Preoperative Neutrophil Lymphocyte Ratio and Platelet Lymphocyte Ratio Cannot Predict Lymph Node Metastasis and Prognosis in Patients with Early Gastric Cancer：a Single Institution Investigation in China

In the present study,we aimed at exploring the applied value of preoperative neutrophil lymphocyte ratio(NLR) and platelet lymphocyte ratio(PLR) in the prediction of lymph node metastasis(LNM) and prognosis in patients with early gastric cancer(EGC).We retrospectively analyzed a total of 248 consecutive patients who underwent curative gastrectomy to be identified T1 stage gastric adenocarcinoma between January 1,2010 and May 1,2016 in a single institution.According to median preoperative NLR and PLR value,we divided the patients into four groups:high NLR ≥1.73 and low NLR <1.73,high PLR ≥117.78 and low PLR <117.78.Furthermore,to evaluate the relationship between preoperative NLR and PLR values,we categorized patients according to cutoff preoperative NLR-PLR score of 2 [high NLR(≥1.73) and high PLR(≥117.78)],1 [either high NLR or high PLR],and 0 [neither high NLR nor high PLR].Statistical analyses were conducted using SPSS 20.0 software.The results showed that the preoperative NLR or PLR values,lower or higher,could not predict the LNM in patients with EGC(both P=0.544>0.05).The invasive depth of tumor was significantly correlated with LNM of EGC(P<0.001).Kaplan-Meier plots illustrated that preoperative NLR and PLR values were not associated with overall survival(OS) in patients with EGC.It was concluded that the preoperative NLR and PLR may be the predictors for LNM and prognosis in patients with advanced gastric cancer;nevertheless,they cannot predict LNM and prognosis in patients with EGC.

Apoptotic vesicles ameliorate lupus and arthritis via phosphatidylserine-mediated modulation of T cell receptor signaling

Mesenchymal stem cells(MSCs)influence T cells in health,disease and therapy through messengers of intercellular communication including extracellular vesicles(EVs).Apoptosis is a mode of cell death that tends to promote immune tolerance,and a large number of apoptotic vesicles(apoVs)are generated from MSCs during apoptosis.In an effort to characterize these apoVs and explore their immunomodulatory potential,here we show that after replenishing them systemically,the apoV deficiency in Fas mutant mice and pathological lymphoproliferation were rescued,leading to the amelioration of inflammation and lupus activity.ApoVs directly interacted with CD4^(+)T cells and inhibited CD25 expression and IL-2 production in a dose-dependent manner.A broad range of Th1/2/17 subsets and cytokines including IFNγ,IL17A and IL-10 were suppressed while Foxp3^(+)cells were maintained.Mechanistically,exposed phosphatidylserine(PtdSer/PS)on apoVs mediated the interaction with T cells to disrupt proximal T cell receptor signaling transduction.Remarkably,administration of apoVs prevented Th17 differentiation and memory formation,and ameliorated inflammation and joint erosion in murine arthritis.Collectively,our findings unveil a previously unrecognized crosstalk between MSC apoVs and CD4^(+)T cells and suggest a promising therapeutic use of apoVs for autoimmune diseases.

Control of lupus activity during pregnancy via the engagement of IgG sialylation:novel crosstalk between IgG sialylation and pDC functions

Immunoglobulin(IgG)glycosylation affects the effector functions of IgG in a myriad of biological processes and has been closely associated with numerous autoimmune diseases,including systemic lupus erythematosus(SLE),thus underlining the pathogenic role of glycosylation aberration in autoimmunity.This study aims to explore the relationship between IgG sialylation patterns and lupus pregnancy.Relative to that in serum samples from the control cohort,IgG sialylation level was aberrantly downregulated in serum samples from the SLE cohort at four stages(from preconception to the third trimester of pregnancy)and was significantly associated with lupus activity and fetal loss during lupus pregnancy.The type I interferon signature of pregnant patients with SLE was negatively correlated with the level of IgG sialylation.The lack of sialylation dampened the ability of IgG to suppress the functions of plasmacytoid dendritic cells(pDCs).RNA-seq analysis further revealed that the expression of genes associated with the spleen tyrosine kinase(SYK)signaling pathway significantly differed between IgG-and deSia-IgG-treated pDCs.This finding was confirmed by the attenuation of the ability to phosphorylate SYK and BLNK in deSia-IgG.Finally,the coculture of pDCs isolated from pregnant patients with SLE with IgG/deSia-IgG demonstrated the sialylation-dependent anti-inflammatory function of IgG.Our findings suggested that IgG influences lupus activity through regulating pDCs function via the modulation of the SYK pathway in a sialic acid-dependent manner.

The non-canonical Wnt pathway leads to aged dendritic cell differentiation

Hematopoietic systems undergo a series of changes as they age,including(1)increased hematopoietic stem cell(HSC)pool size,especially for the long-term HSCs(LT-HSCs);(2)skewing of hematopoiesis toward the myeloid lineage and an increase in the myeloid-dominant HSCs in the HSC pool;and(3)decreased repopulation potential per HSC.In line with these changes,myeloid cells(mainly granulocytes)increase,whereas lymphoid cells(B cells)decrease in aged mice.1,2 Studies of the heart,muscle,skin and blood have demonstrated that changes in signaling pathways(i.e.the Wnt,Notch,TGF-β,NFκB and mTOR pathways)may underlay(stem)cell aging,and excitingly,the modulation of these pathways may restore tissues to a more youthful state.3,4 Among these pathways,small RhoGTPase cell division control 42(CDC42)has been identified as a key regulator of aging in HSCs.