J wave syndromes: a decade of progress / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>The objective was to provide a brief history of J wave syndromes and to summarize our current understanding of their molecular, ionic, cellular mechanisms, and clinical features. We will also discuss the existing debates and further direction in basic and clinical research for J wave syndromes.</p><p><b>DATA SOURCES</b>The publications on key words of "J wave syndromes", "early repolarization syndrome (ERS)", "Brugada syndrome (BrS)" and "ST-segment elevation myocardial infarction (STEMI)" were comprehensively reviewed through search of the PubMed literatures without restriction on the publication date.</p><p><b>STUDY SELECTION</b>Original articles, reviews and other literatures concerning J wave syndromes, ERS, BrS and STEMI were selected.</p><p><b>RESULTS</b>J wave syndromes were firstly defined by Yan et al. in a Chinese journal a decade ago, which represent a spectrum of variable phenotypes characterized by appearance of prominent electrocardiographic J wave including ERS, BrS and ventricular fibrillation (VF) associated with hypothermia and acute STEMI. J wave syndromes can be inherited or acquired and are mechanistically linked to amplification of the transient outward current (I to )-mediated J waves that can lead to phase 2 reentry capable of initiating VF.</p><p><b>CONCLUSIONS</b>J wave syndromes are a group of newly highlighted clinical entities that share similar molecular, ionic and cellular mechanism and marked by amplified J wave on the electrocardiogram and a risk of VF. The clinical challenge ahead is to identify the patients with J wave syndromes who are at risk for sudden cardiac death and determine the alternative therapeutic strategies to reduce mortality.</p>

Dynamic changes of electrical remodeling in midmyocardium of rabbit left ventricle during the early stage of chronic pressure-overload / 生理学报

In the previous study, we had found that the action potential duration (APD) of midmyocardial (M) cells was gradually prolonged and M cells were easier to produce early after-depolarization (EAD) in the rabbit left ventricle during the early stage of chronic pressure-overload. The present study was performed to investigate the dynamic changes and significance of ionic current remodeling in M cells of rabbit left ventricle during the early stage of chronic pressure-overload. Sixty-four New Zealand rabbits were randomly divided into constriction groups and sham groups. The rabbit models with chronic pressure-overload were prepared by partial constriction of suprarenal abdominal aorta at the site proximal 5-10 mm away from the left renal artery. At 2 and 8 weeks after operation, the single cardiomyocytes were isolated by enzymatic digestion method. The midmyocardium from the anterolateral free wall of left ventricle was obtained by removing the epicardial and endocardial surfaces. Whole-cell patch-clamp technique was used to record the slowly activating delayed rectifier potassium current (I(Ks)), transient outward potassium current (I(to)), L-type calcium current (I(Ca-L)) of M cells. At 2 weeks after the constriction operation, compared with the sham group, I(Ks) tail current (I(Ks,tail)) and I(to) densities of M cells from constriction group significantly decreased by 33.3% and 51.5%, respectively. There was no significant difference in I(Ca-L) density between the two groups. At 8 weeks after operation, compared with the sham group, I(Ks,tail) and I(to) densities of M cells from constriction group significantly decreased by 37.0% and 49.2%, respectively. There was still no significant difference in I(Ca-L) density between the two groups. These results suggest that during the early phase of chronic pressure-overload, the electrical remodeling of M cells in rabbit left ventricle has developed, representing as the down regulations of I(Ks) and I(to) that can lead to the prolongation of APD, which might be a risk factor for the occurrence of malignant arrhythmia.

Eukaryotic expression vector pcDNA3-HERG transfection inhibits angiotensin II induced neonatal rabbit ventricular myocyte hypertrophy in vitro / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the effects of eukaryotic expression vector pcDNA3-HERG transfection on angiotensin II (Ang II) induced myocyte hypertrophy in cultured neonatal rabbit ventricular myocytes.</p><p><b>METHODS</b>Neonatal rabbit ventricular myocytes and eukaryotic expression vector pcDNA3-HERG transfected ventricular myocytes were cultured in Dulbecco's-modified Eagle medium (DMEM), containing 1% fetal bovine serum (FBS) for 6 h, then stimulated with Ang II (10(-7) mol/L) for 48 h. Control ventricular myocytes were cultured in Dulbecco's-modified Eagle medium (DMEM), containing 1% fetal bovine serum (FBS) for 54 h. At 6 and 54 h, myocyte hypertrophic parameters including myocyte volume, total protein content and membrane capacitance, action potential duration (APD) and Calcineurin (CaN) activity were measured.</p><p><b>RESULTS</b>Compared to control myocytes, APD at 90% repolarization (APD(90)) was prolonged by 19.8% (P < 0.01), without signs of myocyte hypertrophy at 6 h post Ang II stimulation, APD(90) was prolonged by 22.1% (P < 0.01), myocyte volume, total protein content and membrane capacitance and CaN activity were significantly increased by 40.4%, 40.4%, 38.2% and 114.7% respectively (all P < 0.01) at 48 h after Ang II stimulation. HERG gene transfection upregulated I(HERG) tail current (3.6-fold higher than I(Kr)-rapidly activating delayed rectifier potassium current, P < 0.01). HERG gene transfection also accelerated and repolarization and a shortened APD(90) and inhibited myocyte hypertrophy and CaN activation induced by Ang II.</p><p><b>CONCLUSIONS</b>Ang II induced prolongation of APD(90) is directly associated with myocyte hypertrophy by increasing the Ca(2+) influx and resulting in the increment of intracellular Ca(2+) and activation of CaN reaction pathway.</p>

Bone marrow stem cell mobilization to the peripheral blood and tumor necrosis factor-alpha expression in ischemic myocardium in rabbit models of hibernating myocardium / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the changes in peripheral blood bone marrow stem cells and tumor necrosis factor-alpha gene expression in the ischemic myocardium in rabbit models of hibernating myocardium.</p><p><b>METHODS</b>Twenty-four male Japanese white rabbits were randomized into 4 groups, including a sham-operated group and 3 model groups with hibernating myocardium induced by partial ligation of the left anterior descending coronary artery. The percentage of CD34-positive cells in the peripheral blood was evaluated by flow cytometry, and TNF-alpha mRNA expression in the ischemic myocardium was determined by real-time RT-PCR in the 3 model groups (at 3, 7, or 28 days after the operation) and in the sham-operated group.</p><p><b>RESULTS</b>In rabbits with partial ligation of the left anterior descending coronary artery, the percentage of CD34-positive cells in the peripheral blood and myocardial TNF-alpha mRNA expression were significantly increased at 3 and 7 days after the operation in comparison with those in the sham-operated group and those at 28 days postoperatively (P<0.01). No significant differences were found in the percentage of CD34 positive cells or myocardial TNF-alpha mRNA expression between the sham-operated group and the rabbits 28 days after the coronary artery ligation (P>0.05).</p><p><b>CONCLUSION</b>Bone marrow stem cell can be mobilized into the peripheral blood in rabbit hibernating myocardium model possibly by increasing TNF-alpha gene expression in the ischemic myocardium.</p>

Geographical characteristics of single nucleotide polymorphism of candidate genes associated with coronary artery disease in Chinese Han population / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the geographical characteristics of single nucleotide polymorphism (SNP) of candidate genes associated with coronary artery disease in Chinese Han population.</p><p><b>METHODS</b>Study population were Chinese Han nationality recruited from Xi'an, Shiyan and Ningbo districts. Patients with coronary artery disease were defined by coronary angiography with stenosis >or= 50% and control subjects with stenosis < 10%, respectively. The DNA was extracted from peripheral white blood cell by approach comprised proteinase K digestion, phenol and chloroform extraction as well as isopropanol precipitation. The SNP of ATP-binding cassette transporter (ABCA1)-G596A, cholesteryl ester transfer protein (CETP)-Taq1B, Lipoprotein lipase (LPL)-Hind III and LPL-Pvu II were genotyped by PCR-RFLPs, and verified by gene sequencing.</p><p><b>RESULTS</b>A Total of 615 patients undertaken coronary angiography were recruited from cardiac center in Xi'an (220), Ningbo (209) and Shiyan district (186), China (mean age 60 +/- 10 years, 75.9% males). Diabetes mellitus was more prevalent in Xi'an Cohort population than Shiyan and Ningbo cohort (P < 0.01). Plasma total cholesterol, LDL cholesterol and triglyceride levels in Xi'an Cohort population were significantly higher, and HDL-C siginificantly lower than in Shiyan and Ningbo cohort population [HDL-C: (1.17 +/- 0.48) mmol/L vs. (1.25 +/- 0.33) mmol/L and (1.29 +/- 0.44) mmol/L, P < 0.05]. Distribution differences for ABCA1-G596A and CETP-Taq1B genotypes were found in Xi'an Cohort population compared to Ningbo and Shiyan cohorts (for ABCA1, Xi'an: 0.24, 0.53, 0.23 and Shiyan: 0.17, 0.62, 0.21 and Ningbo: 0.34, 0.37, 0.29, for GG, AG, AA, respectively, P < 0.01; and for CETP, Xi'an: 0.29, 0.54, 0.17 and Shiyan: 0.38, 0.40, 0.22 and Ningbo: 0.39, 0.49, 0.12 for B1B1, B1B2, B2B2, respectively, P < 0.01), but not for LPL variants. ABCA1-G596A variant predicted HDL-C [Xi'an: (1.2 +/- 0.3) mmol/L, (1.3 +/- 0.2) mmol/L and (1.4 +/- 0.4) mmol/L, P = 0.01; Shiyan: (1.1 +/- 0.4) mmol/L: (1.2 +/- 0.3) mmol/L and (1.3 +/- 0.4) mmol/L, P = 0.03; Ningbo, (1.2 +/- 0.3) mmol/L, (1.3 +/- 0.4) mmol/L and (1.4 +/- 0.3) mmol/L, across GG, GA to AA genotype, respectively, P = 0.01] and TG levels [Xi'an: (2.4 +/- 1.3) mmol/L, (1.9 +/- 0.9) mmol/L and (1.6 +/- 0.8) mmol/L, P < 0.01; Shiyan: (2.1 +/- 1.0) mmol/L, (1.9 +/- 0.8) mmol/L and (1.8 +/- 0.7) mmol/L, P = 0.03; Ningbo: (1.9 +/- 1.1) mmol/L, (1.8 +/- 0.9) mmol/L and (1.6 +/- 0.7) mmol/L, across GG, GA to AA genotype, P = 0.05] with dose-dependent relationship. LPL-Hind III (+) carriers had higher triglycerides in three cohort population [Xi'an: (2.2 +/- 1.0) mmol/L, (1.8 +/- 0.9) mmol/L, (1.6 +/- 0.7) mmol/L, P = 0.01; Shiyan: (2.1 +/- 0.7) mmol/L, (1.9 +/- 1.0) mmol/L, (1.7 +/- 0.6) mmol/L, P = 0.01; Ningbo: (1.8 +/- 1.0) mmol/L, (1.6 +/- 0.6) mmol/L and (1.4 +/- 0.5) mmol/L, for +/+, +/- and -/- genotypes, respectively, P = 0.001]. SNP of CETP-Taq1B, LPL-Hind III and LPL-Pvu II predicted HDL-C and/or TG levels in different cohort population with different manners. All these SNP were not significantly associated with the development of coronary artery disease (all P > 0.05).</p><p><b>CONCLUSION</b>A geographical heterogeneity of environmental and genetic risk factors related to the development of coronary artery disease exists in Chinese Han population. Irrespective of the different geographical cohort of Chinese Han population, the SNP of candidate genes can partly predict the differences in risk-related plasma HDL-C and/or TG levels rather than angiographic coronary artery disease.</p>

Functional expression of congenital long QT syndrome related HERG mutation A561V in vitro / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the functional expression of HERG mutation A561V detected in a Chinese congenital long QT syndrome family.</p><p><b>METHODS</b>The mutation gene A561V was cloned into eukaryotic expressive vector pcDNA3 by quick site-directed mutagenesis PCR and restriction enzymes. The wild-type HERG, heterozygous type HERG and HERG mutation A561V were respectively cotransfected with pRK5-GFP into HEK293 cells by Suprefact transfection regent. The protein expression was measured by immunofluorescence method and Western blot. The electrophysiological characteristics of transfected cells were determined by whole cell patch-clamp technique.</p><p><b>RESULTS</b>Direct sequence analyses revealed a C to T transition at position 1682. A561V mutation was correctly combined to eukaryotic expressive vector pcDNA3 and expressed in HEK293 cells. The protein expression of mutation and heterozygosis were located in cytoplasm and cellular membrane. 155 kDa and 135 kDa protein bands were detected in wild type HERG channel while only 135 kDa protein band was shown in heterozygous and mutational channels. Significant HERG tail-current was recorded in wild type HERG channel but not in mutation and heterozygosis channels.</p><p><b>CONCLUSION</b>This study evidenced a functional dominant-negative current suppression in HEK293 cells transfected with HERG mutation A561V.</p>

Effect of short-term intensive treatment with insulin pump on beta cell function and the mechanism of oxidative stress in newly diagnosed type 2 diabetic patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of short-term intensive treatment with insulin pump on beta cell function and the mechanism of oxidative stress in newly diagnosed type 2 diabetic patients.</p><p><b>METHODS</b>Totally 120 newly diagnosed type 2 diabetic patients were treated with insulin pump for 2 weeks. The levels of fasting plasma glucose (FPG), 2-hour postprandial blood glucose (2hPG), homeostatic model assessment of the insulin secretion index and insulin resistance index (HOMA-beta and HOMAIR, respectively), blood malondialdehyde (MDA) and superoxide dismutase (SOD) were measured before and after insulin pump treatment.</p><p><b>RESULTS</b>After insulin pump treatment, FPG, 2hPG, HOMAIR and blood MDA were significantly decreased (P<0.01), while HOMA-beta and blood SOD were significantly increased (P<0.01).</p><p><b>CONCLUSION</b>Short-term intensive treatment with insulin pump can effectively improve beta cell function probably by decreasing oxidative stress in newly diagnosed type 2 diabetic patients.</p>

Modified classic risk factors for coronary artery disease in Chinese Han population / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the levels of cardiovascular disease risk factors and their relations to clinical phenotype associated with coronary artery disease (CAD).</p><p><b>METHODS</b>The subjects were recruited from five independent cardiovascular centers. Coronary angiography was employed to define the CAD with stenosis in each major vessel > or = 70% and control with stenosis < 10% in every lesion. The classic risk factors including family history, body mass index, smoking habits, hypertension, diabetes mellitus, and serum lipid levels were surveyed according to established criteria. Associations between risk levels and clinical phenotypes were assessed by case control and correlation analysis.</p><p><b>RESULTS</b>A total of 762 individuals were collected, including 481 men and 281 women, aged from 17 to 81 (mean 60 +/- 10) years. The patients with CAD accounted for 55.5% of all participants, and controls 44.5%, respectively. Compared with the pattern in published data, our study showed that mean serum high density lipoprotein cholesterol (HDL-C) level was significantly lower (P < 0.001) and triglycerides was significantly higher (P < 0.001), while total cholesterol (TC) and low density lipoprotein cholesterol levels were comparative (both P > 0.05). The prevalence of low HDL-C (< 40 g/L) and hypertriglyceridemia (> 150 g/L) were 27.2% and 41.4%, respectively. Mean serum levels of HDL-C and apolipoprotein A1 were significantly higher in female subjects than in male (P < 0.001). Lower HDL-C functioned as an independent risk factor for CAD only in men (RR = 2.8, 95% CI: 1.5-4. 2, P < 0.001), yet increased non-HDL cholesterol combined with diabetes mellitus and obesity seemed to play a key role in the development of CAD in women. Similarity in risk association with CAD was found for hypertension and TC/HDL ratio in male and female subjects, while family history had no relationship with the presence of CAD.</p><p><b>CONCLUSION</b>It is remarkable that emphasis of intervention in future should be given on the prevalent low serum HDL-C and its strong risk correlation with the presence of CAD in male subjects of Chinese Han population.</p>

Construction of eukaryotic expression vector of congenital long QT syndrome related HERG gene A561V mutation and its expression in HEK293 cells / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the protocol of the construction of HERG gene mutations, an A561V mutation which was detected in a Chinese congenital long QT syndrome (LQTS) family had been constructed and expressed in vitro.</p><p><b>METHODS</b>The A561V cloning vector PGEM-HERG-A561V was constructed by quick site-directed mutagenesis PCR. The A561V expressive vector pcDNA3-HERG-A561V was constructed by restriction enzymes. pRK5-GFP was cotransfected with pcDNA3-HERG-A561V or wild type pcDNA3-HERG into HEK293 cells by Superfect transfection reagent. The protein was measured by immunofluorescence.</p><p><b>RESULTS</b>Direct sequence analyses revealed a C to T transition at position 1682. The A561V mutation was correctly combined to eukaryotic expressive vector pcDNA3 and expressed in HEK293 cells. The protein of mutation was expressed in cytoplasm and cellular membrane while the wild type gene was expressed only on cellular membrane.</p><p><b>CONCLUSION</b>The protocol can be used successfully to construct and express HERG A561V mutation and it forms the basement of the further study on functions of mutation.</p>

Single nucleotide polymorphisms of genes associated with high density lipoprotein metabolism in Chinese population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the single nucleotide polymorphisms in genes associated with the high density lipoprotein (HDL) metabolism in Chinese population.</p><p><b>METHODS</b>Two hundred and nine normal Han ethnic subjects, aged 59+/-10 years, were recruited from 5 medical centers in western part of China. DNA was extracted by proteinase K digestion, phenol and chloroform extraction as well as isopropanol precipitation. The polymerase chain reaction (PCR)-restriction fragment length polymorphisms (RFLP) in conjunction with sequencing were employed to test the single nucleotide polymorphisms (SNPs) in ATP-binding cassette transporter (ABCA1), cholesteryl ester transfer protein (CETP) and lipoprotein lipase (LPL) genes.</p><p><b>RESULTS</b>The allelic frequencies of A and G of ABCA1 gene are 53.4% and 46.6%; of B2 and B1 allele of CETP, 41.0% and 59.0%; of HindIII (-) and (+) allele of LPL, 18.9% and 81.1%; and of PvuII(+) and (-) allele of LPL, 66.0% and 34.0%, respectively. All genotype frequencies fit well with the Hardy-Weinberg equilibrium; the significant linkage disequilibrium exists between LPL HindIII(+)and PvuII(+) polymorphisms. All of the RFLP in these genes result from the single nucleic substitution in fragment recognized by corresponding restriction enzymes.</p><p><b>CONCLUSION</b>The genetic polymorphisms of ABCA1, LPL-HindIII and LPL-PvuII in Chinese Han ethnic population are significantly different from Caucasians residing in USA or Europe.</p>

Prevention of pericardial constriction by transcatheter intrapericardial fibrinolysis with urokinase / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate whether intrapericardial urokinase irrigation along with pericardiocentesis could prevent pericardial constriction in patients with infectious exudative pericarditis.</p><p><b>METHODS</b>A total of 94 patients diagnosed as infectious exudative pericarditis (34 patients with purulent pericarditis and 60 with tuberculous pericarditis, the disease courses of all patients were less than 1 month), 44 males and 50 females, aged from 9 to 66 years (mean 45.4 +/- 14.7 years), were consecutively recruited from 1993 to 2002. All individuals were randomly given either intrapericardial urokinase along with conventional treatment in study group, or conventional treatment alone (including pericardiocentesis and drainage) in control group. The dosage of urokinase ranged from 200000 to 600000 U (mean 320000 +/- 70000 U). The immediate effects were detected by pericardiography with sterilized air and diatrizoate meglumine as contrast media. The long-term investigation depended on the telephonic survey and echocardiographic examination. The duration of following-up ranged from 8 to 120 months (mean 56.8 +/- 29.0 months).</p><p><b>RESULTS</b>Percutaneous intrapericardial urokinase irrigation promoted complete drainage of pericardial effusion, significantly reduced the thickness of pericardium (from 3.1 +/- 1.6 mm to 1.6 +/- 1.0 mm in study group, P < 0.001; from 3.4 +/- 1.6 mm to 3.2 +/- 1.8 mm in control group, P > 0.05, respectively), and alleviated the adhesion. Intrapericardial bleeding related to fibrinolysis was found in 6 of 47 patients with non-blood pericardial effusion and no systemic bleeding and severe puncture-related complication was observed. In follow-up, there was no cardiac death, and pericardial constriction events were observed in 9 (19.1%) of study group and 27 (57.4%) of control group. Cox analysis illustrated that urokinase could significantly reduce the occurrence of pericardial constriction (relative hazard coefficient = 0.185, P < 0.0001).</p><p><b>CONCLUSION</b>The early employment of intrapericardial fibrinolysis with urokinase and pericardiocentesis appears to be safe and effective in preventing the development of pericardial constriction in patients with infectious exudative pericarditis.</p>

Adrenergic receptor antagonist prevents the left ventricle with chronic pressure-overload from electrical remodeling / 生理学报

Experiments were performed to investigate the effects of long-term treatment with adrenergic receptor antagonist on electrical remodeling of the left ventricle with chronic pressure-overload. New Zealand rabbits underwent subtotal banding of superrenal abdominal aorta. At 10 weeks after surgery, echocardiography examination was performed, then action potential (AP), inward rectifier potassium current (I(Ki)), delayed rectifier potassium current (I(K)) and Na(+)/Ca(2+) exchanger current (I(Na(+)/Ca(2+))) were recorded in midmyocardial cells isolated from left ventricle of abdominal aorta banded group (banded group), abdominal aorta banding plus Carvedilol intervention group (Carvedilol group), and normal control group rabbits by using the whole-cell patch-clamp techniques. The results showed that left ventricular mass index in control, banded, and Carvedilol groups were 1.78+/-0.06 (n=7), 2.33+/-0.11 (n=7), and 1.87+/-0.08 (n=7), respectively (banded vs control and Carvedilol, P<0.01). At basic cycle length of 2 s, AP duration (measured at 90% repolarization, APD(90), ms) in control, banded, and Carvedilol groups were 522.0+/-19.5 (n=6), 664.7+/-46.2 (n=7), 567.8+/-14.3 (n=8) respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). At test potential of -100 mV, inward I(Ki) density (pA/pF) in control, banded, and Carvedilol groups were -11.8+/-0.50 (n=8), -8.07+/-0.28 (n=8), -10.69+/-0.35 (n=8) respectively (banded vs control and Carvedilol, P<0.01). At test potential of +50 mV, I(K) tail current density (pA/pF) in control, banded, and Carvedilol groups were 0.59+/-0.04 (n=8), 0.40+/-0.02 (n=9), 0.51+/-0.02 (n=8) respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). At test potential of +60 mV, outward I(Na(+)/Ca(2+)) density (pA/pF) in control, banded, and Carvedilol groups were 1.06+/-0.11 (n=8), 1.54+/-0.10 (n=9), 1.24+/-0.07 (n=8), respectively (banded vs control and Carvedilol, P<0.01). At test potential of -120 mV, inward I(Na(+)/Ca(2+)) density (pA/pF) in control, banded, and Carvedilol groups were -0.54+/-0.06 (n =8), -0.75+/-0.04 (n=9), -0.60+/-0.03 (n=8), respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). It is shown that long-term treatment with Carvedilol not only prevents development of cardiac hypertrophy, but also improves the electrophysiological alterations in rabbit hearts with chronic pressure-overload. This finding may add new electrophysiological evidence for the treatment of heart failure and hypertension with adrenergic receptor antagonist.

In vivo distribution of c-myc antisense oligodeoxynucleotides local delivered by gelatin-coated platinum-iridium stents in rabbits and its effect on apoptosis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Post-stenting restenosis is a significant clinical problem, involving vascular smooth muscle cells (VSMCs) proliferation and apoptosis. It is reported that c-myc antisense oligodeoxynucleotides (ASODNs) local delivered by catheter can inhibit VSMCs proliferation. This study was designed to assess tissue distribution of c-myc ASODN local delivered using gelatin-coated platinum-iridium (Pt-Ir) stents, and its effect on apoptosis of VSMCs.</p><p><b>METHODS</b>Gelatin-coated Pt-Ir stents that had absorbed caroboxyfluorescein-5-succimidyl ester (FAM) labeled c-myc ASODNs (550 microg per stent) were implanted into the right carotid arteries of 6 rabbits. Tissue samples were obtained at 45 minutes, 2 hours, and 6 hours. Tissue distribution of c-myc ASODNs was assessed by fluorescence microscopy. In addition, 32 rabbits were randomly divided into two groups. Rabbits in the control group (n = 16) were implanted with gelatin-coated Pt-Ir stents, and those in the treatment group (n = 16) were implanted with gelatin-coated stents that had absorbed c-myc ASODNs. 7, 14, 30, or 90 days (n = 4, respectively, for each group) after the stenting procedure, the stented segments were harvested, and histopathological examinations were performed to calculate neointimal area and mean neointimal thickness. The expression of c-myc was assessed using in situ hybridization (ISH) and immunohistochemical methods. Apoptotic VSMCs were detected using terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and transmission electron microscope (TEM).</p><p><b>RESULTS</b>According to fluorescence microscopic results, FAM-labeled c-myc ASODNs were concentrated in the target vessel media at the 45 minutes time point, and then dispersed to the adventitia. Morphometric analysis showed that neointimal area and mean neointimal thickness increased continuously up to 90 days after stent implantation, but that total neointimal area and mean neointimal thickness were less in the treatment group than in the control group at all time points (P < 0.0001). At day 7 and day 14 after stenting, there were no detectable apoptotic cells in either group. However, apoptotic cells were present in the neointima 30 and 90 days after stenting, and the number of apoptotic cells was less at 30 days than at 90 days. Meanwhile, c-myc ASODNs appeared to induce apoptosis in more cells in the treatment group than that in the control group. Typical apoptotic VSMCs were observable under TEM. The expression of c-myc was positive in the control group and negative or weakly positive in the c-myc ASODN treatment group, according to both ISH and immunohistochemical examination.</p><p><b>CONCLUSION</b>Gelatin-coated Pt-Ir stent mediated local delivery of c-myc ASODNs is feasible. The localization of c-myc ASODN is primarily in the target vessel walls. c-myc ASODNs can inhibit VSMCs proliferation and induce its apoptosis after local delivery in vivo.</p>

Long QT syndrome gene diagnosis by haplotype analysis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>Three long QT syndrome(LQTS) pedigrees were brought together for genetic diagnosis by using short tandem repeat(STR) markers.</p><p><b>METHODS</b>Genomic DNA was extracted from blood samples. STR markers (D7S1824, D7S2439, D7S483, D3S1298, D3S1767, D3S3521) in or spanning the HERG and SCN5A gene were amplified; the haplotype analysis for LQTS was performed.</p><p><b>RESULTS</b>Clinical diagnosis showed that 15 are LQTS patients (3 died) and 11 are probable patients. Linkage analysis showed that LQTS patients are linked with the SCN5A gene in family 1, HERG is linked with the disease in family 2 and 3. Fourteen gene carriers were identified, 2 patients and 7 probable patients were excluded.</p><p><b>CONCLUSION</b>Linkage analysis using STR markers can serve as useful tool for presymptomatic diagnosis.</p>

Effect of xuezhikang on blood lipids, serum oxidized low density lipoprotein, C-reactive protein and fibrinogen in patients with unstable angina pectoris / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the lipid regulatory effect of Xuezhikang (XZK) and its effects on serum oxidized low density lipoprotein (OX-LDL), C-reactive protein (CRP) and fibrinogen (FIB) in patients with unstable angina pectoris (UAP).</p><p><b>METHODS</b>UAP patients with hyperlipidemia were treated with XZK 0.6 g, orally taken, twice a day for 2 successive months followed by half dosage for 2 months. To UAP patients with normal blood lipids, Vit E was given orally for 4 months. Levels of blood lipids, OX-LDL, CRP, FIB at the time of entry, 1st and 2nd month of the therapeutic course were observed and end-point events in the two groups was compared.</p><p><b>RESULTS</b>XZK can reduce the serum level of total cholesterol, low density lipoprotein after being administered for 1 month, and the effect further elevated after 2 months. Its effect in lowering triglycerides and increasing high density lipoprotein initiated after 2 months administration. Compared with effect of Vit E, XZK can significantly lower the serum OX-LDL, CRP and FIB after 2 months administration, and reduce the end-point events in 4 months.</p><p><b>CONCLUSION</b>XZK has good regulatory effect on blood lipids, it also can inhibit the development of inflammation in coronary plaque, therefore, is beneficial to the prognosis of UAP patients.</p>