Knowledge of Alzheimer's disease and associated factors among adults in Zhuhai, China: a cross-sectional analysis.

BACKGROUND: This study aimed to assess the public knowledge regarding Alzheimer's Disease (AD) in Zhuhai, China, focusing on identifying knowledge gaps and the influence of demographic and health factors. METHODS: A cross-sectional study was conducted in Zhuhai, China, from October to November 2022. A total of 1986 residents from 18 communities were selected employing stratified multi-stage equi-proportional sampling. Questionnaires covering general information and the Alzheimer's Disease Knowledge Scale (ADKS) were investigated face-to-face. Ordinal multiclass logistic regression was applied to assess the relationship between AD awareness and demographic and health characteristics. RESULTS: The average ADKS score was 18.5 (SD = 3.36) in Zhuhai. The lowest awareness rates were observed in the "Symptoms" and "Caregiving" subdomains of ADKS, with rates of 51.01% and 43.78%, respectively. The correct rates for the 30 ADKS questions ranged from 16.62 to 92.6%, showing a bimodal pattern with clusters around 80% and 20%. Women (OR = 1.203, 95% CI: 1.009-1.435), individuals aged 60 years or older (OR = 2.073, 95% CI: 1.467-2.932), those living in urban areas (OR = 1.361, 95% CI: 1.117-1.662), higher average monthly household income per capita (OR = 1.641, 95% CI: 1.297-2.082), and without any neurological or mental disorders (OR = 1.810, 95% CI: 1.323-2.478) were more likely to have higher levels of awareness about Alzheimer's disease. CONCLUSIONS: Adults in Zhuhai show a limited knowledge of AD, particularly in the 'Symptoms' and 'Caregiving' subdomains. Upcoming health campaigns must focus on bridging the knowledge gaps in different subdomains of AD, especially among subgroups with lower awareness, as identified in our study.

Comparative outcomes of subcutaneous and transvenous cardioverter-defibrillators.

BACKGROUND: The comparative outcomes of subcutaneous implantable cardioverter-defibrillator (S-ICD) and transvenous ICD (T-ICD) have not been well studied. The aim of this study was to evaluate the safety and efficacy of currently available S-ICD and T-ICD. METHODS: The study included 86 patients who received an S-ICD and 1:1 matched to those who received single-chamber T-ICD by gender, age, diagnosis, left ventricular ejection fraction (LVEF), and implant year. The clinical outcomes and implant complications were compared between the two groups. RESULTS: The mean age of the 172 patients was 45 years, and 129 (75%) were male. The most common cardiac condition was hypertrophic cardiomyopathy (HCM, 37.8%). The mean LVEF was 50%. At a mean follow-up of 23 months, the appropriate and inappropriate ICD therapy rate were 1.2% vs. 4.7% (χ = 1.854, P = 0.368) and 9.3% vs. 3.5% (χ = 2.428, P = 0.211) in S-ICD and T-ICD groups respectively. There were no significant differences in device-related major and minor complications between the two groups (7.0% vs. 3.5%, χ = 1.055, P = 0.496). The S-ICD group had higher T-wave oversensing than T-ICD group (9.3% vs. 0%, χ = 8.390, P = 0.007). Sixty-five patients had HCM (32 in S-ICD and 33 in T-ICD). The incidence of major complications was not significantly different between the two groups. CONCLUSIONS: The efficacy of an S-ICD is comparable to that of T-ICD, especially in a dominantly HCM patient population. The S-ICD is associated with fewer major complications demanding reoperation.

A mechanistic study of proteasome inhibition-induced iron misregulation in dopamine neuron degeneration.

Ubiquitin proteasome system (UPS) impairment and iron misregulation have been implicated in dopamine (DA) neuron degeneration in Parkinson's disease. As previously shown, proteasome inhibition in a rodent model can cause nigral neuron degeneration accompanied by iron accumulation. To investigate the involvement of iron in DA neuron degeneration, we generated an in vitro model by applying proteasome inhibitor lactacystin in DAergic cell line MES23.5 culture. We found that lactacystin caused marked increase in labile iron, reactive oxygen species and ubiquitin-conjugated protein aggregation prior to cell injury. These effects were attenuated by iron chelators or antioxidants. Furthermore, we demonstrated that the iron regulatory protein (IRP)/iron response element system contributed to UPS impairment-mediated DA neuron injury. We documented that IRP2 disruption resulted in an increase in transferrin receptor 1 (TfR1), a decrease in ferritin heavy chain (H-Frt), and eventually cell death. These findings provide insight into the mechanistic interplay between UPS impairment and iron misregulation and suggest that the disturbances in IRP2, TfR1 and H-Frt may contribute to DA neuron degeneration.

[Prevalence and risk factors of peri-procedure electrical storm in acute myocardial infarction patients underwent emergency percutaneous coronary intervention].

OBJECTIVE: To determine the prevalence and to identify risk factors of peri-procedure electrical storm (ES) in patients with acute myocardial infarction (AMI) underwent emergency percutaneous coronary intervention (PCI). METHODS: The clinical data of 228 AMI patients underwent emergency PCI were retrospectively analyzed and patients were divided into ES group (n = 39) and non-ES (n = 189) group. ES was referred to spontaneous ventricular tachycardia or ventricular fibrillation occurring twice or more within 24 h and requiring emergency treatment including anti-arrhythmic medicine and/or cardioversion or defibrillation. RESULTS: ES was diagnosed in 39 out of 228 patients (17.1%) during peri-procedure stage. The incidence of ES in patients with various infarct related arteries (IRA) was as follows: 55.6% with left main artery (LM), 23.7% with right coronary artery (RCA), 12.4% with anterior descending branch (LAD) and 0 with left circumflex artery (LCX). Older age, lager diameter of IRA, higher concentration of CK-MB and cTnT, higher incidence of reperfusion arrhythmia (RA), lower grade of TIMI after PCI and higher mortality were associated with increased risks of ES (The P value was 0.043, 0.012, 0.036, 0.018, 0.001, 0.049, respectively). Gender, systolic pressure, diastolic pressure, random blood glucose level, white blood count and concentration of hs-CRP were similar between ES and non-ES patients. Logistic analysis showed that the diameter of IRA (OR 2.381, 95%CI 1.127-5.028, P = 0.023), TIMI grade of IRA after PCI (OR 4.744, 95% CI 1.773-12.691, P = 0.002) and RA (OR 12.680, 95% CI 4.360-36.879, P = 0.000) were the independent risk factors of per-procedure ES in AMI patients underwent emergency PCI. CONCLUSIONS: The AMI patients with LM as IRA had the highest incidence of ES during emergency PCI and the diameter of IRA, TIMI grade of IRA after PCI and RA were independent risk factors for the development of ES during peri-PCI stage.

Defibrillation threshold testing: is it necessary during implantable cardioverter-defibrillator implantation?

Defibrillation threshold (DFT) testing has traditionally been a routine part of implantable cardioverter-defibrillator (ICD) implantation. DFT testing was developed in the early days of the ICD when failure of defibrillation was common, recipients had a high-risk of ventricular tachycardia (VT) or ventricular fibrillation (VF), and the only therapy for rapid VT or VF was a shock. However, modern ICD systems have such a high rate of successful defibrillation that many electrophysiologists now question whether DFT testing is still worthwhile. Studies found that long-term mortality was not higher among patients not undergoing DFT testing. Moreover, there was no survival difference between patients with a lower DFT and a higher DFT. Other studies have demonstrated that DFT testing poses some risk to the patient such as myocardial damage, embolic stroke in patient with atrial fibrillation and DFT testing-related death. If DFT testing is abandoned, more patients may have the opportunity to be treated with ICD, especially in regions with few or no electrophysiologists. It may be argued that other physicians, such as those currently implanting pacemakers, would more readily implant ICDs if not for the requirement of DFT testing.

Irbesartan attenuates Ang II-induced BMP-2 expression in human umbilical vein endothelial cells.

Bone morphogenetic protein-2 (BMP-2), a transforming growth factor-beta superfamily member cytokine, plays a key role both in vascular development and in pathophysiological processes. However, the effects and mechanisms of angiotensin II (Ang II) on BMP-2 expression remain unknown in human umbilical vein endothelial cells (HUVECs). Here we show that Ang II treatment significantly increased BMP-2 expression, associated with NF-kappaB activation, which was suppressed by treatment with pyrrolidine dithiocarbamate (PDTC) or irbesartan. Furthermore, the increased levels of MDA (malondialdehyde) in conditioned media and the decrease in activities of total superoxide dismutases (SOD) caused by Ang II were reversed by irbesartan or PDTC treatment. Our findings indicate that Ang II-induced BMP-2 expression might contribute to NF-kappaB activation. BMP-2 expression induced by Ang II might involve excessive oxidative stress.

Study on the spatial distribution pattern of Cx40 gap junctions in the atria of patients with coronary heart disease.

BACKGROUND: The aim of this study was to evaluate the association between atrial fibrillation and atrial dilation and the spatial distribution pattern of connexin 40 in the atria of patients with coronary heart disease. METHODS: Twenty-six patients with coronary heart disease undergoing cardiac surgery for coronary artery bypass graft were investigated and were divided into three groups according to the left atrial size and rhythm, atrial fibrillation and left atrial dilatation (AF+AD), sinus rhythm and left atrial dilation (SR+AD) and sinus rhythm as control group SR. The spatial distribution patterns of Cx40 were evaluated using confocal laser scanning microscopy assay. RESULTS: No significant differences were observed in the size and density of Cx40 gap junction in the right atrium among all three groups (p > 0.05). Compared with the control group, the size of Cx40 disk area in termination links and in lateral abutment in left atrium was markedly larger in AF+AD group and SR+AD group than those of the controls (p < 0.01). A comparison of size and density of Cx40 gap junction in the left atrium in the AF+AD group and SR+AD group did not show significant differences. CONCLUSIONS: The present study has shown altered gap junction distribution in coronary heart disease resulting from atrial dilation and atrial fibrillation. A decrease in the size and density of Cx40 gap junction was observed in patients with atrial dilation, which could be an important factor in the initiation and maintenance of atrial fibrillation.

Nr4a2 is essential for the differentiation of dopaminergic neurons during zebrafish embryogenesis.

Nr4a2 is a member of the orphan nuclear receptor gene superfamily, which has been found to be critical for the development and maintenance of mesencephalic dopaminergic (DA) neurons. To uncover the molecular mechanisms by which Nr4a2 contributes to the development of DA neurons, we have applied zebrafish to study the topographic distribution of nr4a2b transcripts, as well as its correlation with neuronal progenitor marker (neurogenin 1) and DA neuron markers (tyrosine hydroxylase, TH and DA transporter, DAT) during neurogenesis. Our studies showed that although nr4a2b transcripts did not co-localize with TH and DAT transcripts in the posterior tuberculum (PT area), knockdown of Nr4a2 resulted in a significant decrease of TH(+) and DAT(+) DA neurons in the PT area, accompanied by a reduction of DA transmitter, which were partially rescued by the injection of mouse Nr4a2 mRNA. Surprisingly, the number of nr4a2b(+) cells in Nr4a2-deficient embryos was increased by 1.6 fold. These results suggest that Nr4a2 may play an important role in the differentiation and maturation rather than the survival of DA progenitors in the PT area during zebrafish early embryogenesis.

Predictive value of early recurrence and delayed cure after catheter ablation for patients with chronic atrial fibrillation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) for curing atrial fibrillation (AF) is often followed by early recurrence and delayed cure, so the present study investigate the predictive factors this in patients with chronic AF. METHODS AND RESULTS: Ninety-two consecutive patients (70 males; mean age, 58.7+/-6.4 years) with chronic AF who underwent RFCA for treatment of symptomatic AF were enrolled. Early recurrence of AF (ERAF) occurred in 45 patients after ablation. Not achieving AF termination could predict ERAF (odds ratio (OR) 0.95; 95% confidence interval (CI) 0.84-1.13; p=0.02) in multivariate analysis. During a follow-up of 12+/-11 (range, 5-25) months, delayed cure occurred in 35.6% (16/45) of the patients with ERAF. Left atrial size and AF termination during ablation were related to delayed cure. AF termination was the only independent predictive factor for delayed cure (OR 1.47; 95% CI 1.05-1.87; p=0.02). CONCLUSION: Not achieving AF termination is the only independent predictor of ERAF. Among patients with ERAF, those with a smaller left atrium and AF termination have a higher probability of delayed cure. AF termination can independently predict delayed cure. These results emphasize the importance of AF termination during ablation for patients with chronic AF.

Association between plasma pregnancy-associated plasma protein a and restenosis after percutaneous coronary angioplasty.

BACKGROUND: Restenosis after percutaneous coronary angioplasty remains an important limitation of this procedure. This study evaluates the association between plasma pregnancy-associated plasma protein A (PAPP-A) levels and restenosis after coronary angioplasty. METHODS AND RESULTS: Blood samples were collected from all patients at baseline, and their levels of PAPP-A, inflammation (high-sensitivity C-reactive protein (hsCRP)) and platelet activation (soluble CD40 ligand (sCD40L)) were determined. Those patients whose PCI was successful underwent a repeat angiography at a median of 6.4 months (interquartile range 6-9.8 months). Their baseline and follow-up angiograms were compared by quantitative coronary angiography to assess the incidence of restenosis. Endpoints were restenosis (> or =50%) and a composite of major adverse cardiac events. Of the 184 patients, 162 patients underwent an angiographic follow up at 6 months. Patients with restenosis had significantly higher PAPP-A levels than those without (19.24+/-2.56 vs 11.95+/-2.32 mIu/L; p<0.001). The PAPP-A levels were significantly correlated to follow up diameter stenosis (r=0.54, p=0.01). Late lumen loss at follow-up was significantly smaller when PAPP-A levels were <12.51 mIu/L (0.55+/-0.61 vs 0.90+/-0.57 mm; p<0.001). The rates for restenosis (28.4 vs 50.6%; p<0.001) and major advent cardiac events (15.6 vs 51.1%, p<0.001) were significantly lower in patients with PAPP-A levels <12.51 mIu/L. Univariate analysis revealed that PAPP-A (p<0.001), hsCRP (p=0.009) and sCD40L (p=0.03) were significantly related to restenosis. However, only PAPP-A could predict restenosis (odds ratio 0.95; 95% confidence interval 0.84-1.13; p=0.02) in multivariate analysis. CONCLUSIONS: The PAPP-A level is a strong independent predictor of restenosis in patients who have undergone coronary angioplasty.

Atorvastatin downregulates BMP-2 expression induced by oxidized low-density lipoprotein in human umbilical vein endothelial cells.

BACKGROUND: Bone morphogenetic protein-2 (BMP-2) plays a key role both in vascular development and pathophysiological processes. However, the effects of oxidized low-density lipoprotein (ox-LDL) combined with atorvastatin on BMP-2 expression are entirely unknown in human umbilical vein endothelial cells (HUVECs). The present study investigates the effects of ox-LDL on BMP-2 expression. Furthermore, the influence of atorvastatin on ox-LDL-induced BMP-2 expression is also examined. METHODS AND RESULTS: The HUVECs were treated by ox-LDL or combined with pyrrolidine dithiocarbamate (PDTC) or atorvastatin. The expression level of BMP-2 mRNA was examined by real-time PCR and RT-PCR analysis. The expression of BMP-2 protein was assayed by enzyme-linked immunosorbent assay. The malondialdehyde (MDA) and activities of total superoxide dismutase (SOD) were detected by routine methods. The activation of nuclear factor kappaB (NF-kappaB) in HUVECs was determined using an assay kit from active motif and western blot analysis. Ox-LDL treatment significantly increased BMP-2 expression, which is associated with NF-kappaB activation, but BMP-2 expression was suppressed by treatment with PDTC or atorvastatin. Furthermore, the increase in MDA levels and decrease in activities of total SOD caused by ox-LDL treatment were reversed by the treatment of PDTC or atorvastatin. CONCLUSIONS: Ox-LDL-induced BMP-2 expression was suppressed by PDTC or atorvastatin treatment. The effects of atorvastatin might contribute to the mechanisms by inhibiting NF-kappaB activation.

Pioglitazone can downregulate bone morphogenetic protein-2 expression induced by high glucose in human umbilical vein endothelial cells.

Bone morphogenetic protein-2 (BMP-2) plays a key role in both vascular development and pathophysiological processes. However, the effect of high glucose on BMP-2 expression remains unclear. Here we show in human umbilical vein endothelial cells that high glucose increased BMP-2 expression, associated with NF-kappaB activation, whereas pioglitazone suppressed BMP-2 expression and NF-kappaB65 activation induced by high glucose. Furthermore, the increase in MDA levels and decrease in activities of total superoxide dismutase of cell culture stimulated by high glucose were reversed by pioglitazone treatment. Our findings indicate that BMP-2 expression induced by high glucose might be closely related to NF-kappaB activation, and both effects can be suppressed by pioglitazone.

A novel hypothesis of atherosclerosis: EPCs-mediated repair-to-injury.

Recent findings demonstrate the vital role of endothelial progenitor cells in the homeostasis of the vessel wall and the development of atherosclerosis. Endothelial progenitor cells (EPCs) play important roles in repair-to-injury of arteries. Many evidences have shown Cardiovascular risk factors closely correlated with EPCs numbers and function. Levels of circulating EPCs represented a better predictor of endothelial function than conventional risk factors. Depletion of bone marrow and Cardiovascular risk factors are the two prerequisits of atherosclerosis. All conditions of manifest atherosclerotic disease are accompanied by reduced EPC numbers and migratory capacity. Therefore, based on response-to-injury hypothesis and these findings, we build up EPCs-mediated repair-to-injury hypothesis, which may have important therapeutic implications in the prevention and therapy of atherosclerosis. The use of EPCs for vascular repair may be important therapy strategies with a maximized benefit for the patient in the future.

[Peripheral vascular complications after the cardiac catheterization].

OBJECTIVE: To explore the cause, the clinical manifestation and the management of peripheral vascular complications after cardiac catheterization. METHODS: Clinical data of patients with peripheral vascular complications were analyzed retrospectively. RESULTS: Of the 4,531 patients, 122 (2.7%) had peripheral vascular complications, including local hematoma (86 cases, 1.90%), pseudoaneurysm (15 cases, 0.33%), arteriovenous fistula (8 cases, 0.18%), femoral venous thrombosis (5 cases, 0.11%), excessive hemorrhage (5 cases, 0.11%), femoral arterial thrombosis (2 cases, 0.04%), and femoral nerve malfunction (1 case, 0.02%). All complications were relieved after conservative therapy except that one case needed surgery. CONCLUSION: Peripheral vascular complications are associated with anticoagulation, diabetes, and hypertension. Prognosis of overwhelming complications is good, as long as patients are treated timely and appropriately.

The mechanism underlying vascular smooth muscle cell apoptosis induced by atorvastatin may be mainly associated with down-regulation of survivin expression.

PURPOSE: Studies have shown that statins may induce vascular smooth muscle cells (VSMCs) apoptosis. But its mechanisms are incompletely understood. In this study, we investigate the effects of atorvastatin and survivin antisense oligonucleotides (ASODN) on VSMCs apoptosis and the relation between survivin and VSMCs apoptosis. MATERIALS AND METHODS: Cultured VSMCs were treated with atorvastatin and vascular endothelial grow factor (VEGF). Apoptosis of VSMCs at 6-72 h after treatment with atorvastatin was detected by means of Hoechst33258 staining. Survivin and Fas factors expression were detected by means of immunohistochemistry. Survivin and Fas mRNA expression were detected by means of RT-PCR. In order to determine the relations between survivin and VSMCs apoptosis, we also performed transfection of VSMCs with survivin ASODN using GenePORTER Transfection Reagent and studied the survivin protein expression by means of western blotting. RESULTS: VSMCs apoptosis after treatment with atorvastatin was increased in a dose- and time-dependent manner. The expression of survivin and survivin mRNA in VSMCs was significantly down-regulated at 24 h and disappeared at 48-72 h after treatment with atorvastatin. Fas and Fas mRNA in VSMCs could only be detected at 72 h and not at 6-48 h after treatment with atorvastatin. We did not observe any effects of VEGF on VSMCs apoptosis, on survivin and survivin mRNA expression, and on Fas and Fas mRNA expression in VSMCs after treatment with atorvastatin. At 48 hours after the start of transfection, survivin protein expression was significantly reduced after transfection with 0.5, 1.0 and 2.0 microg/ml of survivin ASODN and there was no survivin protein expression after transfection with 3.0 and 4.0 microg/ml of survivin ASODN. In contrast, in the GenePORTER only and SODN studies, survivin protein expression was observed with western blotting. Hoechst33258 staining showed that treatment of VSMCs with survivin ASODN resulted in VSMCs apoptosis. CONCLUSIONS: Atorvastatin induces VSMCs apoptosis in a dose- and time-dependent manner. Transfection of survivin ASODN can directly induce VSMCs apoptosis. The mechanisms of VSMCs apoptosis induced by atorvastatin may be mainly associated with down-regulation of survivin expression in VSMCs. Up-regulation of Fas in VSMCs may play a role in later stages following atorvastatin treatment.

[Changes of plasma CD40L and PAPP-A in patients with acute coronary syndrome after the PCI operation].

OBJECTIVE: To observe the changes and significance of plasma CD40L and pregnancy-associated plasma protein-A (PAPP-A) in acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI) operation. METHODS: According to the occurrence of primary heart events or restenosis 6 months after the PCI, 68 patients were divided into the ACS group and the stable angina pectoris (SAP) group. Plasma CD40L and PAPP-A after the PCI operation were measured and compared. Thirty-six patients underwent repeated angiography after the PCI. Their baseline and follow up angiograms were compared by quantitative coronary angiography to assess the incidence of restenosis. RESULTS: CD40L and PAPP-A after the PCI operation were higher in the ACS group than that in the SAP group.The group having primary heart events within 6 months had higher level of PAPP-A after the PCI. The group having restenosis 6 months had higher level of PAPP-A after the PCI. The change of later loss index of coronary artery lumen diameter was correlated with PAPP-A level after the PCI. CONCLUSION: CD40L and PAPP-A were higher in the ACS group, indicating the possible mechanism by which CD40L facilitates the plaque rupture via up-regulating the PAPP-A expression.Plasma PAPP-A level after the PCI possibly for cases the occurrence of primary heart events or restenosis within 6 months.

[Oxidative stress and inflammation with angiographic morphology of coronary lesions in patients with coronary heart disease].

OBJECTIVE: To evaluate the role of oxidative stress and inflammation in the development of plaque rupture. METHODS: One hundred and ten patients enrolled in this study. All patients underwent coronary angiography. It included 85 patients with coronary heart disease (CHD) and 25 controls. The angiographic morphology of plaques was analyzed. According to the morphologic types of plaque, CHD patients were divided into Type I (smooth borders) group (n=31), Type II (irregular lesions) group (n=35), and Type III (long lesions) group (n=19). All patients were measured of MDA-LDL, hs-CRP, creatine kinase (CK), and MB isoenzyme of CK (CK-MB) in the plasma. RESULTS: Plasma MDA-LDL and hs-CRP in the Type II group were significantly higher than those in the control group, Type I group, and Type III group (P<0.01). The plasma levels of MDA-LDL were not correlated to LDL and HDL in patients in Type II group (P>0.05). The plasma levels of MDA-LDL and hs-CRP had a significant positive correlation in patients in Type II group (r=0.630, P<0.01). CONCLUSION: Oxidative stress and inflammation may cause plaque rupture in CHD patients. The oxidative stress is likely to either induce or intensify the inflammatory action, and may co-affect with inflammation factors to cause or accelerate plaque rupture.