Chi Luxiang

Endothelin-Converting Enzyme-1 Promoter Polymorphisms and Susceptibility to Sporadic Late-Onset Alzheimer's Disease in a Chinese Population

Endothelin converting enzyme (ECE-1) is a candidate Alzheimer disease susceptibility gene. It was previously reported that western individuals homozygous for the C-338A polymorphism (AA) within the ECE1 gene promoter region are at reduced risk of developing late onset Alzheimer disease (LOAD). A further polymorphism, T-839G, is present within the ECE1 promoter region but a potential association with LOAD has not been studied. We therefore studied possible associations between these ECE1 polymorphisms and LOAD in a Chinese population. Subjects comprised 376 Chinese LOAD patients and 376 age- and sex-matched controls; all subjects were typed for the ECE1 C-338A and the T-839G polymorphisms. We report that the frequency of the 338A allele was decreased in LOAD patients compared to controls (adjusted OR =0.73; 95% CI=0.54–0.98; P=0.03). There was no significant association between T-839G genotype and LOAD, however the combined 839T/338A haplotype was significantly associated with decreased risk of LOAD (OR=0.73; 95% CI=0.57–0.93; P=0.01). This study argues that the ECE1 338A allele is protective against LOAD in a Chinese population.

C-338A polymorphism of the endothelin-converting enzyme-1 gene and the susceptibility to carotid atherosclerosis

Several lines of evidence supported the involvement of ECE-1 in the development of atherosclerosis disease. We investigated the C-338A polymorphism of the ECE-1b gene in carotid atherosclerosis. A cohort of 518 Chinese carotid atherosclerosis patients and 518 controls matched by age and sex were examined for the ECE-1b C-338A polymorphism. The ECE-1b-338 A allele was significantly frequent in carotid atherosclerosis patients than in controls (chi(2)=9.167; P=0.002). A alleles had a 26% increased risk of carotid atherosclerosis compared with C alleles (OR=1.26; 95% CI=1.05-1.52). In stratified analyses, the A allele carrying genotypes was significantly associated with an increased risk of carotid atherosclerosis in females (adjusted OR=1.57; 95% CI=1.14-2.23) and a subject with age >or=64 years (adjusted OR=1.72; 95% CI=1.23-1.41). Our results suggested that ECE-1b-338 A allele carrying genotypes might be associated with increased risk of carotid atherosclerosis in the Chinese population.

First report of a novel LMNA mutation in a Chinese family with limb–girdle muscular dystrophy

LMNA gene encodes the ubiquitous protein lamin A/C, which is a component of the fibrous meshwork of intermediate filaments located at the inner surface of the nuclear envelope (Worman 2012). Lamin A/C are splicing variants encoded by the LMNA gene and share the first 566 amino acids. Mutations in LMNA gene are recently known to be responsible for more than 10 different clinical syndromes, most of which show overlapping features. Worman and Bonne (2007) classified the disorders into four major types: diseases of skeletal and cardiac muscle, lipodystrophy syndromes, peripheral neuropathy and premature ageing. Of the skeletal and cardiac muscles types, limb–girdle muscular dystrophy type 1B (LGMD1B), autosomal dominant Emery–Dreifuss muscular dystrophy 2 (EDMD2) and dilated cardiomyopathy 1A (CMD1A) are common (Capell and Collins 2006). Among the muscle type disorders related to LMNA gene mutations, LGMD1B is slowly progressive, with age-related atrioventricular cardiac conduction disturbance, dilated cardiomyopathy, muscle weakness and the absence of early contractures. However, EDMD2 is characterized by early contractures of elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and cardiomyopathywith a variable degree of conduction system disease (Capell and Collins 2006). In this report, we characterized a large Chinese family with atrioventricular block (AVB) as the most prominent feature, with concomitant moderate pelvic limb skeletal muscle defects. Due to the medical history, clinical manifestations and neurological/cardiological examinations, this family was diagnosed with autosomal LGMD1B. Then, a mutation

EXPERIMENTAL RESEARCH ABOUT EFFECT OF CELL–CELL CONTACT TO MESENCHYMAL STEM CELLS DIFFERENTIATE INTO VASCULAR ENDOTHELIAL CELLS

Objectives Use the method of HUVECs were cultured with human mesenchymal stem cells by cell–cell contact to simulate intravascular environment after angioplasty and stent implantation, and research the role of cell–cell contact to induce MSCs differentiate into endothelial cells. The research provides the experimental basis for MSCs repair the damage to vascular endothelium and prevention of vascular restenosis after intervention. Methods 1. We mixed HUVECs and MSCs by the same density (5×105/ml) and volumes to construct the model of cell–cell direct contact. Used Millicell Culture Plate Inserts of 0.4 µm pore size to construct the model of cell–cell indirect contact, MSCs grew on its lower chamber and HUVECs grew on its lower chamber with the same density (5×105/ml) and volumes. 2. The VEGF levels of experimental group (culture media of co-cultured for 48 h) and control group (MSCs and HUVECss mixed culture media after them were cultured alone for 48 h) were confirmed using ELISA assays. Co-cultured for 5 days. The MSCss expression of fetal liver kinase-1(Flk-1), von Willebrand factor (vWF) and the ingestible ability of Dil labelled acetylated low-density lipoprotein (Dil-ac-LDL) were analysed by immunofluorescence staining, at the same time the changes of ultrastructure of cell–cell contact co-cultured cells were observed by transmission electron microscopy. Results 1. MSC were negative expressed Flk-1 and vWF protein; HUVECs typically expressed the endothelial characteristics of vWF. The cells of cell–cell direct contact were observed under inverted phase contrast microscope and showed two kinds of cells gradually fused, the cells gradually close and difficult to distinguish. 2. the VEGF content of Experimental groups (559.55±66.19) pg/ml were significantly higher than control groups (373.98±57.28) pg/ml (p<0.05, n=3). Identified by immunofluorescence techniques, in direct contact co-culture system, by excited of different light from the laser scanning confocal microscope, fluorescence of MSCs nuclear labelled DAPI showed blue fluorescence, some MSCs of blue nuclear expressed Flk-1 protein and showed red fluorescence, then part of the Flk-1 positive MSCs expressed vWF protein and showed green fluorescence; besides, some MSCs could phagocytose Dil-ac-LDL. However, in indirect contact co-culture system, MSCs were negative expressed Flk-1 and vWF protein. Observed ultrastructure of cell–cell contact co-cultured cells under transmission electron microscopy, we found karyoplasmic ratio of undifferentiated MSCs was big (karyoplasmic ratio>1.5); the nuclear forms was irregular, had notch and had 2–3 nucleoli inside nucleus; scarce and less developed organelles in cytoplasm. However, proportion of Mature HUVECs nucleoplasm was small (karyoplasmic ratio<0.5), HUVECs had regular nuclear shape, prominent nucleoli, abundant cytoplasmic organelles. MSCs during differentiation was observed the reduced karyoplasmic ratio and relatively abundant organelles, and electronic gap junctions between HUVECs and MSCss the local of membrane; besides, cell fusion be seen. Conclusions 1. MSCs can differentiate into endothelial cells through cell–cell contact by direct co-culture with HUVECs and have phagocytic ability of Dil-ac-LDL. 2. The mechanism that the cell–cell contact co-culture system can induce MSCs differentiation into endothelial cells may associated with the following factors: (1) Cell–cell direct contact promote cell autocrine and paracrine VEGF increase significantly, involving in promoting the differentiation of MSCs. (2) Exist of cell fusion takes part in this process. (3).The form gap junction of intercellular communication between HUVECs and MSCss the local of membrane.

Clinical application of different cerebral protection devices in Carotid angioplasty and stenting in 1148 patients with carotid stenosis

Objectives To investigate the efficacy and safety of Carotid angioplasty and stenting (CAS) by different cerebral protection devices in 1148 patients with carotid stenosis. Methods Carotid angioplasty and stenting by different cerebral protection device were performed in 1148 patients with carotid artery stenosis from April 2003 to June 2007. There were 812 males and 336 females in all patients. Age were from 56 to 84 (average 68±5). Transient ischaemia attach (TIA) occurred in 894 patients, and cerebral infarction (CI) occurred in 254 patients. 854 Angioguard (Cordis, Co.), 350 Spide (EV3, Co.), 25 Filterwire (Boston Scientific, Co.), 16 Emboshield (Abbott, Co.), 8 MoMa (Invetech, Co.) and 2 Aether (MicroPort, Co.) were used in CAS. Results 1255 cerebral protection device were successfully placed in internal carotid arteries with 1148 patients, 8 MoMa were placed respectively in external and common carotid artery. Predilations were performed in 18 patients by Angioguard because of severe carotid stenosis. Cerebral protection device disrupture occurred in one patient during retrieve of Spide. The mean diameter of carotid stenosis was from (87.6±6.8)% to (18.9±10.8)% after CAS (p<0.01). no death and ischaemic stroke or cerebral arterial thrombosis occurred in 684 patients during 1 year of follow up. Conclusions By option usage of cerebral protection device, CAS be successfully performed in patients with carotid stenosis, Mean while, CAS is a safe and effective method and improve cerebral ischaemia and prevent ischaemic stroke.

CURATIVE EFFECT OF ENDOVASCULAR THERAPY ON TAKAYASU ARTERITIS

Objective To observe the curative effect of endovascular therapy including percutaneous transluminal angioplasty (PTA) and PTA plus stenting on Takayasu arteritis (TA). Methods Forty-eight inpatients with TA (17 males and 31 females) at the age of 19–53 years (mean 27.6±18.1 years), who underwent endovascular therapy (PTA only or PTA plus stenting)in Department of Cardiology, Southwest Hospital, Third Military Medical University (Chongqing, China) from January 2002 to May 2009, were enrolled in this study. Treatment outcome and data including erythrocyte sedimentation rate, C-reactive protein, CTA, MRA, Doppler vascular ultrasound findings obtained during a follow-up period of 42.8 months were analysed. Results A total of 180 lesions were detected in the 48 patients by angiography. Of the 101 lesions that underwent endovascular therapy, 29 were found in subclavian artery and arteria innominata, 28 in carotid, 34 in renal artery, two pulmonary, and eight coronary artery, respectively. Good revascularisation was achieved in all these lesions. No residual stenosis occurred in 76 lesions (75.2%) with only minimal residual stenosis observed in 25 patients (24.8%). Restenosis was observed in three lesions (12.0%) after treatment with PTA only and in five lesions (6.5%) after treatment with PTA plus stenting during the follow-up period of 3–6 months. No significant complication occurred in all recurrent stenoses after endovascular therapy. Conclusions Endovascular therapy including simple PTA or PTA plus stenting is a safe and effective treatment modality for chronic inactive TA.

The variation of the carotid arteriosclerotic plaque and intima–media thickness before and after therapy patients of the coronary heart disease

Objective To investigate the variation of the carotid arteriosclerotic plaque and intima–media thickness before and after therapy in the patient of coronary heart disease. Evaluate the correlation between carotid intima-media thickness and coronary heart disease to provide prevention and treatment evidence for coronary heart disease. Methods Two hundred and fourty coronary heart disease patients validated through angiographic examinations with the carotid arteriosclerotic plaque and abnormal intima–media thickness certified by Doppler ultrasound assessment were enrolled. Regular inspection of the carotid intima-media thickness by Doppler ultrasound after conventional coronary heart disease drug therpy, comparing the variation of the carotid arteriosclerotic plaque and intima–media thickness before and after therapy. Results The difference of the carotid intima–media thickness, the number and the total area of the carotid arteriosclerotic plaque between before and after both at 6 months and 1 year of the treatment was highly significant (p<0.001). After conventional durg therapy, the amelioration of the carotid atherosclerotic plaque and intima–media thickness was observed most notably after the mean 6 months reatment. Conclusion The amelioration of the carotid arteriosclerotic plaque and intima–media thickness was observed most notably after conventional durg therapy, the coronary heart disease is in close relations with the carotid atherosclerosis and its treatment outcome.

e0498 Case report: percutaneous multiple overlapped, overlength self-expanding stent placement treatment Superficial femoral artery chronic subtotal occlusions

PAD is a significant cause of both morbidity and death. In spite of TASC II recommendation that surgery is the preferred treatment for femoro-popliteal Type C&D lesions, promising clinical results of percutaneous revascularization had been obtained with a low risk of morbidity and mortality. We present a case of multiple overlapped, overlength self-expanding stent (extend as long as 450mm) placement to treat superficial femoral artery (SFA) chronic subtotal occlusions. No stent fractures or restenoses were observed at 1-year follow-up and with a favourable clinical results. Clinical and research medicine.