BACKGROUND:Aging of human body may be due to the senescence and depletion of various stem cells in the body.Bone marrow mesenchymal stromal cells have important physiological functions and have shown certain therapeutic effects on various diseases.It is of great significance to study the senescence and mechanism of bone marrow mesenchymal stromal cells.OBJECTIVE:To investigate whether human bone marrow mesenchymal stromal cells exhibit senescence phenotypes with increasing donor age,and further determine whether endogenous retrovirus drives the senescence of bone marrow mesenchymal stromal cells,offering a novel reference for the investigation of stem cell senescence mechanism.METHODS:The senescence of bone marrow mesenchymal stromal cells at different ages was characterized by flow cytometry,β-galactosidase staining,qPCR,western blotting,and EdU fluorescence imaging.Bone marrow mesenchymal stromal cells and cell culture supernatant were collected from donors of different ages.The content of human endogenous retrovirus was detected by qPCR.Furthermore,highly sensitive droplet digital PCR was used to detect the expression of endogenous retrovirus-like particles in the cell culture supernatant.The content of endogenous retrovirus in bone marrow plasma samples of different ages was detected by ELISA.RESULTS AND CONCLUSION:Bone marrow mesenchymal stromal cells exhibited obvious senescence with increasing age,including significant morphological changes,increased proportion of β-galactosidase positive cells,increased expression of senescence markers P16 and P21 protein,decreased expression of LMNB1 protein,and reduced cell proliferation ability.There was no significant difference in the content of endogenous retrovirus in bone marrow mesenchymal stromal cells at different ages,almost no endogenous retrovirus-like particles in the cell culture supernatant.There was no significant difference in endogenous retrovirus-like particles detected in bone marrow plasma samples at different ages.These findings indicate that human bone marrow mesenchymal stromal cells have normal physiological senescence with increasing age,but the mechanism of senescence is not mediated by abnormal activation of endogenous retroviruses,which may have a more complex driving mechanism.

BACKGROUND:Aging of human body may be due to the senescence and depletion of various stem cells in the body.Bone marrow mesenchymal stromal cells have important physiological functions and have shown certain therapeutic effects on various diseases.It is of great significance to study the senescence and mechanism of bone marrow mesenchymal stromal cells.OBJECTIVE:To investigate whether human bone marrow mesenchymal stromal cells exhibit senescence phenotypes with increasing donor age,and further determine whether endogenous retrovirus drives the senescence of bone marrow mesenchymal stromal cells,offering a novel reference for the investigation of stem cell senescence mechanism.METHODS:The senescence of bone marrow mesenchymal stromal cells at different ages was characterized by flow cytometry,β-galactosidase staining,qPCR,western blotting,and EdU fluorescence imaging.Bone marrow mesenchymal stromal cells and cell culture supernatant were collected from donors of different ages.The content of human endogenous retrovirus was detected by qPCR.Furthermore,highly sensitive droplet digital PCR was used to detect the expression of endogenous retrovirus-like particles in the cell culture supernatant.The content of endogenous retrovirus in bone marrow plasma samples of different ages was detected by ELISA.RESULTS AND CONCLUSION:Bone marrow mesenchymal stromal cells exhibited obvious senescence with increasing age,including significant morphological changes,increased proportion of β-galactosidase positive cells,increased expression of senescence markers P16 and P21 protein,decreased expression of LMNB1 protein,and reduced cell proliferation ability.There was no significant difference in the content of endogenous retrovirus in bone marrow mesenchymal stromal cells at different ages,almost no endogenous retrovirus-like particles in the cell culture supernatant.There was no significant difference in endogenous retrovirus-like particles detected in bone marrow plasma samples at different ages.These findings indicate that human bone marrow mesenchymal stromal cells have normal physiological senescence with increasing age,but the mechanism of senescence is not mediated by abnormal activation of endogenous retroviruses,which may have a more complex driving mechanism.

OBJECTIVE: To analyze the current status and temporal trends of the disease burden of spinal fractures in China from 1990 to 2021 based on data from the Global Burden of Disease Study 2021 (GBD 2021), aiming to provide evidence for developing prevention and treatment strategies. METHODS: Epidemiological data on spinal fractures in China, the United States of America (USA), and globally were extracted from the GBD 2021 database. Joinpoint regression models were applied to analyze temporal trends. Age-standardized incidence, prevalence, and disability-adjusted life years (DALYs) rates were calculated, with comparisons of gender- and age-group disparities. RESULTS: In 2021, the number of incident cases, prevalent cases, and DALYs of spinal fractures in China increased by 52.28%, 113.68%, and 106.98%, respectively, compared to 1990. The age-standardized incidence, prevalence, and DALYs rates rose by 11.80%, 16.11%, and 14.79%, respectively. The disease burden escalated significantly with age, peaking in individuals aged ≥75 years. Males exhibited higher age-standardized incidence and DALYs rates than females. Comparative analysis revealed that the age-standardized DALYs rate in China (4.19/100 000) was lower than that in globally (6.62/100 000) and USA (15.92/100 000). However, China showed an upward trend [annual average percentage change (AAPC)=0.19%], contrasting with a declining trend in the USA (AAPC=-0.08%). CONCLUSION The escalating disease burden of spinal fractures in China is closely linked to population aging, gender disparities, and insufficient targeted prevention policies. Future strategies should integrate age- and gender-specific interventions, including strengthened osteoporosis prevention, trauma risk control, and big data-driven precision measures, to mitigate this burden.
Humans ; China/epidemiology* ; Global Burden of Disease/trends* ; Male ; Female ; Spinal Fractures/epidemiology* ; Middle Aged ; Aged ; Disability-Adjusted Life Years ; Prevalence ; Incidence ; Adult ; Young Adult ; Adolescent ; Aged, 80 and over ; United States/epidemiology* ; Cost of Illness ; Quality-Adjusted Life Years ; Child

BACKGROUND:Mesenchymal stem cells have been widely used in the treatment of various diseases due to their wide range of sources,their ease of proliferation in vitro and their ability to secrete a range of immunomodulatory factors to suppress inflammation and promote tissue repair and regeneration.However,in the treatment of many diseases,the therapeutic effect is limited.The effort to engineer and modify mesenchymal stem cells for specific disease pathogenesis or intervention targets is an important development for cell therapy in the future.OBJECTIVE:Interleukin-10 is a typical anti-inflammatory cytokine that helps to modulate the immune response and induces macrophage polarization towards an anti-inflammatory phenotype.This study investigated the therapeutic effect of interleukin-10 engineered human umbilical cord mesenchymal stem cells on inflammatory bowel disease.METHODS:Human umbilical cord mesenchymal stem cells stably overexpressing interleukin-10 were established by electro-transfection,and screened for clinical-grade cells based on the cell therapy product criteria.C57BL/6J mice were given 5%aqueous dextran sulfate sodium ad libitum to establish a model of acute colitis.Empty plasmid-transfected human umbilical cord mesenchymal stem cells or interleukin-10-human umbilical cord mesenchymal stem cells(1×106 cells/each mouse)were injected on day 1 before modeling(tail vein injection)and day 4(intraperitoneal injection)after modeling,respectively.On day 6 after modeling,colon tissue sections were taken for hematoxylin-eosin staining to assess histological changes.Immunofluorescence staining was performed to detect the expression of proliferating cell nuclear antigen and CD31.RESULTS AND CONCLUSION:The engineered human umbilical cord mesenchymal stem cells stably overexpressing interleukin-10 were constructed,and met the quality standard of clinical-grade human umbilical cord mesenchymal stem cells.Human umbilical cord mesenchymal stem cells could repair acute colitis in mice.The therapeutic effect of interleukin-10-human umbilical cord mesenchymal stem cells was more efficacious,which more significantly suppressed body weight loss(P<0.05),colon shortening(P<0.05),and damage of colonic tissues(P<0.05)in acute colitis mice.In interleukin-10-human umbilical cord mesenchymal stem cell treatment group,there were significantly more proliferating cell nuclear antigen-positive cells and CD31-positive cells in the colon sections than in the human umbilical cord mesenchymal stem cell treatment group,suggesting that interleukin-10-overexpressing human umbilical cord mesenchymal stem cells contributed to the repair of colon tissue by significantly promoting the proliferation of intestinal tissues and angiogenesis.

Objective:To develop and validate a nomogram prediction model for major adverse cardiovascular events (MACE) in elderly patients with chronic heart failure (CHF) based on the ratio of homocysteine to free triiodothyronine (HCY/FT3).Methods:This research was a prognostic study. A total of 1 301 elderly patients with CHF admitted to the Department of General Practice of Shanghai Fifth People′s Hospital Affiliated to Fudan University from January 2018 to January 2023 were enrolled and divided into MACE group ( n=564) and non-MACE group ( n=737) according to whether MACE occurred at the end of the follow-up. Baseline clinical data was collected. The follow-up period was 18 months, with the follow-up deadline being June 30, 2024. The primary endpoint was the occurrence of MACE, including death from any cause or re-hospitalization due to heart failure. Multivariate logistic regression analysis was used to determine the independent risk factors for MACE of elderly patients with CHF ( P<0.05). All patients included were randomly allocated into a training cohort ( n=913) and a validation cohort ( n=388) in a 7∶3 ratio. A nomogram prediction model was developed. The model was internally validated by bootstrapping. The discriminative ability of the model was assessed by calibration curves and receiver operating characteristic (ROC) curves. Results:Multivariable logistic regression analysis demonstrated that atrial fibrillation history, lower diastolic blood pressure, elevated uric acid, elevated free thyroxine (FT4), higher HCY/FT3 ratio, and lower left ventricular ejection fraction (LVEF) were independent predictors of MACE in elderly CHF patients ( P<0.05). A nomogram model incorporating these factors was developed. Internal validation using bootstrapping showed good calibration, as both training and validation cohort calibration curves closely approximated the ideal line. ROC curve analysis indicated an area under the curve of 0.721 (95% CI: 0.661-0.782) for the nomogram in predicting MACE. Conclusions:We developed and internally validated a nomogram incorporating the HCY/FT3 ratio to predict MACE risk in elderly CHF patients. This model demonstrated acceptable discrimination and good calibration, suggesting potential clinical utility for risk stratification.

Objective To explore the causal association between immune cells and allergic rhi-nitis using Mendelian randomization(MR)approach.Methods GWAS data for 731 types of im-mune cells and allergic rhinitis were obtained from genome-wide association study(GWAS)databas-es.A two-sample bidirectional MR analysis was conducted,with the inverse-variance weighted(IVW)method as the primary analytical approach,and the weighted median method,MR-Egger re-gression,simple mode method,and weighted mode method as supplementary approaches.Sensitivity analyses,including heterogeneity tests,pleiotropy tests,and the leave-one-out method,were per-formed.Bonferroni correction was applied to the preliminary results to enhance their reliability and rigor.Results The two-sample forward MR analysis revealed correlations between 67 immune cell phenotypes and allergic rhinitis.After Bonferroni correction,four immune cell phenotypes were finally identified.Among them,the expression of CD3 on CD39-positive activated CD4 regulatory T cells(OR=0.953,95％CI,0.931 to 0.978,P＜0.001,Padj=0.007),the expression of herpesvirus entry mediator(HVEM)on CD45RA-negative CD4+T cells(OR=0.965,95％CI,0.948 to 0.983,P＜0.001,Padj=0.008),and the percentage of human leukocyte antigen class DR(HLA-DR)-high-expressing monocytes among leukocytes(OR=0.929,95％CI,0.885 to 0.974,P=0.002,Padj=0.157)were protective factors for allergic rhinitis.In contrast,the percentage of transitional B cells among B cells(OR=1.094,95％CI,1.032 to 1.161,P=0.003,Padj=0.183)was a risk factor for allergic rhinitis.The reverse MR analysis showed no causal relationship between allergic rhinitis and the four immune cell phenotypes.Conclusion The two-sample forward MR analysis confirms a caus-al link between immune cells and allergic rhinitis.MR analysis has the advantages of reducing con-founding factor interference and avoiding reverse causation,providing a theoretical basis for in-depth research on immune mechanisms,sensitive biomarkers,and drug treatment targets of allergic rhinitis.

Objective To investigate the expression of Cyclin F in clear cell renal cell carcinoma (ccRCC), its clinicopathological characteristics, and its effect on the biological behavior of renal cancer cell lines Methods RT-qPCR and Western blot were used to detect the mRNA and protein expression of Cyclin F in fresh ccRCC specimens. Immunohistochemistry assay was performed to detect the expression of Cyclin F protein in 80 paraffin samples. CCK-8 assay, scratch assay, and flow cytometry were conducted to determine the effects of Cyclin F overexpression on the proliferation, migration, and apoptosis of renal cancer cell lines. Results The expression of Cyclin F in cancer tissues was higher than that in adjacent tissues at the mRNA level (P<0.0285). The expression of Cyclin Fprotein in cancer tissues was lower than that in adjacent tissues (P<0.001). The analysis of clinicopathological parameters showed that the low expression of Cyclin F was correlated with WHO/ISUP grade, Ki67 index, and age (P=0.041, 0.047, 0.008,). In vitro experiments confirmed that overexpression of Cyclin F promoted the proliferation (P<0.001) and migratory ability (24 h P=0.003, 48 h P=0.0058) of the RCC 786-O cell line, while inhibiting apoptosis (P=0.0019). Conclusion The low expression of Cyclin F protein in ccRCC tissuesis associated with high ISUP grade, high Ki67 index, oldage, and prognosis of patients.

Objective:To explore the effects of happy PERMA intervention on resilience, stigma and quality of life in colostomy patients with colorectal cancer.Methods:According to convenience sampling method, 120 patients with colorectal cancer who underwent permanent colostomy in the hospital were enrolled from September 2021 to August 2023. According to admission order, they were divided into control group (60 cases, September 2021-August 2022) and study group (60 cases, September 2022-August 2023). The control group was given routine nursing, while the study group was additionally given happy PERMA mode nursing intervention for 8 weeks. The scores of Connor-Davidson resilience scale (CD-RISC), social impact scale (SIS), ostomy adjustment inventory-20 (OAI-20), quality of life questionnaire core 30(QLQ-C30), general well-being schedule(GWB) and self-care ability before and after 8 weeks of intervention were compared between the two groups using SPSS 22.0 software.Results:After the intervention, the scores of resilience (45.28±2.59), strength (26.34±2.47), optimism (11.05±0.78), and the total CD-RISC score (80.95±3.47) in the study group were significantly higher than those in the control group (37.46±2.08, 18.55±1.96, 8.96±0.63, 65.11±2.32) ( t=18.235, 19.137, 16.146, 29.394, all P<0.05). The scores of internalized stigma (13.09±1.97), economic discrimination (6.85±0.78), social isolation (14.15±1.98), social exclusion (16.93±2.54), and the total SIS score (50.17±2.35) in the study group were significantly lower than those in the control group (13.97±2.44, 7.36±0.95, 16.94±2.37, 19.55±3.42, 58.69±2.83)( t=2.174, 3.214, 6.998, 4.764, 13.756, all P<0.05). The score of persistent worry (11.95±2.16) in the study group was significantly lower than that in the control group (16.57±1.92) ( t=12.383, P<0.05), while the score of acceptance (15.28±1.16), positive life attitude (17.38±2.31), and the total OAI-20 score (58.64±2.08) in the study group were significantly higher than those in the control group (12.19±0.97, 14.55±1.94, 46.30±1.57) ( t=15.829, 7.267, 36.679, all P<0.05). The scores of role function (86.27±3.15), emotional function (81.25±4.33), social function (79.63±3.16), cognitive function (83.55±3.97), general health (83.15±3.16), and the total QLQ-C30 score (407.13±15.92) in the study group were significantly higher than those in the control group (77.62±4.38, 73.85±4.96, 71.80±3.98, 79.42±4.31, 75.34±3.62, 372.65±11.58)( t=12.419, 8.706, 11.935, 5.459, 12.590, 13.567, all P<0.05). The GWB score (86.95±3.57) and self-care ability score (91.13±3.45) in the study group were significantly higher than those in the control group (73.82±4.06, 87.55±4.68)( t=18.812, 4.769, both P<0.05). Conclusion:Happy PERMA mode intervention can effectively improve resilience, reduce stigma and improve quality of life in colostomy patients with colorectal cancer.

Objective:To explore the effects of happy PERMA intervention on resilience, stigma and quality of life in colostomy patients with colorectal cancer.Methods:According to convenience sampling method, 120 patients with colorectal cancer who underwent permanent colostomy in the hospital were enrolled from September 2021 to August 2023. According to admission order, they were divided into control group (60 cases, September 2021-August 2022) and study group (60 cases, September 2022-August 2023). The control group was given routine nursing, while the study group was additionally given happy PERMA mode nursing intervention for 8 weeks. The scores of Connor-Davidson resilience scale (CD-RISC), social impact scale (SIS), ostomy adjustment inventory-20 (OAI-20), quality of life questionnaire core 30(QLQ-C30), general well-being schedule(GWB) and self-care ability before and after 8 weeks of intervention were compared between the two groups using SPSS 22.0 software.Results:After the intervention, the scores of resilience (45.28±2.59), strength (26.34±2.47), optimism (11.05±0.78), and the total CD-RISC score (80.95±3.47) in the study group were significantly higher than those in the control group (37.46±2.08, 18.55±1.96, 8.96±0.63, 65.11±2.32) ( t=18.235, 19.137, 16.146, 29.394, all P<0.05). The scores of internalized stigma (13.09±1.97), economic discrimination (6.85±0.78), social isolation (14.15±1.98), social exclusion (16.93±2.54), and the total SIS score (50.17±2.35) in the study group were significantly lower than those in the control group (13.97±2.44, 7.36±0.95, 16.94±2.37, 19.55±3.42, 58.69±2.83)( t=2.174, 3.214, 6.998, 4.764, 13.756, all P<0.05). The score of persistent worry (11.95±2.16) in the study group was significantly lower than that in the control group (16.57±1.92) ( t=12.383, P<0.05), while the score of acceptance (15.28±1.16), positive life attitude (17.38±2.31), and the total OAI-20 score (58.64±2.08) in the study group were significantly higher than those in the control group (12.19±0.97, 14.55±1.94, 46.30±1.57) ( t=15.829, 7.267, 36.679, all P<0.05). The scores of role function (86.27±3.15), emotional function (81.25±4.33), social function (79.63±3.16), cognitive function (83.55±3.97), general health (83.15±3.16), and the total QLQ-C30 score (407.13±15.92) in the study group were significantly higher than those in the control group (77.62±4.38, 73.85±4.96, 71.80±3.98, 79.42±4.31, 75.34±3.62, 372.65±11.58)( t=12.419, 8.706, 11.935, 5.459, 12.590, 13.567, all P<0.05). The GWB score (86.95±3.57) and self-care ability score (91.13±3.45) in the study group were significantly higher than those in the control group (73.82±4.06, 87.55±4.68)( t=18.812, 4.769, both P<0.05). Conclusion:Happy PERMA mode intervention can effectively improve resilience, reduce stigma and improve quality of life in colostomy patients with colorectal cancer.

BACKGROUND:Mesenchymal stem cells have been widely used in the treatment of various diseases due to their wide range of sources,their ease of proliferation in vitro and their ability to secrete a range of immunomodulatory factors to suppress inflammation and promote tissue repair and regeneration.However,in the treatment of many diseases,the therapeutic effect is limited.The effort to engineer and modify mesenchymal stem cells for specific disease pathogenesis or intervention targets is an important development for cell therapy in the future.OBJECTIVE:Interleukin-10 is a typical anti-inflammatory cytokine that helps to modulate the immune response and induces macrophage polarization towards an anti-inflammatory phenotype.This study investigated the therapeutic effect of interleukin-10 engineered human umbilical cord mesenchymal stem cells on inflammatory bowel disease.METHODS:Human umbilical cord mesenchymal stem cells stably overexpressing interleukin-10 were established by electro-transfection,and screened for clinical-grade cells based on the cell therapy product criteria.C57BL/6J mice were given 5%aqueous dextran sulfate sodium ad libitum to establish a model of acute colitis.Empty plasmid-transfected human umbilical cord mesenchymal stem cells or interleukin-10-human umbilical cord mesenchymal stem cells(1×106 cells/each mouse)were injected on day 1 before modeling(tail vein injection)and day 4(intraperitoneal injection)after modeling,respectively.On day 6 after modeling,colon tissue sections were taken for hematoxylin-eosin staining to assess histological changes.Immunofluorescence staining was performed to detect the expression of proliferating cell nuclear antigen and CD31.RESULTS AND CONCLUSION:The engineered human umbilical cord mesenchymal stem cells stably overexpressing interleukin-10 were constructed,and met the quality standard of clinical-grade human umbilical cord mesenchymal stem cells.Human umbilical cord mesenchymal stem cells could repair acute colitis in mice.The therapeutic effect of interleukin-10-human umbilical cord mesenchymal stem cells was more efficacious,which more significantly suppressed body weight loss(P<0.05),colon shortening(P<0.05),and damage of colonic tissues(P<0.05)in acute colitis mice.In interleukin-10-human umbilical cord mesenchymal stem cell treatment group,there were significantly more proliferating cell nuclear antigen-positive cells and CD31-positive cells in the colon sections than in the human umbilical cord mesenchymal stem cell treatment group,suggesting that interleukin-10-overexpressing human umbilical cord mesenchymal stem cells contributed to the repair of colon tissue by significantly promoting the proliferation of intestinal tissues and angiogenesis.