BACKGROUND:Mesenchymal stem cells show extremely therapeutic potential for radiation-induced lung injury through delivering exosomes.Age is a primary factor affecting the function and biological efficacy of mesenchymal stem cells.OBJECTIVE:To investigate the protective effects of exosomes derived from bone marrow mesenchymal stem cells of different mouse ages on radiation-induced lung injury in mice.METHODS:Bone marrow mesenchymal stem cells of young mice and old mice were obtained by whole bone marrow adherent culture.The exosomes were isolated from the supernatant of passage 3 bone marrow mesenchymal stem cells.Ten 2-month-old C57BL/6J mice were randomly selected as the control group after anesthesia and not irradiated.The remaining 30 2-month-old C57BL/6J mice were used to establish a mouse radiation-induced lung injury model and were randomly divided into three groups.Exosomes derived from bone marrow mesenchymal stem cells of young mice,exosomes derived from bone marrow mesenchymal stem cells of old mice,and PBS were injected through the tail vein,respectively.The survival rate of mice was monitored.The lung function,lung inflammation and fibrosis were assessed at 1 and 12 weeks after irradiation.RESULTS AND CONCLUSION:(1)The concentrations of particles and proteins in exosomes derived from bone marrow mesenchymal stem cells of young mice were higher than those in exosomes derived from bone marrow mesenchymal stem cells of old mice.(2)Compared with the control group,the survival rate of mice in the PBS group was low,and lung inflammation was obvious at week 1 after irradiation,and the levels and mRNA expressions of interleukin-1β,interleukin-6,and tumor necrosis factor-α were increased.Collagen deposition in lung tissues was observed at week 12 after irradiation,and the mRNA level of E-cadherin was decreased,while the mRNA levels of α-smooth muscle actin,transforming growth factor-β1,and β-catenin were increased.(3)Compared with the PBS group,the survival rate of mice in the exosome group was significantly improved,and the level of proinflammatory factors and their mRNA expression were reduced at week 1 after irradiation,the mRNA level of E-cadherin was increased,and the mRNA levels of α-smooth muscle actin,transforming growth factor β1 and β-catenin were reduced at week 12 after irradiation.(4)Among all the above indicators,the therapeutic effect of exosomes derived from bone marrow mesenchymal stem cells of young mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice.(5)The results showed that exosomes derived from bone marrow mesenchymal stem cells of young mice contained more particles and proteins,and the effect of alleviating early inflammation and late fibrosis of radiation-induced lung injury in mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice.

BACKGROUND:Mesenchymal stem cells show extremely therapeutic potential for radiation-induced lung injury through delivering exosomes.Age is a primary factor affecting the function and biological efficacy of mesenchymal stem cells.OBJECTIVE:To investigate the protective effects of exosomes derived from bone marrow mesenchymal stem cells of different mouse ages on radiation-induced lung injury in mice.METHODS:Bone marrow mesenchymal stem cells of young mice and old mice were obtained by whole bone marrow adherent culture.The exosomes were isolated from the supernatant of passage 3 bone marrow mesenchymal stem cells.Ten 2-month-old C57BL/6J mice were randomly selected as the control group after anesthesia and not irradiated.The remaining 30 2-month-old C57BL/6J mice were used to establish a mouse radiation-induced lung injury model and were randomly divided into three groups.Exosomes derived from bone marrow mesenchymal stem cells of young mice,exosomes derived from bone marrow mesenchymal stem cells of old mice,and PBS were injected through the tail vein,respectively.The survival rate of mice was monitored.The lung function,lung inflammation and fibrosis were assessed at 1 and 12 weeks after irradiation.RESULTS AND CONCLUSION:(1)The concentrations of particles and proteins in exosomes derived from bone marrow mesenchymal stem cells of young mice were higher than those in exosomes derived from bone marrow mesenchymal stem cells of old mice.(2)Compared with the control group,the survival rate of mice in the PBS group was low,and lung inflammation was obvious at week 1 after irradiation,and the levels and mRNA expressions of interleukin-1β,interleukin-6,and tumor necrosis factor-α were increased.Collagen deposition in lung tissues was observed at week 12 after irradiation,and the mRNA level of E-cadherin was decreased,while the mRNA levels of α-smooth muscle actin,transforming growth factor-β1,and β-catenin were increased.(3)Compared with the PBS group,the survival rate of mice in the exosome group was significantly improved,and the level of proinflammatory factors and their mRNA expression were reduced at week 1 after irradiation,the mRNA level of E-cadherin was increased,and the mRNA levels of α-smooth muscle actin,transforming growth factor β1 and β-catenin were reduced at week 12 after irradiation.(4)Among all the above indicators,the therapeutic effect of exosomes derived from bone marrow mesenchymal stem cells of young mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice.(5)The results showed that exosomes derived from bone marrow mesenchymal stem cells of young mice contained more particles and proteins,and the effect of alleviating early inflammation and late fibrosis of radiation-induced lung injury in mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice.

Gastric ulcer （GU） is a high-incidence digestive system disease characterized pathologically by disruption of gastric mucosal integrity， with clinical features including a prolonged course and periodic recurrence. Modern medicine attributes its pathogenesis to the dynamic imbalance between aggressive and defensive factors，while traditional Chinese medicine （TCM） posits its development as closely linked to spleen deficiency. Current therapies combining acid suppressants and antibiotics face challenges such as high recurrence rates，poor mucosal healing，and adverse drug reactions. Long-term use may induce metabolic disturbances like hypergastrinemia and reduced intestinal microbiota diversity. Therefore，exploring safer and longer-lasting therapeutic strategies has become a critical focus. TCM has extensive clinical experience and unique advantages in GU prevention and treatment. Studies demonstrate that the classic formula Shenling Baizhu San exhibits therapeutic properties of "invigorating spleen and tonifying Qi to restore physiological balance and eliminating dampness and regulating middle energizer to unblock Qi movement"， enabling a holistic approach targeting both symptoms and root causes in GU with spleen deficiency as the core pathology by suppressing aggressive factors and strengthening defensive factors. Experimental research reveals its mechanisms involve enhancing the physicochemical barrier of the mucus layer，repairing epithelial barriers and microcirculation，modulating gastric acid secretion and gastrointestinal motility，and regulating microecological barriers and mucosal immunity. Clinical evidence confirms its synergistic effects in promoting ulcer healing，improving Helicobacter pylori eradication rates，and reducing recurrence risks. This review examined the etiology and pathogenesis of GU and systematically evaluated Shenling Baizhu San from three perspectives-clinical application，pharmacological effects， and experimental research-to provide insights for optimizing integrated traditional Chinese and Western medicine protocols and expanding its clinical applications.

Objective: To evaluate the risk of donation-related adverse reactions, donation behavior, and contributions to the blood supply among donors aged 56-65 years following extension of the upper age limit for voluntary blood donation, and to provide real-world evidence for optimizing blood donation age policies in China. Methods: A multicenter retrospective cohort was established using blood donation databases from Hainan, Shenzhen, and Jiangxi. A total of 1 180 767 donors contributing 2 020 407 whole-blood and apheresis donations were included. Donations were classified by donor age at each donation into the 18-55-year and 56-65-year groups. Generalized estimating equation (GEE) models were used to compare the risks of overall, local, and systemic donation-related adverse reactions between the two age groups. Restricted cubic spline analysis was used to assess the continuous association between donor age and the risk of overall adverse reactions. Poisson GEE models were used to compare annual donation frequency, and donation participation and contributions to the blood supply among donors aged 56-65 years were evaluated. The study was approved by the Ethics Committee of the Institute of Blood Transfusion, Chinese Academy of Medical Sciences (No.2025012) and registered with the Chinese Clinical Trial Registry (ChiCTR2500114960). Results: A total of 1 960 711 donations were included in the 18-55-year group and 59 696 in the 56-65-year group. The overall donation-related adverse reaction rates were 3.890‰and 0.704‰, respectively. Multivariable GEE analysis showed that, compared with donors aged 18-55 years, those aged 56-65 years had lower risks of overall adverse reactions (adjusted OR=0.294, 95%CI: 0.217-0.398, P<0.001) and systemic adverse reactions (adjusted OR=0.163, 95%CI: 0.101-0.263, P<0.001), whereas no statistically significant difference was observed in the risk of local adverse reactions (adjusted OR=1.337, 95%CI: 0.487-3.670, P=0.573). Donor age was nonlinearly associated with the risk of overall adverse reactions (P overall<0.001, P nonlinear<0.001), with the risk generally decreasing with increasing age between 18 and 65 years. The mean annual donation frequency was higher among donors aged 56-65 years than among those aged 18-55 years (1.63 vs 1.24 donations per year; adjusted IRR=1.34, 95%CI: 1.30-1.39, P<0.001). During the study period, donors aged 56-65 years contributed 2.95% of all donations; their whole-blood donations and whole-blood collection volume accounted for 2.36% and 2.37% of the corresponding totals, respectively. Conclusion: Under current health screening and standardized donor management, donors aged 56-65 years did not show an increased risk of short-term donation-related adverse reactions and demonstrated a higher annual donation frequency, together with a measurable contribution to the blood supply. These findings support appropriately extending the upper age limit for voluntary blood donation under strict health screening to broaden the donor pool and supplement the blood supply.

Objective: To investigate the dose response relationship between waist-to-height ratio (WHtR) and elevated blood pressure among primary and secondary school students in Meishan City, so as to provide a reference for precise prevention and control of elevated blood pressure in children and adolescents. Methods: From September to October 2025, a stratified cluster random sampling method was used to select 10 399 primary and secondary school students in Meishan City for measurements of height, weight, waist circumference, and blood pressure. Chi-square trend test, Logistic regression and restricted cubic spline model were used to analyze the association and dose response relationship between WHtR and elevated blood pressure among primary and secondary school students. Results: WHtR showed a linear association with elevated blood pressure among boys of all age groups (7-11，12-14，15-17 years) groups and girls aged 10-12, 13-15, and 16-17 years (all P non linear >0.05); whereas girls aged 7-9 years exhibited a U shaped association ( P non linear<0.05). WHtR was stratified by age and sex and divided into quartile groups ( Q1-Q 4). Multivariate Logistic regression analysis showed that after adjusting for age and body mass index (BMI), the risks of elevated blood pressure increased among boys in groups Q2-Q 4 [ OR (95% CI )=1.33(1.07-1.67), 1.43(1.14-1.80), 1.45( 1.08- 1.95), respectively], and among girls aged 10-17 years in Q 4 group [ OR (95% CI )=1.43(1.04-1.97)] (all P <0.05). Based on the left and right side thresholds (0.36 and 0.46) identified from the U shaped curve among girls aged 7-9 years, WHtR was categorized into low , medium , and high value groups. Without adjusting for BMI, the risks of elevated blood pressure increased in the low and high groups[ OR (95% CI )=2.36(1.44-3.89), 1.48(1.06-2.08)]; after adjusting for BMI, the risk of elevated blood pressure increased in the low group[ OR (95% CI )=2.93(1.76-4.88)] (all P <0.05). Conclusions WHtR is linearly and positively associated with elevated blood pressure among boys aged 7-17 years and girls aged 10-17 years, independent of BMI. Among girls aged 7-9 years, both low and high WHtR are associated with an increased risk of elevated blood pressure, and the risk effect of low WHtR is independent of BMI.

OBJECTIVE To explore the effect and mechanism of Zhiqiao gancao decoction （ZQGCD） on pathological angiogenesis of degenerative intervertebral disc. METHODS The rats were randomly divided into sham operation group （normal saline）， model group （normal saline）， hypoxia inducible factor-1α （HIF-1α） inhibitor （YC-1） group [2 mg/（kg·d）， tail vein injection]， and ZQGCD low-dose， medium-dose and high-dose groups [3.06， 6.12， 12.24 g/（kg·d）]， with 8 rats in each group. Except for sham operation group， lumbar disc degeneration model of rat was constructed in all other groups. After modeling， they were given relevant medicine once a day， for consecutive 3 weeks. After the last medication， pathological changes and angiogenesis of the intervertebral disc tissue in rats were observed； the levels of inflammatory factors [interleukin-1β （IL-1β）， IL-6， tumor necrosis factor-α （TNF-α）] and the expressions of angiogenesis-related proteins [HIF-1α， vascular endothelial growth factor （VEGF）， VEGF receptor 2 （VEGFR2）， angiotensin 1（Ang 1）， Ang 2] in the com intervertebral disc tissue in rats were all determined. In cell experiment， the primary nucleus pulposus cells were isolated and cultured from rats， and cellular degeneration was induced using 50 ng/mL TNF-α. The cells were divided into blank control group （10% blank control serum）， TNF-α group （10% blank control serum）， YC-1 group （10% blank control serum+0.2 mmol/L YC-1）， and 5%， 10%， 15% drug-containing serum group （5%， 10%， 15% drug-containing serum）. After 24 hours of intervention， the nucleus pulposus cells were co-cultured with HUVEC. The expressions of Collagen Ⅱ， matrix metalloproteinase-3 （MMP-3） in nucleus pulposus cells were detected. HUVEC proliferation， migration and tube forming ability were detected， and the expression levels of the HIF-1α/VEGF/Ang signal axis and angiogenesis- related proteins （add MMP-2， MMP-9） in HUVEC were detected. RESULTS Animal experiments had shown that compared with model group， the positive expression of CD31 in the intervertebral disc tissues of rats in each drug group was down-regulated （P＜ 0.05）， the levels of inflammatory factors and angiogenesis-related proteins were decreased significantly （P＜0.05）， and the pathological changes in the intervertebral disc were alleviated. Cell experiments had shown that compared with TNF-α group， the expression of Collagen Ⅱ in nucleus pulposus cells of all drug groups was significantly up-regulated （P＜0.05）， and the expression of MMP-3 was significantly down-regulated （P＜0.05）； the proliferation， migration and tubulogenesis of HUVEC were significantly weakened （P＜0.05）. The mRNA and protein expressions of HIF-1α， VEGF， Ang 2 as well as the expression of angiogenesis-related proteins （except for the expression of Ang 2 mRNA and HIF-1α， VEGFR2， Ang 2 protein in 5% drug- containing serum group） were significantly down-regulated （P＜0.05）. CONCLUSIONS ZQGCD may inhibit the HIF-1α/VEGF/ Ang signal axis to weaken the angiogenic ability of vascular endothelial cells， improve pathological angiogenesis in the intervertebral disc， and delay the degeneration of the intervertebral disc.

ObjectiveTo investigate the prevalence of gynecological and breast diseases among retired or economically disadvantaged women in part of Pudong New Area of Shanghai under the policy support of screening gynecological diseases and breast diseases for retired and women with economic difficulties in life in Shanghai, to analyze the characteristics of these diseases, so as to provide a scientific basis for the improvement of relevant prevention and treatment strategies. MethodsBased on the gynecological census data of 13 031 cases in five towns, including Xinchang Town, Xuanqiao Town, Laogang Town, Wanxiang Town and Shuyuan Town, conducted by Shanghai Pudong Hospital in 2023, descriptive analysis methods were used to explore the prevalence and age characteristics of common gynecological and breast diseases. ResultsThe total detection rate of gynecological and breast diseases among women in the screening area in this study was 68.29%, with uterine fibroid (22.35%), sarcoidosis of the breast (17.06%), cervicitis (15.37%), vaginitis (8.39%) and ovarian cyst (2.61%) ranking the top 5 in the detection rate among the screening population. The differences of the detection rates in the four major diseases [uterine fibroid (χ²=233.217, P<0.001), breast nodules(χ²=169.896, P<0.001), cervicitis (χ²=388.683, P<0.001), and ovarian cysts (χ²=72.298, P<0.001)] by different age groups were statistically significant (P<0.05) . Moreover, the results of pairwise comparison of different age groups showed that the detection rates in the age group under 45 years old and 45‒55 years old were higher than that in the age group of 55‒65 years old and over 65 years old. ConclusionThe detection rate of gynecological and breast diseases in the younger age group was higher, indicating a certain trend of younger onset of diseases. Uterine fibroid, sarcoidosis of the breast , and reproductive tract diseases such as cervicitis, vaginitis, and ovarian cyst are the main diseases affecting the research subjects. Therefore, medical institutions can combine routine work in screening diseases and carry out corresponding health education and health promotion activities for these key diseases to improve women’s health.

Objective To identify the enhancer profile marked by histone H3K27ac modification in high-grade intraepithelial neoplasia(HGIN)in order to reveal the novel regulatory mechanism of HGIN pathogensis.Methods Gastric tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA between June 2022 and June 2023,including 14 normal gastric tissues(Nor group),31 HGIN tissues(HGIN group)and 17 gastric cancer tissues(GC group).Cleavage under targets and tagmentation(CUT&Tag)technique was employed to capture enhancer regions modified by histone H3K27ac.Multi-omics analysis was performed to identify HGIN-specific active enhancers and their potentially regulated genes.Immunohistochemical profiling was performed to assess differential expression of the gene of interest across clinically stratified specimens,combined with CRISPR-dCas9-mediated ablation of active enhancers to monitor the gene of interest transcriptional dynamics and validate enhancer-mediated regulatory mechanisms.Results Epigenomic sequencing obtained the data with excellent quality,and indicated that obvious remodeling was observed in H3K27ac enhancers in HGIN and GC groups(P<0.05),though no significant difference in the genome-wide distribution of H3K27ac modification among the 3 groups.Combining transcriptome data revealed that enhancer remodeling may up-regulate the expression of the proliferation-related target gene,CD24,in the HGIN tissue;while,inhibiting enhancer activity can notably reduce CD24 expression level(P<0.05).Immunohistochemical assay displayed a positive correlation between the expression levels of CD24 and Ki-67(P<0.001).Conclusion The remodeling of H3K27ac enhancer represents a significant epigenetic feature of the transformation from normal condition to HGIN.Remodeling of H3K27ac enhancer up-regulates CD24,which may facilitate the abnormal proliferation of gastric epithelial cells.

Objective To analyze clinical characteristics of mesenchymal-subtype gastric cancer(Mes-GC)by integrating multi-omics data and explore the characteristics of tumor cells and microenvironment associated with the risk for recurrence.Methods Gastric tumor tissue samples were collected from the patients who visited Department of Gastroenterology of Army Medical Center of PLA from January 2022 to December 2023.Transcriptome and genome sequencing were applied for these tissue samples,including 19 cases of diffuse-type gastric cancer,22 cases of intestinal-type gastric cancer,and 23 cases of mixed-type gastric cancer patients.Bioinformatics analysis was employed to investigate the differences in clinical characteristics and tumor microenvironment between Mes-GC and non-mesenchymal-subtype gastric cancer(non-Mes-GC)by integrating data resources including The Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO),and National Genomics Data Center(NGDC).Results Compared to non-Mes-GC patients,Mes-GC ones were characterized by later clinical stages,deeper tumor infiltration,and higher rates of lymph node metastasis.Kaplan-Meier survival analysis confirmed that Mes-GC patients were associated with shorter survival time,poor prognosis as well as increased risk of cancer recurrence(P<0.05).Single-cell RNA sequencing data revealed that tumor cells in Mes-GC showed higher expression levels of the genes related to stemness,metastasis(P<0.05),and epithelial-mesenchymal transition(EMT).And in the tumor microenvironment,there were significant more myeloid cells,smooth muscle cells,endothelial cells and fibroblasts,with the most pronounced elevation in the proportion of fibroblasts(P<0.05).Moreover,the patients with larger proportion of fibroblasts were associated with poorer prognosis.Conclusion Mes-GC tumor cells exhibit higher stemness and EMT characteristics,and stromal cells such as myeloid cells,endothelial cells,and fibroblasts are enriched in the tumor microenvironment.These features may be key factors contributing to poor prognosis and high recurrence rate of Mes-GC.

Objective To identify the enhancer landscape marked by histone H3K27ac modifications in diffuse-type gastric cancer(DGC)tissues,and to elucidate the epigenetic remodeling mechanisms by which active enhancers regulate cachexia-related genes.Methods Gastric mucosal tissue samples were collected from Department of Gastroenterology of Army Medical Center of PLA during January 2022 to March 2023,including 10 normal gastric mucosa tissues(Normal group),10 DGC tissues diagnosed with cachexia(DGC group),and 10 organoids derived from DGC tissues(Organoid group).Using H3K27ac chromatin targeting cleavage and tagmentation(CUT&Tag)technology,genomic modification regions were captured to screen specific active enhancers and their potential target genes in DGC tissues.CRISPR-dCas9 gene editing technology was used to intervene with the enhancers,and the expression of target genes was detected with Western blotting and qRT-PCR.Sixteen female SPF-grade BALB/c Nude mice(6～8 weeks old,weighing 18～21 g)were utilized to establish an orthotopic xenograft tumor model using the human diffuse-type gastric cancer cell line MKN45.Cachexia-related phenotypes were evaluated in 3 groups:normal group(n=4),silencing group(n=6),and control group(n=6).Results Significant differential enhancer regions were identified between DGC and normal gastric mucosa tissues.DGC tissues exhibited a marked increase in enhancer abundance(P<0.05)and signal intensity when compared with the normal counterparts.Integrated analysis of transcriptome data revealed that some of these active enhancers up-regulated the expression of GDF15,a cachexia-associated target gene in DGC.Targeted silencing of the active enhancer of GDF15 using CRISPR/dCas9-KRAB plasmid technology resulted in a significant reduction in GDF15 expression at both mRNA levels(P<0.05)and protein.Results from orthotopic transplantation experiments of DGC demonstrated that silencing of active enhancers alleviated the cachexia phenotype in nude mice(P<0.05).Conclusion DGC exhibits enhancer remodeling,which regulates the expression of the cachexia-associated gene GDF15,and thereby contributes to the pathogenesis and progression of cancer cachexia.