BackgroundPoor medication adherence can have negative consequences for the patients, the provider, the physician, and the sustainability of the healthcare system. To our knowledge, the association between medication adherence and glycemic control among newly diagnosed diabetes patients has not been studied. This study aims to bridge the gap.MethodThis is a retrospective cohort study of 2463 patients managed in the National Healthcare Group in Singapore with newly diagnosed diabetes. Patients were followed up for the first two years from their first medication dispensed for measuring medication adherence, proportion of days covered (PDC); and for another three years for investigating outcomes of glycemic control, emergency department visit, and hospitalization. Multivariable regressions were performed to study the association between medication adherence and the outcomes as well as the risk factors of poor adherence.ResultsThe prevalence of medication adherence (PDC≥80%) was 65.0% (95% CI 63.1% to 66.9%) among newly diagnosed diabetes patients in Singapore. Male, Indian, or patients without hypertension or dyslipidemia were associated with poorer medication adherence. The HbA1c level of poor adherent patients (PDC <40%) increased by 0.4 (95% CI 0.2 to 0.5) over the two years, and they were also more likely to have hospitalization (OR 2.6,95% CI 1.7 to 3.8) or emergency department visit (OR 2.4,95% CI 1.7 to 3.4) compared with the fully adherent patients (PDC=100%).ConclusionsThe medication adherence in the early stage of diabetes is important for maximizing the effectiveness of pharmaceutical therapy. Health policies or interventions targeting the improvement of medication adherence among newly diagnosed diabetes patients are in need.

BackgroundHeme oxygenase-1 (HO-1) is an inducible defense gene which plays a significant role in inflammation. HO-1 protects cells and tissues through the mechanism of anti-oxidation, maintaining microcirculation and anti-inflammation. The aim of the current study is to investigate the role of HO-1 on systemic inflammatory response in severe acute pancreatitis (SAP).MethodsForty male Sprague-Dawley (SD) rats were randomly assigned into four groups: control group (n = 10); SAP group (n = 10), SAP model was induced by retrograde injection of 3% sodium taurocholate through pancreatic duct; HO-1 stimulation group (n = 10), SD rats were injected 75 μg/kg hemin intraperitoneally 30 min after induction of SAP; HO-1 inhibition group (n = 10), SD rats were injected 20 μg/kg Zinc porphyrin (Zn-PP) intraperitoneally 30 min after induction of SAP. After 24 h of SAP establishment, tissues were collected for HO-1, tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) mRNA expression, and blood samples were collected for cytokines and biochemical measurements. Meanwhile, the histopathological changes of pancreas and liver tissues were observed.ResultsThe expression of HO-1 mRNA and protein were significantly induced by SAP in rat pancreas and liver. Hemin treatment significantly decreased oxidative stress and TNF-α in plasma and tissues, while the IL-10 was significantly increased. Pancreas and liver injury induced by SAP was markedly attenuated by Hemin treatment. Moreover, inhibition of HO-1 expression by Zn-PP administration aggravated the injury caused by SAP.ConclusionsInduction of HO-1 in early SAP may modulate systemic inflammatory response and prevent pancreas and nearby organs such as liver injury through inhibition of TNF-α and augmentation of IL-10.

Background: Pyroptosis is closely relevant to sepsis. However, the molecular mechanisms of pyroptosis in pneumonia-induced sepsis are still not fully understood. Thus, this study aimed to find the specific molecular pathways associated with pyroptosis and explore their relationship in pneumonia-induced sepsis.Methods: First, significant signaling pathways related to pneumonia-induced sepsis were screened by bioinformatics analysis based on GSE48080. The peripheral blood samples from patients with pneumoniainduced sepsis and healthy subjects were collected. Pneumonia-induced sepsis rat models were also established. Then, inflammatory response, pyroptosis, and regulatory T cells (Tregs)/T-helper 17 (Th17), Th1/Th2, and M1/M2 cell ratios in pneumonia-induced sepsis were evaluated.Results: IL-17 signaling pathway was significantly related to pneumonia-induced sepsis by bioinformatics analysis. Compared with healthy groups, the higher of Th17/Treg, Th1/Th2 and M1/M2 cell radios in the patients and sepsis rat model indicated that pneumonia-induced sepsis caused a severe inflammatory response. This result was confirmed by higher levels of pro-inflammatory factors (IL-6, TNF-α, IL-1β, and IL-18) and an inflammation indicator (LDH), as well as pyroptosis occurrence in sepsis. Additionally, the up-regulation of key molecules (HMGB1, RAGE, IL-17A, TRAF6 and NK-κB) in the IL-17 signaling pathway suggested the IL-17 pathway was activated. Moreover, the release of IL-1β and IL-18 and the levels of the molecules (NLRP3, NLRC4, Cleaved caspase-1, and Cleaved GSDMD) associated with caspase-1dependent pyroptosis were up-regulated in pneumonia-induced sepsis.Conclusions: As NK-κB activation can promote the development of caspase-1-dependent pyroptosis, these findings suggested that the activation of the IL-17 signaling pathway could promote pyroptosis in pneumonia-induced sepsis.

Background Atopic dermatitis (AD) presents with the wide spectrum of clinical phenotypes within and between various populations. Recent study showed low frequency of filaggrin loss-of-function (FLG LOF) mutations in Croatian AD patients. At present, there are no data on biomarkers of immune response in Croatian AD patients that might be useful in the selection and monitoring of novel immune therapies. Objectives To investigate levels of cytokines of various signature in the stratum corneum (SC) collected from lesional and non-lesional skin of AD patients and healthy controls and to evaluate their relationship with the severity of disease and skin barrier function.Methods SC samples were collected from 100 adult patients with moderate-to-severe AD and 50 healthy controls. The levels of 21 cytokines were measured by multiplex immunoassay. We conducted machine learning analysis to assess whether a small number of cytokine measurements can discriminate between healthy controls and AD patients and can predict AD severity (SCORAD). ResultsThe SC levels of thirteen cytokines representing innate immunity, Th-1, Th-2 and Th-17/22 immune response showed significant differences between healthy and AD skin. Our analysis demonstrated that as few as three cytokines measured in lesional skin can discriminate healthy controls and AD with an accuracy of 99% and that the predictive models for SCORAD did not achieve a high accuracy. Cytokine levels were highly correlated with the levels of filaggrin degradation products and skin barrier function.Conclusions Stratum corneum analysis revealed aberrant levels of cytokines representing innate immunity, Th-1-, Th-2-and Th-17/22-mediated immune response in Croatian AD patients. Increased Th-2 cytokines and their strong association with natural moisturizing factor (NMF) can explain low NMF levels despite of low frequency of FLG LOF mutations in Croatian population. Predictive models for SCORAD identified cytokines associated with SCORAD but warrants further investigation.

A19 fusion protein was highly expressed. The specific anti-A19 antiserum was prepared successfully.

The development of AD-like ocular pathologies in this model supports the idea that in humans, AD-associated disease of the eye may be driven by Th2-mediated inflammation and demonstrates that the Stat6VT mouse may be a useful system in which to further investigate pathogenesis of and treatment strategies for blepharitis and other ocular diseases that develop in association with AD.

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Severe pneumonia with sepsis is characterized by a dysregulated inflammatory response of endotoxin. In our study, we attempted to investigate the roles of the immune guardian cells (monocytes) in the immune-inflammatory response of severe pneumonia-induced sepsis. We performed analysis in the blood samples of human and animals with ELISA, western blot, flow cytometry (FCM) methods, etc. Results showed that the proinflammatory status shifted to hypoinflammatory phases during the sepsis process. In a clinical study, the levels of IL-1β, IL-6, TNF-α, etc., except for IL-10, were inhibited in the late phase of sepsis, while, in an animal study, the immune suppression status was attenuated with administration of the adenovirus Ade-HIF-1α. Conversely, the amount of IL-10 was lower in the adenovirus Ade-HIF-1α group compared with the sepsis model group and the Ade-control group. Moreover, in the clinical study, the programmed cell death-ligand 1 (PD-L1) was overexpressed in monocytes in the late phase of sepsis, while the expression of proteins HIF-1α and STAT3 was decreased in the late phase of sepsis. However, in the animal study, we found that the HIF-1α factor facilitated the inflammatory response. The expression of the proteins HIF-1α and STAT3 was increased, and the PD-L1 protein was decreased with the adenovirus Ade-HIF-1α administration compared with the rats without Ade-HIF-1α injection and with the Ade-control injection. Additionally, the proteins HIF-1α and STAT3 were coregulated at transcriptional levels during the inflammatory responses of sepsis. Taken together, monocytes undergo reprogramming to generate immunosuppression through the HIF-1α signaling pathway in the late phase of sepsis.