Cost-effectiveness of mepolizumab for severe eosinophilic asthma in China.

OBJECTIVE: To evaluate the economic value of mepolizumab as an add-on therapy to the standard of care (SoC) for patients with severe eosinophilic asthma in China. METHODS: A Markov model with three health conditions was constructed to calculate the incremental cost per quality-adjusted life year (QALY) in mepolizumab with SoC and SoC only groups from the perspective of the Chinese healthcare system throughout an entire lifespan. The model was populated with local costs, while efficacy parameters were obtained from the global Phase III MENSA trial and mortality was derived from two surveys. One-way and probabilistic sensitivity analyses were conducted. Additional scenario analysis was used to estimate the cost-effectiveness impact of changes in the price of mepolizumab. RESULTS: Over the lifetime treatment horizon, the incremental cost-effectiveness ratio (ICER) of mepolizumab plus SoC compared to SoC alone was $170 648.73 per QALY. Sensitivity analyses focused on these results. Scenario analysis showed that mepolizumab would require a price reduction of at least 82% to reach the current willingness-to-pay (WTP=$38 223.34/QALY) threshold. CONCLUSION: Mepolizumab is not a cost-effective healthcare resource in China at its current pricing.

Sodium tanshinone IIA sulphate inhibits angiogenesis in lung adenocarcinoma via mediation of miR-874/eEF-2K/TG2 axis.

CONTEXT: Sodium tanshinone IIA sulphate (STS) is a product originated from Salvia miltiorrhiza Bunge [Lamiaceae], which exerts an antitumour effect. However, the role of STS on lung adenocarcinoma (LUAD) remains unexplored. OBJECTIVE: Our study explores the effect and mechanism of STS against LUAD. MATERIALS AND METHODS: LUAD cells were treated with 100 µM STS for 24 h and control group cells were cultured under normal medium conditions. Functionally, the viability, migration, invasion and angiogenesis of LUAD cells were examined by MTT, wound healing, transwell and tube formation assay, respectively. Moreover, cells were transvected with different transfection plasmids. Dual luciferase reporter and RNA immunoprecipitation (RIP) assays were used to verify the relationship between miR-874 and eEF-2K. RESULTS: STS significantly decreased the viability (40-50% reduction), migration (migration rate of A549 cells from 0.67 to 0.28, H1299 cells from 0.71 to 0.41), invasion (invasion numbers of A549 cells from 172 to 55, H1299 cells from 188 to 35) and angiogenesis (80-90% reduction) of LUAD cells. Downregulation of miR-874 partially abolished the antitumour effect of STS. EEF-2K was identified to be the target of miR-874, and its downregulation markedly abolished the effects of miR-874 downregulation on tumourigenesis of LUAD. Moreover, silencing of TG2 abrogated eEF-2K-induced progression of LUAD. DISCUSSION AND CONCLUSIONS: STS attenuated the tumourigenesis of LUAD through the mediation of the miR-874/eEF-2K/TG2 axis. STS is a promising drug to fight against lung cancer, which might effectively reverse drug resistance when combined with classical anticancer drugs.

Spectral assemblage using light emitting diodes to obtain specified lighting characteristics.

Light emitting diodes (LEDs) are considered next-generation light sources. Because of their narrow emission spectrum, easy adjustment, and various other characteristics, LEDs can be used in many situations, especially those that require dimming or spectral assemblage. In this paper we discuss spectral assemblage with LEDs. We cover possible valid arrangements in a spectrum from 400 to 700 nm by an exhaustive and genetic algorithm, calculate the highest luminous efficacy of a source for each correlated color temperature and color-rendering index, and present the corresponding energy distribution.

STS â ¡A inhibited angiogenesis of lung adenocarcinoma by activating FOXO3 to inhibit CXCL1/STAT3/VEGF pathway.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most popular type of lung cancer. Sulfotanshinone IIA sodium (STS IIA) has been proven to have an anticancer effect. However, its role in LUAD and its underlying mechanism remain unclear. OBJECTIVE: To investigate the role and mechanism of STS IIA in LUAD angiogenesis. METHODS: The mRNA levels of genes, including forkhead box O3 (FOXO3) and chemokine C-X-C motif ligand 1 (CXCL1), were detected by qRT-PCR. The levels of proteins, including FOXO3, CXCL1, and vascular endothelial growth factor (VEGF), were measured by Western blot. The proliferation and angiogenesis of human umbilical vein endothelial cells (HUVECs) were detected by the EdU assay and the tubule formation assay, respectively. The binding relationship between FOXO3 and CXCL1 was detected by dual-luciferase reporter assay. RESULTS: Our results illustrated that different concentrations of STS IIA inhibited the proliferation and angiogenesis of HUVECs. FOXO3 regulated the proliferation and angiogenesis of HUVECs inhibited by STS ⅡA via targeting CXCL1. Subsequently, we proved that exogenous CXCL1 alleviated the inhibition of proliferation and angiogenesis of HUVECs regulated by STS IIA via activating the STAT3/VEGF pathway. Finally, we found that STS IIA inhibited the angiogenesis of lung adenocarcinoma though FOXO3 to inhibit the CXCL1/STAT3/VEGF pathway. CONCLUSION: Our study finally elucidated the underlying molecular mechanism by which STS ⅡA inhibits LUAD angiogenesis.

Morphometric analysis of the YESS and TESSYS techniques of percutaneous transforaminal endoscopic lumbar discectomy.

Posterior lateral endoscopic nucleotomy is widely accepted as a minimally invasive surgery for lumbar disc herniation, but few studies have compared the transforaminal approach using two different techniques, YESS and TESSYS. One hundred and fifty lumbar IVFs of cadaveric spines were studied. Eighteen-gauge needles were inserted percutaneously toward IVFs into the discs by either YESS or TESSYS. The distances from the needle to the nerve root and from the needle to the spinal dura were measured and compared across different spinal segments. The incidence of nerve roots compression by the operating endoscope was measured. The mean distances from needle to the nerve root and spinal dura in YESS were 3.5 ± 1.4 mm and 6.6 ± 1.9 mm. The respective mean distances in TESSYS were 4.6 ± 1.5 mm and 5.9 ± 1.4 mm. The distance from needle to the nerve root was longer in TESSYS, while the distance from the needle to spinal dura was longer in YESS. The distance from needle to nerve was shorter in proximal segments. The incidence of operating endoscope compression of the nerve root was high in both of techniques. The difference in theory and design between YESS and TESSYS, "intradisc" versus "intracanal", was confirmed by comparison of anatomic distances from the needle to the nerve. Puncture of the annulus in the distal lumbar is safer than proximal puncture. The high incidence of endoscope compression of the nerve root may be related with the transient postoperative dysaesthesia.

Electrochemical sensor based on a three dimensional nanostructured MoS2 nanosphere-PANI/reduced graphene oxide composite for simultaneous detection of ascorbic acid, dopamine, and uric acid.

A three dimensional (3D) nanostructured composite based on the self-assembly of MoS2 nanospheres and polyaniline (PANI) loaded on reduced graphene oxide (denoted by 3D MoS2-PANI/rGO) was prepared via a feasible one-pot hydrothermal process. The 3D MoS2-PANI/rGO nanocomposite not only exhibits good functionality and bioaffinity but also displays high electrochemical catalytic activity. As such, the developed 3D MoS2-PANI/rGO nanocomposite can be employed as the sensing platform for simultaneously detecting small biomolecules, i.e., ascorbic acid (AA), dopamine (DA), and uric acid (UA). The peak currents obtained from the differential pulse voltammetry (DPV) measurements depended linearly on the concentrations in the wide range from 50 µM to 8.0 mM, 5.0 to 500 µM, and 1.0 to 500 µM, giving low detection limits of 22.20, 0.70, and 0.36 µM for AA, DA, and UA, respectively. Furthermore, the 3D MoS2-PANI/rGO-based electrochemical sensor also exhibited high selectivity, good reproducibility and stability toward small molecule detection. The present sensing strategy based on 3D MoS2-PANI/rGO suggests a good reliability in the trace determination of electroactive biomolecules.

Novel Peptidomimetics for Inhibition of HER2:HER3 Heterodimerization in HER2-Positive Breast Cancer.

The current approach to treating HER2-overexpressed breast cancer is the use of monoclonal antibodies or a combination of antibodies with traditional chemotherapeutic agents or kinase inhibitors. Our approach is to target clinically validated HER2 domain IV with peptidomimetics and inhibit the protein-protein interactions (PPI) of HERs. Unlike antibodies, peptidomimetics have advantages in terms of stability, modification, and molecular size. We have designed peptidomimetics (compounds 5 and 9) that bind to HER2 domain IV, inhibit protein-protein interactions, and decrease cell viability in breast cancer cells with HER2 overexpression. We have shown, using enzyme fragment complementation and proximity ligation assays, that peptidomimetics inhibit the PPI of HER2:HER3. Compounds 5 and 9 suppressed the tumor growth in a xenograft mouse model. Furthermore, we have shown that these compounds inhibit PPI of HER2:HER3 and phosphorylation of HER2 as compared to control in tissue samples derived from in vivo studies. The stability of the compounds was also investigated in mouse serum, and the compounds exhibited stability with a half-life of up to 3 h. These results suggest that the novel peptidomimetics we have developed target the extracellular domain of HER2 protein and inhibit HER2:HER3 interaction, providing a novel method to treat HER2-positive cancer.