Overexpression of miR-431 inhibits cardiomyocyte apoptosis following myocardial infarction via targeting HIPK3.

OBJECTIVE: Acute myocardial infarction (AMI) is a common acute cardiovascular crisis. Although the diagnosis and treatment of AMI are constantly improving, the mortality of AMI is still very high, and its pathogenesis is still unclear. This article focuses on the role of microRNA-431 (miR-431) in regulating myocardial apoptosis after myocardial infarction (MI) and its potential molecular mechanism. MATERIALS AND METHODS: We constructed cell models and animal models of MI. Quantitative reverse-transcription polymerase chain reaction (RT-PCR) was used to detect miR-431 expression in myocardium after MI. Western blot, cell counting kit-8 (CCK-8) assay, flow cytometry and terminal dexynucleotidyl transferase(TdT)-mediated dUTP nick end labeling (TUNEL) staining were performed to detect myocardial apoptosis; pathological sections of myocardium, serum lactate dehydrogenase (LDH) levels and Caspase-3 activity in myocardium were employed to evaluate myocardial injury of MI rats; echocardiography was utilized to assess cardiac function of rats. RESULTS: We revealed that miR-431 expression was decreased in H2O2-treated H9c2 cells and myocardium of MI rats. The expression of Cleaved Caspase-3 (C-Caspase-3) in H9c2 cells treated with H2O2 was significantly increased, the cell viability was dramatically decreased, the apoptosis rate and the percentage of TUNEL positive cells were notably increased, but up-regulation of miR-431 could reverse these effects. At the same time, compared with the sham group, serum LDH levels were observably increased, myocardial Caspase-3 activity was also increased, and cardiac function was greatly reduced, while overexpression of miR-431 could reduce myocardial injury and improve cardiac function of MI rats. Through the Luciferase reporter gene experiment, we found that miR-431 could directly target HIPK3. CONCLUSIONS: In summary, overexpression of miR-431 can inhibit apoptosis after myocardial infarction via targeting HIPK3, thereby reducing myocardial injury and improving cardiac function in MI rats.

Genetic and morphology analysis among the pentaploid F1 hybrid fishes (Schizothorax wangchiachii ♀ × Percocypris pingi ♂) and their parents.

Triploid and pentaploid breeding is of great importance in agricultural production, but it is not always easy to obtain double ploidy parents. However, in fishes, chromosome ploidy is diversiform, which may provide natural parental resources for triploid and pentaploid breeding. Both tetraploid and hexaploid exist in Schizothorax fishes, which were thought to belong to different subfamilies with tetraploid Percocypris fishes in morphology, but they are sister genera in molecule. Fortunately, the pentaploid hybrid fishes have been successfully obtained by hybridization of Schizothorax wangchiachii (♀, 2n = 6X = 148) × Percocypris pingi (♂, 2n = 4X = 98). To understand the genetic and morphological difference among the hybrid fishes and their parents, four methods were used in this study: morphology, karyotype, red blood cell (RBC) DNA content determination and inter-simple sequence repeat (ISSR). In morphology, the hybrid fishes were steady, and between their parents with no obvious preference. The chromosome numbers of P. pingi have been reported as 2n = 4X = 98. In this study, the karyotype of S. wangchiachii was 2n = 6X = 148 = 36m + 34sm + 12st + 66t, while that the hybrid fishes was 2n = 5X = 123 = 39m + 28sm + 5st + 51t. Similarly, the RBC DNA content of the hybrid fishes was intermediate among their parents. In ISSR, the within-group genetic diversity of hybrid fishes was higher than that of their parents. Moreover, the genetic distance of hybrid fishes between P. pingi and S.wangchiachii was closely related to that of their parental ploidy, suggesting that parental genetic material stably coexisted in the hybrid fishes. This is the first report to show a stable pentaploid F1 hybrids produced by hybridization of a hexaploid and a tetraploid in aquaculture.

Effectiveness of the multidisciplinary Risk Assessment and Management Program for Patients with Diabetes Mellitus (RAMP-DM) for diabetic microvascular complications: A population-based cohort study.

AIM: To evaluate the effectiveness of the multidisciplinary Risk Assessment and Management Program for Patients with Diabetes Mellitus (RAMP-DM) in reducing the risks of microvascular complications. METHODS: This prospective cohort study was conducted with 29,670 propensity-score-matched RAMP-DM participants and diabetes patients under the usual primary care (14,835 in each group). Study endpoints were the first occurrence of any diabetic microvascular complications, non-proliferative diabetic retinopathy/preproliferative diabetic retinopathy (NPDR/prePDR), sight-threatening diabetic retinopathy (STDR) or blindness, nephropathy, end-stage renal disease (ESRD), neuropathy and lower-limb ulcers or amputation. Log-rank tests and multivariable Cox proportional-hazards regressions were employed to estimate between-group differences in incidences of study endpoints. RESULTS: After a median follow-up of 36 months with>41,000 person-years in each group, RAMP-DM participants had a lower incidence of microvascular complications (760 vs 935; adjusted hazard ratio [HR]: 0.73; 95% confidence interval [CI]: 0.66-0.81; P<0.001) and lower incidences of all specific microvascular complications except neuropathy (adjusted HR: 0.94; 95% CI: 0.61-1.45; P=0.778). Adjusted HRs for the RAMP-DM vs control group for ESRD, STDR or blindness, and lower-limb ulcers or amputation were 0.40 (95% CI: 0.24-0.69; P<0.001), 0.55 (95% CI: 0.39-0.78; P=0.001) and 0.49 (95% CI: 0.30-0.80; P=0.005), respectively. CONCLUSION: The RAMP-DM intervention was associated with lower incidences of all microvascular complications except neuropathy over a 3-year follow-up. These encouraging results constitute evidence that structured risk assessment and risk-stratified management provided by a multidisciplinary team is effective for reducing microvascular complications in diabetes patients. CLINICAL TRIAL REGISTRY: NCT02034695, www.ClinicalTrials.gov.

Effect of a structured diabetes education programme in primary care on hospitalizations and emergency department visits among people with Type 2 diabetes mellitus: results from the Patient Empowerment Programme.

AIM: To assess whether a structured diabetes education programme, the Patient Empowerment Programme, was associated with a lower rate of all-cause hospitalization and emergency department visits in a population-based cohort of patients with Type 2 diabetes mellitus in primary care. METHODS: A cohort of 24 250 patients was evaluated using a linked administrative database during 2009-2013. We selected 12 125 patients with Type 2 diabetes who had at least one Patient Empowerment Programme session attendance. Patients who did not participate in the Patient Empowerment Programme were matched one-to-one with patients who did, using the propensity score method. Hospitalization events and emergency department visits were the events of interest. Cox proportional hazard and negative binomial regressions were performed to estimate the hazard ratios for the initial event, and incidence rate ratios for the number of events. RESULTS: During a median 30.5 months of follow-up, participants in the Patient Empowerment Programme had a lower incidence of an initial hospitalization event (22.1 vs 25.2%; hazard ratio 0.879; P < 0.001) and emergency department visit (40.5 vs 44%; hazard ratio 0.901; P < 0.001) than those who did not participate in the Patient Empowerment Programme. Participation in the Patient Empowerment Programme was associated with a significantly lower number of emergency department visits (incidence rate ratio 0.903; P < 0.001): 40.4 visits per 100 patients annually in those who did not participate in the Patient Empowerment Programme vs. 36.2 per 100 patients annually in those who did. There were significantly fewer hospitalization episodes (incidence rate ratio 0.854; P < 0.001): 20.0 hospitalizations per 100 patients annually in those who did not participate in the Patient Empowerment Programme vs. 16.9 hospitalizations per 100 patients annually in those who did. CONCLUSIONS: Among patients with Type 2 diabetes, the Patient Empowerment Programme was shown to be effective in delaying the initial hospitalization event and in reducing their frequency.

Cost-effectiveness simulation and analysis of colorectal cancer screening in Hong Kong Chinese population: comparison amongst colonoscopy, guaiac and immunologic fecal occult blood testing.

BACKGROUND: The aim of this study was to evaluate the cost-effectiveness of CRC screening strategies from the healthcare service provider perspective based on Chinese population. METHODS: A Markov model was constructed to compare the cost-effectiveness of recommended screening strategies including annual/biennial guaiac fecal occult blood testing (G-FOBT), annual/biennial immunologic FOBT (I-FOBT), and colonoscopy every 10 years in Chinese aged 50 year over a 25-year period. External validity of model was tested against data retrieved from published randomized controlled trials of G-FOBT. Recourse use data collected from Chinese subjects among staging of colorectal neoplasm were combined with published unit cost data ($USD in 2009 price values) to estimate a stage-specific cost per patient. Quality-adjusted life-years (QALYs) were quantified based on the stage duration and SF-6D preference-based value of each stage. The cost-effectiveness outcome was the incremental cost-effectiveness ratio (ICER) represented by costs per life-years (LY) and costs per QALYs gained. RESULTS: In base-case scenario, the non-dominated strategies were annual and biennial I-FOBT. Compared with no screening, the ICER presented $20,542/LYs and $3155/QALYs gained for annual I-FOBT, and $19,838/LYs gained and $2976/QALYs gained for biennial I-FOBT. The optimal screening strategy was annual I-FOBT that attained the highest ICER at the threshold of $50,000 per LYs or QALYs gained. CONCLUSION: The Markov model informed the health policymakers that I-FOBT every year may be the most effective and cost-effective CRC screening strategy among recommended screening strategies, depending on the willingness-to-pay of mass screening for Chinese population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02038283.

Patient Empowerment Programme in primary care reduced all-cause mortality and cardiovascular diseases in patients with type 2 diabetes mellitus: a population-based propensity-matched cohort study.

AIMS: To assess whether a structured diabetes education programme, the Patient Empowerment Programme (PEP), was associated with a lower risk of first cardiovascular disease (CVD) event and all-cause mortality in a population-based cohort of patients with type 2 diabetes mellitus (T2DM) in primary care. METHODS: A Chinese cohort of 27 278 patients with T2DM and without previous CVD events on or before the baseline study recruitment date was linked to the Hong Kong administrative database from 2008 to 2013. The PEP was provided to patients with T2DM treated at primary care outpatient clinics through community trained professional educators. PEP non-participants were matched one-to-one with the PEP participants using a propensity score method with respect to their baseline covariates. Cox proportional hazard regression was performed to estimate the associations of the PEP with the occurrence of first CVD event, coronary heart disease, stroke, heart failure and death from any cause, controlling for baseline characteristics. RESULTS: During a median of 21.5 months follow-up, 795 (352 PEP participants and 443 PEP non-participants) patients experienced a first CVD event. After adjusting for confounding variables, PEP participants had a lower rate of all-cause mortality [hazard ratio (HR) 0.564, 95% confidence interval (CI) 0.445-0.715; p < 0.001], first CVD (HR 0.807, 95% CI 0.696-0.935; p = 0.004) and stroke (HR 0.702; 95% CI 0.569-0.867; p = 0.001) than those without PEP. CONCLUSIONS: Enrolment in the PEP was associated with lower all-cause mortality and a lower number of first CVD events among patients with T2DM. The CVD benefit of PEP might be attributable to improving metabolic control through empowerment of self-care and the enhancement of quality of diabetes care in primary care.

Effects of Patient Empowerment Programme (PEP) on clinical outcomes and health service utilization in type 2 diabetes mellitus in primary care: an observational matched cohort study.

BACKGROUND: To evaluate the effects of a large population-based patient empowerment programme (PEP) on clinical outcomes and health service utilization rates in type 2 diabetes mellitus (T2DM) patients in the primary care setting. RESEARCH DESIGN AND SUBJECTS: A stratified random sample of 1,141 patients with T2DM enrolled to PEP between March and September 2010 were selected from general outpatient clinics (GOPC) across Hong Kong and compared with an equal number of T2DM patients who had not participated in the PEP (non-PEP group) matched by age, sex and HbA1C level group. MEASURES: Clinical outcomes of HbA1c, SBP, DBP and LDL-C levels, and health service utilization rates including numbers of visits to GOPC, specialist outpatient clinics (SOPC), emergency department (ED) and inpatient admissions, were measured at baseline and at 12-month post-recruitment. The effects of PEP on clinical outcomes and health service utilization rates were assessed by the difference-in-difference estimation, using the generalized estimating equation models. RESULTS: Compared with non-PEP group, PEP group achieved additional improvements in clinical outcomes over the 12-month period. A significantly greater percentage of patients in the PEP group attained HbA1C≤7% or LDL-C≤2.6 mmol/L at 12-month follow-up compared with the non-PEP group. PEP group had a mean 0.813 fewer GOPC visits in comparison with the non-PEP group. CONCLUSIONS: PEP was effective in improving the clinical outcomes and reduced the general outpatient clinic utilization rate over a 12-month period. Empowering T2DM patients on self-management of their disease can enhance the quality of diabetes care in primary care. TRIAL REGISTRATION: ClinicalTrials.gov NCT01935349.

Predicting SF-6D from the European Organization for Treatment and Research of Cancer Quality of Life Questionnaire scores in patients with colorectal cancer.

OBJECTIVES: To develop a mapping model for estimating six-dimensional health state short form (SF-6D) utility scores from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (QLQ-C30 and QLQ-CR29) scores in patients with colorectal cancer (CRC), with and without adjustment for clinical and demographic characteristics. METHODS: Ordinary least squares regression models were applied to a cross-sectional data set of 216 patients with CRC collected from a regional hospital in Hong Kong. Item responses or scale scores of cancer-specific (QLQ-C30) and colorectal-specific health-related quality-of-life (QLQ-CR38/CR29) data and selected demographic and clinical characteristics of patients were used to predict the SF-6D scores. Model goodness of fit was examined by using exploratory power (R(2) and adjusted R(2)), Akaike information criterion, and Bayesian information criterion, and predictive performance was evaluated by using root mean square error, mean absolute error, and Spearman's correlation coefficients between predicted and observed SF-6D scores. Models were validated by using an independent data set of 56 patients with CRC. RESULTS: Both scale and item response models explained more than 67% of the variation in SF-6D scores. The best-performing model based on goodness of fit (R(2) = 75.02%), predictive ability in the estimation (root mean square error = 0.080, mean absolute error = 0.065), and validation data set prediction (root mean square error = 0.103, mean absolute error = 0.081) included variables of main and interaction effects of the QLQ-C30 supplemented by QLQ-CR29 subset scale responses and a demographic (sex) variable. CONCLUSIONS: SF-6D scores can be predicted from QLQ-C30 and QLQ-CR38/CR29 scores with satisfactory precision in patients with CRC. The mapping model can be applied to QLQ-C30 and QLQ-CR38/CR29 data sets to produce utility scores for the appraisal of clinical interventions targeting patients with CRC using economic evaluation.

Hierarchy in Au nanocrystal ordering in supracrystals: a potential approach to detect new physical properties.

Here we describe the morphologies of Au nanocrystals self-assembled in fcc 3D superlattices called supracrystals. The average size of the nanocrystals is either 5 or 7 nm with a very small size distribution (<7%). The coating agents used to stabilize the nanocrystals are dodecanethiol (C12H25-SH), tetradecanethiol (C14H29-SH), and hexadecanethiol (C16H33-SH). The influences of the evaporation time, the volume of the chamber used to evaporate the toluene solvent, and the substrate temperature are studied. For nanocrystals characterized by the same size and coating agent, the supracrystal morphologies markedly change on increasing the evaporation time from 8 to 9 to 25 h whereas a slight change takes place on increasing the chamber volume. The nanocrystals' ability to self-order in supracrystals decreases upon increasing the chain length of the coating agent from dodecanethiol (C12) to tetradecanethiol (C14) to hexadecanethiol (C16). Decreasing the evaporation rate (25 h) and/or increasing the substrate temperature (50 °C) improves the nanocrystal ordering in fcc supracrystals. A hierarchy in nanocrystal ordering has the following sequence disordered assemblies, supracrystal film sitting on a disordered nanocrystal film, supracrystal films grown layer-by-layer, and finally supracrystals grown in solution with various well-defined shapes.

Sequence and properties of HMW subunit 1Bx20 from pasta wheat (Triticum durum) which is associated with poor end use properties.

The gene encoding high-molecular-weight (HMW) subunit 1Bx20 was isolated from durum wheat cv. Lira. It encodes a mature protein of 774 amino acid residues with an M(r) of 83,913. Comparison with the sequence of subunit 1Bx7 showed over 96% identity, the main difference being the substitution of two cysteine residues in the N-terminal domain of subunit 1Bx7 with tyrosine residues in 1Bx20. Comparison of the structures and stabilities of the two subunits purified from wheat using Fourier-transform infra-red and circular dichroism spectroscopy showed no significant differences. However, incorporation of subunit 1Bx7 into a base flour gave increased dough strength and stability measured by Mixograph analysis, while incorporation of subunit 1Bx20 resulted in small positive or negative effects on the parameters measured. It is concluded that the different effects of the two subunits could relate to the differences in their cysteine contents, thereby affecting the cross-linking and hence properties of the glutenin polymers.