No abstract

No abstract

The present study is to measure the expression of programmed death (PD)-1 / programmed death ligand-1 (PD-L1) negative costimulatory molecules, soluble format sPD-1 in patients with immune thrombocytopenia (ITP), and to investigate their correlation with the secretion of cytokines. A total of 35 patients with ITP were included in the present study. Twenty healthy subjects who received physical examination at our hospital were included as control group. Peripheral blood was collected from all ITP patients and healthy subjects. Flow cytometry was performed to determine the percentages of PD-1CD4T cells and PD-L1DCs in ITP patients and healthy subjects. Enzyme-linked immunosorbent assay was performed to measure the concentrations of interferon (IFN)-γ, interleukin (IL)-17 and sPD-1 in peripheral blood from ITP patients and healthy subjects. Percentages of PD-1CD4T cells and PD-L1DCs in peripheral blood from ITP patients before treatment were significantly higher than that from healthy subjects, but were not different from those after treatment. Serum concentrations of IFN-γ, IL-17 and sPD-1 in ITP patients before treatment were significantly higher than those in healthy subjects, and these concentrations were significantly reduced after treatment. The concentration of sPD-1 was positively correlated with the concentration of IFN-γ, and negatively correlated with platelet count. Percentages of PD-1CD4T cells and PD-L1DCs in ITP patients are higher than those in healthy subjects, but elevated sPD-1 concentration in the blood blocks PD-1/PD-L1 signaling pathway, leading to unaffected Th cell function. Elevated concentrations of IFN-γ and IL-17 in the blood may participate in the occurrence and development of ITP.

Abstract. The present study aimed to investigate the expression, clinical association, and prognosis of RecQ protein-like 4 (RECQL4) protein in human gastric cancers (GCs). The expression levels and prognostic value of RECQL4 were initially predicted by using bioinformatics. GC specimens and matched normal gastric tissues were evaluated by immunohistochemistry (IHC), and patient clinicopathological parameters and survival times were analyzed. Multivariate Cox analysis was used to determine the prognostic role of RECQL4 expression. The Oncomine database predicted that RECQL4 mRNA expression levels were significantly increased in GCs as compared with those in normal gastric tissues (P<0.05) and that patients with increased RECQL4 mRNA expression levels had significantly lower overall survival (OS) (P<0.001). The results of IHC showed that the positive rate of RECQL4 in the GC samples was significantly higher than that in the normal gastric mucosa specimens (P<0.05). RECQL4 expression was positively associated with depth of invasion and TNM (P<0.05). High RECQL4 expression in GC samples was significantly associated with poor OS (P=0.024). Positive RECQL4 expression, depth of invasion, lymphatic invasion, and TNM staging were independent factors for predicting worse OS rates by using multivariate analysis. Compared with expression levels in normal gastric tissues, RECQL4 was significantly overexpressed in GC samples, and increased RECQL4 expression was an independent predictor of poor prognosis in GC patients.

This study investigates the regulatory effect of plasmacytoid dendritic cells (pDC)/myeloid dendritic cells (mDC) imbalance on balance of Th1/Th2 and Th17/Treg in primary immune thrombocytopenia (ITP). A total of 30 untreated ITP patients and 20 healthy controls were recruited. Compared with healthy control, the pDC proportion of ITP patients was significantly reduced ( P = 0.004), while the mDC proportion was not significantly changed ( P = 0.681), resulting in a decrease in the pDC/mDC ratio ( P = 0.001). Additionally, compared with controls, serum levels of interleukin (IL)-6, IL-12, and IL-23 were increased in ITP patients ( P < 0.001), and mRNA levels of IL-12p40, IL-12p35, and IL-23p19 were also increased ( P =0.014, P = 0.043, P < 0.001). Compared with the healthy control, the proportion of Th1 and Th17 cells in ITP patients increased ( P = 0.001, P = 0.031). Serum levels of interferon gamma (IFN-γ) and IL-17 in ITP patients also increased ( P = 0.025, P = 0.005). Furthermore, T-bet and RORγt mRNA levels were increased in peripheral blood of ITP patients ( P = 0.018, P < 0.001). Correspondingly, the proportion of Th2 and Treg cells decreased ( P = 0.007, P < 0.001), along with a decrease in serum IL-4 and transforming growth factor beta (TGF-β) ( P = 0.028, P = 0.042), and an increase in GATA-3 mRNA ( P < 0.001). However, there was no significant difference in Foxp3 mRNA levels ( P = 0.587). Pearson correlation analysis showed that the proportion of total dendritic cells (DCs) was positively correlated with IL-12 ( r = 0.526, P = 0.003) and IL-23 ( r = 0.501, P = 0.005) in ITP patients. Th1/Th2 ratio, IFN-γ, and IL-12 levels were negatively correlated with platelet counts ( r = −0.494, P = 0.009; r = –0.415, P = 0.028; r = –0.492, P = 0.032). However, IL-23 was positively correlated with IL-17 ( r = 0.489, P = 0.006) and negatively correlated with platelet count ( r = –0.564, P = 0.001). The ratio of IL-6 and Th17 cells was negatively correlated with platelet count ( r = –0.443, P = 0.014; r = –0.471, P = 0.011). The imbalance of pDC/mDC and the increase of IL-6, IL-12, and IL-23 lead to the increased differentiation of CD4+ T cells into Th1 and Th17 cells, which might be the important mechanisms underlying the imbalance of Th1/Th2 and Th17/Treg in ITP patients.