[Predictive value of four score systems on the bleeding risk in atrial fibrillation patients treated with dabigatran].

Objective: To compare the predictive value of HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT scores on the bleeding risk in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran. Methods: Data of 942 NVAF patients participating a non-interventional prospective study of anticoagulant therapy with dabigatran, which was conducted in 12 centers from February 2015 to December 2017 in China, were analyzed. Complete HAS-BLED HEMORR2HAGES, ATRIA and ORBIT bleeding risk scores data and follow-up data were available in the enrolled patients. The endpoint of the study was bleeding events occurred during a 6 months follow-up. Cox proportional hazards models were constructed to analyze the associations between HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT scores and risk of bleeding, and the area under the curve (AUC) of receiver operating characteristics curves (ROC) of each score was used to set the predictive value for bleeding risk. Results: Among the 942 patients, the mean age was (65.3±11.2) years old, 542 (57.5%) were males. A total of 93 (9.9%) bleeding events occurred during follow up, 89 (9.4%) events were minor bleeding, and 4 (0.4%) events were major bleeding. Patients with a high-risk HAS-BLED score had a 1.87-fold increased risk of bleeding compared with low-risk patients (HR = 2.87, 95% CI:1.26-6.51, P = 0.012). There was no statistically significant difference between low-medium-high-risk grading in other scoring systems and bleeding risk (all P>0.05). The AUC (95%CI) of HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT bleeding risk scores were 0.558 (0.525-0.590), 0.520 (0.487-0.553), 0.513(0.480-0.545), 0.523(0.490-0.555), respectively. The AUC of all bleeding score systems were of ≤ 0.700. Conclusion: Among the NVAF patients taking dabigatran in China, the HAS-BLED bleeding risk score is superior to other 3 bleeding risk score on predicting the bleeding risk in these patients, but its predictive value is still relatively low.

[Cardioversion efficacy of nifekalan in patients with sustained atrial fibrillation after radiofrequency ablation].

Objective: To evaluate the efficacy and safety of nifekalan (NIF) on cardioversion in atrial fibrillation (AF) patients post radiofrequency ablation, and investigate the relevant factors related to the cardioversion efficacy of NIF. Methods: We screened patients with sustained AF rhythm after radiofrequency ablation between November 2016 and July 2018. Participants were treated with intravenous NIF 0.4 mg/kg within 5-10 minutes after ablation. We observed the adverse reaction, and monitored the rhythm, heart rate, QT interval and QTc interval before the medication and at 5, 10, 20, 120 min after the medication. According to the drug outcome of NIF, patients were divided into conversion group and non-conversion group, related factors affecting conversion efficacy were evaluated using logistic regression analysis. Results: (1)A total of 116 patients were enrolled in the study (63 males and 53 females, mean age was (64±18) years). Among them, 72 patients were converted to sinus rhythm, and the overall successful rate was 62.1%. There were 84 patients with persistent AF, of which 50 cases (59.2%) were restored to sinus rhythm. There were 32 patients with paroxysmal AF, 22 cases (68.8%) of them were restored to sinus rhythm. The conversion time was 1.5 to 12 (6.8±3.4)min. (2) In 116 patients, the QT interval and QTc interval were significantly longer after medication than before the drug administration (P<0.01), and peaked at about 10th min, and restored to the level before drug administration at about 120th min. (3) There were 8 cases of bradycardia (6.9%), 3 cases of frequent and short ventricular tachycardia (2.6%). (4) The duration of atrial fibrillation was shorter and left atrial diameter was smaller in the cardioversion group than in the non-cardioversion group (both P<0.05). There were no significant differences in gender, disease history, atrial fibrillation type and structural heart disease between the two groups (P>0.05). (5) Multifactorial logistic regression analysis showed that the duration of atrial fibrillation (OR=0.980, 95%CI 0.966-0.994, P=0.004) and the left atrial diameter (OR=0.888, 95%CI 0.814-0.967, P=0.007) were the factors that influence the cardioversion efficacy of NIF on atrial fibrillation post ablation. Conclusions: The total effective rate of NIF was 62.1% in patients witrh sustained AF post radiofrequency ablation, was 68.8% in patients with paroxysmal AF. Besides, NIF has the advantage of short conversion time and few adverse reactions. Left atrium diameter and AF duration were relevant factors that influence the efficacy of NIF of cardioversion in patients with sustained AF after radiofrequency ablation.

Double ventricular response in dual AV nodal pathways mimicking interpolated premature beat.

Double ventricular response in dual atrioventricular (AV) nodal pathways can result in nonreentrant supraventricular tachycardia. Since this condition was first described in 1979, around 20 cases have been reported. Here, we present the case of a patient with a confirmed diagnosis of double ventricular response in dual AV nodal pathways resembling an interpolated premature beat who underwent successful radiofrequency ablation of the slow pathway.

[Relationship between FGF23/FGFR4 expression in atrial tissue and atrial fibrosis in patients with atrial fibrillation].

Objective: To observe the expression of fibroblast growth factor 23 (FGF23) and FGFR4 in patients with atrial fibrillation (AF) and its relationship with atrial fibrosis. Methods: Fifty-one patients with rheumatic heart disease undergoing cardiac surgery at the Second Affiliated Hospital of Nanchang University from October 2016 to April 2017 were divided into two groups according to whether they were complicated with atrial fibrillation: 39 patients with persistent AF(AF group), and 12 patients with sinus rhythm (SR group). The right atrial appendage was cut out during cardiac surgery. The expression of FGF23 and FGFR4 mRNA was detected by quantitative real-time PCR. The expression of FGFR4 protein was detected by Western blot. Atrial structure was evaluated by echocardiography. Masson staining was used to evaluate the degree of atrial fibrosis. The expression of FGF23 and FGFR4 was compared between the two groups.Additionally, the relationship between FGF23 and FGFR4 expression and atrial fibrosis was evaluated. Results: AF group had significantly higher right and left atrial diameter than SR group((40.1±1.6 )mm vs (34.1±1.5)mm, (52.4±2.9)mm vs (41.3±2.4)mm, all P<0.05) . There were no statistically significant differences in age, gender, ejection fraction between the two groups. The expression of FGF23 and FGFR4 mRNA in AF group were significantly higher than those in SR group (1.93±0.32 vs 0.93±0.14, 1.89±0.17 vs 0.91±0.11, both P<0.05). Compared with the SR group, the protein expression of FGFR4 in the AF group was significantly higher(1.76±0.21 vs 0.84±0.12). In AF group, there was no correlation between FGF23 mRNA and atrial diameter (r=0.274 (left atrial), r=0.238 (right atrium), both P>0.05). Meanwhile, FGFR4 mRNA and protein expression had no correlation with atrial diameter either. There was positive correlation between FGF23 mRNA and atrial collagen volume fraction in AF group (r=0.42, P<0.05). The expression of FGFR4 mRNA and protein were positively correlated with the atrial collagen volume fraction (r=0.573, r=0.478, all P<0.05). Conclusion: The expression of FGF23 and FGFR4 in atrial fibrillation patients is increased, which is positively correlated with atrial fibrosis, suggesting that FGF23/FGFR4 pathway may play an important role in atrial fibrillation by promoting atrial fibrosis.

[Prevalence and influential factors of stroke in Jiangxi Province in 2014].

Objective: To discuss the prevalence and influential factors of stroke among population in Jiangxi Province. Methods: Four cities in urban areas and four counties in rural areas were selected firstly, in which two districts or townships were selected; and then three communities or villages were chosen from each district and township, respectively, using the simple random sampling (SRS) method. Finally 15 269 subjects aging 15 years old or above, living in Jiangxi Province ≥6 months were randomly selected to participate in this survey from November 2013 to August 2014. Information of population characteristics, life behavior way, individual disease history were collected through questionnaire survey, and height, weight, waist circumference, blood pressure, body fat rate, visceral fat index and so on were measured by instruments. Risk factors of stroke prevalence were analyzed by the unconditioned logistic regression analysis. Results: A total of 15 269 participants (6 267 males) from 15 364 eligible participants were included in the statistical analysis. Out of which, 7 793 participants came from urban areas, and their average age was (53.04±17.91) years old. In this study, 226 stroke patients (117 males) were found among15 269 participants, including 122 urban participants and 104 rural participants, whose average age was (67.76±9.74) years old. The prevalence of stroke was 1 480.12/100 000 in 2014, which was separately 1 866.92/100 000 and 1 210.84/100 000 among males and females. The prevalence of people aging (45-49) years old was 413.79/100 000 (6/1 450) , while which among people aging 75 years old and above was 3 311.62/100 000 (61/1 842) . The prevalence of stroke among residents in Jiangxi presented an uprising tendency with age increasing (linear-by-linear association χ(2)=62.23, P<0.01). The research showed that when other influencing factors including gender, BMI, waist circumference, pulse-pressure difference, VAI, and sleeping time in non-working days were controlled, hypertensive patients had a higher risk of stroke than people without hypertension (OR=6.88, 95%CI: 4.90-9.67), drinkers had a higher risk of stroke than non-drinkers (OR=1.56, 95%CI: 1.17-2.08), compared with people <65 years old, people aged 65-74 years old and ≥75 years old had a higher risk of stroke, the value of OR (95%CI) were 1.88 (1.36-2.59) and 1.97 (1.39-2.80), respectively, compared with people with normal body fat percentage, people whose body fat percentage on high side and people who with high body fat percentage had a higher risk of stroke, the value of OR (95%CI) were 1.71 (1.18-2.48) and 1.74 (1.18-2.56), respectively, people with sleep time >8 h had a higher risk of stroke than those with sleep time of 6-8 h. Conclusion: There was a high stroke prevalence among residents in Jiangxi province. Hypertension, drinking, age, BFP and sleep duration were associated with stroke prevalence. Corresponding measures for high-risk population and risk factors should be strengthened to prevent and control the stroke.

[Homocysteine induces calcium overload in neonatal rat atrial cells through activation of sodium current and CaMK⠡δ].

Objective: To investigate the effect and related mechanism of homocysteine (Hcy) on calcium overload in neonatal rat atrial cells (NRICs). Methods: NRICs were assigned to 9 groups after culture for 3 days: (1) control group; (2) Hcy group (0, 50, 100, 200, 500 µmol/L for 48 hours); (3) antioxidant group (NAC, 10 µmol/L for 24 hours); (4) Hcy+NAC group (500 µmol/L Hcy for 48 hours, then treated with 10 µmol/L NAC for 24 hours); (5) calcium/calmodulin dependent protein kinase Ⅱδ (CaMKⅡδ) inhibitor group (KN-93, 3 µmol/L KN-93 for 5 hours); (6) specific sodium current inhibitor group (ELE, 1 µmol/L ELE for 5 hours); (7) Hcy+KN-93 group (500 µmol/L Hcy for 48 hours, then treated with 3 µmol/L KN-93 for 5 hours); (8) Hcy+ELE group (500 µmol/L Hcy for 48 hours, then treated with 1 µmol/L ELE for 5 hours; (9) Hcy+KN-93+ELE group (500 µmol/L Hcy for 48 hours, then treated with 3 µmol/L KN-93 and 1 µmol/L ELE for 5 hours). Moreover, NRICs were also treated with CaMKⅡδ-siRNA lentivirus, and Nav1.5-siRNA lentivirus, negative lentivirus carrier containing green fluorescent protein (GFP) for 24 hours. The MOI values of the three groups were 10. Infection efficiency of lentivirus was determined by observing the percentage of GFP fluorescence under inverted fluorescence microscope after transfection for 24 hours, and cultured regularly with simultaneous Puro screening, then cells were grouped as Hcy+CaMKⅡδ-siRNA group, Hcy+Nav1.5-siRNA group and Hcy+negative group. The concentration of Ca(2+) in NRICs ([Ca(2+)]i) of various groups was detected through Fluo-4/AM fluorescence probe, then 2', 7'- two chlorofluorescein diacetate (DCFH-DA) was used as a probe to detect reactive oxygen species (ROS) in NRICs by flow cytometry. The malondialdehyde (MDA) was detected by the activity of superoxide dismutase (SOD) and xanthine oxidase was detected by thiobarbituric acid colorimetry. The protein and mRNA expression level of CaMKⅡδ and Nav1.5 in NRICs were detected by Western blot and quantitative real-time PCR. Results: (1) ROS, MDA and SOD were similar between NAC group and control group, ROS and MDA were significantly increased, while SOD was significantly reduced in Hcy group in a concentration-dependent manner. (2) [Ca(2+)]i: The level of [Ca(2+)]i was (155.57+7.25), (187.43+13.07), (248.98+27.22) and (307.36+15.09) nmol/L in 50, 100, 200 and 500 µmol/L Hcy groups, which was significantly higher than that in the control group ((123.18+7.24) nmol/L, P<0.01). In addition, the level of [Ca(2+)]i in Hcy+NAC group ((222.87+23.71)nmol/L) was significantly lower than that in Hcy 500 µmol/L group ((305.15+39.45) nmol/L, P<0.05), while [Ca(2+)]i level was similar between NAC group and the control group. (3) The protein expression of CaMKⅡδ and Nav1.5 was significantly upregulated in Hcy groups than in the control group. The protein expression level of CaMKⅡδ-Thr287 was significantly lower in NAC group than in Hcy 500 µmol/L group (P<0.01), however, there was no significant difference on the protein expression levels of CaMKⅡδ-Thr287 and Nav1.5 between NAC group and control group (all P>0.05). (4) The protein expression levels of CaMKⅡδ-Thr287 and the concentration of [Ca(2+)]i were significantly lower in Hcy+KN-93 group and Hcy+KN-93+ELE group than in Hcy 500 µmol/L group (P<0.05). [Ca(2+)]i concentration was significantly lower in Hcy+KN-93 group, Hcy+ELE group and KN-93+ELE+Hcy group than in Hcy 500 µmol/L group (P<0.05). (5) The mRNA and protein expression levels of CaMKⅡδ and Nav1.5 in each group infected with lentivirus: the GFP expression was ideal post lentivirus transfection for 24 hours (up to 90%), which was significantly lower in the CaMKⅡδ-siRNA group and Nav1.5-siRNA group than in the negative infection group (all P<0.05), which was similar between negative infection group and control group (P>0.05). Moreover, the mRNA and protein expression levels of CaMKⅡδ and CaMKⅡδ-Thr287 was significantly lower in Hcy+Nav1.5-siRNA group than in Hcy+negative infection group (P<0.05). The protein and mRNA levels of Nav1.5 were similar between Hcy+CaMKⅡδ-siRNA group and Hcy+negative infection group (P>0.05). Conclusions: Hcy can induce calcium overload in NRICs by increasing oxidative stress, upregulating the sodium channel protein, and activating the late sodium current and phosphorylating CaMKⅡδ.

[Status of intra-aortic balloon pump application and related factors in Chinese patients with acute myocardial infarction].

Objective: To investigate the current status of application of intra-aortic balloon pump(IABP) and analyze the factors which might impact the application of IABP in patients with acute myocardial infarction complicated with cardiac shock in China. Methods: In China Acute Myocardial Infarction (CAMI) Registry,a nationwide, multicenter(107 hospitals), prospective study, 26 592 patients with acute myocardial infarction were enrolled consecutively between January 1, 2013 and September 30, 2014. After excluding of 30 cases due to missing important data,26 562 cases were analyzed.The application status of IABP was analyzed and multivariate logistic regression analysis was performed to determine the factors related to IABP application. Results: A total of 785(3.0%) patients with acute myocardial infarction received IABP implantation, and 381(49.9%) patients belonged to preventive application of IABP before primary percutaneous coronary intervention,and 6(0.8%) patients were complicated with mechanical complications.There were 118(15.0%) patients with cardiac shock received IABP implantation, which accounted for 12.0%(118/984) of all patients with cardiac shock.Multivariate logistic regression analysis showed that the clinical independent factors of the decision of IABP insertion included dyslipidemia (OR=2.858, 95%CI 1.397-5.846, P=0.004),left ventricular ejection fraction (OR=0.977, 95%CI 0.961-0.994, P=0.009),usage of dopamine (OR=2.817, 95%CI 1.495-5.308, P=0.001), left main disease (OR=2.817, 95%CI 1.495-5.308, P=0.001), GRACE score (OR=1.006, 95%CI 1.000-1.011, P=0.034), receiving primary percutaneous coronary intervention (OR=4.508, 95%CI 1.673-12.146, P=0.003), teritiary hospitals (OR=2.562, 95%CI 1.498-4.384, P=0.001), and higher education of the patients (OR=2.183, 95%CI 1.056-4.509, P=0.016). Conclusions: Among the Chinese acute myocardial infarction patients who received IABP implantation, nearly half application of IABP are preventive implantation before primary percutaneous coronary intervention. Only a few patients complicated with cardiac shock received IABP insertion. The clinical conditions, grade of hospitals, degree of education impact the decision of IABP insertion for the patients with acute myocardial infarction. Clinical Trial Registry National Institutes of Health, NCT018746.

[Clinical features of Takayasu arteritis patients with pulmonary hypertension due to pulmonary artery involvement].

OBJECTIVE: To summarize the clinical features of Takayasu arteritis (TA) patients with pulmonary hypertension due to pulmonary artery involvement. METHODS: Ninety-four TA patients with pulmonary artery involvement treated in Fuwai Hospital from Jun 1988 to Jun 2014 were retrospectively summarized. Patients were divided into two groups according to whether aorta and its main branches affected (APTA, n=48) or not (PTA, n=46). Clinical features and angiographic data were further analyzed. RESULTS: Of all the patients, male to female rate was 1∶3.3, age ranged from 8 to 60 years with median age of 33.5 years when symptom onset. Main symptoms included dyspnea on exertion. Heart murmur and mid-systolic murmur in pulmonic area were commonly found by physical examination. All patients had pulmonary hypertension by echocardiographic examination. Angiographic data showed that multi-lobular and multi-segmental pulmonary branches were predominantly affected, followed by sub-segmental and peripheral branches. Both sides of pulmonary artery involvement were more common than one side involvement, while the right pulmonary arteries were more often affected than the left. Most of the clinical symptoms and signs between APTA group and PTA group were comparable. However, erythrocyte sedimentation rate and N-terminal pro-natriuretic peptide were significant higher in APTA group than that in PTA group when admission [14.0(5.0, 28.0) vs 8.5(3.0, 19.3) mm/1 h and (1 936±1 769) vs (1 627±1 153) ng/L, both P<0.05]. CONCLUSIONS: Dyspnea on exertion may be the main manifestation of TA with pulmonary artery involvement. All patients present with pulmonary hypertension and moderate to severe heart failure when symptom onset.

[A large-scale, multicenter, retrospective study on efficacy of bivalirudin use during peri-percutaneous coronary intervention period for Chinese patients with coronary heart disease].

OBJECTIVE: To observe the efficacy and safety of bivalirudin use in Chinese patients with coronary heart disease (CHD) during the peri-percutaneous coronary intervention(PCI) period. METHODS: A total of 3 271 patients who underwent PCI and received periprocedural bivalirudin treatment between July 2013 and October 2015 from 88 centers of China were involved in this study. The primary outcome was 30-day net adverse clinical events (NACE a composite of major adverse cardiac or cerebral events (MACE, all-cause death, reinfarction, urgent target vessel revascularization, or stroke) or bleeding), the secondary outcome was stent thrombosis at 30 days. RESULTS: The mean age of enrolled patients was (65.12±12.44) years old, 27.4%(889/3 244) of them were female. Percent of stable coronary disease (SCD), non-ST segment elevation acute coronary syndrome (NSTE-ACS) and ST elevation myocardial infarction (STEMI) was 5.0%(162/3 248), 44.6%(1 450/3 248) and 50.4%(1 636/3 248) respectively. Radial access was performed in 89.5% (2 879/3 271) patients, and 9.7% (316/3 271) and 34.1% (1 115/3 271) patients also received ticagrelor and tirofiban medication. 69.3% (2 266/3 271) patients received post-procedural bivalirudin infusion, in which 46.3% (1 050/2 266) was treated at PCI-does, with a median duration of 2.5(1.0, 4.0) h. During the 30-day follow-up, NACE occurred in 3.45% (103/2 988) patients, the incidence of MACE, death was 2.17% (65/2 994) and 1.03% (31/3 017), respectively and bleeding events were recorded in 1.37% (41/2 996) patients. Four cases (0.13%) of stent thrombosis (3 acute stent thrombosis) were recorded. CONCLUSION: Peri-PCI Bivalirudin use is safe and related with low bleeding risk in Chinese CHD patients.

Metformin reduces decline in the estimated glomerular filtration rate during progression of autosomal dominant polycystic kidney disease: a systematic review and meta-analysis.

OBJECTIVE: A meta-analysis (MA) was carried out to examine the influence of metformin on autosomal dominant polycystic kidney disease (ADPKD) patient prognosis. MATERIALS AND METHODS: We reviewed and examined scientific articles from PubMed, Clinicalkey, Google Scholar, Medline, Embase, and Cochrane from the initiation date till June 2023 to identify investigations that examined metformin performance in managing ADPKD. Among the employed search terminology, we searched for terms such as "metformin" and "ADPKD". MA was conducted using the Cochrane Collaboration's RevMan version 5.3.0 (The Cochrane Collaboration, Oxford, UK). RESULTS: We identified 4 investigations, with 164 total subjects who fulfilled our inclusion criteria. The experimental cohort displayed a marked reduction in the decline of estimated glomerular filtration rate (eGFR) relative to controls [mean difference (MD) = 2.31, 95% confidence interval (CI) = 0.82-3.79, p = 0.002]. We observed no obvious difference in the height-adjusted total kidney volume alteration, gastrointestinal side effects, and hypoglycemia between the two cohorts. CONCLUSIONS: Metformin was easily tolerable and safe and substantially reduced the eGFR decline among ADPKD patients. Moreover, although metformin-treated patients were more likely to suffer gastrointestinal adverse events, we observed no discernible difference between the two cohorts.

Effect of low contrast medium-dose CTA on device sizing and access vessel assessment for TAVR.

PURPOSE: Chronic kidney disease (CKD) is prevalent in transcatheter aortic valve replacement (TAVR) candidates, leading to concerns regarding contrast medium (CM) safety. We evaluated (a) the impact of low-CM imaging on pre-TAVR measurements and (b) postcontrast acute kidney injury (PC-AKI) prevalence after dual-source computed tomography (DSCT) in TAVR candidates. METHODS: All TAVR candidates with CKD (SCr≥1.5 mg/dL) who underwent weight-based low-CM, low-pitch helical 3rd-generation DSCT in a one-year period were included, and matched to standard-CM, non-CKD controls (N = 50). Image quality (IQ) and pre-TAVR measurement interobserver variability were evaluated. Renal function change and PC-AKI were studied in the entire TAVR cohort, irrespective of scan mode (N = 153). RESULTS: Low-CM in CKD (N = 25) was performed with median 68 mL CM [52-87], 90 kV [80-90] and SCr 1.6 mg/dL [1.5-1.9], and standard-CM without CKD with median 116 mL CM [96-134], 100 kV [90-110] and SCr 1.0 mg/dL [0.9-1.1](P < 0.00). Low-CM IQ was good, though lower compared with standard-CM (P < 0.02). Interobserver measurement reliability was excellent (ICCs>0.85). Interobserver-agreement was lower in low-CM, causing prosthesis size disagreement in 5/25 (kappa-0.73) versus 0/25 with standard-CM (kappa-1.00), and transfemoral eligibility disagreement in 4/25 (kappa-0.68) versus 2/25 (kappa-0.84), respectively. Mean 1-month SCr-change in the low-CM TAVR cohort (N = 35) was -1 % [-12 to +7 %] and in standard-CM (N = 118) 0 % [-8 to +10 %](P > 0.3). PC-AKI occurred in none. CONCLUSION: Low-CM third-generation-DSCT achieves good IQ in TAVR candidates with CKD, and seems safe, with no apparent renal function deterioration or prevalence of PC-AKI. However, standard-CM protocols in non-CKD patients provide higher measurement reproducibility. Low-CM protocols should therefore be reserved for patients at high risk for PC-AKI.

The extracellular matrix protein mindin attenuates colon cancer progression by blocking angiogenesis via Egr-1-mediated regulation.

Mindin, a secreted, highly conserved extracellular matrix (ECM) protein, exerts a broad spectrum of effects on the innate immune system. However, its function in colorectal cancer (CRC) progression is not well established, and its upstream regulation mechanisms remain unclear. Contrary to previous reports, this study used two different enzyme-linked immunosorbent assay (ELISA) kits to show that the serum level of mindin was significantly decreased in CRC patients and that this decreased level is more significantly associated with the early stages of the disease. To explore the regulation of mindin, we used a bioinformatics approach to predict potential transcription factors and determined that early growth response factor (Egr)-1 directly regulates mindin expression at the transcriptional level using dual luciferase, chromatin immunoprecipitation (ChIP) DNA and electrophoretic mobility shift assay (EMSA) methods. Egr-1 regulates mindin mRNA and protein expression in CRC cells, and the protein expression of both Egr-1 and mindin was significantly decreased in tumor lesions of patients compared with adjacent control tissues. Mindin is essential for Egr-1-mediated inhibition of endothelial cell tube formation, and mindin inhibits endotheliocyte proliferation, migration and angiogenic sprouts in vitro. Overexpression of mindin suppressed xenograft tumor growth by blocking angiogenesis instead of directly suppressing CRC cell proliferation. Mechanically, mindin inhibits the hypoxia-induced HIF-1a and VEGFA protein expression in CRC cells and the phosphorylation of VEGFR-2 in endothelial cells. The results suggest that the serum level of mindin can be used as a novel biomarker for early detection of CRC and that the Egr-1/mindin axis is a potential therapeutic target for the inhibition of angiogenesis in CRC development.

Role of superoxide anion in the pathogenesis of cytokine-induced myocardial dysfunction in dogs in vivo.

OBJECTIVE: Although studies in vitro have implicated oxygen-derived free radicals as possible mediators of inflammatory cytokine-induced cell injury, the role of the radicals in the cytokine-induced myocardial dysfunction in vivo remains unclear. The present study was designed to address this point in our novel canine model of cytokine-induced myocardial dysfunction in vivo. METHODS: Studies were performed in mongrel dogs, in which microspheres (MS, 15 microns in diameter) with and without interleukin-1 beta (IL-1 beta) were injected into the left main coronary artery (control and IL-1 beta group). Left ventricular ejection fraction (LVEF) was evaluated by echocardiography for 1 week. RESULTS: Immediately after the intracoronary injection of MS (10(6)/kg), LVEF equally decreased to approximately 30% in both the control and IL-1 beta group. While LVEF rapidly recovered within 2 days in the control group, it remained depressed in the IL-1 beta group until day 7 (p < 0.0001 vs. control group). Pretreatment with OPC-6535 (an inhibitor of superoxide production) before (2 mg/kg i.v.) and 1 and 2 days after IL-1 beta MS application (1 mg/kg i.v.) prevented the IL-1 beta-induced myocardial dysfunction. Superoxide production in the myocardium was significantly higher in the IL-1 beta group than in the control group at day 2 (p < 0.01), and OPC-6535 significantly suppressed the IL-1 beta-induced superoxide production (p < 0.01). An HPLC assay showed that nitrotyrosine, a marker of the formation of peroxynitrite by superoxide anion and nitric oxide, was present in the myocardium treated with IL-1 beta but not in that with control MS. OPC-6535 abolished the IL-1 beta-induced formation of myocardial nitrotyrosine. CONCLUSION: These results indicate that superoxide anion and the resultant formation of peroxynitrite may substantially be involved in the pathogenesis of the cytokine-induced myocardial dysfunction in dogs in vivo.

Association between high grade ventricular arrhythmia and extent of left ventricular hypertrophy in hypertrophic cardiomyopathy.

The association between the extent of left ventricular (LV) hypertrophy and severity of ventricular or atrial arrhythmias are examined. Two-dimensional echocardiography and 24-h Holter electrocardiography monitoring were performed in 60 patients with hypertrophic cardiomyopathy (HCM). According to the distribution of the LV hypertrophy, the patients were divided into three groups: 1. Apical hypertrophy (APH), 2. Septal hypertrophy, and 3. Extensive hypertrophy. Ventricular arrhythmias were found in 82% of the patients and supraventricular arrhythmias were detected in 70% of the patients. Lown grade III and IV arrhythmias occurred significantly more frequently in patients with extensive than with septal hypertrophy. Lown grade III to IV arrhythmias did not occur in patients with APH. Present results show a significant association between the extent of LV hypertrophy and the severity of ventricular arrhythmias in HCM.

[Analysis of the misdiagnoses of obliterative pulmonary hypertension].

In order to reduce the misdiagnostic rate of obliterative pulmonary hypertension (OPH), the clinical data was analysed of 126 cases of OPH, including 83 cases of unexplained pulmonary hypertension (UPH) and 43 cases of thromboembolic pulmonary hypertension (TEPH). The results showed that the misdiagnostic rate of UPH and TEPH was 93.98% and 79.07% respectively, with a total misdiagnostic rate of 88.89%. UPH was frequently misdiagnosed as congenital heart disease (63.86%), valvular heart disease (13.5%) and coronary heart disease (9.64%). TEPH was usually misdiagnosed as cardiomyopathy (37.21%), coronary heart disease (18.61%), and valvular heart disease (18.61%). The possible causes of misdiagnosis were discussed.

[An analysis of 21 cases of idiopathic dilatation of the pulmonary artery].

Idiopathic dilatation of the pulmonary artery (IDPA) is a disease which, generally speaking, does not need treatment. But a correct differential diagnosis is of great importance. 21 cases of IDPA were reported. The clinical data showed that 66.67% of the patients were asymptomatic and all the patients had normal respiratory and cardiovascular functions. 10% of the cases had had a history of more than 20 years. The results showed that IDPA was a benign anomaly and most of its symptoms were iatrogenic. It was usually misdiagnosed as pulmonary stenosis (42.86%), atrial septal defect (38.10%), pulmonary hypertension (28.57%), and so on. Careful chest X-ray, ECG and UCG examinations are useful for the differential diagnosis, but a clinical diagnosis should be based on the normal result of right heart catheterization.

[Perfusion lung scan in unexplained pulmonary hypertension].

Thirty-two patients were diagnosed as unexplained pulmonary hypertension by clinical history, physical examination, hemodynamics, pulmonary angiography and perfusion lung scanning. The findings of pulmonary scans in twenty patients (62.5%) showed patchy heterogeneous perfusion defects, which suggested chronic silent pulmonary thromboembolism (CSPT) and in twelve cases (37.5%) demonstrated normal or equally diffuse radionuclide scattering due to primary pulmonary hypertension (PPH). This result corresponded with the pathological data in some of the relevant references. Pulmonary perfusion scan is a noninvasive, safe and simple procedure for determining whether CSPT or PPH is the causative factor in patients with unexplained pulmonary hypertension.

Glycation exacerbates the neuronal toxicity of ß-amyloid.

Accumulation evidence shows that ß-amyloid (Aß) is a neurotoxic and accumulation of Aß is responsible for the pathology of Alzheimer's disease (AD). However, it is currently not fully understood what makes Aß toxic and accumulated. Previous studies demonstrate that Aß is a suitable substrate for glycation, producing one form of the advanced glycation endproducts (AGEs). We speculated that Aß-AGE formation may exacerbate the neurotoxicity. To explore whether the Aß-AGE is more toxic than the authentic Aß and to understand the molecular mechanisms, we synthesized glycated Aß by incubating Aß with methylglyoxal (MG) in vitro and identified the formation of glycated Aß by fluorescence spectrophotometer. Then, we treated the primary hippocampal neurons cultured 8 days in vitro with Aß-AGE or Aß for 24 h. We observed that glycation exacerbated neurotoxicity of Aß with upregulation of receptor for AGE (RAGE) and activation of glycogen synthase kinase-3 (GSK-3), whereas simultaneous application of RAGE antibody or GSK-3 inhibitor reversed the neuronal damages aggravated by glycated Aß. Thereafter, we found that Aß is also glycated with an age-dependent elevation of AGEs in Tg2576 mice, whereas inhibition of Aß-AGE formation by subcutaneously infusion of aminoguanidine for 3 months significantly rescued the early cognitive deficit in mice. Our data reveal for the first time that the glycated Aß is more toxic. We propose that the glycated Aß with the altered secondary structure may be a more suitable ligand than Aß for RAGE and subsequent activation of GSK-3 that can lead to cascade pathologies of AD, therefore glycated Aß may be a new therapeutic target for AD.