Longitudinal analysis of blood-brain barrier status and correlation with neurological outcomes in patients with subarachnoid hemorrhageAbstract:Objective To investigate the longitudinal changes in blood-brain barrier(BBB)status and their correlation with neurological outcomes in patients with subarachnoid hemorrhage(SAH).Methods A retrospective study was conducted on 180 SAH patients admitted to our department from January 2020 to January 2025.According to whether the patients developed delayed cerebral ischemia(DCI),they were divided into a DCI group(49 cases)and a non-DCI group(131 cases).Based on the modified Rankin scale(mRS)scores at 3 months after treatment,they were also assigned into a good prognosis group(123 cases)and a poor prognosis group(57 cases).The volume transfer constant,Ktrans,at admission and during the DCI time window was collected and compared.Multivariate logistic regression analysis was used to identify independent predictors of DCI occurrence and poor functional outcomes.Results The DCI group exhibited significantly more advanced age,and larger proportions of Hunt-Hess(H-H)grade Ⅲ,World Federation of Neurological Surgeons(WFNS)grade Ⅲ and modified Fisher scale(mFS)grade Ⅲ(P<0.05,P<0.01),and higher Ktrans values at admission and during the DCI time window(P<0.05,P<0.01)when compared with the non-DCI group.And with the extension of time,the Ktrans values were decreased obviously in both groups(P<0.05).Multivariate logistic regression analysis showed that age(OR=1.170,95%CI:1.028-1.332,P<0.05),Ktrans value at admission(OR=75.491,95%CI:4.099-1390.262,P<0.01),H-H grade(OR=2.275,95%CI:1.063-4.872,P<0.05)and WFNS grade(OR=2.305,95%CI:1.107-4.798,P<0.05)were all independent risk factors for DCI in SAH patients.Advanced age and higher proportions of H-H grade Ⅲ,WFNS grade Ⅲ,mFS grade Ⅲ and DCI were observed in the poor prognosis group than the good prognosis group(P<0.01).Multivariate logistic regression analysis indicated that age(OR=1.881,95%CI:1.476-2.398,P<0.01),Ktrans value during the DCI time window(OR=111.804,95%CI:1.787-6993.622,P<0.05),mFS grade(OR=6.256,95%CI:2.341-16.718,P<0.01)and DCI(OR=5.057,95%CI:1.789-14.294,P<0.01)were all independent risk factors for poor prognosis in SAH patients.Conclusion An elevated Ktrans at admission is associated with the occurrence of DCI in SAH patients.Continuous monitoring of Ktrans from admission to the DCI time window can predict neurological outcomes at 3 months after treatment.
Diagnostic efficiency of diffusion tensor imaging combined with amide proton transfer weighted imaging for early Parkinson's disease in the elderlyAbstract:Objective To investigate the diagnostic efficiency of combining diffusion tensor imaging(DTI)and amide proton transfer(APT)imaging for early Parkinson's disease(PD)in the elderly.Methods A total of 127 elderly patients(PD group)with early PD admitted in the Affiliated Hospital of Guizhou Medical University from June 2022 to June 2024 were enrolled,and another 113 healthy individuals who took physical examinations were also recruited and served as the control group.The general data were collected in the two groups.Both groups underwent multimodal magnetic resonance imaging(MRI),and received DTI and APT sequence scans.And DTI[mean diffusivity(MD),fractional anisotropy(FA)]and APT sequence parameters were collected and compared between groups.The diagnostic efficiency of DTI combined with APT for early PD in the elderly was analyzed by receiver operating characteristic(ROC)curve analysis.Results There were no statistical differences in MD,FA and magnetization transfer ratio asymmetry(MTRasym)values of the bilateral regions of interest(ROI)between the two groups.The PD group exhibited significantly higher DTI-MD values of the substantia nigra,red nucleus,putamen and globus pallidus than the control group(P<0.05),and obvious difference was observed in the MTRasym value of the caudate nucleus head between two groups(P<0.05).ROC curve analysis showed that the area under the curve(AUC)of DTI-MD values of the substantia nigra,red nucleus,putamen and globus pallidus combined with APT sequence caudate nucleus MTRasym value was 0.905(95%CI:0.865-0.945),significantly higher than that of single parameter(P<0.05).Conclusion DTI and APT imaging have certain diagnostic efficiency for early PD in the elderly,and the combination of the two techniques can further enhance the diagnostic efficiency.
Neuroprotective effects and mechanism of calycosin in a mouse model of post-stroke depressionAbstract:Objective To investigate the neuroprotective effect of calycosin(CA)on post-stroke depression(PSD)in mice and its potential association with NOD-like receptor protein 3(NLRP3).Methods A total of 60 SPF-grade male C57BL/6 mice(8 weeks old)were randomly divided into control,model,low-dose CA treatment(CA-L,20 mg/kg),high-dose CA treatment(CA-H,40 mg/kg),and high-dose CAplus NLRP3 agonist treatment(40 mg/kg CA+0.1 mg/kg nigericin)groups,with 12 animals in each group.A PSD model was established by transient middle cerebral artery occlusion(tMCAO)followed by chronic restraint stress(CRS).Tail suspension test(TST)and sucrose preference test(SPT)were used to assess depressive-like behaviors.HE staining was employed to observe the pathological changes,immunofluorescence assay was utilized to detect the NLRP3 expression in the basolateral amygdala(BLA),and ELISA was performed to measure the contents of IL-1β and IL-18 in BLA tissue.Results Compared with the model group,the CA-L and CA-H groups exhibited significantly increased sucrose preference,reduced immobility time in TST,downregulated NLRP3,and decreased IL-1β and IL-18 contents in the BLA.Co-administration of nigericin,NLRP3 agonist,resulted in increased cellular disorganization,degeneration,and necrosis,and lower sucrose preference[(82.25±4.77)%vs(65.46±5.04)%],longer immobility time(95.66±9.23 s vs 144.75±11.35 s),lower NLRP3 level(61.36±6.01 AU vs 105.26±6.31 AU),and decreased contents of IL-iβ(15.28±1.42 ng/mL vs 26.35±2.41 ng/mL),and IL-18(16.47±1.31 ng/mL vs 28.72±2.15 ng/mL)when compared with the CA-H group(P<0.05).Conclusion CA exerts significant neuroprotective effects in a mouse model of PSD,potentially due to its inhibiting NLRP3 inflammasome-mediated neuroinflammatory responses.
Relationship and clinical significance of plasma taurine up-regulated gene 1 and heart failure with preserved ejection fraction in elderly patients with essential hypertensionAbstract:Objective To investigate the clinical significance of plasma long non-coding RNA taurine up-regulated gene 1(lncRNA TUG1)in predicting the development of heart failure with preserved ejection fraction(HFpEF)in elderly patients with essential hypertension.Methods A prospective study was conducted on 75 elderly patients(HFpEF group)with HFpEF and essential hypertension admitted in our hospital from April 2022 to March 2025.Another 75 patients with essential hypertension but normal heart function were enrolled and served as control group.All patients underwent echocardiography,and plasma TUG1 level was measured using RT-qPCR.Results The plasma TUG1 level was significantly higher in the HFpEF group than the control group(P<0.01).The plasma TUG1 level was positively correlated with aortic annulus diameter,left atrial diameter,left ventricular end diastolic and end systolic diameters,interventricular septal thickness,mitral E-wave to early diastolic mitral annulus velocity ratio,and left ventricular mass index,while it was negatively correlated with left ventricular fractional shortening,cardiac output,and left ventricular ejection fraction(P<0.01).Plasma TUG1 was an risk factor for HFpEF occurrence(OR=1.136-1.314,P<0.05).The AUC value of TUG1 in predicting HFpEF in hypertensive patients was 0.804,while the value of TUG1 combined with NT-proBNP or LVMI reached 0.883 and 0.855,respectively.Conclusion Elevated plasma TUG1 level is observed in the elderly patients with HFpEF and primary hypertension.TUG1 is considered as an effective biomarker for diagnosing the development of HFpEF in elderly patients with primary hypertension.
Role and mechanism of cinnamaldehyde-activated TRPA1 in the dedifferentiation of vascular smooth muscle cellsAbstract:Objective To explore the role and mechanism cinnamaldehyde-activated of transient receptor potential channel A1 subtype(subfamily A,member 1,TRPA1)in the dedifferentiation of vascular smooth muscle cells(VSMC).Methods Oxidized low-density lipoprotein(ox-LDL)was utilized to induce VSMC differentiation.The VSMCs were divided into control group(without ox-LDL treatment),ox-LDL group(50 ug/mL)and combination group(50 μg/mL ox-LDL+10 μmol/L cinnamaldehyde).Western blotting was used to detect protein expression levels.Immunofluorescence staining was employed to measure the production of mitochondrial derived vesicles(MDV).Results With prolonged of ox-LDL stimulation,the expression of TRPA1 was gradually decreased in VSMC,showing the most significant reduction at 6 and 12 h(P<0.05).Compared with the control group,the expression levels of osteopontin(OPN)and proliferating cell nuclear antigen(PCNA)were notably up-regulated,while that of α-smooth muscle actin(α-SMA)was obviously down-regulated in the ox-LDL group(P<0.05).Significantly down-regulated levels of OPN and PCNA(1.33±0.13 vs 1.72±0.20,1.09±0.10 vs 1.36±0.11,P<0.05),while up-regulation of α-SMA(0.79±0.09 vs 0.57±0.12,P<0.05)were observed in the combination group than the ox-LDL group.MDV in VSMC was significantly reduced in the ox-LDL group than the control group,whereas,it was increased in the combination group when compared with the ox-LDL group.Conclusion Reduced TRPA1 expression is involved in the dedifferentiation process of VSMC induced by ox-LDL.Activating TRPA1 with cinnamaldehyde may inhibit VSMC dedifferentiation by promoting MDV generation.
Role and underlying mechanism of resveratrol in trimethylamine N-oxide-induced vascular aging in miceAbstract:Objective To investigate the role and underlying mechanism of resveratrol(RSV)in trimethylamine N-oxide(TMAO)-induced vascular aging in senescence-accelerated mouse prone 8(SAMP8)mice.Methods A total of 36 male SAMP8 mice(24 weeks old)were randomly divided into control,TMAO,and TMAO+RSV groups,with 12 mice per group.The control group received drinking water and intragastric administration of RSV vehicle,0.5%sodium carboxymethyl cellulose(NaCMC).The TMAO group received drinking water containing 1.5% TMAO and intragastric administration of NaCMC.The TMAO+RSV group received 1.5% TMAO in drinking water and intragastric administration of 50 mg/kg RSV.After 16 weeks of intervention,pulse wave velocity(PWV)and maximum endothelium-dependent relaxation(Emax)were measured,aortic structure and senescence-associated β-galactosidase(SA-β-gal)were observed,and the protein expression levels of P53,P21,silent mating type information regulation 2 homolog-1(SIRT1),peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),and superoxide dismutase 2(SOD2)were detected.Results Compared with the control group,the TMAO group exhibited significantly larger aortic lumen diameter,thicker wall thickness,increased wall area,more elastic fiber breaks,enhanced SA-β-gal positive area,and higher PWV and protein levels of P53 and P21,whereas obviously decreased Emax and expression levels of SIRT1,PGC-1α,and SOD2(P<0.05).RSV treatment resulted in significant decreases in aortic lumen diameter,wall thickness,wall area,elastic fiber breaks,PWV and protein levels of P53 and P21 in the aorta,and increases in Emax and expression levels of SIRT1,PGC-1α and SOD2[(47.43±7.27)%vs(29.48±4.28)%,0.43±0.18 vs 0.18±0.14,0.80±0.26 vs 0.22±0.08,1.22±0.41 vs 0.25±0.07,P<0.05].Conclusion RSV can ameliorate TMAO-accelerated vascular aging in SAMP8 mice,potentially through activation of the SIRT1/PGC-1α/SOD2 pathway.
Influencing factors for vascular aging in the elderly peopleAbstract:Objective To investigate the relationship between the triglyceride-glucose(TyG)index and brachial-ankle pulse wave velocity(baPWV)in the elderly.Methods A total of 162 elderly inpatients with atherosclerotic cardiovascular disease(ASCVD)admitted to our department from October 2016 to August 2025 were enrolled as the ASCVD group,and another 125 elderly individuals who taking regular physical examinations in Department of Health Management of our hospital during the same period were selected as the non-ASCVD group.Basic clinical data and inflammatory and biochemical indicators were collected from all the participants.Estimated glomerular filtration rate(eGFR)and TyG index were calculated.The influencing factors of baPWV were analyzed in the two groups,respectively.Spearman correlation analysis and multiple linear regression analysis were employed to analyze the correlation between baPWV and clinical indicators.Results The ASCVD group exhibited significantly higher waist-hip ratio,TyG index,and proportion of antiplatelet agents use,while obviously lower ratio of males,diastolic blood pressure,and high-density lipoprotein cholesterol levels than the non-ASCVD group(P<0.05,P<0.01).In the non-ASCVD group,baPWV was positively correlated with age(r=0.366,P<0.01),systolic blood pressure(SBP,r=0.352,P<0.01)and TyG index(r=0.226,P<0.05),and negatively with eGFR(r=-0.290,P<0.01).In the ASCVD group,baPWV was positively correlated with age(r=0.448,P<0.01),SBP(r=0.252,P<0.01)and TyG index(r=0.167,P<0.05),and negatively with eGFR(r=-0.255,P<0.01)and body mass index(r=-0.203,P<0.05).Stepwise multiple linear regression analysis identified age,SBP,TyG index,eGFR and hypertension as influencing factors for baPWV in the non-ASCVD group(P<0.05,P<0.01);whereas only SBP and age were influencing factors for baPWV in the ASCVD group(P<0.05,P<0.01).Conclusion In elderly population,baPWV is associated with age and SBP.TyG index is correlated with vascular aging in elderly non-ASCVD individuals,and is one of the important risk factors.
Relationship of 25-hydroxyvitamin D3 and high-sensitivity C-reactive protein to albumin ratio with cardiac function and prognosis in elderly patients with severe pneumonia and heart failureAbstract:Objective To investigate the relationship of 25-hydroxyvitamin D3(25-OH VitD3)and ratio of high-sensitivity C-reactive protein(hs-CRP)to albumin(HCAR)with cardiac function and prognosis in elderly patients with severe pneumonia and heart failure.Methods A retrospective study was conducted on 183 elderly patients with severe pneumonia and heart failure admitted to our hospital from January 2023 to January 2025.Based on 28-day follow-up results,they were divided into a survival group(121 cases)and a death group(62 cases).25-OH VitD3 and HCAR were collected from all the participants.Pearson and Spearman correlation analyses were used to explore the relationship of 25-OH VitD3 and HCAR with cardiac function and prognosis in the patients.Results The death group exhibited significantly lower 25-OH VitD3 level and higher HCAR than the survival group(P<0.01).Pearson correlation analysis showed that 25-OH VitD3 was positively correlated with cardiac index and left ventricular ejection fraction(r=0.184,P<0.05;r=0.209,P<0.01),while HCAR was negatively correlated with cardiac index(r=-0.184,P<0.05)in elderly patients with severe pneumonia and heart failure.Spearman correlation analysis indicated that the prognosis of the elderly patients with severe pneumonia and heart failure was negatively correlated with 25-OH VitD3(r=-0.615,P<0.01),but positively with HCAR(r=0.281,P<0.01).N-terminal pro-B-type natriuretic peptide,B-type natriuretic peptide,25-OH VitD3,and HCAR were influencing factors for poor prognosis in elderly patients with severe pneumonia and heart failure(P<0.05).Conclusion 25-OH VitD3 and HCAR are closely associated with cardiac function and prognosis in elderly patients with severe pneumonia and heart failure,and both of them are influencing factors for prognosis.
Prognostic value of stress hyperglycemia ratio versus triglyceride-glucose index in critically ill elderly patients with strokeAbstract:Objective To compare the predictive value of stress hyperglycemia ratio(SHR)and triglyceride-glucose index(TyG)for short-term all-cause mortality in elderly critically ill stroke patients.Methods A retrospective study was conducted on the 1800 ICU patients with cerebrovascular diseases based on the Medical Information Mart for Intensive Care-Ⅳ database.Based on the quartiles of SHR and TyG,patients were categorized into Q1,Q2,Q3 and Q4 groups.The primary outcome was 30-day all-cause mortality after ICU admission,and the 7-and 90-day mortality incidences were taken as secondary outcomes.Kaplan-Meier survival analysis was used to construct survival curves.Multivariate Cox proportional hazards regression was employed to assess the risk of patient mortality.ROC curves were used to evaluate the predictive performance of SHR and TyG at 7-,30-,and 90-day.Results With the increase of SHR quantile,the 7-,30-,and 90-day mortality incidences were gradually raised(P<0.01),and the survival curves showed consistent risk stratification across SHR quartiles at all time points(Log-rank P<0.01).Multivariate Cox regression analysis showed a clear dose-response relationship in SHR.Compared with the Q1 group,the Q4 group had a significantly increased risk of 30-day mortality(HR=2.63,95%CI:1.77-3.89,P<0.01).TyG was associated with 7-and 30-day mortality risk,but not with the 90-day mortality risk among 4 groups(P>0.05),without showing a clear gradient.Time-dependent ROC curve analysis indicated that the AUC values of the addition of SHR increased to 0.680,0.750 and 0.753,respectively,but adding TyG had no such significant effect.The predictive performance was not improved notably after the combination of SHR and TyG.Conclusion In elderly critically ill stroke patients,SHR demonstrates superior and more stable discriminative performance than TyG in predicting short-term all-cause mortality,and may serve as a potential practical biomarker for early risk stratification.
Risk factors for contrast-induced acute kidney injury and its impact on prognosis in elderly patients with coronary artery disease undergoing percutaneous coronary interventionAbstract:Objective To assess the risk factors associated with contrast-induced acute kidney injury(CIAKI)in elderly patients(≥ 60 years)with coronary artery disease(CAD)undergoing percutaneous coronary intervention(PCI),and to analyze the impact of CIAKI on cardiac and renal prognosis in these patients.Methods A retrospective study was conducted on 584 elderly CAD patients undergoing PCI in our department from January 2022 to December 2023.Based on the occurrence of CIAKI or not at 72 h after the procedure,they were divided into a CIAKI group(36 cases)and a non-CIAKI group(548 cases).Clinical data were compared between two groups.Binary logistic regression analysis was used to identify the risk factors for CIAKI.All patients were followed for at least one year,and the incidences of major adverse cardiac events(MACE)and major adverse kidney events(MAKE)were recorded during follow-up.Results The incidence rate of CIAKI was 6.2%in the cohort.When compared with the non-CIAKI group,the CIAKI group exhibited significantly more advanced age,higher proportions of comorbidities such as diabetes,acute myocardial infarction,anemia,estimated glomerular filtration rate(eGFR)<60 ml/(min·1.73 m2)and left ventricular ejection fraction(LVEF)<45%,elevated high-sensitivity C-reactive protein(hs-CRP)level,prolonged length of hospital stay,and higher total cost of hospital stay(P<0.05,P<0.01).Binary logistic regression analysis showed that eGFR<60 mL/(min·1.73 m2)(OR=2.687,95%CI:1.353-5.337),LVEF<45%(OR=1.305,95%CI:1.015-1.677),anemia(OR=3.693,95%CI:1.802-7.567),and hs-CRP(OR=1.133,95%CI:1.072-1.198)were risk factors for CIAKI.During a median follow-up of 13(12.0,14.5)months,the incidence rates of MACE and MAKE were obviously higher in the CIAKI group than the non-CIAKI group(x2=35.19,10.17,P<0.05).Conclusion CIAKI can increase the length and cost of hospital stay in elderly CAD patients,and significantly affect their cardiac and renal prognosis.
Effects of deep transcranial magnetic stimulation on motor function of lower extremity in stroke patientsAbstract:Objective To investigate the effects of deep transcranial magnetic stimulation(dTMS)on lower extremity motor dysfunction in stroke patients.Methods A total of 75 stroke patients with lower extremity motor dysfunction admitted to our hospital from January 2024 to May 2025 were prospectively recruited and randomly divided into dTMS group(n=25),repetitive transcranial magnetic stimulation(rTMS)group(n=25),and control group(n=25).Fugl-Meyer assessment of lower extremity(FMA-LE),Berg balance scale(BBS),timed up and go test(TUGT),three-dimensional gait analysis system(including walking speed,stride frequency,stride length and gait cycle),and resting motor threshold(RMT)were used to assess the conditions in all groups before and after treatment.Adverse reactions during treatment were also monitored.Results The FMA-LE score after treatment was significantly increased in the dTMS and rTMS groups when compared with the control group(P<0.05,P<0.01),and the score in the dTMS group was significantly higher than that of the rTMS group(23.97±5.08 vs 21.56±5.11,P<0.05).After treatment,both dTMS and rTMS groups exhibited significantly increased BBS scores,walking speed and stride length,and the dTMS group had a significantly shorter TUGT times when compared with the control group(P<0.05,P<0.01).The dTMS group exhibited significantly improved BBS scores,walking speed and stride length,as well as notably reduced TUGT times when compared with the rTMS group(P<0.05,P<0.01).Additionally,RMT was significantly lower in the dTMS and rTMS groups than in the control group after treatment(P<0.05,P<0.01),and the dTMS group had a significantly lower RMT than the rTMS group(P<0.05).Conclusion dTMS can effectively improve lower extremity motor function,balance and walking ability,and enhance cerebral cortical excitability in stroke patients.
Construction of a nomogram prediction model for new-onset postoperative atrial fibrillation in elderly patients with acute type A aortic dissectionAbstract:Objective To construct a nomogram prediction model for new-onset postoperative atrial fibrillation(POAF)in elderly patients with acute type A aortic dissection(ATAAD).Methods A total of 150 elderly ATAAD patients undergoing surgical treatment in our department from May 2023 to May 2025 were recruited,and based on whether POAF occurred or not,they were divided into a POAF group(n=67)and a non-POAF group(n=83).A nomogram model for POAF risk in elderly ATAAD patients was constructed using R software.ROC curves were plotted to evaluate the discrimination of the model for POAF in elderly ATAAD patients.Results The POAF group had significantly more advanced age,longer cardiopulmonary bypass time(CPBT),and higher C-reactive protein(CRP)levels and left atrial diameter(LAD)than the non-POAF group(P<0.01).Age,CPBT,CRP,and LAD were risk factors for POAF in elderly ATAAD patients(P<0.05).The risk nomogram model for POAF in elderly ATAAD patients was constructed using R software,with a sensitivity of 79.10%,a specificity of 87.95%,and an area under the curve of 0.832(95%CI:0.762-0.903).Conclusion New-onset POAF in elderly ATAAD patients is related to age,CPBT,CRP,and LAD.Our nomogram prediction model for POAF constructed based on these factors has good predictive performance for POAF occurrence in elderly ATAAD patients.
Effect of plasma lipid adsorption filtration on intracranial hemodynamics and neurological function in elderly patients with acute strokeAbstract:Objective To determine the effects of plasma lipid adsorption filtration on intracranial hemodynamics and neurological function in elderly patients with acute stroke(AS).Methods A prospective study was conducted on 200 elderly AS patients complicated with hypertriglyceridemia admitted to No.940 Hospital of Joint Logistics Support Force of Chinese PLA from January 2023 to December 2024.They were randomly divided into an observation group(100 cases)and a control group(100 cases).Both groups received conventional treatment,and the observation group received plasma lipid adsorption filtration on this basis.Lipid metabolism,inflammatory factors,hemodynamics,and neurological function were detected,evaluated and then compared between the two groups.Results After treatment,the observation group exhibited significantly lower levels of total cholesterol(TC),triglycerides(TG),LDL-C,IL-6 and C-reactive protein(CRP),and decreased National Institute of Health Stroke Scale(NIHSS)scores at 3 and 7 d,and higher average blood flow velocity in the middle cerebral artery when compared with the control group(P<0.05,P<0.01).The Δ NIHSS score of the elderly AS patients was positively correlated with ΔTC,ΔTG,and Δ LDL-C(r=0.485,r=0.502,r=0.282,P<0.01).There was no statistical difference in the incidence of adverse reactions during treatment between the observation group and the control group(12.0% vs 8.0%,P>0.05).Conclusion Plasma lipid adsorption filtration can significantly reduce inflammation levels,improve lipid metabolism and hemodynamics,and thus promote neurological rehabilitation in elderly AS patients.
Mechanism of lactoferrin in alleviating atherosclerosis by inhibiting senescence-associated secretory phenotype of macrophagesAbstract:Objective Our investigate the correlation between lactoferrin(LTF)expression and severity of coronary stenosis,and the potential mechanism of LTF in regulating macrophage senescence-associated secretory phenotype(SASP).Methods The arterial samples from the left anterior descending coronary artery were collected from the corpses in Forensic Identification Center of Guizhou Medical University from January 2020 to December 2023,and divided into a control group(n=20),a mild coronary artery disease(CAD)group(n=20,stenosis<50%),and a severe CAD group(n=20,stenosis ≥50%).Western blotting and immunohistochemical staining were used to detect the protein expression of LTF and SASP markers,such as IL-1β,IL-6,matrix metalloproteinase 9(MMP-9),and cyclin-dependent kinase inhibitor 2A(CDKN2A or P16).Pearson correlation analysis was employed to study the relationship between LTF and IL-1β,IL-6,MMP-9,and P16.In vitro,there were four groups of cells,that is,PMA group(macrophages differentiated from THP-1 monocytes by phorbol ester),ox-LDL group[foam cells induced by oxidized low-density lipoprotein(ox-LDL)],siRNA-NC group(foam cells transfected with non-targeting siRNA,siRNA-negative control),and siRNA-LTF group(foam cells transfected with LTF-targeting siRNA).Intracellular lipid levels were observed by Oil Red O staining.Cell senescence was detected by senescence-associated β-galactosidase staining.The protein expression levels of IL-1β,IL-6,MMP-9 and P16 were measured by Western blotting.The expression and localization of LTF and P16 were observed with immunofluorescence assay.Results The degree of stenosis and the protein levels of LTF,IL-1β,IL-6,MMP-9,and P16 in coronary artery tissues were significantly higher in the mild CAD group than the control group(P<0.05,P<0.01),and further elevated in the severe CAD group than the mild CAD group(P<0.05,P<0.01).Correlation analysis showed LTF was positively correlated with the expression levels of IL-1β,IL-6,MMP-9 and P16(r=0.895,r=0.912,r=0.917,r=0.855,P<0.01).In in vitro experiments,the ox-LDL group exhibited significantly more lipid deposition,higher rate of senescent cell,and increased protein levels of IL-1β,IL-6,MMP-9,P16,and LTF when compared with the PMA group(P<0.05,P<0.01);The siRNA-LTF group showed significantly increased levels of the aforementioned indicators compared to the ox-LDL group,while LTF expression was obviously reduced(P<0.05,P<0.01).Conclusion LTF expression is upregulated in coronary atherosclerotic plaques and positively correlated with coronary stenosis severity.LTF can alleviate atherosclerosis progression by inhibiting macrophage senescence.
Correlation between Zhejiang University index and progressive stroke in the elderlyAbstract:Objective To evaluate the correlation between Zhejiang University(ZJU)index levels at admission and progressive stroke(PS)in elderly patients.Methods A retrospective study was conducted on 7549 patients diagnosed with cerebral infarction who were consecutively admitted to Cangzhou People's Hospital between January 2019 and December 2024.According to the inclusion and exclusion criteria,1349 patients were finally enrolled in this study.According to the presence or absence of PS,they were divided into a PS group(351 cases)and a non-PS group(998 cases).Multivariate logistic regression analysis was used to assess the relationship between the ZJU index and PS,and receiver operating characteristic(ROC)curves were plotted to analyze the predictive performance of the ZJU index for PS risk.Results During hospitalization,351 patients developed PS.The ZJU index was significantly higher in the PS group than the non-PS group(P<0.01).Multivariate logistic regression analysis revealed that the ZJU index was an independent risk factor for PS(OR=1.145,95%CI:1.117~1.174,P<0.01).The area under the curve(AUC)of the ZJU index in predicting PS among older adult patients was 0.667(95%CI:0.642~0.692,P<0.01),indicating a certain predictive capacity.Conclusion ZJU index is an independent risk factor for PS in elderly patients.The index at admission demonstrates important reference value for predicting PS.
Correlation between serum microRNA expression and vascular endothelial function in patients with essential hypertensionAbstract:Objective To analyze the correlation of serum microRNA(miR)-126,miR-18b,miR-29b levels with vascular endothelial function in patients with essential hypertension(EH).Methods A total of 206 EH patients admitted to Second Department of Cardiovascular Medicine of Qingdao Traditional Chinese Medicine Hospital from June 2022 to January 2025 were enrolled and served as the hypertension group.Based on the classification of hypertension,they were assigned into grade 1(n=89),grade 2(n=70)and grade 3(n=47)subgroups,and according to the presence or absence of vascular endothelial dysfunction,they were assigned into endothelial dysfunction subgroup(n=110)and normal endothelial function subgroup(n=96).Additionally,another 103 healthy individuals undergoing physical examination during the same period were included as the control group.Serum expression levels of miR-126,miR-18b and miR-29b,and endothelium-dependent flow-mediated dilation(FMD),reactive hyperaemia index(RHI),and serum endothelin-1 were compared between groups and across subgroups.Results The hypertension group exhibited significantly lower miR-126,FMD and RHI levels,and obviously higher miR-18b,miR-29b and endothelin-1 levels compared with the control group(P<0.01).Obviously lower miR-126,FMD and RHI levels,and higher miR-18b,miR-29b and endothelin-1 levels were observed in the grade 2 and grade 3 subgroups than the grade 1 subgroup(P<0.05).In the endothelial dysfunction subgroup,the serum miR-126 expression was notably lower,while the miR-18b and miR-29b expression was remarkably higher than those in the normal endothelial function subgroup(P<0.01).Pearson correlation analysis revealed that serum miR-126 was negatively correlated with systolic blood pressure,diastolic blood pressure and endothelin-1,and positively with FMD and RHI(P<0.01);serum miR-18b and miR-29b were positively correlated with SBP,DBP and endothelin-1,and negatively with FMD and RHI(P<0.01).Multivariate logistic regression analysis suggested that serum miR-18b,miR-29b,and grade of hypertension were risk factors for endothelial dysfunction in EH patients,while serum miR-126 was a protective factor(P<0.05,P<0.01).ROC curve analysis indicated that the AUC values of serum miR-126,miR-18b,and miR-29b in predicting endothelial dysfunction in the patients were 0.724,0.703,and 0.742,respectively,with sensitivities of 0.727,0.646,and 0.764,and specificities of 0.698,0.688,and 0.635,separately.Conclusion Serum miR-126,miR-18b,and miR-29b expression is closely associated with vascular endothelial function in EH patients,and can serve as predictors for endothelial dysfunction in these patients.
Effect of orientin on myocardial injury in rats with diabetic cardiomyopathyAbstract:Objective To investigate the effect of orientin(Ori)on myocardial injury in DCM rats by regulating the lncRNA NEAT1/miR-34a-5p axis.Methods A rat DCM model was established by combining high-fat diet feeding and streptozotocin(STZ)injection in SPF-grade male Wistar rats.Then,totally 60 DCM rats were randomly divided into DCM group,low-and high-dose Ori groups(Ori-LD and Ori-HD groups),Ori-HD+si-NC group,and Ori-HD+si-NEAT1 group,with 12 rats in each group.In addition,another 12 rats fed with a normal diet were set as the healthy control group(NC group).Echocardiography was applied to assess cardiac function.MDA content,SOD activity,and expression levels of NEAT 1 and miR-34a-5p in heart tissues were determined.Dual-luciferase reporter assay was performed to validate the targeting relationship between NEAT1 and miR-34a-5p.Results Compared with the NC group,the DCM group increased levels of fasting blood glucose,TC and TG,higher apoptotic rate,larger cross-sectional area of myocardial tissue,and elevated MDA content and miR-34a-5p expression level,and lower LVEF,fractional shortening(FS),SOD activity,and NEAT1 expression level(P<0.05).Ori treatment at both low and high doses decreases in fasting blood glucose,TC,TG,apoptotic rate,cross-sectional area of myocardial tissue,MDA content,and miR-34a-5p expression level,while increases in LVEF,FS,SOD activity,and NEAT1 expression level when compared with the DCM group(P<0.05).Conversely,the addition of si-NEAT1 elevated fasting blood glucose,TC,TG,apoptotic rate,cross-sectional area of myocardial tissue,MDA content,and miR-34a-5p expression level(P<0.05),while induced the decreases in LVEF[(62.87±2.70)%vs(79.52±3.59)%],FS[(31.28±1.76)%vs(48.39±3.65)%],SOD activity(162.67±17.38 U/mg vs 218.11±22.42 U/mg)and NEAT1 expression level(0.69±0.08 vs 0.87±0.09)in comparison with simple high-dose Ori treatment(P<0.05).The relative luciferase activity was reduced in the NEAT1-WT and miR-34a-5p mimics co-transfected cells than the cells co-transfected with miR-NC(P<0.01).Conclusion Ori can alleviate myocardial injury in DCM rats by inhibiting the expression of lncRNANEAT1 and upregulating the expression of miR-34a-5p.
M1 macrophage-derived exosomal microRNA-22-3p regulates vascular endothelial senescenceAbstract:Objective To investigate the role of M1 macrophage-derived exosomes(M1-Exo)in regulating vascular endothelial senescence and explore the related molecular mechanism.Methods Six young mice and 6 aged mice were randomly subjected and assigned into a young group and an aged group.The flow-mediated dilation(FMD)of the brachial artery was compared between the two groups.Endothelial cells were co-cultured with solvent control(solvent group),100 ng/μL M1-Exo(M1-Exo 100 ng/μL group),and 200 ng/μL M1-Exo(M1-Exo 200 ng/μL group)respectively.Senescence-associatedβ-galactosidase(SA-β-gal)staining was carried out,and confocal imaging was used to detect the production of intracellular mitochondrial reactive oxygen species(ROS).The following groups were established:microRNA(miRNA)blank control group,miR-22-3p mimic group,miRNA negative control group,and miR-22-3p inhibitor group.The protein expression of silent mating type information regulation 2 homolog-1(SIRT1)was compared among these above groups.Short hairpin RNA(shRNA)transfection was performed with shRNA-SIRT1 plasmid to establish a sh-SIRT1 group,and the cells transfected with shRNA blank plasmid served as control group(sh-NC group).Western blotting was used to detect protein expression in both groups.Results The FMD was significantly decreased in the aged group than the young group[(48.330±3.807)% vs(28.650±3.209)%,P<0.05].In vitro experiments showed that compared with solvent group,the SA-β-gal expression and mitochondrial ROS levels were elevated in both M1-Exo 100 ng/μL and M1-Exo 200 ng/μL groups(P<0.05).The SIRT1 level was decreased in the miR-22-3p mimic group than the miRNA blank control group,but increased in the miR-22-3p inhibitor group than the miR-22-3p mimic group(P<0.05).Compared with the sh-NC group,the nuclear factor κB/cyclin-dependent kinase inhibitor P21(NF-κB/P21)and Forkhead box O3α/superoxide dismutase 2(FOXO3α/SOD2)signaling pathways were activated in the sh-SIRT1 group.Conclusion M1 macrophage-derived exosomal miR-22-3p promotes vascular endothelial cell senescence.
Effectiveness of speech training combined with electrical nerve stimulation on elderly nonfluent aphasia after strokeAbstract:Objective To explore the effectiveness of the combination of speech training and electrical nerve stimulation on nonfluent aphasia after stroke in elderly patients.Methods A total of 102 elderly patients with post-stroke nonfluent aphasia admitted to our department from January 2020 to June 2024 were prospectively enrolled,and then randomly assigned into a study group(51 cases,speech training combined with electrical nerve stimulation)and a control group(51 cases,speech training only).All patients received corresponding interventions for 14 d.The differences in disease symptoms(China Rehabilitation Research Center Standard Aphasia Examination),cognitive function[Non-Language-based Cognitive Assessment(NLCA)],psychological status[Stroke Aphasia Depression Questionnaire(SADQ),Chinese version of Geriatric Anxiety Inventory-Short Form(GAI-SF)]and quality of life[Stroke Aphasia Quality of Life Scale-39(SAQOL-39g)]were compared between groups.Results After treatment,the study group demonstrated significantly higher scores in the dimensions of auditory comprehension,retelling ability,cartoon description,noun enumeration,spontaneous conversation,and reading,description,dictation and computing abilities when compared with the control group(P<0.05,P<0.01).Moreover,the total score of NLCA and scores of dimensions of memory,attention,execution,visual space and logical reasoning in the study group were obviously higher than those in the control group(P<0.05,P<0.01).Notably lower the GAI-SF score and SADQ score were observed in the study group in comparison to the control group(2.10±0.65 vs 2.45±0.72,P<0.05;20.15±4.83 vs 23.42±4.95,P<0.01).The total score of SAQOL-39g and the scores of dimensions of communication and psychosociology in the study group after treatment were statistically higher than those in the control group(131.90±13.78 vs 126.15±15.02,P<0.05;24.30±2.85 vs 22.45±2.90,P<0.01;55.30±5.80 vs 51.75±6.10,P<0.01).Conclusion For elderly patients with nonfluent aphasia after stroke,speech training combined with electrical nerve stimulation can help alleviate the symptoms of aphasia,enhance cognitive function,relieve psychological distress,and effectively improve the quality of life.
Relationship of serum levels of CTRP5 and SCUBE1 with left ventricular remodeling and prognosis in elderly patients with acute myocardial infarctionAbstract:Objective To investigate the relationship between serum levels of complement C1q/tumor necrosis factor-related protein 5(CTRP5)and signal peptide-CUB-epidermal growth factor-like domain-containing protein 1(SCUBE1)and left ventricular remodeling(LVR)as well as prognosis in elderly patients with acute myocardial infarction(AMI).Methods A prospective study was conducted on 104 elderly AMI patients(study group)undergoing percutaneous coronary intervention(PCI),and another 50 age-matched patients with stable coronary artery disease(control group)admitted to our department between March 2022 and December 2023.Based on the occurrence of major adverse cardiovascular events(MACE)within 1 year of follow-up,the study group was further divided into a good prognosis subgroup(68 cases)and a poor prognosis subgroup(36 cases).Serum levels of CTRP5 and SCUBE1,as well as LVR parameters,were measured in all participants.Pearson correlation analysis was used to assess the relationship between CTRP5 and SCUBE1 levels and LVR indicators.Results The study group showed significantly higher serum levels of CTRP5 and SCUBE1,and higher left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic volume(LVESV),and left ventricular mass index(LVMI),and lower left ventricular ejection fraction(LVEF)compared to the control group(P<0.01).Serum levels of CTRP5 and SCUBE1 were positively correlated with LVEDD,LVESV,and LVMI,and negatively correlated with LVEF in elderly AMI patients(P<0.01).Higher serum CTRP5 and SCUBE1 levels were observed in the poor prognosis group than the good prognosis group(P<0.01).ROC curve analysis indicated that the AUC value of combined CTRP5 and SCUBE1 in predicting prognosis was 0.914,which was significantly higher than that of CTRP5(AUC=0.759)or SCUBE1(AUC=0.836)alone(Z=12.719,9.237,P<0.01).Killip class,LVESV,LVEF,NT-proBNP,cTnT,CTRP5,and SCUBE1 were influencing factors for prognosis in elderly AMI patients(P<0.01).Conclusion Elevated serum levels of CTRP5 and SCUBE1 are associated with LVR and prognosis in elderly AMI patients,and their combination may serve as an effective indicator for predicting prognosis in these patients.