Objective:To discuss the role of nuclear factor of activated T-cells 5(NFAT5)inhibitor KRN5 in high salt-induced senescence of mouse vascular smooth muscle cells(VSMCs),and to clarify its mechanism.Methods:Thirty 8-week-old male ApoE-/-mice were divided into normal group,senescence group and high-salt treatment senecence group,with 10 mice in each group;the mice in senescence group and high-salt treatment senecence group were used to establish natural senecence mouse models;the mouse VSMCs were isolated and cultured,and divided into normal group,senescence group,high-salt treatment senecence group and high-salt treatment senecence+KRN5 group.β-galactosidase(Sa-β-gal)staining was used to detect the senescence of aortic tissues and VSMCs in various groups;immunofluorescence method was used to detect the expressions of NFAT5 and phosphorylated histone H2A variant X(γ-H2AX)proteins in mouse aortic tissues and VSMCs in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the mRNA expression levels of NFAT5,γ-H2AX,cyclin-dependent kinase inhibitor 2A(P16)and cyclin-dependent kinase inhibitor 1A(P21)in the cells in various groups;Western blotting method was used to detect the protein expression levels of NFAT5,γ-H2AX,P16 and P21 in VSMCs in various groups.Results:The Sa-β-gal staining results showed that compared with normal group,the proportions of senescence-positive area in aortic tissues of the mice in senescence group and high-salt treatment senecence group were significantly increased(P<0.05),and the proportion of senescence-positive cells in the VSMCs of the mice was significantly increased(P<0.05);compared with senecence group,the proportion of senescence-positive cells in the VSMCs mice in high-salt treatment senecence group was significantly increased(P<0.05);compared with high-salt treatment senecence group,the proportion of senescence-positive cells in the VSMCs of the mice in high-salt treatment senecence+KRN5 group was significantly decreased(P<0.01).The immunofluorescence results showed that compared with normal group,the expression level of γ-H2AX protein in mouse VSMCs of the mice in senescence group was significantly increased(P<0.05);compared with senescence group,the expression levels of SA-β-gal staining and NFAT5 protein in aortic tissue of the mice in high-salt treatment senecence group were significantly increased(P<0.05);compared with normal group,the expression level of NFAT5 protein in the VSMCs of the mice in senecence group and high-salt treatment senecence group was significantly increased(P<0.05);compared with senecence group,the expression level of NFAT5 protein in the VSMCs of the mice in high-salt treatment senecence group was significantly increased(P<0.05).The RT-qPCR results showed that compared with normal group,the expression levels of NFAT5,γ-H2AX,P16,and P21 mRNA in the VSMCs of the mice in senescence group and high-salt treatment senecence group were significantly increased(P<0.05);compared with senecence group,the mRNA expression levels of NFAT5,γ-H2AX,P16,and P21 mRNA in the VSMCs of the mice in high-salt treatment senecence group were significantly increased(P<0.05);compared with senecence group,the expression levels of NFAT5,γ-H2AX,P16,and P21 mRNA in the VSMCs of the mice in high-salt treatment senecence group and high-salt treatment senecence+KRN5 group were significantly increased(P<0.05);compared with high-salt treatment senecence group,the mRNA expression levels of NFAT5,γ-H2AX,P16,and P21 in the VSMCs of the mice in high-salt treatment senecence+KRN5 group were significantly decreased(P<0.05).The Western blotting results showed that compared with normal group,the expression levels of NFAT5,γ-H2AX,P16,and P21 proteins in the VSMCs of the mice in senescence group and high-salt treatment senecence group were significantly increased(P<0.05);compared with senescence group,the expression levels of NFAT5,γ-H2AX,P16,and P21 proteins in the VSMCs of the mice in high-salt treatment senecence group were significantly increased(P<0.05);compared with senecence group,the expression levels of NFAT5,γ-H2AX,P16,and P21 proteins in the VSMCs of the mice in high-salt treatment senecence group and high-salt treatment senecence+KRN5 group were significantly increased(P<0.05);compared with high-salt treatment senecence group,the expression levels of NFAT5,γ-H2AX,P16,and P21 proteins in the VSMCs of the mice in high-salt treatment senecence+KRN5 group were significantly decreased(P<0.05).Conclusion:NFAT5 may play a promoting role in high salt-induced senescence of the mouse VSMCs.

Objective:To discuss the clinical value of pan-immune inflammation index(PIV)in predicting the major adverse cardiovascular events(MACE)within 1 year after percutaneous coronary intervention(PCI)in the elderly patients with coronary heart disease,and to clarify the role of inflammatory response in postoperative recovery and prognosis of the patients with coronary heart disease.Methods:A total of 150 elderly patients with coronary heart disease who underwent PCI from July 2020 to August 2023 were selected as the research subjects;according to the occurrence of MACE within 1 year after operation,they were divided into MACE group(n=28)and non-MACE group(n=122);the baseline data and biochemical indicators of the patients were collected,and PIV was calculated;multivariate Logistic regression was used to analyze the influencing factors of MACE within 1 year after PCI in the elderly patients with coronary heart disease;receiver operating characteristic(ROC)curve was used to analyze the predictive value of PIV for MACE within 1 year after PCI in the elderly patients with coronary heart disease.Results:Compared with non-MACE group,the levels of total cholesterol(TC)and low-density lipoprotein cholesterol(LDL-C),neutrophils(NEUT),platelets(PLT)counting and PIV in the patients in MACE group were significantly increased(P<0.05);there were no significant differences in other data between two groups(P>0.05).The multivariate Logistic regression analysis results showed that the levels of TC(OR=1.571,95％CI:1.088-2.270)and LDL-C(OR=32.506,95％CI:8.880-118.994)and PIV(OR=1.014,95％CI:1.010-1.019)were the influencing factors of MACE within 1 year after PCI in the elderly patients with coronary heart disease(P<0.05).The ROC curve analysis results showed that the area under the ROC curve(AUC)of PIV for predicting MACE was 0.857(95％CI:0.762-0.951),the sensitivity was 0.821,the specificity was 0.959,the maximum Youden index was 0.780,and the best cut-off value was 778.805(P<0.01).Conclusion:PIV has important predictive value for MACE within 1 year after PCI in elderly patients with coronary heart disease.

Objective To explore the mechanism by which CD137 signal regulates the aging of vas-cular smooth muscle cells(VSMCs).Methods Thirty 8-week-old male C57BL/6J mice were ran-domly divided into a young group(8 weeks old)and an aged group(80 weeks old),with 30 mice in each group.After corresponding periods of feeding,the mice were euthanized,and the plasma and aortic blood vessels were isolated.In the cell experiments,normal VSMCs were divided into a control group,bleomycin(BLM)group,combined agonist group,and combined inhibitor group.The cellular senescence level of VSMCs was assessed using a cellular senescence β-galactosidase staining kit.Western blotting and PCR were employed to examine the expression of senescence-related proteins in tissues and cells,while ELISA was utilized to measure the expression of senes-cence-related inflammatory factors.Results The expression of CD137 and γ-H2AX in the aorta was significantly higher,while that of PCNA was obviously lower in the aged group than the young group(P＜0.05).The plasma level of CD137 was notably higher in the aged group than the young group(154.0±4.1 pg/ml vs 98.0±2.3 pg/ml,P＜0.05).Compared with the normal control group,there were significantly more aged VSMCs in the BLM group(P＜0.05).While,treatment of combined agonist resulted in larger amount of aged VSMCs when compared with the BLM group(P＜0.05),which was reversed by combined inhibitor treatment(P＜0.05).The levels of TNF-α,IL-6 and IL-1β were significantly elevated in the BLM group than the normal control group(P＜0.05).The combined agonist group had even higher levels of TNF-α,IL-6,and IL-1βthan the BLM group(P＜0.05),but the levels were decreased in the combined inhibitor group(P＜0.05).Compared with the normal control group,the expression of Bcl-2,γ-H2AX,P53,and P21 were significantly increased in the BLM group,combined agonist group,and combined inhibi-tor group,while that of PCNA was significantly decreased(P＜0.05).Compared with the BLM group,the expression of P53 and P21 in the combined agonist group showed an increase(P＜0.05),and the expression of P53 was significantly decreased in the combined inhibitor group(P＜0.05).Conclusion CD137 signal regulates the P53/P21 pathway to promote VSMC aging.

Objective To explore the relationship between polymorphisms of brain-derived neurotrophic factor(BDNF) gene (rs6265 and rs12273539) and cognitive impairment in depressive disorder.Methods All participants including 73 depressed patients and 71 healthy controls were received clinical and cognitive assessments at admission,and then the depression group was divided into two groups by the score of Beijing version of the Montreal Cognitive Assessment (MoCA-BJ).One was depression with cognitive dysfunction group,and the other was depression without cognitive dysfunction group,with 36 and 37 cases respectively.The polymorphisms of BDNF gene was identified by PCR-RFLP.Results No significant difference for rs6265 gene types(x2=5.18,P=0.27),A allele carries (x2 =4.28,P=0.12) and G allele carries (x2 =1.95,P=0.38) among the three groups.There was no significant difference for rs12273539 gene types,allele carries between patients without cognitive dysfunction and controls groups(P＞0.05).There was much more C-allele carries (x2=5.40,P=0.02)and less T-allele(x2=6.06,P=0.01) in patients with cognitive disorder than those in health and it was different in rs12273539 gene types between the two groups(x2=8.38,P=0.02).CC/CT/CT gene type performed different on attention function (P＜0.01).Conclusion BDNF rsl2273539(T/C) gene type has relationship with the onset of cognitive disorder in depressed patients,and there are more C-allele carries in depressive patients.The depression patients with CC gene type are worse on the attention function impairement.

Objective To explore the relationship of attentional function,coping style and depressive symptoms in depression disorders.Methods Sixty-eight depression disorder and seventy-one normal healthy people were assessed by Hamilton depression scale(HAMD),coping style questionnaire and digit span forward.Independent samples t test and hierarchical multiple linear regression analysis were used to analyze all data.Resuits Compared with the control group,depressed patients had higher blaming(0.57 ± 0.29 vs 0.29 ± 0.25,P ＜0.01),wishful thinking(0.55 ± 0.22 vs 0.42 ± 0.26,P ＜ 0.01) and avoidant (0.63 ± 0.18 vs 0.46 ± 0.21,P ＜0.0l),lower problem solving (0.67 ± 0.23 vs 0.80 ± 0.18,P ＜ 0.01),rationalization (0.51 ± 0.20 vs 0.59 ±0.06,P＜0.01) and poorer attentional function(6.90 ± 1.65 vs 7.54 ±0.98,P＜0.01) ;but there was no significant differences in support seeking score.Hierarchical multiple linear regression analysis revealed that,even when controlling for age,sex,low score of support seeking were independently predicted attentional function impairment (β =-0.25,P＜0.05).In addition,the use of support seeking was found to mediate the relationship between digit span forward and retardation completely.Conclusion Retardation indirectly influence the attention function by the mediating of support seeking.

Objective To investigate the characteristics of cognitive dysfunction in patients with depression,and identify the correlation between cognitive dysfunction and serum brain-derived neurotrophic factor (BDNF) level.Methods All participants including 73 depressed patients and 71 healthy controls were received clinical and cognitive assessments at admission,the depression group was divided into two groups by the score of Beijing version of the Montreal Cognitive Assessment (MoCA-BJ),one was depression with cognitive dysfunction group which had 36 cases,the other was depression without cognitive dysfunction group which had 37 cases.Concentration of BDNF was measured by the ELISA method.Results Cognitive impairments were found in numerous cognitive domains of depressed patients,including visuospatial and executive abilities,attention,delayed recall and orientation(P ＜ 0.05).The incidence of cognitive dysfunction in depression was 49.3％.There was not significant difference between two depressive groups (depression with cognitive disorder(12.08 ± 7.08)ng/ml,depression without cognitive disorder (12.22 ± 7.93)ng/ml,P ＞ 0.05),and the levels were significantly lower than that in healthy people ((16.55 ± 7.47) ng/ml,P＜ 0.01),and serum BDNF level had no positively relevant with different cognitive functions (P ＞ 0.05).Conclusion Depression patients have cognitive dysfunction in numerous cognitive domains,including visuospatial and executive abilities,attention,delayed recall and orientation.Serum BDNF level is closely related with depression,while,it has no obvious relationship with cognition function in depression.