Background and Aims The evolution and clinical significance of abnormal liver chemistries and the impact of hepatitis B infection on outcome in patients with COVID-19 is not well characterized. This study aimed to explore these issues. Methods This large retrospective cohort study included 2073 patients with COVID-19 having definite outcomes in Wuhan, China. Longitudinal liver function tests were conducted and determined their associated factors and death risk by multivariate regression analyses. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. The characteristics of liver abnormalities and outcomes of patients with COVID-19 with and without hepatitis B were compared after 1:3 propensity score matching. Results Of the 2073 patients, 1282 (61.8%) had abnormal liver chemistries during hospitalization, and 297 (14.3%) had a liver injury. The mean levels of AST and D-Bil increased early after symptom onset in deceased patients and showed disparity compared with that in discharged patients throughout the clinical course of the disease. Abnormal admission AST (adjusted hazard ratio [HR]: 1.39, 95%CI: 1.04-1.86, P =0.027) and D-Bil (adjusted HR: 1.66, 95%CI: 1.22-2.26, P =0.001) levels were independent risk factors for mortality due to COVID-19. A nomogram was established based on the results of multivariate analysis and showed sufficient discriminatory power and good consistency between the prediction and the observation. HBV infection in patients did not increase the risk of COVID-19-associated poor outcomes. Conclusions Abnormal AST and D-Bil levels at admission were independent predictors of COVID-19 mortality. Therefore, monitoring liver chemistries, especially AST and D-Bil levels, in hospitalized patients with COVID-19, is necessary.

ObjectivesTo systematically review the efficacy and safety of anti-inflammatory agents for patients with major depressive disorders.MethodsWe searched the literature to identify potentially relevant randomised controlled trials (RCTs) up to 1 January 2019. The primary outcome was efficacy, measured by mean changes in depression score from baseline to endpoint. Secondary outcomes included response and remission rates and quality of life (QoL). Safety was evaluated by incidence of classified adverse events. Heterogeneity was examined using the I2 and Q statistic. Pooled standard mean differences (SMDs) and risk ratios (RRs) were calculated. Subgroup meta-analyses were conducted based on type of treatment, type of anti-inflammatory agents, sex, sponsor type and quality of studies.ResultsThirty RCTs with 1610 participants were included in the quantitative analysis. The overall analysis pooling from 26 of the RCTs suggested that anti-inflammatory agents reduced depressive symptoms (SMD −0.55, 95% CI −0.75 to −0.35, I2=71%) compared with placebo. Higher response (RR 1.52, 95% CI 1.30 to 1.79, I2=29%) and remission rates (RR 1.79, 95% CI 1.29 to 2.49, I2=41%) were seen in the group receiving anti-inflammatory agents than in those receiving placebo. Subgroup analysis showed a greater reduction in symptom severity in both the monotherapy and adjunctive treatment groups. Subgroup analysis of non-steroidal anti-inflammatory drugs, omega-3 fatty acids, statins and minocyclines, respectively, disclosed significant antidepressant effects for major depressive disorder (MDD). For women-only trials, no difference in changes of depression severity was found between groups. Subanalysis stratified by sponsor type and study quality led to the same outcomes in favour of anti-inflammatory agents in both subgroups. Changes of QoL showed no difference between the groups. Gastrointestinal events were the only significant differences between groups in the treatment periods.ConclusionsResults of this systematic review suggest that anti-inflammatory agents play an antidepressant role in patients with MDD and are reasonably safe.

Background: Migraine is one of the most common neurological disorders that leads to disabilities. However, the conventional drug therapy for migraine might be unsatisfactory at times. Therefore, this meta-analysis aimed to evaluate the efficacy and safety of calcitonin-gene-related peptide binding monoclonal antibody (CGRP mAb) for the preventive treatment of episodic migraine, and provide high-quality clinical evidence for migraine therapy. Methods: A systematic electronic database search was conducted to identify the potentially relevant studies. Two independent authors performed data extraction and quality appraisal. Mean difference (MD) and risk ratio (RR) were pooled for continuous and dichotomous data, respectively. The significance levels, weighted effect sizes and homogeneity of variance were calculated. Results: Eleven high-quality randomized control trials that collectively included 4402 patients were included in this meta-analysis. Compared to placebo group, CGRP mAb therapy resulted in a reduction of monthly migraine days [weighted mean difference (WMD) = − 1.44, 95% CI = (− 1.68,− 1.19)] and acute migraine-specific medication days [WMD = − 1.28, 95% CI = (− 1.66,− 0.90)], with an improvement in 50% responder rate [RR = 1.51, 95% CI = (1.37,1.66)]. In addition, the adverse events (AEs) and treatment withdrawal rates due to AEs were not significantly different between CGRP mAb and placebo groups. Similar efficacy and safety results were obtained for erenumab, fremanezumab, and galcanezumab in subgroup analysis. Conclusions: The current body of evidence reveals that CGRP mAb is an effective and safe preventive treatment for episodic migraine.

1These two authors contributed equally to this work.Abbreviations used: BBB, Basso, Bresnahan, and Beattie; BSCB, blood-spinal cord barrier; LFB, Luxol Fast Blue; MAG, myelin-associated glycoprotein; OD, optical density.SCI, spinal cord injury.

To investigate the effects of VitalStim therapy coupled with conventional swallowing training on recovery of post-stroke dysphagia, a total of 120 patients with post-stroke dysphagia were randomly and evenly divided into three groups: conventional swallowing therapy group, VitalStim therapy group, and VitalStim therapy plus conventional swallowing therapy group. Prior to and after the treatment, signals of surface electromyography (sEMG) of swallowing muscles were detected, swallowing function was evaluated by using the Standardized Swallowing Assessment (SSA) and Videofluoroscopic Swallowing Study (VFSS) tests, and swallowing-related quality of life (SWAL-QOL) was evaluated using the SWAL-QOL questionnaire. There were significant differences in sEMG value, SSA, VFSS, and SWAL-QOL scores in each group between prior to and after treatment. After 4-week treatment, sEMG value, SSA, VFSS and SWAL-QOL scores were significantly greater in the VitalStim therapy plus conventional swallowing training group than in the conventional swallowing training group and VitalStim therapy group, but no significant difference existed between conventional swallowing therapy group and VitalStim therapy group. It was concluded that VitalStim therapy coupled with conventional swallowing training was conducive to recovery of post-stroke dysphagia.

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Decidualization is a critical step during embryo implantation and characterized by the differentiation of endometrial stromal cells (ESCs) into decidual cells. Because miRNAs are important determinants of cellular fate specification, in this study, the miRNA expression in ESCs during in vitro decidualization was profiled by using a microarray. Significance analysis of microarrays revealed that 49 miRNA genes were differently (>2-fold) expressed between the noninduced ESCs and induced ESCs with a false discovery rate of 0. The expression variance of hsa-miR-222, 221, 143, 101, 30d, 30c, 181b, 27b, 29b, 507, and 23a was validated by using quantitative PCR (P < 0.05). Based on microRNA (miRNA) and mRNA expression variance and predicted target genes of miRNAs, a bioinformatic model of miRNAs controlling ESCs differentiation was formulated. Finally, we proved that down-regulation of has-miR-222 could decrease the number of cells in S phase during ESCs differentiation (P < 0.05). Antisense oligonucleotides of has-miR-222 could increase reporter gene expression by targeting the 3' untranslated regions of CDKN1C/p57kip2 mRNAs as well as increase CDKN1C/p57kip2 protein levels (P < 0.05). In conclusion, our results suggest that a subset of miRNAs play a key role in gene reprogramming during ESCs decidualization and that hsa-miR-222 participates in ESC differentiation by regulating ESCs terminally withdrawing from the cell cycle.

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