lower t=17.58( P<0.05).In contrast, the expression level of FTO did not exhibit a significant difference.It is hypothesized that the increased m 6A modification of total RNA in aged IPF patients is closely associated with METTL3.Furthermore, the degree of lung fibrosis in aged mice was more severe than that in young mice.Immunohistochemistry results indicated that TGF-β1 expression was elevated in the lung fibrosis group, with higher levels observed in group D compared to group B( t=5.891, P<0.05), and in group C compared to group A t=4.135( P<0.05).The percentage of positive area for α-SMA was significantly greater in the lung fibrosis mouse model than in the control group t=20.08( P<0.05).The level of m 6A modification was increased in both lung fibrosis groups relative to the normal control group( P<0.05), although no significant difference was found between group D and group B. Overall, METTL3 mRNA and protein expression were upregulated in the lung fibrosis group, with expression in group D being lower than in group B( P<0.05). Conclusions:The level of m 6A modification is elevated in pulmonary fibrosis, and the expression of METTL3 is upregulated in this condition.The downregulation of METTL3 may be associated with the extent of aging, which subsequently exacerbates the progression of pulmonary fibrosis.

Objective:To study the risk factors and dosiomics-based prediction model of bone marrow suppression in patients with esophageal cancer during radiotherapy.Methods:Clinic data and radiotherapy planning documents of 107 patients with oesophageal cancer who underwent radiotherapy at the First Affiliated Hospital of Nanjing Medical University from January 2021 to May 2024 were retrospectively analyzed. Blood test results before and during radiotherapy were collected, and patients were classified into myelosuppressive groups (≤grade 1 and ≥grade 2). Clinical features, traditional dosimetric features and dosiomics features were collected, respectively. According to the stratified randomization grouping method, all patients were divided into the training and test sets in a 7 vs. 3 ratio. The region of interest was obtained by automatically outlining the thoracic skeleton (including the sternum, thoracic vertebrae and ribs) by AccuContour software. Dosiomics features were extracted from the dose distribution of the thoracic skeleton, and these features were screened using the independent samples t-test, the muse selector and the least absolute shrinkage operator. Subsequently, the dosiomic scores were calculated. Statistically significant clinical characteristics were screened using univariate and multivariate logistic regression analyses. Support vector machine method was used to construct a clinical model and a clinical combined with dosiomic model. Subsequently, nomogram was drawn for clinical prediction. The clinical efficacy and clinical benefit of predictive model were assessed by plotting the receiver operating characteristic (ROC) curve and evaluating its performance through the area under the ROC curve (AUC), the calibration curve and decision curve analysis (DCA). Results:Thirteen dosiomic features associated with bone marrow suppression were screened. Based on both univariate and multivariate logistic regression analyses, simultaneous chemotherapy, V 35 Gy and the average dose to bone were identified as statistically significant clinical predictors (all P<0.05). The AUC values of the combined model in the training and test sets were 0.800 and 0.776, higher than 0.709 and 0.650 of the clinical model. The calibration curves showed good agreement between the predicted and actual probabilities of the combined model. The DCA results showed that the net clinical benefit of the combined model was higher than that of the clinical model. Conclusions:The combined dosiomics-based model is effective in improving the predictive performance of bone marrow suppression occurring after radiotherapy for esophageal cancer.

Objective:To investigate the correlation between immune function and age-related pulmonary fibrosis, as well as the potential impact of bacterial lysates on this condition.Methods:Twenty-four healthy male C57BL/6 mice, aged 24, were randomly divided into three groups: a control group(Group N), a pulmonary fibrosis group(Group M), and a pulmonary fibrosis+ bacterial lysis product intervention group(Group P). Mice in Groups M and P were intratracheally injected with bleomycin(5 mg/kg)to induce a mouse pulmonary fibrosis model, while mice in Group N were injected with saline.After modeling, mice in Group P were orally administered 0.4 ml of a bacterial lysis product once a day.After 28 days, lung tissue and blood samples were collected for analysis.Pathological changes in lung tissue were assessed using hematoxylin and tosin staining(HE)and Masson staining and the Ashcroft score.The expression of CD4+ and CD8+ in lung tissue was evaluated using immunohistochemistry.The levels of serum interferon-γ(INF-γ), interleukin-3(IL-13), and immunoglobulin A(IgA)protein were measured using Enzyme-linked Immuno Sorbent Assay(ELISA). The levels of INF-γ and IL-13 mRNA in lung tissue were determined using Real-Time Quantitative Transcription PCR(RT-qPCR). Additionally, the protein expression levels of matrix metalloprotein-9(MMP-9)and tissue inhibitor of metalloproteincise 1(TIMP-1)in lung tissue were assessed using blot analysis.Results:The degree of lung fibrosis was significantly reduced in mice in group P compared with group M when treated with bacterial lysis products.Group M showed a significant decrease in the expression of CD4+ T cells and an increase in the expression of CD8+ T cells( P<0.05)compared to group N. Additionally, the content of IgA was decreased( P<0.05)in group M. On the other hand, group P showed a significant increase in the expression of CD4+ T cells and a decrease in the expression of CD8+ T cells( P<0.05)compared to group M. Furthermore, the content of IgA was elevated( P<0.05)in group P. After bacterial lysis product intervention, mRNA and protein expression levels of IFN-γ were elevated( P<0.05), while mRNA and protein expression levels of IL-13 were reduced( P<0.05). Moreover, protein expression of MMP-9 and TIMP-1 was significantly up-regulated in group M compared with group N( P<0.05), and decreased after bacterial lysis product intervention( P<0.05). Conclusions:It is well-known that immune mechanisms play a crucial role in the development of pulmonary fibrosis.The use of bacterial lysates has been found to effectively regulate immune balance and mitigate the severity of pulmonary fibrosis in elderly mice.