Objective. Gestational diabetes mellitus (GDM) is a pathological condition, affecting an increasing number of pregnant women worldwide. Safe and effective treatment for GDM is very important for the public health. In this study, we utilized a high‐fat diet‐induced GDM model to evaluate the effects of LBP on GDM and examined the changes of exosomal microRNA expression profiling to decipher the potential underlying mechanism of LBP. Methods. Female C57BL/6J mice were fed a control diet, HFD, or 150 mg/kg LBP‐supplemented HFD for 6 weeks before conception and throughout gestation. Oral glucose tolerance test and plasma lipid levels were determined, and liver histopathology was assessed. Sequencing was used to define the microRNA expression profiling of plasma exosomes in the three groups of mice, and protein expression levels of the candidate target genes were analyzed. Results. LBP significantly relieved glucose intolerance, abnormal plasma lipid levels, and pathomorphological changes of liver histopathology in HFD‐induced GDM mice. Moreover, we found that this effect of LBP was mediated by downregulation of the increase of 6 miRNAs (miR‐93‐3p, miR‐188‐5p, miR‐466k, miR‐1188‐5p, miR‐7001‐3p, and miR‐7115‐5p) and reversing the increase of the protein expression of CPT1A, which is the target gene of miR‐188‐5p. Conclusions. Our findings provide novel insights into the biological activities of LBP in the treatment of GDM.
Although the effectiveness of lung cancer screening by low-dose computed tomography (LDCT) could be shown in China, there could be variation in the evidence concerning the economic impact. Our study explores the cost-effectiveness of lung cancer screening and optimizes the best definition of a high-risk population. A Markov model consisting of the natural history and post-diagnosis states was constructed to estimate the costs and quality-adjusted life years (QALYs) of LDCT screening compared with no screening. A total of 36 distinct risk factor-based screening strategies were assessed by incorporating starting ages of 40, 45, 50, 55, 60 and 65 years, stopping ages of 69, 74 and 79 years as well as smoking eligibility criteria. Screening data came from community-based mass screening with LDCT for lung cancer in Guangzhou. Compared with no screening, all screening scenarios led to incremental costs and QALYs. When the willingness-to-pay (WTP) threshold was USD37,653, three times the gross domestic product (GDP) per capita in China, six of nine strategies on the efficiency frontier may be cost-effective. Annual screening between 55 and 79 years of age for those who smoked more than 20 pack-years, which yielded an incremental cost-effectiveness ratio (ICER) of USD35,000.00 per QALY gained, was considered optimal. In sensitivity analyses, the result was stable in most cases. The trends of the results are roughly the same in scenario analyses. According to the WTP threshold of different regions, the optimal screening strategies were annual screening for those who smoked more than 20 pack-years, between 50 and 79 years of age in Zhejiang province, 55–79 years in Guangdong province and 65–74 years in Yunnan province. However, annual screening was unlikely to be cost-effective in Heilongjiang province under our modelling assumptions, indicating that tailored screening policies should be made regionally according to the local epidemiological and economic situation.
Ca2+ waves in cardiac myocytes can lead to arrhythmias owing to delayed after-depolarisations. Based on Ca2+ regulation from the junctional sarcoplasmic reticulum (JSR), a mathematical model was developed to investigate the interplay of clustered and rogue RyRs on Ca2+ waves. The model successfully reproduces Ca2+ waves in cardiac myocytes, which are in agreement with experimental results. A new wave propagation mode of “spark-diffusion-quark-spark” is put forward. It is found that rogue RyRs greatly increase the initiation of Ca2+ sparks, further contribute to the formation and propagation of Ca2+ waves when the free Ca2+ concentration in JSR lumen ([Ca2+]lumen) is higher than a threshold value of 0.7 mM. Computational results show an exponential increase in the velocity of Ca2+ waves with [Ca2+]lumen. In addition, more CRUs of rogue RyRs and Ca2+ release from rogue RyRs result in higher velocity and amplitude of Ca2+ waves. Distance between CRUs significantly affects the velocity of Ca2+ waves, but not the amplitude. This work could improve understanding the mechanism of Ca2+ waves in cardiac myocytes.