Background. Gastric cancer (GC), an extremely aggressive tumor with a very different prognosis, is the third leading cause of cancer-related mortality. We aimed to construct a ferroptosis-related prognostic model that can be distinguished prognostically. Methods. The gene expression and the clinical data of GC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO). The ferroptosis-related genes were obtained from the FerrDb. Using the “limma” R package and univariate Cox analysis, ferroptosis-related genes with differential expression and prognostic value were identified in the TCGA cohort. Last absolute shrinkage and selection operator (LASSO) Cox regression was applied to shrink ferroptosis-related predictors and construct a prognostic model. Functional enrichment, ESTIMATE algorithm, and single-sample gene set enrichment analysis (ssGSEA) were applied for exploring the potential mechanism. GC patients from the GEO cohort were used for validation. Results. An 8-gene prognostic model was constructed and stratified GC patients from TCGA and meta-GEO cohort into high-risk groups or low-risk groups. GC patients in high-risk groups have significantly poorer OS compared with those in low-risk groups. The risk score was identified as an independent predictor for OS. Functional analysis revealed that the risk score was mainly associated with the biological function of extracellular matrix (ECM) organization and tumor immunity. Conclusion. In conclusion, the ferroptosis-related model can be utilized for the clinical prognostic prediction in GC.

Activation of inflammatory responses regulates the transmission of pain pathways through an integrated network in the peripheral and central nervous systems. The immunopotentiator thymosin alpha-1 (Ta1) has recently been reported to have anti-inflammatory and neuroprotective functions in rodents. However, how Ta1 affects inflammatory pain remains unclear. In the present study, intraperitoneal injection of Ta1 attenuated complete Freund's adjuvant (CFA)-induced pain hypersensitivity, and decreased the up-regulation of pro-inflammatory cytokines (TNF-a, IL-1b, and IL-6) in inflamed skin and the spinal cord. We found that CFA-induced peripheral inflammation evoked strong microglial activation, but the effect was reversed by Ta1. Notably, Ta1 reversed the CFA-induced up-regulation of vesicular glutamate transporter (VGLUT) and down-regulated the vesicular c-aminobutyric acid transporter (VGAT) in the spinal cord. Taken together, these results suggest that Ta1 plays a therapeutic role in inflammatory pain and in the modulation of microgliainduced pro-inflammatory cytokine production in addition to mediation of VGLUT and VGAT expression in the spinal cord.Keywords Thymosin alpha-1 Á Cytokine Á Microglia Á Vesicular glutamate transporter type 2 Á Vesicular caminobutyric acid transporter

Background:Myasthenia gravis (MG) is an autoimmune disease caused by the transmission of dysfunction in the neuromuscular junction, manifesting partial or systemic skeletal muscle weakness and fatigue, which are exacerbated by activities and relieved after rest. Currently, the conventional therapy is applying cholinesterase inhibitors, steroids, immunosuppressant, and thymectomy. However, these drugs have obvious side effects. According to traditional Chinese medicine (TCM) theory, Buzhong Yiqi decoction (BYD) is a Qi-supplementing formula which is suitable for MG management as MG is generally diagnosed as “flaccidity syndrome” and considered caused by Qi-deficiency. An increasing number of clinical controlled studies also have found that BYD could improve the efficacy and reduced adverse effects in treating MG, but there is no systematic review of it. Therefore, we will use meta-analysis to evaluate the efficacy and safety of BYD for MG.Methods:PubMed, MEDLINE, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang data, Chinese Scientific Journals Database (VIP), and China biomedical literature database (CBM) will be searched to obtain the eligible studies published up to June 1, 2018. The primary outcome will be clinical absolute score before and after treatment, clinical relative score as well as effective rate. The secondary outcome will be the concentration of acetylcholine receptor antibody (AchRAb) in serum and adverse events incidence. Data analysis will be conducted using RevMan5.3 and Stata V.9.0 software. Trial sequential analysis (TSA) will be performed to assess the risk of random error and the validity of conclusion using TSA program version 0.9 beta.Results:This systematic review will provide a high-quality synthesis of BYD and its modified forms for MG from various evaluation aspects including clinical absolute score before and after treatment, clinical relative score, effective rate, the concentration of AchRAb in serum and adverse events incidence.Conclusion:The systematic review will provide evidence to assess the efficacy and safety of BYD and its modified forms in the treatment of MG.Prospero registration number:PROSPERO CRD42018095241.

The mechanism of inflammatory pain involves the central nervous system (CNS) and the immune system. It is reported that immunopotentiator thymosin alpha-1 (Tα1) can reduce inflammation, protect neurons and strengthen the immune function. However, the roles of Tα1 in inflammatory pain still remain unclear. In this study, we found Tα1 can attenuate the complete Freund’s adjuvant (CFA)-induced mechanical allodynia and heat hyperalgesia. Meanwhile, it reduced the upregulation of CFA-induced inflammatory mediators (interferon (IFN)-γ, tumor necrosis factor-α and brain-derived neurotrophic factor). In addition, we found the Wnt3a/β-catenin pathway was activated in spinal cord after the injection of CFA, paralleling with pain hypersensitivity. However, Tα1 reversed this status. In summary, Tα1 could attenuate inflammatory pain by modulating the Wnt3a/β-catenin pathway. It might be related to the downregulation of inflammatory mediators.