Impaired local Vitamin D3 metabolism contributes to IL-36g overproduction in epithelial cells in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Vitamin D (VD) possesses immunomodulatory properties, but its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains poorly studied. Herein, we aim to explore the regulation and function of VD3 in CRSwNP. METHODS: 25-hydroxyvitamin D3 (25VD3) levels in serum and tissue lysates were detected by ELISA. The expression of VD receptor (VDR) and cytochrome P450 family 27 subfamily B member 1 (CYP27B1), the enzyme that converts 25VD3 to the active 1,25-hydroxyvitamin D3 (1,25VD3), and their expression regulation in human nasal epithelial cells (HNECs) were studied by RT-PCR, western blotting, immunofluorescence, and flow cytometry. RNA sequencing was performed to identify genes regulated by 1,25VD3 in HNECs. HNECs and polyp tissue explants were treated with 1,25VD3, 25VD3, and dexamethasone. RESULTS: 25VD3 levels in serum and nasal tissue lysates were decreased in patients with eosinophilic and noneosinophilic CRSwNP than control subjects. The expression of VDR and CYP27B1 were reduced in eosinophilic and noneosinophilic CRSwNP, particularly in nasal epithelial cells. VDR and CYP27B1 expression in HNECs were downregulated by interferon y and poly (I:C). Polyp-derived epithelial cells demonstrated an impaired ability to convert 25VD3 to 1,25VD3 than control tissues. 1,25VD3 and 25VD3 suppressed IL-36y production in HNECs and polyp tissues, and the effect of 25VD3 was abolished by siCYP27B1 treatment. Tissue 25VD3 levels negatively correlated with IL-36y expression and neutrophilic inflammation in CRSwNP. CONCLUSION: Reduced systemic 25VD3 level, local 1,25VD3 generation and VDR expression result in impaired VD3 signaling activation in nasal epithelial cells, thereby exaggerating IL-36y production and neutrophilic inflammation in CRSwNP.

[Efficacy of arteriovenous argatroban versus heparin flush anticoagulation after cardiovascular surgery].

Objective: To compare the effects of arteriovenous argatroban and heparin flushes on platelet count and assess the occurrence of heparin-induced thrombocytopenia (HIT) and other complications in patients undergoing cardiovascular surgeries. Methods: A single-center, prospective randomized control study was conducted. Patients who underwent cardiovascular surgery at Fuwai Hospital, Chinese Academy of Medical Sciences from March to December 2019 were randomly divided into the argatroban group (250 ml normal saline plus 2.5 mg of argatroban) and the heparin group (250 ml normal saline plus 10 mg of heparin). Platelet count, hemorrhage, and thrombosis were assessed. The 4T scores of HIT, the incidences of HIT and other complications were also evaluated. Results: A total of 491 patients (307 males and 184 females) were included in the study, with a mean age of (52.3±13.7) years. There were 245 cases in the argatroban group and 246 cases in the heparin group, respectively. There was no statistically significant difference in the preoperative platelet count between the argatroban and heparin groups [198.0 (161.0, 248.0)×109/L vs 194.0 (157.2, 243.8)×109/L, P=0.498]. Likewise, there were no statistically significant differences in the platelet count between the argatroban and heparin groups at 12 h, 1 day, and 5 days after operation [127.0 (100.0, 154.0)×109/L vs 121.5 (90.2, 149.0)×109/L, 126.0 (97.0, 162.0)×109/L vs 123.5 (88.0, 151.0)×109/L, 168.0 (130.0, 215.0) ×109/L vs 161.0 (101.0, 210.5)×109/L] (repeated measures ANOVA between groups: F=3.327, P=0.069; time comparison: F=532.523, P<0.001; time interaction between groups: F=0.675, P=0.512). The proportion of 4T scores of medium and high scores (≥4)[9.8% (24/245) vs 10.6% (26/246), P=0.777] and incidence of HIT antibody positive [1.63% (4/245) vs 1.63% (4/246), P=0.726] were similar between argatroban group and the heparin group. Mechanical ventilation time was shorter in the argatroban group than that in the heparin group [13.0 (11.0, 21.0) vs 15.5 (12.0, 21.0) h, P=0.020]. Conclusion: Compared with heparin, routine management with argatroban for arteriovenous flush in patients undergoing cardiovascular surgery does not affect the HIT incidence.

Near-GeV Electron Beams at a Few Per-Mille Level from a Laser Wakefield Accelerator via Density-Tailored Plasma.

A simple, efficient scheme was developed to obtain near-gigaelectronvolt electron beams with energy spreads of few per-mille level in a single-stage laser wakefield accelerator. Longitudinal plasma density was tailored to control relativistic laser-beam evolution, resulting in injection, dechirping, and a quasi-phase-stable acceleration. With this scheme, electron beams with peak energies of 780-840 MeV, rms energy spreads of 2.4‰-4.1‰, charges of 8.5-23.6 pC, and rms divergences of 0.1-0.4 mrad were experimentally obtained. Quasi-three-dimensional particle-in-cell simulations agreed well with the experimental results. The dechirping strength was estimated to reach up to 11 TeV/mm/m, which is higher than previously obtained results. Such high-quality electron beams will boost the development of compact intense coherent radiation sources and x-ray free-electron lasers.

Nuclear receptor hormone receptor 39 is required for locust moulting by regulating the chitinase and carboxypeptidase genes.

The nuclear receptor-mediated 20-hydroxyecdysone (20E) signalling pathway plays crucial roles in insects by initiating and regulating moulting and metamorphosis. In the present study, we identified and characterized a cDNA encoding a putative nuclear receptor protein (Locusta migratoria hormone receptor 39, LmHR39) based on L. migratoria transcriptomics data. Reverse-transcription quantitative PCR (RT-qPCR) revealed that LmHR39 shows low-level expression in the early days of fifth-instar nymphs, and peak expression occurs on day 5, which is followed by a decrease before ecdysis. LmHR39 transcription could be induced by 20E in vivo and was significantly suppressed by knocking down the expression of the L. migratoria ecdysone receptor gene and early-late gene LmHR3. After RNA interference of LmHR39 with double-stranded RNA (dsRNA), 85% of the insects showed abnormal morphology, with curly wings after moulting and delayed eclosion time. Haematoxylin and eosin staining indicated that apolysis of the integument and wing pad cuticle in the dsLmHR39-treated insects was delayed compared to that in the dsRNA for green fluorescent protein-injected control. Furthermore, RNA-sequencing and RT-qPCR analysis showed the expression level of carboxypeptidase genes (Carboxypeptidase A (CPA) and Carboxypeptidase M (CPM)) and chitin degrading genes (LmChitinase5 (LmCHT5) and LmChitinase10 (LmCHT10)) dramatically declined in the dsLmHR39-treated insects, implying that the LmHR39-mediated 20E signalling pathway is involved in the regulation of carboxypeptidase genes (CPA and CPM) and chitinase genes (LmCHT5 and LmCHT10), and participated in apolysis of the integument and wing pads during locust moulting.

High-Brightness High-Energy Electron Beams from a Laser Wakefield Accelerator via Energy Chirp Control.

By designing a structured gas density profile between the dual-stage gas jets to manipulate electron seeding and energy chirp reversal for compressing the energy spread, we have experimentally produced high-brightness high-energy electron beams from a cascaded laser wakefield accelerator with peak energies in the range of 200-600 MeV, 0.4%-1.2% rms energy spread, 10-80 pC charge, and ∼0.2 mrad rms divergence. The maximum six-dimensional brightness B_{6D,n} is estimated as ∼6.5×10^{15} A/m^{2}/0.1%, which is very close to the typical brightness of e beams from state-of-the-art linac drivers. These high-brightness high-energy e beams may lead to the realization of compact monoenergetic gamma-ray and intense coherent x-ray radiation sources.

Prognostic value of epidermal growth factor receptor amplification and EGFRvIII in glioblastoma: meta-analysis.

OBJECTIVES: Epidermal growth factor receptor (EGFR) gene amplification and the EGFRvIII mutation may have prognostic value in patients with glioblastoma. This meta-analysis was to determine whether EGFR gene amplification or the EGFRvIII mutation are predictors of survival in patients with glioblastoma and anaplastic astrocytoma. MATERIALS AND METHODS: Medline, the Cochrane Central Register of Controlled Trials, EMBASE, and Google Scholar databases were searched until July 31, 2014. Studies were selected for inclusion in the analysis if they included patients with anaplastic astrocytoma and/or glioblastoma, EGFR and/or EGFRvIII mutation status was reported, and overall survival (OS) data were reported. RESULTS: Of 113 articles initially identified, only eight contained data with respect to the outcome of interest and were included in the meta-analysis. The number of cases ranged from 14 to 268, and the majority of patients were 60 or more years of age. There was no significant difference in OS between EGFR amplification-positive and EGFR amplification-negative glioblastoma patients (pooled hazard ratio [HR] = 1.101, 95% confidence interval [CI] 0.845, 1.434, P = 0.475) or anaplastic astrocytoma patients (pooled HR = 1.455, 95% CI 0.852, 2.482, P = 0.169). There was no significant difference in OS between EGFRvIII-positive and EGFRvIII-negative glioblastoma patients (pooled HR = 1.321, 95% CI: 0.881-1.981, P = 0.178). Significant heterogeneity existed between the studies, and the significance changed when the analysis was performed with studies removed in turn. CONCLUSIONS: There is insufficient evidence that either EGFR amplification or the EGFRvIII mutation has prognostic value in patients with glioblastoma.

[Effects of basic fibroblast growth factor on anoxia/reoxygenation injury of rat neonatal cardiomyocytes].

The effects of basic fibroblast growth factor (bFGF) on anoxia/reoxygenation (A/R) injury and protein kinase C (PKC) activity were studied on a model of A/R injury of neonatal rat cardiomyocytes to investigate the possibility of its using as a substrate for pharmacological preconditioning. The data indicated that bFGF improved the viability of cardiomyocytes, lowered the deplection of ATP and leakage of intracellular lactate dehydrogenase (LDH) in a concentration-dependent manner. PKC inhibitor, H7, completely abolished the protective effects. It was also found that bFGF directely activated PKC in cardiomyocytes in a time course similar to that in hypoxic preconditioning. The data suggested that the protective effect of bFGF on cardiomyocyte A/R injury might be mediated by PKC.

An experimental study by single blind method on the anti-obesity effect of Xiaopangmei.

To evaluate the anti-obesity effect of Xiaopangmei, an experimental study by single method in three groups of rats was done. The first group were fed with Xiaopangmei-01, the second group with a placebo, and the third group were controls. As compared with the control and the placebo groups, the rats that had been fed Xiaopangmei for six weeks showed body weight, food intake, weight of epididymis fat pad and the intestinal absorption of glucose all significantly decreased. The swimming tolerance test showed they swam longer than the other two groups. No significant difference was found between the three groups in the growth and development indices such as body length, length of femur and tibia, weight of heart, lungs, spleen, kidneys, stomach, small intestines, gastrocnemius muscle, and adrenal glands. No side effects were found on the liver and kidney. The secretion of insulin was inhibited after the swimming tolerance test and the gastrocnemius muscle test was similar for all three groups of rats. We concluded that Xiaopangmei is an effective anti-obesity drug.