Roles of circulating soluble interleukin (IL)-6 receptor and IL-6 receptor expression on CD4+ T cells in patients with chronic hepatitis B

SummaryObjectivesThe objective of this study was to investigate the potential clinical roles of circulating soluble interleukin (IL)-6 receptor (sIL-6R) and IL-6R expression on CD4+ T cells (CD4+ IL-6R+ T cells) in chronic hepatitis B (CHB) patients.MethodsOne hundred and thirty-three subjects, including 72 CHB patients, 27 asymptomatic carriers, eight acute hepatitis B (AHB) patients, and 26 healthy donors were included in this study. Plasma IL-6 and sIL-6R levels were measured by enzyme-linked immunosorbent assay (ELISA); the frequency of CD4+ IL-6R+ T cells was detected by flow cytometry analysis.ResultsOur data showed a significant increase in plasma sIL-6R levels and the frequency of CD4+ IL-6R+ T cells in peripheral blood in CHB patients compared to asymptomatic carriers and healthy controls (both p<0.05). The elevated prevalence of CD4+ IL-6R+ T cells was positively associated with increased serum alanine aminotransferase levels in CHB patients (r = 0.316, p = 0.007), but was not correlated with serum hepatitis B virus (HBV) DNA load. Moreover, CHB patients with an HBV DNA load >1.0×106 copies/ml had a lower level of plasma sIL-6R than those with an HBV DNA load <1.0×106 copies/ml.ConclusionsCirculating sIL-6R and CD4+ IL-6R+ T cells were increased in CHB patients. Elevated plasma sIL-6R is probably associated with HBV elimination, and CD4+ IL-6R+ T cells in peripheral blood might contribute to the pathogenesis of liver injury in CHB patients

Challenges of fully online learning for dermatology education: a retrospective study

BackgroundBlended learning has proven to be an effective teaching strategy. During the COVID-19 pandemic in 2019, educational institutions worldwide switched to online learning. However, there is limited research on the effectiveness of blended learning and fully online learning. This study aims to evaluate and compare whether pure online learning is as effective as traditional blended learning by taking the example of dermatology education.MethodsThe researchers compared traditional blended learning and fully online learning by evaluating the achievement scores of undergraduate students in a dermatology course in the academic years 2019 and 2020, respectively, at the Shandong First Medical University, China. In 2019, students undertook small private online courses (SPOCs) combined with face-to-face teacher-led learning. In 2020, live teacher-led learning replaced face-to-face teacher-led learning. The researchers also conducted a questionnaire survey in 2020.ResultsThe scores of students in 2019 were significantly higher than in 2020 (p = 0.002). There was no significant difference in the distribution of achievement variance in the scores between the two academic years. In the questionnaire survey, the majority of the students rated highly the fully online education mode and responded that pure online learning enhanced their self-study ability.ConclusionThe present study shows that fully online learning currently does not perform as well as traditional blended learning in terms of examination scores due to some limitations. However, pure online education has several advantages over traditional blended education. Online courses should be improved to ignite students’ interest and increase their learning efficiency

Elevated IL-6 Receptor Expression on CD4+ T Cells contributes to the increased Th17 Responses in patients with Chronic Hepatitis B

<p>Abstract</p> <p>Background</p> <p>Increased numbers of Interleukin-17-producing CD4⁺T cells (Th17) have been found in association with hepatitis B virus (HBV)-induced liver injury. However, the mechanism underlying the increase of Th17 responses in patients with HBV infection remains unclear. In this study, we investigate the possible regulatory mechanisms of increased Th17 responses in patients with chronic hepatitis B(CHB).</p> <p>Methods</p> <p>Th17 response and IL-6R expression on CD4⁺T cells in peripheral blood samples were determined by flow cytometry. Cytokines TGF-β, IL-1β, IL-6 and IL-17 in plasma and/or supernatant samples were determined by ELISA and the IL-17 and IL-6R mRNA levels were quantified by quantitative real-time reverse polymerase chain reaction.</p> <p>Results</p> <p>All these data indicated that the frequency of periphery Th17 cells is significantly correlated with the percentage of CD4<b>⁺</b>T cells expressing IL-6R in CHB patients. CD4⁺T cells from patients with CHB, but not those from healthy donors, produced higher levels of IL-17 and had more IL-6R expression upon stimulation with the HBV core antigen (HBcAg) in vitro. The PMA/ionomycin and HBcAg -stimulated up-regulation of IL-17 production by CD4⁺T cells could be reversed by a neutralizing antibody against IL-6R.</p> <p>Conclusion</p> <p>we showed that enhancement of IL-6R expression on CD4⁺T cells upon HBV infection contributes to increased Th17 response in patients with CHB.</p

MicroRNA-483 amelioration of experimental pulmonary hypertension.

Endothelial dysfunction is critically involved in the pathogenesis of pulmonary arterial hypertension (PAH) and that exogenously administered microRNA may be of therapeutic benefit. Lower levels of miR-483 were found in serum from patients with idiopathic pulmonary arterial hypertension (IPAH), particularly those with more severe disease. RNA-seq and bioinformatics analyses showed that miR-483 targets several PAH-related genes, including transforming growth factor-β (TGF-β), TGF-β receptor 2 (TGFBR2), β-catenin, connective tissue growth factor (CTGF), interleukin-1β (IL-1β), and endothelin-1 (ET-1). Overexpression of miR-483 in ECs inhibited inflammatory and fibrogenic responses, revealed by the decreased expression of TGF-β, TGFBR2, β-catenin, CTGF, IL-1β, and ET-1. In contrast, inhibition of miR-483 increased these genes in ECs. Rats with EC-specific miR-483 overexpression exhibited ameliorated pulmonary hypertension (PH) and reduced right ventricular hypertrophy on challenge with monocrotaline (MCT) or Sugen + hypoxia. A reversal effect was observed in rats that received MCT with inhaled lentivirus overexpressing miR-483. These results indicate that PAH is associated with a reduced level of miR-483 and that miR-483 might reduce experimental PH by inhibition of multiple adverse responses

The chaos in calibrating crop models

Calibration, the estimation of model parameters based on fitting the model to experimental data, is among the first steps in many applications of system models and has an important impact on simulated values. Here we propose and illustrate a novel method of developing guidelines for calibration of system models. Our example is calibration of the phenology component of crop models. The approach is based on a multi-model study, where all teams are provided with the same data and asked to return simulations for the same conditions. All teams are asked to document in detail their calibration approach, including choices with respect to criteria for best parameters, choice of parameters to estimate and software. Based on an analysis of the advantages and disadvantages of the various choices, we propose calibration recommendations that cover a comprehensive list of decisions and that are based on actual practices.HighlightsWe propose a new approach to deriving calibration recommendations for system modelsApproach is based on analyzing calibration in multi-model simulation exercisesResulting recommendations are holistic and anchored in actual practiceWe apply the approach to calibration of crop models used to simulate phenologyRecommendations concern: objective function, parameters to estimate, software usedCompeting Interest StatementThe authors have declared no competing interest

Environmental regulation and financial performance of Chinese listed companies.

ObjectiveThe answer to this article lies in: Does the financial activities of physical enterprises have an adverse impact on their main business? Is it conducive to the sustainable development of the national economy? However, when most scholars study the impact of environmental regulations on companies performance, they have not classified companies performance. This article will study the relationship between environmental regulations and performance levels based on the classification of companies performance, and then divide the nature of industry pollution, companies location and nature of property for in-depth research.MethodsFirst, this article uses a random effect variable-intercept model to measure companies financial performance and non-financial performance. Then, the variables are divided into two variable groups: light pollution and heavy pollution according to the nature of industry pollution. Next, the companies are divided into three variable groups: the eastern region, the central region, and the western region. Finally, the company is divided into two variable groups: state-owned and non-state-owned according to the nature of property.ConclusionsThe study found that: (1) Environmental regulations have inhibited companies financial activities. And the inhibitory effect of environmental regulations on the financial performance of enterprises is more obvious in the heavily polluting industries and enterprises in central and eastern regions. (2) Environmental regulations and companies non-financial performance are also negatively related, environmental regulations have also inhibited the non-financial performance of companies, this effect is more pronounced in heavily polluting industries and enterprises in western regions. (3) Income crowding effect brought by China's environmental regulations is greater than the income compensation effect brought by stimulating technological innovation

Robust Semi-Supervised Manifold Learning Algorithm for Classification

In the recent years, manifold learning methods have been widely used in data classification to tackle the curse of dimensionality problem, since they can discover the potential intrinsic low-dimensional structures of the high-dimensional data. Given partially labeled data, the semi-supervised manifold learning algorithms are proposed to predict the labels of the unlabeled points, taking into account label information. However, these semi-supervised manifold learning algorithms are not robust against noisy points, especially when the labeled data contain noise. In this paper, we propose a framework for robust semi-supervised manifold learning (RSSML) to address this problem. The noisy levels of the labeled points are firstly predicted, and then a regularization term is constructed to reduce the impact of labeled points containing noise. A new robust semi-supervised optimization model is proposed by adding the regularization term to the traditional semi-supervised optimization model. Numerical experiments are given to show the improvement and efficiency of RSSML on noisy data sets

Dual Negativity of CD56 and CD117 Links to Unfavorable Cytogenetic Abnormalities and Predicts Poor Prognosis in Multiple Myeloma

The prognostic value of CD56 and CD117 expression on myeloma cells is controversial. This study aims to analyze the correlation of CD56 and CD117 expression with cytogenetic abnormalities and survival. A total of 128 patients with newly diagnosed multiple myeloma (NDMM) were recruited in this single-center retrospective study. Flow cytometry and FISH tests of marrow cells were performed for all of the subjects. The statistical methods included a chi-squared test, univariate and multivariate COX regressions, and a Kaplan-Meier survival curve analysis. Regarding the cytogenetics, the incidence of IgH/FGFR3 translocation was more frequent in patients with a negative CD56 (p = 0.003). CD56 negativity was an independent adverse factor associated with a poor prognosis (p = 0.019) and indicated a shorter overall survival (OS) (p = 0.021). Patients with dual negative CD56 and CD117 trended toward a poorer OS (CD56&minus;CD117&minus; vs. CD56+CD117&minus;, p = 0.011; CD56&minus;CD117&minus; vs. CD56+CD117+, p = 0.013). In conclusion, CD56 is a prognostic marker that independently affects OS and is associated with adverse cytogenetic abnormalities. Patients with a dual negativity of CD56 and CD117 have a worse clinical outcome