Search

Several studies have investigated the use of simple in vitro tests for the assessment of rabies antibody titers in serum samples from vaccinated human subjects, which would allow the effectiveness of rabies vaccination to be conveniently evaluated. To this end, a novel time-resolved fluoroimmunoassay (TRFIA) for the assessment of rabies antibody titers was established in this study for evaluating the effectiveness of protection against rabies. The TRFIA had a satisfactory limit of detection value (0.035 IU/mL) under optimal conditions. Additionally, the application of the TRFIA was demonstrated in 68 serum samples with satisfactory results. The coefficient variations (CVs) were all

Background: Factor Xa (FXa) is a mediator initiating and accelerating atherosclerosis (AS). Both macrophage and vascular smooth muscle cells (VSMCs) participate in AS progression. This study was aimed to investigate the mechanisms underlying the effects of the FXa inhibitor rivaroxaban on AS.Methods: Rivaroxaban was administered to AS mice. Primary macrophages were exposed to FXa, treated with rivaroxaban, and transfected with siRNA silencing protease-activated receptor 2 (PAR2), hypoxia-inducible factor 1α (HIF1α), delta-like receptor 4 (Dll4), and Akt. Interaction between macrophages and VSMCs was assessed by co-culturing systems. Atherosclerotic lesions were evaluated by oil red O stain. Fluorescent staining was used to determine the cell phenotypes. Secretions of inflammatory cytokines and collagen were assessed by ELISA and Sircol assays. Western blotting was used to evaluate the protein expression and phosphorylation levels.Results: Rivaroxaban reduced lesion area, accumulation of M1 macrophages, and contractile-synthetic phenotypic conversion of VSMCs in atherosclerotic plaques. FXa exposure induced polarization of macrophages toward M1 and Dll4 high expression, which were inhibited by PAR2, Akt1, and HIF1α silencing. Rivaroxaban treatment inhibited PAR2/Akt/HIF1α signaling activation and Dll4 expression in FXa-exposed macrophages. By cell-to-cell contact, M1 macrophages induced Notch signaling activation in VSMCs which committed contractile-synthetic conversion. Rivaroxaban treatment and Dll4 silencing incapacitated macrophage in inducing phenotypic conversion of VSMCs upon cell-to-cell contact.Conclusion: Rivaroxaban suppresses AS by inhibiting FXa-induced PAR2/Akt/HIF1α signaling activation-mediated macrophage M1 polarization and high Dll4 expression. These macrophages facilitated VSMCs to perform contractile-synthetic phenotypic conversion upon macrophage-VSMCs cell-to-cell contact.

Currently, quality control of glycoprotein in the human rabies vaccine is based on enzyme-linked immunosorbent assay (ELISA). However, ELISA does not match the needs of a modernised quality control system. For a long time, human rabies virus vaccine manufacturers have been devoted to seeking a detection platform that is sensitive, accurate, automatic, and feasible for practical applications. Therefore, our team invested major efforts into establishing a fully automated micromagnetic particle (MMP)-based chemiluminescence immunoassay (CLIA) platform. For vaccine quality control, MMP-coupled rabies virus glycoprotein monoclonal antibodies (S037) were used to capture the rabies virus. Another rabies virus glycoprotein antibody (S053) labelled with acridinium ester was added as a signal tracer. After pretreating the vaccine sample, the entire analysis was performed using a fully automated machine, which had a limited detection time (only 30 min) and eliminated manual error. Multiple experiments have identified the optimal conditions allowing valid and reliable assessment of vaccine potency. The CLIA platform has exhibited merits in terms of speed, robustness, high sensitivity (with a minimum detection value of 0.45 mIU/mL), considerable accuracy, and a wide linear range of detection (9.4-1200 mIU/mL). Furthermore, the results showed that the CLIA platform is consistent with the National Institutes of Health test and time-resolved fluorescent immunoassay (TRFIA) in quantitative analysis, and had a better analytic performance than TRFIA. Therefore, the CLIA platform presented here may be important for application in modern vaccine quality control.

Background: This study is intended to explore the confounding factors associated with posttraumatic stress disorder (PTSD) in Chinese Han population with acute myocardial infarction (MI).Methods: 300 acute MI patients were enrolled in this study, the demographic data, complicating diseases, medication, and perioperative procedures were documented. The PTSD was evaluated using the PTSD checklist-civilian version (PCL-C) scale one month after the occurrence of MI. Results: 97 (32.3%) patients were diagnosed as PTSD after finishing the PCL-C scale. The intra-aortic balloon pump (IABP) implantation and use of diuretic in PTSD patients with acute MI were significantly higher than those in non-PTSD patients with acute MI. The age, body mass index (BMI), heart rate, number of stents, urea nitrogen, white blood cells counts, creatine kinase-MB, myoglobin, troponin I, brain natriuretic peptide (BNP), total cholesterol, triglyceride, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, apolipoprotein A and apolipoprotein B were significantly and positively correlated with PTSD score (all P < 0.05). After the adjustment of the confounding factors, the number of stents was significantly associated with PTSD in acute MI patients (OR = 4.131, P = 0.003), meanwhile we also documented the troponin I and BNP were also significantly associated with PTSD in acute MI patients (OR = 1.066, P = 0.046; OR = 1.002, P = 0.019; respectively). The PTSD scores were 39.72 ± 11.12, 44.85 ± 13.46, 47.69 ± 9.39 and 49.33 ± 18.14 in acute MI patients with 1, 2, 3 and 4 stents respectively (P = 0.008).Conclusion: The study found that the number of implanted stents may predict PTSD in Chinese Han patients with acute MI.

BACKGROUND Although previous studies had confirmed the effectiveness and safety of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), respectively, direct head-to-head comparison of SCIT vs SLIT is sparse. We aimed to compare the efficacy, safety, and compliance of SCIT and SLIT in allergic rhinitis (AR) children. METHODS This study is a prospective, open-label, and single-center study performed between June 2017 and June 2018. A total of 325 children were grouped into SLIT, Alutard (SCIT1), and NovoHelisen Depot (NHD) (SCIT2) according to the parents' wishes. The adherence and reasons for dropout were recorded. The efficacy of SLIT and SCIT was evaluated by a combined symptom medication score. Adverse events (AEs) were recorded and graded during the whole treatment. RESULTS The compliance rate was higher in the SCIT group compared with the SLIT group (P < .05). The total nasal symptom score (TNSS), rescue medication score (RMS), and symptom medication score (SMS) after 6-month, 12-month, and 2-year treatment were lower in the SCIT group compared with the SLIT group (P < .05). But the scores between the Alutard and NHD groups were not significantly different. The occurrence of AEs in the SCIT group was significantly higher compared with the SLIT group (P < .05). CONCLUSION Our results suggested SCIT is more effective compared with SLIT to a certain degree, whereas SLIT had less AEs compared with SCIT. The AIT routes can be chosen according to personal specific conditions.

Three-dimensional (3D) printing is a type of rapid prototyping technology known as “additive manufacturing”. To meet the stacking layer-by-layer requirements, the fresh materials should have sufficient strength to ensure there is no collapse and plastic flow during the printing process. In addition, the fresh materials should exhibit enough stiffness to resist the intolerable elastic deformation to ensure printing accuracy. Since most of the printed structures have large height-to-thickness ratios, stabilities of printed structures should be taken into account. In this study, we investigated the rheological properties of 3D printed recycled coarse aggregate concrete (RAC), including their rheological behaviors when subjected to shear, the growth pattern of yield stress and shear modulus with resting time. Based on rheological parameters, buildability of RAC with 0%, 50% and 100% replacement rates were evaluated from the perspectives of strength, deformation and stability. It was found that yield stress of RAC exponentially increased with resting time, while the shear modulus linearly increased with resting time. Furthermore, within the first 15 min of printing, RAC exhibited better buildability with increasing replacement rate, however, the open time was shortened. In addition, the relationship between flowability and yield stress of the printing material was evaluated. Compared to the linear relationship of mortar, the relationship between flowability and yield stress was found to be exponential in RAC.

Background: Glucose- induced insulin resistance (IR) is a typical character of diabetes. Nicorandil is widely used in ischemic heart disease. Nicorandil shows protective effects against oxidative and endoplasmic reticulum (ER) stress which are involved in insulin resistance. Here we investigated mechanisms of nicorandil’s novel pharmacological activity on IR in diabetes. Methods: Nicorandil was administrated to diabetic animals and high-glucose exposed skeletal muscle cells. IR and glucose tolerance were evaluated. Molecular mechanisms concerning oxidative stress, ER stress and glucose uptake were assessed. Findings: Nicorandil attenuated high- glucose induced IR without affecting fasting blood glucose and glucose tolerance in whole body and skeletal muscle in diabetic rats. Nicorandil treatment suppressed protein kinase C(PKC)/ nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) system activities by reducing cytoplasmic free calcium level in skeletal muscle cells exposed to high glucose. As a result, the oxidative stress- mediated ER stress protein kinase RNA- like endoplasmic reticulum kinase (PERK)/ eukaryotic initiation factor (EIF) 2α/ activating transcription factor (ATF)4/CEBP homologous protein (CHOP)/tribbles homolog (TRB)3 signaling pathway activation was inhibited. Nicorandil down-regulated expression of TRB3 and thus facilitated Akt phosphorylation in response to insulin stimulation, leading to glucose transporter (GLUT)4 plasma membrane translocation which promoted glucose uptake capability of skeletal muscle cells. Interpretation: By reducing cytoplasmic calcium, nicorandil alleviated high-glucose induced IR by inhibiting oxidative stress- mediated ER stress PERK pathway. This study indicated nicorandil as a promising agent in treatment of patients with ischemic heart disease complicated with diabetes. Funding Statement: This study was supported by Innovative Talents Promotion Project of Shaanxi Province (2019KJXX-019); Fundamental Scientific Research Foundation of Xi’an Jiaotong University (xzy012019131); Health Scientific Foundation of Shaanxi Province (2018E11); Natural Science Basic Research Foundation of Shaanxi Province (2020JQ-941). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: The experimental protocols were reviewed and approved by Institutional Animal Care and Use Committee of Medical Research Institute of Northwestern Polytechnical University.

IntroductionGlucose-induced insulin resistance is a typical character of diabetes. Nicorandil is now widely used in ischemic heart disease. Nicorandil shows protective effects against oxidative and endoplasmic reticulum (ER) stress, which are involved in insulin resistance. Here, we investigated mechanisms of nicorandil’s novel pharmacological activity on insulin resistance in diabetes.Research design and methodsNicorandil was administrated to streptozotocin-induced animals with diabetes and high glucose exposed skeletal muscle cells. Insulin resistance and glucose tolerance were evaluated. Molecular mechanisms concerning oxidative stress, ER stress signaling activation and glucose uptake were assessed.ResultsNicorandil attenuated high glucose-induced insulin resistance without affecting fasting blood glucose and glucose tolerance in whole body and skeletal muscle in rats with diabetes. Nicorandil treatment suppressed protein kinase C/nicotinamide adenine dinucleotide phosphate oxidases system activities by reducing cytoplasmic free calcium level in skeletal muscle cells exposed to high glucose. As a result, the oxidative stress-mediated ER stress protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2α/activating transcription factor 4/CEBP homologous protein/tribbles homolog (TRB)3 signaling pathway activation was inhibited. Nicorandil downregulated expression of TRB3 and thus facilitated Akt phosphorylation in response to insulin stimulation, leading to glucose transporter4 plasma membrane translocation which promoted glucose uptake capability of skeletal muscle cells.ConclusionsBy reducing cytoplasmic calcium, nicorandil alleviated high glucose-induced insulin resistance by inhibiting oxidative stress-mediated ER stress PERK pathway.

Chunhui He,1,* Hua Ma2,* 1Internal Medicine of Traditional Chinese Medicine, 2Medical Image Center, The First Affiliated Hospital of Xinjiang Medical University, Wulumuqi, People’s Republic of China *These authors contributed equally to this work Background: Plantar heel pain can be managed with dry needling of myofascial trigger points (MTrPs); however, whether MTrP needling is effective remains controversial. Thus, we conducted this meta-analysis to evaluate the effect of MTrP needling in patients with plantar heel pain. Materials and methods: PubMed, Embase, Web of Science, SinoMed (Chinese BioMedical Literature Service System, People’s Republic of China), and CNKI (National Knowledge Infrastructure, People’s Republic of China) databases were systematically reviewed for randomized controlled trials (RCTs) that assessed the effects of MTrP needling. Pooled weighted mean difference (WMD) with 95% CIs were calculated for change in visual analog scale (VAS) score, and pooled risk ratio (RR) with 95% CIs were calculated for success rate for pain and incidence of adverse events. A fixed-effects model or random-effects model was used to pool the estimates, depending on the heterogeneity among the included studies. Results: Extensive literature search yielded 1,941 articles, of which only seven RCTs met the inclusion criteria and were included in this meta-analysis. The pooled results showed that MTrP needling significantly reduced the VAS score (WMD =–15.50, 95% CI: –19.48, –11.53; P

Sensitive, precise and rapid detection tests are needed in the quality control of rabies vaccine for rabies virus nucleoprotein. Previous studies for quantitation of rabies virus nucleoprotein focused on enzyme-linked immunosorbent assay (ELISA). A novel immunoassay for rapid determination of rabies virus nucleoprotein in rabies vaccine was first established by time-resolved fluoroimmunoassay (TRFIA). Based on a sandwich-type immunoassay format, analytes in samples were captured by one monoclonal antibody coating in the wells and "sandwiched" by another monoclonal antibody labeled with europium chelates. The immunocomplex was retained after washing, and then adopted treatment with enhancement solution; fluorescence was then measured according to the number of europiumions dissociated. Levels of the rabies virus nucleoprotein were measured in a linear range (5-2500 mEU/mL) with a lower limit of quantitation (0.95 mEU/mL) under optimal conditions. The repeatability, recovery, and linearity of the immunoassay were demonstrated to be acceptable. The correlation coefficient of nucleoprotein values obtained by novel TRFIA method and ELISA method was 0.981. These results showed good correlation and confirmed that this sensitive, precise and rapid TRFIA was feasible and could be more suitable for the quality control in the process of rabies vaccine production than ELISA.

Nursing aides is one profession that is dominated by shift work as care needs to be provided 24 hour a day and 7 days a week. To date, there is limited information about how the physical and postural demands vary across different shifts—different lengths and times. Fifty-four nursing aides from local long-term health care facilities were observed for an entire shift to document the whole body postural response and physical activities. The results indicate a very active demand for nursing aides on the 8-hr day shift and a more sedentary demand on 8-hr and 12-hr night shifts. The discomfort felt by the nursing aides appeared to be more related to the job demands rather than the length of exposure (e.g. not that much difference between 8-hr and 12-hr shifts).

The aim of this study was to evaluate the pharmacokinetic profiles of betamethasone (BOH, CAS 378-44-9) and betamethasone 17-monopropionate (B17P), the active metabolites of betamethasone phosphate (BSP) and betamethasone dipropionate (BDP), respectively, after administration of betamethasone i.m. (BSP 2 mg and BDP 5 mg). After ten healthy volunteers had received a single-dose intramuscular adminitration of betamethasone i.m., blood samples were collected pre-dose and for 336 h postdose. The plasma levels of B17P and BOH were measured by liquid chromatography-tandem mass spectrometry (LC-MS/ MS). When compared to BOH, B17P exhibited a longer time to maximum concentration (15.0 +/- 9.0 h vs. 2.8 +/- 1.7 h), a lower Cmax (0.6 +/- 0.2 ng/mL vs. 14.5 +/- 3.7 ng/mL), and a much longer half-life (80.8 +/- 22.7 h vs. 9.6 +/- 3.6 h). Betamethasone i.m. produced rapid onset and sustained action through an initial rapid-increased plasma concentration of BOH and a sustained plasma concentration of B17P, respectively.