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Background Infliximab was the first approved biologic treatment for moderate to severe Crohn's disease (MS-CD) in China. However, the cost-effectiveness of infliximab maintenance therapy (IMT) for MS-CD relative to conventional maintenance therapy remained unclarified. Aim To assess the cost-effectiveness of IMT for MS-CD in Chinese patients from the perspective of Chinese public insurance payer. Methods A cohort of MS-CD patients managed in a Chinese tertiary care hospital was created to compare IMT with conventional maintenance therapy (CMT) for clinical outcomes and direct medical costs over a 1-year observation time using conventional regression analyses. A decision-analytic model with the generated evidence was constructed to assess the cost-effectiveness of IMT relative to CMT using reimbursed medical costs. Results Based on the included 389 patients, IMT was associated with significantly higher disease remission chance [odds ratio: 4.060, P = 0.003], lower risk of developing new complications (odds ratio: 0.527, P = 0.010), higher utility value for quality of life (coefficient 0.822, P = 0.008), and lower total hospital costs related to disease management (coefficient -0.378, P = 0.008) than CMT. Base-case cost-effectiveness analysis estimated that IMT could cost Chinese health insurance payers ¥55260 to gain one quality-adjusted life year (QALY). The cost-effectiveness of IMT was mainly driven by the estimate of quality of life, treatment efficacy of maintenance therapy, mortality risk associated with active disease, and unit price of infliximab. The probability that IMT was cost-effective at a willingness-to-pay threshold of three times gross domestic product [2018 Chinese gross domestic product per capita (GDPPC)] was 86.4%. Conclusion IMT significantly improved real-world health outcomes and cost the Chinese public health insurance payers less than one GDPPC to gain one QALY in Chinese MS-CD patients.

Orexin is a peptide neurotransmitter released in the globus pallidus. Morphological evidence reveals that both orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) exist in the globus pallidus. Here we showed that bilateral microinjection of both orexin-A and orexin-B into the globus pallidus alleviated motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mice. Further in vivo extracellular single-unit recording revealed that the basal spontaneous firing rate of the globus pallidus neurons in MPTP parkinsonian mice was slower than that of normal mice. Application of orexin-A or orexin-B significantly increased the spontaneous firing rate of pallidal neurons. The influx of Ca2+ through the L-type Ca2+ channel is the major mechanism involved in orexin-induced excitation in the globus pallidus. Orexin-A-induced increase in firing rate of pallidal neurons in MPTP parkinsonian mice was stronger than that of normal mice. Orexin-A exerted both electrophysiological and behavioral effects mainly via OX1R, and orexin-B exerted the effects via OX2R. Endogenous orexins modulated the excitability of globus pallidus neurons mainly through OX1R. The present behavioral and electrophysiological results suggest that orexins ameliorate parkinsonian motor deficits through increasing the spontaneous firing of globus pallidus neurons.

Alpinia officinarum Hance, a perennial natural medicine-food herb, has been traditionally used to treat colds, stomachache, and diabetes for thousands of years. 1,7-Diphenyl-4E-en-3-heptanone (DPH5), a diarylheptanoid isolated from the rhizome of A. officinarum has been reported to be safe and to have antioxidant and hypoglycemic effects, suggesting its potential in the treatment of insulin resistance (IR).Aim of to investigate the protective effect of DPH5 on IR and elucidate its underlying mechanism of action.HepG2 cells were used as the research objects. Glucose uptake and reactive oxygen species (ROS) levels in high glucose-induced insulin-resistant HepG2 cells were assessed using flow cytometry. Glucose consumption and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed using the corresponding assay kits. The expression of mRNA and proteins related to insulin signaling, glucose metabolism, and antioxidant factor, including insulin receptor substrate-1 (IRS1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), translocation of glucose transporter-4, glycogen synthase kinase-3β (GSK3β), glucokinase (GCK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH quinoneoxidoreductase (NQO1), and glutathione peroxidase (GSH-Px) was determined using real-time quantitative polymerase chain reaction and western blotting. Furthermore, molecular docking was performed to determine the spatial mechanism of DPH5 on the key targets PI3K, AKT, Nrf2, and GSK3β.DPH5 could improve IR that manifested as increased glucose uptake and glucose consumption in insulin-resistant HepG2 cells. Moreover, DPH5 could enhance antioxidant capacity by activating Nrf2/HO-1 elements, including increasing Nrf2, HO-1, SOD, NQO1, and GSH-Px expression and reducing MDA, ROS, and JNK levels, thereby improving oxidative stress and ultimately alleviating IR. Additionally, DPH5 could promote the expression of IRS1, PI3K, AKT, GSK3β, GCK, and PK, and downregulate the expression of PEPCK and G6pase, thereby accelerating glucose utilization and enhancing insulin sensitivity. The mechanism underlying the effect of DPH5 in alleviating IR was related to the PI3K/AKT- and Nrf2/HO-1-mediated regulation of the GSK3β signaling pathway, and the results were further confirmed using the specific inhibitors LY294002 and ML385. Results from molecular docking indicated that there were different regulatory sites and interacting forces between DPH5 and PI3K, AKT, Nrf2, and GSK3β; however, the binding force was relatively strong.DPH5 improved oxidative stress and glucose metabolism via modulating the PI3K/AKT-Nrf2-GSK3β pathway, thereby ameliorating IR. Overall, our findings suggest the potential of DPH5 as a natural medicine to treat type-2 diabetes mellitus.

In order to improve the high temperature oxidation resistance of exhaust pipes, the nanocomposite coatings are carried out on the surface of exhaust pipe by electrodeposition technology, and the microstructure and oxidation behavior of the nanocomposite coatings are investigated experimentally. This paper mainly focuses on the experimental work to determine the structural characteristics and oxidation resistance of nanocomposite coatings in presence of Al2O3 and cerium oxide CeO2. The results show that the amount of the Al2O3-CeO2 has significant influence on the structural properties of nanocomposite coatings. The surface of coating becomes more compact and smooth with the increase of the amount of the Al2O3 and CeO2. Furthermore, the anti-oxidation performance of the nanocomposite coatings formed with Al2O3 and CeO2 were both better than those of the composite coatings formed without Al2O3 and CeO2.

In order to improve the corrosion resistance of shock absorber for ships, the alumina ceramic coatings are carried out on the surface of aluminum alloy shock absorber by micro arc oxidation (MAO) technology. The microstructure and anti-corrosion performance of the MAO coatings were investigated experimentally. This paper mainly focuses on the experimental work to determine the effect of current density on the structural characteristics and corrosion resistance of MAO coatings. The results show that the current density has a significant influence on the preparation of MAO coating during the process. The surface of the coating becomes more compact and smooth with the cathode voltage of 7 A.dm-2. Furthermore, the anti-corrosion performance of the MAO coatings can effectively be improved at the current density of 7 A.dm-2.

To assess the cost-effectiveness of reimbursing infliximab for moderate-to-severe Crohn’s disease (MS-CD) in China from the perspective of public insurance payers. A decision-analytic model with a lifetime time horizon was constructed to simulate the disease progression and direct medical costs in Chinese MS-CD patients under two scenarios: reimbursing infliximab vs. not reimbursing infliximab. A cross-sectional study and literature review were conducted to estimate model variables. The constructed decision-analytic model ran the base case, one-way sensitivity, and probabilistic sensitivity analyses (PSA) to assess the cost-effectiveness of reimbursing infliximab using reimbursed medical costs. Base case analysis discounting health benefits and costs estimated that reimbursing infliximab could increase overall survival by 0.604 years, increase total quality-adjusted life years (QALY) by 0.697 QALY, reduce absolute lifetime surgery risk by 13.1%, and increase reimbursed costs by ¥29,409. The incremental cost-effectiveness ratio per gained additional QALY (ICER) based on discounted health benefits and reimbursed medical costs (3% per year) was ¥42,198. The one-way sensitivity analyses identified that the cost-effectiveness of reimbursing infliximab for MS-CD was mainly driven by the treatment efficacies of maintenance therapy, quality of life, and unit price of infliximab. PSA estimated that reimbursing infliximab was associated with a 63.8% chance to be cost-effective under the willingness-to-pay of the 2018 Chinese gross domestic product per capita (GDPPC). Reimbursing infliximab for MS-CD in Chinese patients was highly attractive, costing Chinese public insurance payers less than the 2018 Chinese GDPPC to gain 1 QALY.

The amygdala is a complex structure involved in the regulation of emotional behaviors including fear and anxiety. The central amygdala is the main output of the amygdala and plays an important role in emotional processing. Recent studies indicate that orexin, a kind of neuropeptides responsible for maintaining wakefulness, is also associated with emotion-related behaviors, such as depression- and anxiety-like behaviors. Central amygdala receives orexinergic fibers originating from the lateral hypothalamus and expresses OX1 receptors in rats. To test the electrophysiological and behavioral effects of orexins in the central amygdala, single unit in vivo extracellular recordings, open field and elevated plus maze tests were performed in rats. Micro-pressure administration of orexin-A (0.01 mmol/L) increased the firing rate in 18 out of the 31 central amygdala neurons, while the other 13 neurons were not excited by orexin-A. The excitatory effects of orexin-A on central amygdala neurons were mainly mediated by OX1 receptors rather than OX2 receptors. Orexin-B (0.01 mmol/L) did not change the firing activity in all recorded central amygdala neurons. Selectively blocking OX1 receptors by SB-334867 (0.01 mmol/L) significantly decreased the spontaneous firing rate in 14 out of the 33 central amygdala neurons, leaving the remaining 19 neurons were not affected. However, blocking OX2 receptors by TCS-OX2–29 (0.01 mmol/L) did not change the firing activity. Finally, both open field test and elevated plus maze test showed that bilateral microinjection of orexin-A into the central amygdala induced significantly anxiolytic-like behaviors. The specific OX1 receptor antagonist tended to produce opposite effects although there was no statistical difference. The present electrophysiological and behavioral studies suggested that orexin-A participates in anxiety-like behaviors by modulating the spontaneous firing activity of central amygdala neurons.