Effects of Drosophila melanogaster regular exercise and apolipoprotein B knockdown on abnormal heart rhythm induced by a high-fat diet.

Abnormal heart rhythm is a common cardiac dysfunction in obese patients, and its pathogenesis is related to systemic lipid accumulation. The cardiomyocyte-derived apoLpp (homologous gene in Drosophila of the human apolipoprotein B) plays an important role in whole-body lipid metabolism of Drosophila under a high-fat diet (HFD). Knockdown of apoLpp derived from cardiomyocytes can reduce HFD-induced weight gain and abdominal lipid accumulation. In addition, exercise can reduce the total amount of apoLpp in circulation. However, the relationship between regular exercise, cardiomyocyte-derived apoLpp and abnormal heart rhythm is unclear. We found that an HFD increased the level of triglyceride (TG) in the whole-body, lipid accumulation and obesity in Drosophila. Moreover, the expression of apoLpp in the heart increased sharply, the heart rate and arrhythmia index increased and fibrillation occurred. Conversely, regular exercise or cardiomyocyte-derived apoLpp knockdown reduced the TG level in the whole-body of Drosophila. This significantly reduced the arrhythmia induced by obesity, including the reduction of heart rate, arrhythmia index, and fibrillation. Under HFD conditions, flies with apoLpp knockdown in the heart could resist the abnormal cardiac rhythm caused by obesity after receiving regular exercise. HFD-induced obesity and abnormal cardiac rhythm may be related to the acute increase of cardiomyocyte-derived apoLpp. Regular exercise and inhibition of cardiomyocyte-derived apoLpp can reduce the HFD-induced abnormal cardiac rhythm.

Cryptococcosis in patients with liver cirrhosis: Death risk factors and predictive value of prognostic models.

BACKGROUND: Liver cirrhosis is associated with immune deficiency, which causes these patients to be susceptible to various infections, including cryptococcus infection. Mortality in cirrhotic patients with cryptococcosis has increased. The present study was to explore the risk factors of mortality and the predictive ability of different prognostic models. METHODS: Forty-seven cirrhotic patients with cryptococcosis at a tertiary care hospital were included in this retrospective study. Data on demographics, clinical parameters, laboratory exams, diagnostic methods, medication during hospitalization, severity scores and prognosis were collected and analyzed. Student's t test and Mann-Whitney test were used to compare characteristics of survivors and non-survivors at a 90-day follow-up and cerebrospinal fluid (CSF) manifestations of cryptococcal meningitis. Multivariate Cox regression analysis was used to identify the independent risk factors for mortality. Kaplan-Meier curves were used to analyze patient survival. Receiver operating characteristic (ROC) curves were used to evaluate the different prognostic factors. RESULTS: The 30- and 90-day survival rates were 93.6% and 80.9%, respectively, in cirrhotic patients with cryptococcosis. Cryptogenic liver diseases [hazard ratio (HR) = 7.567, 95% confidence interval (CI): 1.616-35.428, P = 0.010], activated partial thromboplastin time (APTT) (HR = 1.117, 95% CI: 1.016-1.229, P = 0.022) and Child-Pugh score (HR = 2.146, 95% CI: 1.314-3.504, P = 0.002) were risk factors for 90-day mortality in cirrhotic patients with cryptococcosis. Platelet count (HR = 0.965, 95% CI: 0.940-0.991, P = 0.008) was a protective factor. APTT (HR = 1.120, 95% CI: 1.044-1.202, P = 0.002) and Child-Pugh score (HR = 1.637, 95% CI: 1.086-2.469, P = 0.019) were risk factors for 90-day mortality in cirrhotic patients with cryptococcal meningitis. There was significant difference in the percentage of lymphocytes in CSF between survivors and non-survivors [60.0 (35.0-75.0) vs. 95.0 (83.8-97.2), P < 0.001]. The model of end-stage liver disease-sodium (MELD-Na) score was more accurate for predicting 30-day mortality both in patients with cryptococcosis [area under curve (AUC): 0.826, 95% CI: 0.618-1.000] and those with cryptococcal meningitis (AUC: 0.742, 95% CI: 0.560-0.924); Child-Pugh score was more useful for predicting 90-day mortality in patients with cryptococcosis (AUC: 0.823, 95% CI: 0.646-1.000) and those with cryptococcal meningitis (AUC: 0.815, 95% CI: 0.670-0.960). CONCLUSIONS: These results showed that cryptogenic liver diseases, APTT and Child-Pugh score were associated with mortality in cirrhotic patients with cryptococcosis and cryptococcal meningitis. MELD-Na score was important for predicting 30-day mortality, and Child-Pugh score was critical for predicting 90-day mortality.

[Establishment and Application of Performance Evaluation and Obstacle Diagnosis Model for Regional Water Ecological Civilization Construction].

A scientific performance evaluation of the regional water ecological civilization construction and clarifying the obstacle factor are key points to improve the performance of regional water ecological civilization construction theory. This study analyzes the coupling relationship between humans and regional water ecology by applying the thinking logic of "driving force-pressure-state-influence-response-management." The regional water ecological civilization construction performance evaluation index system based on the DPSIRM model was established. Combining the unascertained measurement model and obstacle diagnosis model, the water ecological civilization construction performance of Shizuishan City during the past 10 years was empirically evaluated, and the obstacle factors affecting local construction performance were diagnosed and analyzed. The analytical results reveal the following points:First, the performance of the water ecological civilization construction in Shizuishan City gradually increased annually and revealed three development stages:the site visit and slow improvement (2010-2014), intermediate but fast improvement (2015-2017) and good and fast improvement (2018-2019). Second, each subsystem performance index trend varied, but generally, the fluctuations rose. Third, from 2010 to 2014, the average obstacle degree of the subsystem state, subsystem response, and subsystem pressure reached 58.81%, which became the main obstacles restricting the performance of the local water ecological civilization construction. From 2015 to 2017, the average pressure barrier degree reached 21.73%, which was the most significant obstacle to the construction performance. From 2018 to 2019, the average pressure barrier degree remained the largest obstacle by reaching 24.49%. Lastly, the index barrier of the obstacle degree among the top five factors are primarily distributed in the pressure subsystem. A comprehensive frequency ranking of the obstacles, the irrigation water use coefficient, and the pressure of the water consumption per ten thousand yuan of value-added by industry as a representative subsystem are the key directions to future construction. In this paper, the concepts and methods of the research can provide a theoretical reference for the performance evaluation of regional water ecological civilization construction and its obstacle factor diagnosis analysis.

MicroRNA­125a­mediated regulation of the mevalonate signaling pathway contributes to high glucose­induced proliferation and migration of vascular smooth muscle cells.

Hyperglycemia contributes to the excessive proliferation and migration of vascular smooth muscle cells (VSMC), which are closely associated with atherosclerosis. MicroRNAs (miRNAs/miRs) constitute a novel class of gene regulators, which have important roles in various pathological conditions. The aim of the present study was to identify miRNAs involved in the high glucose (HG)­induced VSMC phenotype switch, and to investigate the underlying mechanism. miRNA sequencing and reverse transcription­quantitative PCR results indicated that inhibition of miR­125a expression increased the migration and proliferation of VSMCs following HG exposure, whereas the overexpression of miR­125a abrogated this effect. Furthermore, dual­luciferase reporter assay results identified that 3­hydroxy­3-methyglutaryl­coA reductase (HMGCR), one of the key enzymes in the mevalonate signaling pathway, is a target of miR­125a. Moreover, HMGCR knockdown, similarly to miR­125a overexpression, suppressed HG­induced VSMC proliferation and migration. These results were consistent with those from the miRNA target prediction programs. Using a rat model of streptozotocin­induced diabetes mellitus, it was demonstrated that miR­125a expression was gradually downregulated, and that the expressions of key enzymes in the mevalonate signaling pathway in the aortic media were dysregulated after several weeks. In addition, it was found that HG­induced excessive activation of the mevalonate signaling pathway in VSMCs was suppressed following transfection with a miR­125a mimic. Therefore, the present results suggest that decreased miR­125a expression contributed to HG­induced VSMC proliferation and migration via the upregulation of HMGCR expression. Thus, miR­125a­mediated regulation of the mevalonate signaling pathway may be associated with atherosclerosis.