Nano-designed carbon monoxide donor SMA/CORM2 exhibits protective effect against acetaminophen induced liver injury through macrophage reprograming and promoting liver regeneration.

Acetaminophen (APAP) induced liver injury is the most common drug-induced liver injury, accounting for the top cause of acute liver failure in the United State, however the therapeutic options for it is very limited. Excess generation of reactive oxygen species (ROS) and the subsequent inflammatory responses are the major factors of the liver injury. Carbon monoxide (CO) is an important gaseous molecule with versatile functions including anti-oxidation and anti-inflammation, and we previous reported the therapeutic potential of a nano-designed CO donor SMA/CORM2 in a dextran sulphate sodium (DSS) induced mouse colitis model. In this context, we investigated the effect of SMA/CORM2 in an APAP-induced mouse acute liver injury model and tackled the mechanisms involved. We found upregulation of heme oxygenase-1 (HO-1, endogenous CO generating enzyme) and the dynamic changes of macrophage polarization (pro-inflammatory M1/anti-inflammatory M2), which played important roles in the process of live injury. SMA/CORM2 treatment remarkably increased the CO levels in the liver and circulation, by which oxidative stresses in the liver were significantly reduced, and more importantly, it remarkably suppressed the expression of M1 macrophages but alternatively increased M2 polarization. Consequently the liver injury was significantly ameliorated, and the proliferation and regeneration were greatly promoted through the Pi3k/Akt/mTOR signaling pathway. The shift of macrophage polarization accompanied with the downregulated hypoxia-inducible factor-1α (HIF-1α) level. These findings suggested CO released from SMA/CORM2 manipulated the macrophage reprogramming toward M2 phenotype by inhibiting HIF-1α, which subsequently protected liver against inflammatory injury and benefited tissue repair. Moreover, compared to native CORM2, SMA/CORM2 exhibited superior bioavailability and protective effect. We thus anticipate the application of SMA/CORM2 as a therapeutic regimen for APAP induced liver injury as well as other inflammatory diseases and disorders.

Cost-effectiveness of the Da Qing diabetes prevention program: A modelling study.

OBJECTIVE: The Da Qing Diabetes Prevention program (DQDP) was a randomized lifestyle modification intervention conducted in 1986 for the prevention and control of type 2 diabetes in individuals with impaired glucose tolerance. The current study estimated long-term cost-effectiveness of the program based on the health utilities from the Chinese population. METHODS: A Markov Monte Carlo model was developed to estimate the impact of the intervention from the healthcare system perspective. The analysis was run over 30-year and lifetime periods and costs were estimated respectively as health management service costs. Baseline characteristics and intervention effects were assessed from the DQDP. Utilities and costs were generated from relevant literature. The outcome measures were program cost per quality-adjusted life-years (QALYs) gained and incremental cost-effectiveness ratio (ICER) of the intervention. Sensitivity analyses and threshold analyses were performed. RESULTS: Using a 30-year horizon, the intervention strategy was cost-saving and was associated with better health outcomes (increase of 0.74 QALYs per intervention participant). Using a lifetime horizon, the intervention strategy was cost-saving and was associated with additional 1.44 QALYs. Sensitivity analyses showed that the overall ICER was most strongly influenced by the hazard ratio of cardiovascular disease event. CONCLUSIONS: The Da Qing lifestyle intervention in a Chinese population with impaired glucose tolerance is likely to translate into substantial economic value. It is cost-saving over a 30-year time and lifetime frame.

Physical Disorders are Associated with Health Risk Behaviors in Chinese Adolescents: A Latent Class Analysis.

It is known that health risk behaviors (HRBs) can lead to a variety of physical and mental health problems among adolescents, but few studies have paid attention to the relationship between latent classes of HRBs and adolescent diseases. The purpose of this study was to use latent class analysis (LCA) to clarify the potential subgroups of HRBs (smoking, drinking, screen time, non-suicidal self-injuries, suicidal behaviors, and unintentional injuries) and examine the association between the subgroups of HRBs and physical disorders (diarrhea, fever, cough, and vomiting) with multiple logistic regression analysis, in Chinese adolescents. Self-reported HRBs and physical disorders were used to evaluate 22,628 middle school students in six cities of China, from November 2015 to January 2016, based on a multistage stratified cluster sampling approach. The prevalence of diarrhea, fever, cough, and vomiting was 23.5%, 15.9%, 50.6%, and 10.7%, respectively. We identified four latent classes of HRBs by LCA, including low-risk class, moderate-risk class 1 (smoking, drinking, and screen time), moderate-risk class 2 (non-suicidal self-injuries and suicidal behaviors, unintentional injuries), and high-risk class (smoking, drinking, screen time, non-suicidal self-injuries, suicidal behaviors, and unintentional injuries), which were 64.0%, 4.5%, 28.8% and 2.7% of participants, respectively. Compared to the low-risk class, all other classes showed higher risk for these physical disorders (P < 0.01 for each). In particular, the high-risk class had the highest risk (diarrhea (odds ratio (OR) = 2.628, 95% confidence interval (CI) 2.219 to 3.113), fever (OR = 3.103, 95% CI 2.591 to 3.717), cough (OR = 2.142, 95% CI 1.805 to 2.541), and vomiting (OR = 3.738, 95% CI 3.081 to 4.536). In conclusion, these results indicated that heterogeneity exists in HRBs, and subgroups of HRBs were correlated to the occurrence of common physical disorders in Chinese adolescents. Therefore, multiple HRBs rather than single factors should be considered for the prevention of common physical disorders in schools.