Objective:To investigate the role of human dermal microvascular endothelial cells(HMEC-1)exosome hsa-miR-4488_L in regulating the osteogenic and lipogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and to elucidate the mechanism of action underlying fate differentiation.Methods:The hsa-miR-4488_L mimic or negative control mimic was transfected into BMSCs, which were then cultured under osteogenic or lipogenic conditions, respectively.RT-qPCR was employed to detect the mRNA expression levels of osteogenic and lipogenic genes in BMSCs.Alizarin red staining was utilized to assess the osteogenic differentiation capability of hsa-miR-4488_L in BMSCs, while oil red O staining was used to evaluate the lipogenic differentiation potential of BMSCs.The mimic control and hsa-miR-4488_L mimic were transfected into elderly BMSCs, and age-related phenotypes were assessed using RT-qPCR and SA-β-gal staining.The direct target genes of hsa-miR-4488_L acting on BMSCs were identified through bioinformatics analysis and subsequently validated by RT-qPCR and Western blot.Results:After treatment with the hsa-miR-4488_L mimic, the expressions of osteogenic-related genes ALP( P=0.007), BSP( P=0.001), and Col1( P<0.001)in BMSCs were upregulated.Additionally, alizarin red staining results indicated an increase in the number of calcified nodules Pparγ( P=0.002).Concurrently, under adipogenic induction conditions, the adipogenic-related genes Pparγ( P=0.008)and Perilipin( P<0.001)were significantly downregulated in the hsa-miR-4488_L mimic treatment group, and oil red O staining demonstrated a reduction in lipid droplet production( P=0.032).The mRNA expression of the aging-related gene P16( P=0.009)was downregulated following treatment with the hsa-miR-4488_L mimic, and the number of senescent cells decreased as indicated by SA-β-gal staining.Bioinformatics analysis revealed that Smad3 was the direct target gene of hsa-miR-4488_L in BMSCs.RT-qPCR results confirmed that the expression of Smad3 was downregulated after treatment with the hsa-miR-4488_L mimic( P=0.040).Furthermore, Western blot analysis showed a reduction in the protein level of Smad3. Conclusions:HMEC-EXOs-derived hsa-miR-4488_L regulates the balance between osteogenic and adipogenic differentiation in BMSCs through Smad3.Consequently, hsa-miR-4488_L may serve as a potential miRNA biomarker for age-related osteoporosis.

Objective:To investigate the role of human dermal microvascular endothelial cells(HMEC-1)exosome hsa-miR-4488_L in regulating the osteogenic and lipogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and to elucidate the mechanism of action underlying fate differentiation.Methods:The hsa-miR-4488_L mimic or negative control mimic was transfected into BMSCs, which were then cultured under osteogenic or lipogenic conditions, respectively.RT-qPCR was employed to detect the mRNA expression levels of osteogenic and lipogenic genes in BMSCs.Alizarin red staining was utilized to assess the osteogenic differentiation capability of hsa-miR-4488_L in BMSCs, while oil red O staining was used to evaluate the lipogenic differentiation potential of BMSCs.The mimic control and hsa-miR-4488_L mimic were transfected into elderly BMSCs, and age-related phenotypes were assessed using RT-qPCR and SA-β-gal staining.The direct target genes of hsa-miR-4488_L acting on BMSCs were identified through bioinformatics analysis and subsequently validated by RT-qPCR and Western blot.Results:After treatment with the hsa-miR-4488_L mimic, the expressions of osteogenic-related genes ALP( P=0.007), BSP( P=0.001), and Col1( P<0.001)in BMSCs were upregulated.Additionally, alizarin red staining results indicated an increase in the number of calcified nodules Pparγ( P=0.002).Concurrently, under adipogenic induction conditions, the adipogenic-related genes Pparγ( P=0.008)and Perilipin( P<0.001)were significantly downregulated in the hsa-miR-4488_L mimic treatment group, and oil red O staining demonstrated a reduction in lipid droplet production( P=0.032).The mRNA expression of the aging-related gene P16( P=0.009)was downregulated following treatment with the hsa-miR-4488_L mimic, and the number of senescent cells decreased as indicated by SA-β-gal staining.Bioinformatics analysis revealed that Smad3 was the direct target gene of hsa-miR-4488_L in BMSCs.RT-qPCR results confirmed that the expression of Smad3 was downregulated after treatment with the hsa-miR-4488_L mimic( P=0.040).Furthermore, Western blot analysis showed a reduction in the protein level of Smad3. Conclusions:HMEC-EXOs-derived hsa-miR-4488_L regulates the balance between osteogenic and adipogenic differentiation in BMSCs through Smad3.Consequently, hsa-miR-4488_L may serve as a potential miRNA biomarker for age-related osteoporosis.

Objective:To explore the correlation between the triglyceride glucose (TyG) index and the risk of vitamin D deficiency (VDD) in patients with type 2 diabetes (T2DM).Methods:T2DM patients admitted to the Department of Geriatrics, the Second Xiangya Hospital of Central South University from February 2020 to February 2023 were included. We collected general clinical and biochemical data from patients and calculated the TyG index. Divide the study subjects into VDD group and control (CON) group based on serum 25 hydroxyvitamin D [25 hydroxyvitamin D, 25(OH)D] levels, and compare the general clinical characteristics between the two groups; Pearson rank correlation analysis was used to study the correlation between TyG index and 25(OH)D; According to the third percentile of the TyG index, the study subjects were divided into three groups (Q1, Q2, Q3), and logistic regression analysis was used to explore the association between the TyG index and the risk of VDD.Results:This study included 526 patients with T2DM, including 312 males and 214 females, aged 37 to 78 years old. There were 300 VDD patients, accounting for 57.03%, and 226 in the CON group. The TyG index of VDD patients was higher than that of the CON group ( P<0.05), and there was a negative correlation between the TyG index and serum 25(OH)D levels ( P<0.05). Logistic regression analysis showed that compared with the Q1 group, the risk of VDD in Q3 group patients was 2.892 times higher than that in Q1 group ( OR=2.892, 95% CI: 1.865-4.485, P<0.001). After adjusting for age, gender, smoking, obesity, insulin, oral hypoglycemic drugs, statin use, and blood biochemical indicators, the risk of illness in the Q3 group was 2.303 times higher than that in the Q1 group ( OR=2.303, 95% CI: 1.288-4.117, P=0.005). Conclusions:In T2DM patients, the TyG index is negatively correlated with serum 25 (OH) D levels. T2DM patients with high TyG index have an increased risk of VDD, and the TyG index can be used to observe the possibility of VDD occurrence, which is beneficial for early detection of VDD patients.

Objective:To explore the relationship between triglyceride-glucose(TyG)index and bone mineral density(BMD)in elderly patients with type 2 diabetes mellitus(T2DM).Methods:Elderly inpatients with T2DM in Department of Geriatrics of the Second Xiangya Hospital of Central South University were enrolled from January 2019 to December 2021.General clinical characteristics and the calculated TyG index were collected.BMDs at the lumbar spine, femoral neck, and total hip were measured using dual-energy X-ray absorptiometry.Multiple linear regression was used to detect the correlation between TyG index and BMDs; Logistic regression analysis was used to analyze the relationship between TyG index and osteoporosis(OP)risk.Results:A total of 822 subjects were included in this study.In elderly men with T2DM, TyG index was significantly positively correlated with BMDs of lumbar spine( β=0.465, P=0.004), femoral neck( β=0.348, P=0.031)and total hip( β=0.317, P=0.022)after adjusting for confounders, but these results were not observed in elder women with T2DM(all P>0.05). Binary Logistic regression analysis showed that in elderly men with T2DM, after adjusting for confounders, the TyG index was a protective factor for osteoporosis( OR=0.349, 95% CI: 0.144-0.846, P=0.020). However, in elderly women with T2DM, the TyG index was not significantly associated with the risk of osteoporosis( OR=1.748, 95% CI: 0.782-3.912, P=0.174). Conclusions:TyG index, which is used to evaluate insulin resistance, is strongly and correlated with BMDs of lumbar spine, femoral neck and total femoral in elderly male patients with T2DM, and is a protective factor for osteoporosis.

The prevalence of type 2 diabetes mellitus(T2DM)in China is about 9.1%.Compared with healthy adults, life expectancy for patients with T2DM at 60 years of age can be cut short by 7.3-9.5 years and time for a good quality of life by 11.1-13.8 years.It is important for elderly patients with T2DM to stay functionally active.Frailty, as a common geriatric syndrome, is an important factor affecting the functional status of the elderly, a strong predictor for disability, death and hospitalization, and also a strong predictor for adverse health outcomes in elderly patients with T2DM.This article reviews the relationship between frailty/sarcopenia and T2DM, and the management and treatment of elderly T2DM patients with frailty/sarcopenia.

Objective: To explore the correlation between serum level of high molecular weight adiponectin (HMW-ADPN) and arteriosclerosis. Methods: Clinical data of 87 middle-aged and aged people living in home, who underwent health examinations in Xiangya second hospital from Jan 2011 to Dec 2011, were collected. According to carotid-femoral pulse wave velocity (cf-PWV) = 9 m/s, they were divided into group A (cf-PWV<9 m/s, n=21) and group B (cf-PWV≥9 m/s, n=66). Blood pressure, blood lipid, blood glucose etc. were measured and compared between two groups. Results: Compared with group A, there were significant rise in blood pressure, levels of low density lipoprotein cholesterol, triglyceride and total cholesterol, and significant reduction in levels of high density lipoprotein cholesterol (HDL-C), serum total ADPN and HMW-ADPN in group B, P<0.05 or <0.01. Multiple regression analysis indicated that serum HMW-ADPN (B= - 4.469，P=0.011), total ADPN ((B= - 3.965，P=0.012), HDL-C（B= - 2.077，P=0.015) and systolic blood pressure levels (B= 0.045，P=0.045) were independent predictors of cf-PWV. Conclusion: Serum high molecular weight adiponectin and total adiponectin levels may be protective factors against arteriosclerosis. Its role in predicting occurrence and development of arteriosclerosis is worthy of further study.

Objective To investigate the effect and mechnism of preptin on connect tissue growth factor (CTGF) in human osteoblasts. Methods Recombinant human preptin was used to treat primary human osteoblasts, and Western blot was used to detect CTGF protein level. Mitogen-activated protein kinase p38(p38MAPK), extracellular signal-regulated kinase (ERK1/2), c-jun N-terminal Kinase (JNK), and their phosphorylation levels were also detected by Western blot. MAPK inhibitors (PD98059, SP600125, or SB203580)were used to elucidate the mechnism of preptin induced expression of CTGF in human osteoblasts. Results Treatment of human osteoblasts with preptin caused a time and dose-dependent increase in CTGF secretion. Preptin induced activation of ERK, but not p38MAPK or JNK in human osteoblasts. Furhermore, pretreatment of human osteoblasts with the ERK inhibitor PD98059 abolished the preptin-induced CTGF secretion. Conclusion Preptin induces CTGF expression in human osteoblasts by means of ERK/MAPK pathway.

Objective To investigate the effect of preptin on proliferation and differentiation of human osteoblasts. Methods After human osteoblasts were incubated with 10-10, 10-9, 10-8 , 10-7 mol/L preptin for 24 h,the proliferation of osteoblasts was determined by[3H]thymidine incorporation and alkaline phosphatase (ALP)activity was assayed by spectrophotometric measurement. The phosphorylation levels of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase ( MAPK), extracellular signal-regulated kinase (ERK) 1/2 were assayed by Western blot. ERK inhibitor PD98059, p38MAPK inhibitor SB203580, and JNK inhibitor SP600125were used for investigating the signal pathway of preptin-stimulated osteoblast proliferation and differentiation.Results Preptin dose-dependently increased human proliferation of osteoblasts and ALP activity with the maximum effect at the concentration of l0-9 mol/L (both P<0.01 ). Preptin stimulated ERK phosphorylation in human osteoblasts, but not p38 MAPK and JNK phosphorylation. PD98059 blocked preptin-sitmulated human osteoblasts proliferation and ALP activity (both P<0.05 ), while SB203580 and SP600125 had no effect. Conclusions Preptin promotes the proliferation and differentiation of human osteoblasts through ERK pathway.

，and 17.47%.Conclusions Xylitol can lower the blood glucose a littte but without significant difference.It has little effect on blood glucose variability of patients with type 2 diabetes mellitus and can be safely used for rehydration.

ObjectiveTo evaluate the therapeutic efficacy of low-dosage methyltestosterone or andriol in men with senile osteoporosis. MethodsA total of 134 male patients with senile osteoporosis and the decreased serum level of free testosterone were divided into three groups. 45 patients were treated with low-dosage methyhestosterone(100 mg, once a day, sublingual) and 46 patients were treated with low-dosage andriol (40 mg, once a day, orally), while 43 patients were treated with placebo. The duration of treatment in each group was 1 year. The bone density, blood and urine biochemical indexes related to bone metaholites,the quality of life indexes, ultrasonography for prostate,serum prostate specific antigen,blood routine, urine routine, hepatic and renal function were detected before and after the treatment. ResultsBoth low-dosage methyltestosterone and low-dosage andriol could prevent the decrease of bone mineral density and improve patients' general health, role-emotional function and vitality (all P＜0.05). The difference values of femoral neck bone mineral density before and after treatment with low-dosage andriol and low-dosage methyltestosterone were (0.14+0.18)g/cm2 and (0.12±0.09)g/cm2 , respectively(P＜0.05). Low-dosage andriol hadstronger effects in increasing the level of estradiol (32.5±14.2 )ng/L than low-dosage methyltestosterone(19.3±9.2)ng/L(P＜0.05) and showed more notable effects in improving the physical functioning and role-physical function than low-dosage methyhestosterone. The use of the two androgenic hormones at low dosage showed safety. ConclusionsBoth low-dosage methyltestosterone and low-dosage andriol can be used to treat senile osteoporosis in men and to improve life quality. Both of them are effective and safe therapeutic choices.