Objective:This study aimed to investigate the morphological and functional changes of jejunal and ileal epithelium in aged mice using 3D organoid culture, to elucidate the age-related alterations in epithelial function across different regions of the intestine.Methods:The C57BL/6J male mice were divided into two groups: a young group(5 months)and an old group(24 months).Epithelial tissues from the jejunum and ileum were harvested, and the jejunal and ileal epithelial crypt units were separated for 3D organoid culture in vitro.Histological analyses, including H&E and PAS staining, immunofluorescence staining, and quantitative PCR, were employed to assess changes in crypt depth, villi length, goblet cell numbers, inflammation, and mucosal barrier function in the aged mice.Results:With aging, the crypt of jejunum became deeper and the ratio of villi length to crypt depth decreased, while the villi length of ileum became longer and the ratio of villi length to crypt depth increased.The rate of organoid formation in jejunal and ileal crypts and the number of crypto-like regions of organoid formation were significantly decreased in the aged mice, along with a decrease in the expression of the stem cell proliferation marker Ki67.The inflammation of the jejunal and ileal epithelium increased in the aged mice, and the mechanical barrier function of the epithelial mucosa was enhanced.Conclusions:In aged mice, both the jejunal and ileal epithelium exhibited similar changes in stem cell proliferation, inflammation, and mucosal mechanical barrier function, though the changes in villus length and crypt depth ratio were opposite.This study provides a foundation for further investigation of the differences in jejunal and ileal epithelial function and its potential mechanisms during aging.

Objective:To investigate the associations between thyroid homeostasis and risk of carotid plaque in healthy euthyroid individuals.Methods:In this retrospective cohort study, 4 726 healthy euthyroid adults who received health examination two times or more in the Health Promotion Center of the First Affiliated Hospital with Nanjing Medical University from January 2018 to December 2024 and had no carotid artery plaques at the baseline were selected. Data encompassed demographics, physical and laboratory tests, carotid ultrasound, and calculated thyroid sensitivity indices [thyroid feedback quantile-based index (TFQI), thyroid hormone resistance index (TT4RI), thyroid-stimulating hormone index (TSHI), and free triiodothyronine (FT3)/free thyroxine (FT4) ratio] were recorded. The participants were divided into two groups based on whether they had newly-developed carotid plaques. The associations between thyroid homeostasis indices and risk of carotid plaque were analyzed using Cox proportional hazards regression and restricted cubic splines.Results:During 11 459 person-years of follow-up, the cumulative incidence of carotid plaque was 16.84%, with an incidence density of 6.95 cases per 100 person-years. After multivariable adjustment, FT3 ( HR=0.79, 95% CI: 0.68-0.93) and FT4 ( HR=0.95, 95% CI: 0.91-0.98) were inversely associated with risk of carotid plaque. TSH and thyroid hormone sensitivity showed no significant association with the occurrence of carotid plaques. Subgroup analysis showed that there was no significant interaction between thyroid function indicators and risk of carotid plaque among different subgroups, but the decreased FT3 and FT4 levels significantly increased the risk of new-onset carotid plaques in individuals aged<60 years, without diabetes, without hypertension, or without lipid-lowering medication use. Restricted cubic spline analysis indicated that when TFQI (nonlinear P=0.028, node value was 0.29) and TT4RI (nonlinear P=0.014, node value was 54.95) exceeded specific thresholds, their increase were associated with a reduced risk of carotid plaque. Conclusions:The reduction of FT3 and FT4 in healthy euthyroid adults is associated with an increased risk of carotid plaque. When TFQI and TT4RI are higher than specific thresholds, their increase are associated with a reduced risk of new-onset plaques.

Objective:This study aimed to investigate the morphological and functional changes of jejunal and ileal epithelium in aged mice using 3D organoid culture, to elucidate the age-related alterations in epithelial function across different regions of the intestine.Methods:The C57BL/6J male mice were divided into two groups: a young group(5 months)and an old group(24 months).Epithelial tissues from the jejunum and ileum were harvested, and the jejunal and ileal epithelial crypt units were separated for 3D organoid culture in vitro.Histological analyses, including H&E and PAS staining, immunofluorescence staining, and quantitative PCR, were employed to assess changes in crypt depth, villi length, goblet cell numbers, inflammation, and mucosal barrier function in the aged mice.Results:With aging, the crypt of jejunum became deeper and the ratio of villi length to crypt depth decreased, while the villi length of ileum became longer and the ratio of villi length to crypt depth increased.The rate of organoid formation in jejunal and ileal crypts and the number of crypto-like regions of organoid formation were significantly decreased in the aged mice, along with a decrease in the expression of the stem cell proliferation marker Ki67.The inflammation of the jejunal and ileal epithelium increased in the aged mice, and the mechanical barrier function of the epithelial mucosa was enhanced.Conclusions:In aged mice, both the jejunal and ileal epithelium exhibited similar changes in stem cell proliferation, inflammation, and mucosal mechanical barrier function, though the changes in villus length and crypt depth ratio were opposite.This study provides a foundation for further investigation of the differences in jejunal and ileal epithelial function and its potential mechanisms during aging.

Objective:To investigate the associations between thyroid homeostasis and risk of carotid plaque in healthy euthyroid individuals.Methods:In this retrospective cohort study, 4 726 healthy euthyroid adults who received health examination two times or more in the Health Promotion Center of the First Affiliated Hospital with Nanjing Medical University from January 2018 to December 2024 and had no carotid artery plaques at the baseline were selected. Data encompassed demographics, physical and laboratory tests, carotid ultrasound, and calculated thyroid sensitivity indices [thyroid feedback quantile-based index (TFQI), thyroid hormone resistance index (TT4RI), thyroid-stimulating hormone index (TSHI), and free triiodothyronine (FT3)/free thyroxine (FT4) ratio] were recorded. The participants were divided into two groups based on whether they had newly-developed carotid plaques. The associations between thyroid homeostasis indices and risk of carotid plaque were analyzed using Cox proportional hazards regression and restricted cubic splines.Results:During 11 459 person-years of follow-up, the cumulative incidence of carotid plaque was 16.84%, with an incidence density of 6.95 cases per 100 person-years. After multivariable adjustment, FT3 ( HR=0.79, 95% CI: 0.68-0.93) and FT4 ( HR=0.95, 95% CI: 0.91-0.98) were inversely associated with risk of carotid plaque. TSH and thyroid hormone sensitivity showed no significant association with the occurrence of carotid plaques. Subgroup analysis showed that there was no significant interaction between thyroid function indicators and risk of carotid plaque among different subgroups, but the decreased FT3 and FT4 levels significantly increased the risk of new-onset carotid plaques in individuals aged<60 years, without diabetes, without hypertension, or without lipid-lowering medication use. Restricted cubic spline analysis indicated that when TFQI (nonlinear P=0.028, node value was 0.29) and TT4RI (nonlinear P=0.014, node value was 54.95) exceeded specific thresholds, their increase were associated with a reduced risk of carotid plaque. Conclusions:The reduction of FT3 and FT4 in healthy euthyroid adults is associated with an increased risk of carotid plaque. When TFQI and TT4RI are higher than specific thresholds, their increase are associated with a reduced risk of new-onset plaques.

Objective In order to determine the incidence and mortality of uterine body cancer in Gansu province in 2019,the epidemic characteristics and the change trend of incidence and death from 2010 to 2019 were analyzed.Methods The quality control qualified data in Gansu province tumor registration center were used,uterine body cancer in urban and rural,age-specific inci-dence(mortality),the China standardized rate by Chinese population,the World standardized rate by World population,cumulative rate,crude incidence(mortality),composition ratio and rank,average annual percentage change(AAPC)and other indicators were calculated.Results In 2019,uterine body cancer in Gansu province ranked the seventh in the incidence of female malignant tumors,with a crude incidence of 4.43/100,000,the China standardized incidence was 3.28/100,000,and the World standardized incidence was 3.19/100,000.In 2019,uterine body cancer in Gansu province ranked the sixth among the mortality of female malignant tumors,with the crude mortality of 0.56/100,000,the China standardized mortality was 0.36/100,000,and the World standardized mortality was 0.35/100,000.The peak of morbidity(mortality)was in the age range of 50 to 54 years old.From 2010 to 2019,the incidence of uterine body cancer in Gansu province showed an overall upward trend.The China standardized incidence was AAPC=4.34%(95%CI:1.60%-7.15%),with a statistically significant trend(P<0.05);The mortality of uterine body cancer showed a fluctuating pat-tern of first rising,then decreasing,and increasing again,showing an overall downward trend.The China standardized mortality was AAPC=-11.35%(95%CI:-26.77%-7.32%),and the trend was not statistically significant(P>0.05).The incidence(mortali-ty)in rural areas was higher than that in urban areas.Conclusion The overall incidence of uterine body cancer in Gansu province is on the rise,and the death is on the decline.However,mortality in rural areas is on the rise.It is recommended to vigorously promote women′s health science popularization and education throughout the province,strictly implement the comprehensive measures of"early detection,early diagnosis,early treatment",and focus on the prevention and control of women aged 50-54,especially strengthening the early diagnosis and treatment of uterine body cancer in rural areas.

Objective:To investigate the correlation of peripheral blood relative mitochondrial DNA copy number(mtDNAcn)with intrinsic capacity and body composition, and to identify potential biomarkers for healthy aging.Methods:Clinical data of 416 patients admitted to our hospital from September 2019 to June 2021 were consecutively collected.MtDNA was extracted from peripheral blood of these subjects, and mtDNAcn was determined by a real-time fluoresence quantitative reverse transcription-polymerase chain reaction(qRT-PCR). Intrinsic capacity assessment included 5 aspects that were exercise[Morse Fall Scale(MFS), Physiological Frailty Phenotype(PFP), Sarcopenia Questionnaire(SARC-CALF), Short Physical Performance Battery(SPPB), Time Up and Go Test(TUG)]; vitality[Mini Nutritional Assessment(MNA), Multidimensional Prognostic Index(MPI)]; cognition[Mini-Mental State Examination(MMSE)scale]; psychology[Geriatric Depression Scale(GDS), Self-rating Anxiety Scale(SAS)]; sensory capacities[Cumulative Illness Rating Scale-the Comorbidity Index(CIRS-CI)]. To assess body composition, dual-energy X-ray absorptiometry was used to measure body fat, including trunk fat, total body fat, fat in the abdominal region, fat in the buttock region, and then to calculate fat index(FMI)and limb skeletal muscle mass index(ASMI).Results:Spearman correlation analysis showed that mtDNAcn had a negatively correlation with age( r=-0.176, P<0.05). After adjustment for gender and body mass index, partial correlation analysis showed mtDNAcn were still negatively correlated with age( r=-0.144, P<0.05). Furthermore, mtDNAcn was significantly correlated with 4 m gait speed, the scores of SARC-CalF, MFS, MNA, MMSE, MPI and its sub-scale's Activities of Daily Living(ADL)and Short Portable Mental Status Questionnaire(SPMSQ)( r=0.171, -0.207, -0.163, 0.221, 0.184, -0.210, 0.241, -0.269, all P<0.05). After adjustment for age, gender and body mass index, partial correlation analysis showed mtDNAcn still had a significant correlation with gait speed, the scores of MFS, MNA, MPI and SPMSQ( r=0.170, -0.170, 0.148, -0.242, -0.188, all P<0.05). In addition, the Spearman correlation analysis showed that mtDNAcn was positively correlated with FMI, trunk fat, total body fat, abdominal fat and fat in the buttock region( r=0.168, 0.143, 0.175, 0.116, 0.199, all P<0.05). However, after adjustment for age and gender, mtDNAcn was only correlated with FMI, total body fat, fat in the buttock region( r=0.126, 0.131, 0.127, all P<0.05). On the other hand, multiple linear regression analysis showed that mtDNAcn was significantly correlated with age, gait speed, FMI, total body fat, fat in the buttock region, the scores of MFS, PFP, MNA and MPI( β=-0.191, 0.156, 0.126, 0.131, 0.125, -0.119, -0.145, 0.151, -0.171, all P<0.05). Conclusions:MtDNAcn is correlated with physical function, frailty, nutrition, falling, cognition and body composition, and may be considered as a biomarker for the evaluation of the locomotion and vitality of human intrinsic capacity.

Objective:To explore the feasibility of using ultrasound to evaluate the abdominal fat volume to predict bone quality.Methods:A total of 376 men, aged from 34 to 90 years, were recruited.The trabecular bone score(TBS)was measured by TBS iNsight ? software.Bone mineral density(BMD)of the femoral neck, total hip, and lumber spine, as well as android and gynoid fat mass were measured using dual-energy X-ray absorptiometry(DXA).Preperitoneal fat thickness and intraperitoneal visceral fat thickness were assessed by ultrasound. Results:BMD of the femoral neck, total hip, and lumber spine was significantly positively correlated with body mass index(BMI)( r=0.346, 0.378, 0.218, all P<0.001), while TBS was significantly negatively associated with BMI( r=-0.353, P<0.001); Femoral neck BMD, lumbar BMD and TBS were positively correlated with total lean mass( β=0.296, P<0.001; β=0.280, P<0.001; β=0.182, P=0.009; respectively), while femoral neck BMD, total hip BMD and TBS were negatively correlated with total fat mass( β=-0.161, P=0.036; β=-0.160, P=0.041; β=-0.354, P<0.001; respectively).Compared with fat mass, BMD was more closely correlated with BMI( P<0.001), while TBS was negatively correlated only with android fat mass( β=-0.297, P=0.017).TBS was inversely associated only with visceral fat thickness( β=-0.244, P=0.04), but not preperitoneal fat thickness( β=-0.119, P=0.256). Conclusions:Abdominal fat mass, especially intraperitoneal visceral fat mass, may have adverse effects on bone quality.Intraperitoneal visceral fat thickness measured by ultrasound is helpful for the prediction of bone quality.

Mitochondrial dynamics regulates mitochondrial morphology and functions.Imbalance in mitochondrial dynamics with aging leads to mitochondrial dysfunction, accelerates the aging process and is closely related to the occurrence and progression of age-related diseases.However, the specifics of the relationship between aging and altered mitochondrial dynamics are still not fully understood.Here, we review the link between mitochondrial dynamics and aging, and discuss mechanisms underlying age-related diseases associated with altered mitochondrial dynamics, aiming to identify novel therapeutic targets and strategies for the management of age-related diseases.

Objective:To explore the correlation between blood glucose levels and the three factors of sarcopenia (muscle mass, strength and function) in older Chinese community dwellers.Methods:This is a retrospective study conducted by collecting the data of patients in Jiangsu Huaqiao Road Community Health Service Center from 2018 to 2019. Two hundred and fifty people aged 60 years or elder were selected. Among them, 101 were men and 149 were women. According to the American Diabetes Association diagnostic criteria for diabetes mellitus in 2018, they were divided into normal glucose tolerance (NGT) group, pre-diabetes group and diabetes group. The patients were assessed for sarcopenia as well.Results:Compared with those in the NGT group, muscle mass and upper limb muscle strength did not change in the diabetic group, but lower limb muscle strength and body function [walking speed, balance, short physical performance battery (SPPB)] decreased significantly in the diabetic group. Pearson correlation analyses showed that fasting plasma glucose(FPG) was negatively correlated with walking speed ( r=-0.248, P=0.001), three-pose balance ( r=-0.166, P=0.013) and SSPB ( r=-0.213, P=0.001). Glycosylated hemoglobin A1c(HbA1c) was positively correlated with sitting and standing time ( r=0.205, P=0.002), and negatively correlated with three-pose balance ( r=-0.186, P=0.006) and SSPB ( r=-0.154, P=0.024). Multiple regression analyses showed that FPG was negatively associated with walking speed (β=-0.125, P=0.005) and SPPB (β=-0.034, P=0.012), and that HbA1c was positively associated with sitting and standing time (β= 0.218, P =0.006) and negatively associated with three-pose balance (β=-0.143, P=0.012), and SPPB (β=-0.117, P =0.036). Conclusions:There is no significant correlation between blood glucose levels and muscle mass in the elderly; however, FPG is closely correlated with gait speed, and HbA1c is closely correlated with muscle strength of lower limbs and balance ability in the elderly.

Objective:To investigate the correlation of mitochondrial respiration function and oxidative phosphorylation of peripheral blood mononuclear cells(PBMCs)with grip strength and muscle mass in the elderly, and to identify potential biomarkers for the diagnosis of sarcopenia.Methods:A total of 65 patients admitted to our hospital from June 2019 to August 2020 were enrolled in this study.PBMCs were extracted from subjects.Mitochondrial oxidative respiration function was assessed via the Seahorse XF24 analyzer.Grip strength was measured using a hydraulic dynamometer, and appendicular skeletal muscle mass(ASM)was estimated by dual-energy X-ray absorptiometry(DXA). Multivariate analysis was conducted by using partial correlation analysis and multiple linear regression, in order to evaluate the correlation of mitochondrial oxidative respiration function with grip strength and ASM.Results:After adjustment for gender and body mass index(BMI), partial correlation analysis showed that grip strength and ASM had a negative correlation with age( r=-0.537 and -0.390, both P<0.001); and basal respiration, maximal respiration, ATP production and spare respiratory capacity of mitochondria in PBMCs were negatively correlated with age( r=-0.558, -0.614, -0.526 and -0.582, all P<0.001), whereas grip strength and ASM were positively correlated with basal respiration, maximal respiration, ATP production, spare respiratory capacity and proton leak of mitochondria in PBMCs(grip strength: r=0.414, 0.451, 0.362, 0.420 and 0.425, P=0.002, 0.001, 0.008, 0.002 and 0.002; ASM: r=0.319, 0.368, 0.299, 0.352 and 0.279, P=0.019, 0.006, 0.028, 0.009 and 0.041). Multiple linear regression analysis showed that grip strength and ASM were positively correlated with basal respiration, maximal respiration, ATP production, spare respiratory capacity and proton leak of mitochondria in PBMCs(grip: β=0.503, 0.548, 0.452, 0.519 and 0.532, t=3.248, 3.604, 2.774, 3.301 and 3.350, P=0.002, 0.001, 0.008, 0.002 and 0.002; ASM: β=0.302, 0.355, 0.289, 0.346 and 0.271, t=2.427, 2.856, 2.263, 2.716 and 2.091, P=0.019, 0.006, 0.028, 0.009 and 0.041). Age was negatively correlated with basal respiration, maximal respiration, ATP production and spare respiratory capacity of mitochondria in PBMCs( β=-0.581, -0.654, -0.558 and -0.640, t=-4.285, -5.157, -3.938 and -4.863, all P<0.001). Multiple linear regression analysis showed that ASM and grip strength had no significant correlation with basal respiration, maximal respiration, ATP production, spare respiratory capacity or proton leak of mitochondria in PBMCs. Conclusions:Age-related mitochondrial oxidative respiration in PBMCs can reflect changes in muscle strength and muscle mass and, combined with grip strength and ASM, may be considered as a biomarker for the evaluation of sarcopenia in the elderly.