BACKGROUND:Bone marrow mesenchymal stem cells are the main effector cells for bone formation.With the increase of age,the regenerative ability of bone marrow mesenchymal stem cells is weakened and the differentiation function is impaired,leading to poor osteoporosis.Therefore,restoring the regenerative capacity and cellular function of aged bone marrow mesenchymal stem cells is essential for the effective treatment of osteoporosis.OBJECTIVE:To investigate the effects of passage 3 and passage 11 bone marrow mesenchymal stem cells-derived exosomes of young rats on the aging of bone marrow mesenchymal stem cells derived from elderly rats.METHODS:Bone marrow mesenchymal stem cells from 6-8-week-old female SD rats were isolated and cultured,and passaged to the passages 3 and 11,respectively.Then,exosomes from passages 3 and 11 bone marrow mesenchymal stem cells were extracted.Bone marrow mesenchymal stem cells from 18-month-old female SD rats were isolated and cultured,passaged to passage 3,and divided into 3 groups.The control group was routinely cultured,and the other two groups were intervened with exosomes from passages 3 and 11 bone marrow mesenchymal stem cells.After 48 hours of exosome intervention,the expression of β-galactosidase in the nucleus was detected by β-galactosidase staining kit.The expression of aging-related genes was detected by qRT-PCR.The expression differences of miRNA in exosomes from passages 3 and 11 bone marrow mesenchymal stem cells were compared by Small RNA sequencing.RESULTS AND CONCLUSION:(1)Compared with the control group and passage 11 bone marrow mesenchymal stem cell-derived exosomes group,theβ-galactosidase activity of bone marrow mesenchymal stem cells of aged rats was significantly lower in the passage 3 bone marrow mesenchymal stem cell-derived exosomes group.(2)Compared with the control group,the expression of aging-related genes p21 and p16 was significantly reduced in the passage 3 bone marrow mesenchymal stem cell-derived exosome group(P＜0.05),while there was no significant difference in the expression of aging-related genes p21 and p16 in the passage 11 bone marrow mesenchymal stem cell-derived exosome group.(3)Sequencing results showed that there was a significant difference in the expression of miRNAs in the two exosomes,among which the miRNAs with the most significant expression differences were let-7c-5p,let-7b-5p,miR-320-3p,and miR-26a-5p.KEGG analysis results showed that significantly different miRNA enrichment pathways include mTOR,AMPK and other aging-related signaling pathways.The above results indicate that passage 3 bone marrow mesenchymal stem cell-derived exosomes have the ability to reverse the aging of bone marrow mesenchymal stem cells in aged rats.

BACKGROUND:Bone marrow mesenchymal stem cells are the main effector cells for bone formation.With the increase of age,the regenerative ability of bone marrow mesenchymal stem cells is weakened and the differentiation function is impaired,leading to poor osteoporosis.Therefore,restoring the regenerative capacity and cellular function of aged bone marrow mesenchymal stem cells is essential for the effective treatment of osteoporosis.OBJECTIVE:To investigate the effects of passage 3 and passage 11 bone marrow mesenchymal stem cells-derived exosomes of young rats on the aging of bone marrow mesenchymal stem cells derived from elderly rats.METHODS:Bone marrow mesenchymal stem cells from 6-8-week-old female SD rats were isolated and cultured,and passaged to the passages 3 and 11,respectively.Then,exosomes from passages 3 and 11 bone marrow mesenchymal stem cells were extracted.Bone marrow mesenchymal stem cells from 18-month-old female SD rats were isolated and cultured,passaged to passage 3,and divided into 3 groups.The control group was routinely cultured,and the other two groups were intervened with exosomes from passages 3 and 11 bone marrow mesenchymal stem cells.After 48 hours of exosome intervention,the expression of β-galactosidase in the nucleus was detected by β-galactosidase staining kit.The expression of aging-related genes was detected by qRT-PCR.The expression differences of miRNA in exosomes from passages 3 and 11 bone marrow mesenchymal stem cells were compared by Small RNA sequencing.RESULTS AND CONCLUSION:(1)Compared with the control group and passage 11 bone marrow mesenchymal stem cell-derived exosomes group,theβ-galactosidase activity of bone marrow mesenchymal stem cells of aged rats was significantly lower in the passage 3 bone marrow mesenchymal stem cell-derived exosomes group.(2)Compared with the control group,the expression of aging-related genes p21 and p16 was significantly reduced in the passage 3 bone marrow mesenchymal stem cell-derived exosome group(P＜0.05),while there was no significant difference in the expression of aging-related genes p21 and p16 in the passage 11 bone marrow mesenchymal stem cell-derived exosome group.(3)Sequencing results showed that there was a significant difference in the expression of miRNAs in the two exosomes,among which the miRNAs with the most significant expression differences were let-7c-5p,let-7b-5p,miR-320-3p,and miR-26a-5p.KEGG analysis results showed that significantly different miRNA enrichment pathways include mTOR,AMPK and other aging-related signaling pathways.The above results indicate that passage 3 bone marrow mesenchymal stem cell-derived exosomes have the ability to reverse the aging of bone marrow mesenchymal stem cells in aged rats.

Objective Taking the hippocampus as seed,to investigate the characteristics of white matter in patients with major depressive disorder (MDD) and bipolar depression (BD).Methods 33 MDD and BD according with the Fourth Edition of Diagnostic and Statistical Manual of Mental Disorders diagnostic criteria,accompanying with 33 healthy controls (HC) matching with age,sex and education years were analyzed.All subjects underwent MRI scanning,acquiring diffusion tensor imaging (DTI)data.Taking the hippocampus as seed,to adopt diffusion tensor fiber tracing by DSIstudio to obtain and calculate basic index of DTI,then find the differences among three groups;furthermore,calculating the fiber number (FN) evaluating the connective strength between areas between hippocampus and other areas.Additionally,Pearson correlation analysis was used to analyses the relationship between the difference index and clinical characteristics.Results Compared with HC,radial diffusivity (RD) in the left hippocampus had significant difference (P=0.014)in BD group.While no significance parameter was found between MDD group and the other two groups.Compared with HC group,the reduction of FN value in MDD patients mainly exists in left inferior frontal gyrus(0(0,25)vs.0(0,1),P=0.018)and left middle occipital gyrus (38.6±6.7 vs.26.9±25.6,P=0.015).Compared with HC,FN value of BD increase in the left parahippocampal gyms (47.2± 24.0 vs.65.8 ± 30.1,P=0.007) and tongue gyrus (50.4 ± 33.2 vs.74.2 ± 35.9) in BD (P=0.012).Pearson correlation analysis found that RD mean of left hippocampus remain positively correlated with the duration of disease in BD group (r=0.418,P=0.016).Conclusions BD has some changes mainly in the left hippocampus,which exists myelin sheath degeneration and the alteration of white matter fiber connected with left parahippocampal gyrus and tongue gyrus,while MDD shows some differences of connectivity between left hippocampus and frontal lobe,and between right hippocampus and occipital lobe as well.

Objective Taking the hippocampus as seed,to investigate the characteristics of white matter in patients with major depressive disorder (MDD) and bipolar depression (BD).Methods 33 MDD and BD according with the Fourth Edition of Diagnostic and Statistical Manual of Mental Disorders diagnostic criteria,accompanying with 33 healthy controls (HC) matching with age,sex and education years were analyzed.All subjects underwent MRI scanning,acquiring diffusion tensor imaging (DTI)data.Taking the hippocampus as seed,to adopt diffusion tensor fiber tracing by DSIstudio to obtain and calculate basic index of DTI,then find the differences among three groups;furthermore,calculating the fiber number (FN) evaluating the connective strength between areas between hippocampus and other areas.Additionally,Pearson correlation analysis was used to analyses the relationship between the difference index and clinical characteristics.Results Compared with HC,radial diffusivity (RD) in the left hippocampus had significant difference (P=0.014)in BD group.While no significance parameter was found between MDD group and the other two groups.Compared with HC group,the reduction of FN value in MDD patients mainly exists in left inferior frontal gyrus(0(0,25)vs.0(0,1),P=0.018)and left middle occipital gyrus (38.6±6.7 vs.26.9±25.6,P=0.015).Compared with HC,FN value of BD increase in the left parahippocampal gyms (47.2± 24.0 vs.65.8 ± 30.1,P=0.007) and tongue gyrus (50.4 ± 33.2 vs.74.2 ± 35.9) in BD (P=0.012).Pearson correlation analysis found that RD mean of left hippocampus remain positively correlated with the duration of disease in BD group (r=0.418,P=0.016).Conclusions BD has some changes mainly in the left hippocampus,which exists myelin sheath degeneration and the alteration of white matter fiber connected with left parahippocampal gyrus and tongue gyrus,while MDD shows some differences of connectivity between left hippocampus and frontal lobe,and between right hippocampus and occipital lobe as well.

AIM: To compare the impacts of adriamycin(ADM) intermittent and continuous heat infusion on respiration, heart rate and temperature of the rabbit as well as the concentration of ADM in VX-2 tumor for the verification of the safety and effectiveness of intermittent heat infusion through VX-2 transplanted tumor model in rabbit liver.METHODS: VX-2 tumor models were established respectively in the thighs of 30 New Zealand rabbits. All 30 rabbits were randomly allocated into three groups with 10 rabbits each. After catheterizing into femoral artery, which was demonstrated as the supply artery of tumors by digital subtraction angiography(DSA), animals in three groups were infused with 100 mL saline at normal temperature and ADM, 100 mL saline at 60 ℃ and ADM continuously and 100 mL saline at 60 ℃ and ADM intermittently respectively. During infusion, the 43 ℃ to 45 ℃ lasting time in the tumor tissues of the two 60 ℃ groups was measured. After infusion, the respiration(time/minute), heart rate(beats/minute) and temperature(℃ )of the rabbits in each group as well as the concentrations of ADM in tumor tissue were measured immediately.RESULTS: The concentration of ADM was (7. 1 ± 2.2) mg/L in normal temperature infusion group, (17.2 ± 1.6) mg/L in 60 ℃ continuous infusion group and(16.5 ±3.4) in 60 ℃ intermittent infusion group. There were significant differences among three groups( F = 48.95, P = 0. 000), but there was no significant difference between 60 ℃ intermittent infusion group and 60 ℃ continuous infusion group( P ＞ 0. 05). 43℃ to 45 ℃ lasting time was(22.5 ±1.4) minutes in 60 ℃continuous infusion and (24.3±2.4)minutes in 60 ℃intermittent infusion group( F =4.20, P ＞ 0.05) . There were significant differences among three groups in respiration, heart rate and temperature( F = 14. 58, 33.07, 10.00, P ＜ 0.01), but there was no significant difference in the respiration, heart rate and temperature between 60℃ intermittent infusion and normal temperature infusion group ( P ＞ 0. 05).CONCLUSION: Intermittent thermochemotherapy is a more effective and safe interventional thermochemotherapy method compared with continuous heat infusion.