Activation of IK1 channel by zacopride attenuates left ventricular remodeling in rats with myocardial infarction.

Activating IK1 channels is considered to be a promising antiarrhythmic strategy. Zacopride has been identified as a selective IK1 channel agonist and can suppress triggered arrhythmias. Whether this drug also exerts a beneficial effect on cardiac remodeling is unknown, and the present study sought to address this question. Cardiac remodeling was induced through coronary ligation-induced myocardial infarction (MI) in male Sprague-Dawley rats. Zacopride (15 µg/kg) was administered (intraperitoneally) daily for 28 days after MI to determine whether it could attenuate MI-induced cardiac remodeling. A 4-week treatment with zacopride attenuated post-MI cardiac remodeling, as shown by the reduced left ventricular end-diastolic dimension and left ventricular end-systolic dimension and the increased ejection fraction and fractional shortening in zacopride-treated animals compared with animals treated with vehicle (all P < 0.05). Furthermore, zacopride significantly decreased myocardial collagen deposition, cardiomyocyte hypertrophy, the plasma level of brain natriuretic peptide, and cardiomyocyte ultrastructural injury. Zacopride also upregulated the expression of the IK1 channel protein and downregulated the expression of phosphorylated p70S6 kinase (p-p70S6K) and mTOR. These beneficial effects of zacopride were partially abolished by the IK1 channel blocker chloroquine. We conclude that the activation of IK1 channel by zacopride attenuates post-MI cardiac remodeling by suppressing mTOR-p70S6 kinase signaling.

[Analysis of relapse factors and risk assessment of adult acute lymphoblastic leukemia].

OBJECTIVE: To explore the risk factors of acute lymphoblastic leukemia (ALL) recurrence in adult patients and establish a prognosis index (PI) calculation model in order to improve the prevention strategy of ALL in adults. METHODS: 104 adult ALL patients from Blood Diseases Hospital & Chinese Academy of Medical Sciences between August 2008 and November 2011 were enrolled. COX proportional hazards regression stratified by Dummy variable was used to set up the prediction model; Kaplan-Meier method and Log-rank test were used to estimate and compare the survival. After calculated individual PI value, patients' expected survival should be estimated by groups. RESULTS: The overall median survival of adult ALL patients was 22.00 months (95% CI 17.00-27.00). COX regression analysis showed that chemotherapy group patients had a higher risk of recurrence than of ASCT group while setting treatment as the dummy variable (RR=2.052, 95%CI 0.877-4.799, P=0.007). Stratified Analysis showed that the risk factors of B-ALL recurrence in adult patients included HGB <100 g/L (RR=0.186, 95% CI 0.068-0.512, P=0.001), CNSL (RR=7.767,95% CI 2.951- 20.433, P=0.001), number of consolidation chemotherapy<3 (RR=0.445, 95% CI 0.211-0.940, P=0.034) and Ph chromosome positive (RR=2.771, 95% CI 1.353-5.674, P=0.005). Grouped by the PI value, the expected survival of each individual patient could be estimated as PI=0.58 base. CONCLUSION: HGB, CNSL, number of consolidation chemotherapy and Ph chromosome were independent risk factors of B-ALL recurrence in adult patients. PI value could predict the survival of adult ALL patients and provide reference for individual therapy and prognostic evaluation.

An epidemiologic study of mitochondrial membrane transporter protein gene polymorphism and risk factors for neural tube defects in Shanxi, China.

The present study involved a questionnaire survey of 156 mothers that gave birth to children with neural tube defects or had a history of pregnancy resulting in children with neural tube defects (case group) and 156 control mothers with concurrent healthy children (control group) as well as detection of mitochondrial membrane transporter protein gene [uncoupling protein 2 (UCP2)] polymorphism. The maternal UCP2 3' untranslated region (UTR) D/D genotype and D allele frequency were significantly higher in the case group compared with the control group (odds ratio (OR) 3.233; 95% confidence interval (CI) 1.103-9.476; P = 0.040; OR: 3.484; 95% CI: for neural tube defects 2.109-5.753; P < 0.001). Univariate and multivariate logistic regression analysis of risk factors for neural tube defects showed that a maternal UCP2 3' UTR D/D genotype was negatively interacted with the mothers' consumption of frequent fresh fruit and vegetables (S = 0.007), positively interacted with the mothers' frequency of germinated potato consumption (S = 2.15) and positively interacted with the mothers' body mass index (S = 3.50). These findings suggest that maternal UCP2 3' UTR gene polymorphism, pregnancy time, consumption of germinated potatoes and body mass index are associated with an increased risk for neural tube defects in children from mothers living in Shanxi province, China. Moreover, there is an apparent gene-environment interaction involved in the development of neural tube defects in offspring.

[Multi-state Markov model in expressing the outcome of mild cognitive impairment among community-based elderly residents].

OBJECTIVE: To introduce the Multi-state Markov model in studying the outcome prediction of mild cognitive impairment (MCI). METHODS: Based on the intelligence quotient (IQ) changes that reflecting the trends in cognitive function in the patients under follow-up program, we constructed a four states model and used Multi-state Markov model to analyze the patients. RESULTS: Among 600 MCI patients, there were 174 (29.0%) males and 426 (71.0%) females, with age range of 65-90 years-old (average 69.7 ± 6.6). For univariate analysis, gender, age, education level, marital status, smoking, household income, cerebral hemorrhage, hypertension, high cholesterol, diabetes, LDL-C, SBP and DBP were found to be associated with cognitive function. For multivariate analysis, female, older age, cerebral hemorrhage and higher SBP were shown to be the risk factors for transition from the state of cognitive stability to the state of severe deterioration, and their coefficients were 0.762, 0.366, 0.885, and 0.069, respectively. Age (0.038) could influence the transition from the state of cognitive stability to slight deterioration. Higher education level was shown to be the protective factor for these transitions (-0.219 and -0.297). Transition intensity from the state of cognitive stability to the state of slight and severe deterioration was 1.2 times that of transition to the state of improving. Transition intensity from state of slight deterioration to cognitive stability was 11.4 times that of transition to severe deterioration. CONCLUSION: Multi-state Markov model was an effective tool in dealing with longitudinal data.