Efficacy and safety of abrocitinib for moderate-to-severe atopic dermatitis in adolescents and adults: Meta-analysis

Objective: This study aims to investigate the safety and efficacy of abrocitinib in treating moderate-to-severe AD in adolescents and adults.Methods: Pubmed, Cochrane, Embase, and Web of science data base were searched from inception to 9 August 2022. All randomized controlled trials (RCTs) evaluating the efficacy and safety of abrocitinib in moderate to severe AD were included in the meta-analysis.Results: This meta-analysis comprised 7 studies and found that 100 mg or 200 mg of abrocitinib significantly improved IGA {[RR = 2.44, 95% CI (1.93–3.08)] [RR = 3.16, 95% CI (2.52–3.96)]} and EASI-75{[RR = 2.18, 95%CI (1.78–2.67)] [RR = 3.04, 95%CI (2.22–4.16)]} responses compared to placebo. Following that, the population was divided into adolescent and adult groups. The abrocitinib improved IGA, EASI-75 responses, and it was still superior to placebo in both the adolescent and the adult groups. PP-NRS4 response index demonstrated that abrocitinib had a greater effect than placebo at 100 mg [RR = 2.22, 95% CI 1.80–2.72] and 200 mg [RR = 3.28, 95% CI 2.59–4.17]. Abrocitinib improved PSAAD, POEM, DLQI, CDLQI, and HADS more than a placebo.Conclusion: In conclusion, this meta-analysis preliminarily demonstrated that abrocitinib had higher efficacy and safety in the treatment of moderate-to-severe AD in adolescents and adults. In addition, abrocitinib could rapidly relieve itching, and effectively improve symptoms and signs, with a greater effect at the dosage of 200 mg than 100 mg

A new partial task offloading method in a cooperation mode under multi-constraints for multi-UE

In Multi-access Edge Computing (MEC), to deal with multiple user equipment (UE)’s task offloading problem of parallel relationships under the multi-constraints, this paper proposes a cooperation partial task offloading method (named CPMM), aiming to reduce UE's energy and computation consumption, while meeting the task completion delay as much as possible. CPMM first studies the task offloading of single-UE and then considers the task offloading of multi-UE based on single-UE task offloading. CPMM uses the critical path algorithm to divide the modules into key and non-key modules. According to some constraints of UE-self when offloading tasks, it gives priority to non-key modules for offloading and uses the evaluation decision method to select some appropriate key modules for offloading. Based on fully considering the competition between multiple UEs for communication resources and MEC service resources, CPMM uses the weighted queuing method to alleviate the competition for communication resources and uses the branch decision algorithm to determine the location of module offloading by BS according to the MEC servers’ resources. It achieves its goal by selecting reasonable modules to offload and using the cooperation of UE, MEC, and Cloud Center to determine the execution location of the modules. Extensive experiments demonstrate that CPMM obtains superior performances in task computation consumption reducing around 6% on average, task completion delay reducing around 5% on average, and better task execution success rate than other similar methods

Surface characterization, mechanical properties and corrosion behaviour of ternary based ZneZnOeSiO2composite coating of mild steel

Zinc coatings are obtained either from cyanide, non-cyanide alkaline or acid solutions. Because of the pollution and high cost associated with cyanide, deposition from other baths is gaining importance. In order to develop a bath with additive that could produce a quality coating is the motivation behind this present work which is surface modification of Zne8ZnOeSiO2 nano composite coating on mild steel surface by electrodeposition route. The influence of SiO2 on Zne8ZnO sulphate electrolyte on the properties and microstructure of the produced nano-coatings were investigated. The SiO2 was varied from 0 to 16wt%. The microstructure characteristics of these produced series composites coating were investigated using scanning electron microscopy couple with energy dispersive spectroscopy (SEM/EDS), X-ray diffraction and atomic force microscopy (AFM). The corrosion degradation properties in 3.65% NaCl medium were studied using potentiodynamic polarization technique and characterized by high resolution optical microscope (HR-OPM). The hardness and wear of the composite coating were measured with high diamond microhardness tester and dry abrasive MTR-300 testers respectively. The results showed that average hardness value of 142.5 and 251.2HV and corrosion rate of 0.13088 and 0.00122 mm/yr were obtained for the 0 and 16wt% SiO2 in Zne8ZnO. The work have established that upto 16% SiO2 in Zne8ZnO composite coating on mild steel can be used in improving the microhardness, wear loss and corrosion resistance of mild stee

Whole exome sequencing of insulinoma reveals recurrent T372R mutations in YY1

Functional pancreatic neuroendocrine tumours (PNETs) are mainly represented by insulinoma, which secrete insulin independent of glucose and cause hypoglycaemia. The major genetic alterations in sporadic insulinomas are still unknown. Here we identify recurrent somatic T372R mutations in YY1 by whole exome sequencing of 10 sporadic insulinomas. Further screening in 103 additional insulinomas reveals this hotspot mutation in 30% (34/113) of all tumours. T372R mutation alters the expression of YY1 target genes in insulinomas. Clinically, the T372R mutation is associated with the later onset of tumours. Genotyping of YY1, a target of mTOR inhibitors, may contribute to medical treatment of insulinomas. Our findings highlight the importance of YY1 in pancreatic β-cells and may provide therapeutic targets for PNETs

Fasting plasma glucose is an independent predictor for severity of H1N1 pneumonia

<p>Abstract</p> <p>Background</p> <p>The pandemic influenza A (H1N1) virus emerged during 2009 and has spread worldwide. This virus can cause injuries to the lungs, liver, and heart. However, data regarding whether this influenza virus can affect pancreatic islets are limited. We investigated the effects of influenza A (H1N1) pneumonia on fasting plasma glucose (FPG) and islet function, and evaluated possible correlations between biochemical test results and the severity of H1N1 pneumonia.</p> <p>Methods</p> <p>We performed a retrospective analysis of patients either diagnosed with or suspected of having H1N1 pneumonia who were admitted to our hospital in 2009. Possible associations between FPG levels and H1N1 virus infection were assessed by logistic regression. Correlation and regression analyses were used to assess relationships between FPG and biochemical test results. Associations between admission days and significant data were assessed by single factor linear regression. To evaluate effects of H1N1 on pancreatic β-cell function, results of a resistance index (homa-IR), insulin function index (homa-β), and insulin sensitivity index (IAI) were compared between a H1N1 group and a non-H1N1 group by t-tests.</p> <p>Results</p> <p>FPG was significantly positively associated with H1N1 virus infection (OR = 1.377, 95%CI: 1.062-1.786; p = 0.016). FPG was significantly correlated with AST (r = 0.215; p = 0.039), LDH (r = 0.400; p = 0.000), BUN (r = 0.28; p = 0.005), and arterial Oxygen Saturation (SaO₂; r = -0.416; p = 0.000) in the H1N1 group. H1N1 patients who were hypoxemic (SaO₂<93%) had higher FPG levels than those who were not hypoxic (9.82 ± 4.14 vs. 6.64 ± 1.78; p < 0.05). FPG was negatively correlated with SaO₂in the H1N1 group with hypoxia (SaO₂<93; r = -0.497; p = 0.041). SaO₂levels in patients with high FPG levels (≥7 mmol/L) were significantly lower than those of H1N1 patients with low FPG levels (<5.6 mmol/L). There were no significant differences in homa-IR, homa-β, or IAI between the H1N1 and non-H1N1 groups after adjusting for age, sex, and BMI.</p> <p>Conclusions</p> <p>FPG on admission could be an independent predictor for the severity of H1N1 pneumonia. Elevated FPG induced by H1N1 pneumonia is not a result of direct damage to pancreatic β-cells, but arises from various factors' combinations caused by H1N1 virus infection.</p

Aqueous extract of Amydrium sinense (Engl.) H. Li alleviates hepatic fibrosis by suppressing hepatic stellate cell activation through inhibiting Stat3 signaling

Background: The present study aimed to investigate the protective effect of the water extract of Amydrium sinense (Engl.) H. Li (ASWE) against hepatic fibrosis (HF) and clarify the underlying mechanism.Methods: The chemical components of ASWE were analysed by a Q-Orbitrap high-resolution mass spectrometer. In our study, an in vivo hepatic fibrosis mouse model was established via an intraperitoneal injection of olive oil containing 20% CCl4. In vitro experiments were conducted using a hepatic stellate cell line (HSC-T6) and RAW 264.7 cell line. A CCK-8 assay was performed to assess the cell viability of HSC-T6 and RAW264.7 cells treated with ASWE. Immunofluorescence staining was used to examine the intracellular localization of signal transducer and activator of transcription 3 (Stat3). Stat3 was overexpressed to analyse the role of Stat3 in the effect of ASWE on HF.Results: Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that candidate targets of ASWE, associated with protective effects against hepatic fibrosis, were related to inflammation response. ASWE ameliorated CCl4-induced liver pathological damage and reduced the liver index and alanine transaminase (ALT) and aspartate transaminase (AST) levels. ASWE also decreased the serum levels of collagen Ⅰ (Col Ⅰ) and hydroxyproline (Hyp) in CCl4-treated mice. In addition, the expression of fibrosis markers, including α-SMA protein and Acta2, Col1a1, and Col3a1 mRNA, was downregulated by ASWE treatment in vivo. The expression of these fibrosis markers was also decreased by treatment with ASWE in HSC-T6 cells. Moreover, ASWE decreased the expression of inflammatory markers, including the Tnf-α, Il6 and Il1β, in RAW264.7 cells. ASWE decreased the phosphorylation of Stat3 and total Stat3 expression and reduced the mRNA expression of the Stat3 gene in vivo and in vitro. ASWE also inhibited the nuclear shuttling of Stat3. Overexpression of Stat3 weakened the therapeutic effect of ASWE and accelerated the progression of HF.Conclusion: The results show that ASWE protects against CCl4-induced liver injury by suppressing fibrosis, inflammation, HSC activation and the Stat3 signaling pathway, which might lead to a new approach for preventing HF

Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: Results from the RA-BUILD study

Background Baricitinib is an oral, reversible, selective Janus kinase 1 and 2 inhibitor. Methods In this phase III, double-blind 24-week study, 684 biologic disease-modifying antirheumatic drug (DMARD)-naïve patients with rheumatoid arthritis and inadequate response or intolerance to ≥1 conventional synthetic DMARDs were randomly assigned 1:1:1 to placebo or baricitinib (2 or 4 mg) once daily, stratified by region and the presence of joint erosions. Endpoint measures included American College of Rheumatology 20% response (ACR20, primary endpoint), Disease Activity Score (DAS28) and Simplified Disease Activity Index (SDAI) score ≤3.3. Results More patients achieved ACR20 response at week 12 with baricitinib 4 mg than with placebo (62% vs 39%, p≤0.001). Compared with placebo, statistically significant improvements in DAS28, SDAI remission, Health Assessment Questionnaire-Disability Index, morning joint stiffness, worst joint pain and worst tiredness were observed. In a supportive analysis, radiographic progression of structural joint damage at week 24 was reduced with baricitinib versus placebo. Rates of adverse events during the treatment period and serious adverse events (SAEs), including serious infections, were similar among groups (SAEs: 5% for baricitinib 4 mg and placebo). One patient had an adverse event of tuberculosis (baricitinib 4 mg); one patient had an adverse event of non-melanoma skin cancer (baricitinib 4 mg). Two deaths and three major adverse cardiovascular events occurred (placebo). Baricitinib was associated with a decrease in neutrophils and increases in low-density and high-density lipoprotein. Conclusions In patients with rheumatoid arthritis and an inadequate response or intolerance to conventional synthetic DMARDs, baricitinib was associated with clinical improvement and inhibition of progression of radiographic joint damage