Hemophagocytic lymphohistiocytosis (HLH) is a relatively rare but life-threatening disease with confusing clinical manifestations, rapidly deteriorating health, high morbidity and mortality. To improve the recognition as well as understanding of this disorder, we analyzed clinical characteristics and prognostic factors from 85 adult patients diagnosed with HLH in our hospital from April 2005 to June 2014. Patients with HLH displayed variable clinical markers across a wide spectrum. These included fever and hyperferritinemia (100%), elevated lactate dehydrogenase (LDH) (98.8%), two or three cytopenia (92.2%), splenomegaly (72.9%), hypofibrinogenemia (69.4%), hypertriglyceridemia (64.7%), hemophagocytosis (51.7%), and hepatomegaly (24.7%). Patients with active Epstien-Barr Virus (EBV) infection had a median overall survival (OS) of 65 days. Those displaying malignancy had very poor survival (median OS: 40 days). However, patients in rheumatic and non-EBV infection groups had relatively superior prognosis (not reached). Univariate analysis showed that Fibrinogen (Fbg) <1.5 g/L, platelet number (PLT) <40 × 109/L and LDH ≥1000 U/L were factors that negatively affected survival (P = 0.004, 0.000, 0.002). Multivariate analysis showed that PLT <40 × 109/L was the independent adverse factor (HR = 0.350, 95% CI: 0.145-0.844, P = 0.019). HLH had very complex clinical manifestations and high death rate. Patients with active EBV infection, malignancy, Fbg <1.5 g/L, PLT <40 × 109/L and LDH ≥1000 U/L had high risk of death as well as inferior survival, and these patients require systemic targeted treatments as early as possible.
Phage peptide display is a powerful technique for discovery of various target-specific ligands. However, target-unrelated peptides can often be obtained and cause ambiguous results. Peptide PB-TUP has been isolated repeatedly in our laboratory on different targets and we conducted a research on PB-TUP phage to investigate their binding properties and rate of propagation. ELISA and phage recovery assay demonstrated that PB-TUP phage had a significant superior affinity to polystyrene solid surface compared with control phage clones. In this study, some incidental bindings are excluded like blocking agents and non-specific binding of secondary antibodies. Propagation rate assays of the selected phage clones showed that the growth rate of PB-TUP phage was not superior to the control phages. Furthermore, the binding of PB-TUB to polystyrene was concentration dependent and varied with solution pH. Molecular modeling revealed that stable structures of α-helix and β-turn may contribute to the binding of PB-TUP to polystyrene plate. The PB-TUP sequence was fused to the N-terminus of peptide P2 and the fusion peptide significantly increased the binding affinity to polystyrene. The fusion peptide also enhanced the cell adhesion ability of peptide P2 with human umbilical vein endothelial cell (HUVEC). The addition of the polystyrene binding peptide provided a convenient method for peptide immobilization.
The expression level of folate receptor alpha (FRα) is located highly rate in ovarian cancer though it is remained absent in normal tissues. This highly tumor restricted expression profile makes FRα a promising target for tumor therapy and diagnosis. In this research we report a FRα binding peptide C7(Met-His-Thr-Ala-Pro-Gly-Trp-Gly-Tyr-Arg-Leu-Ser) discovered by phage display and this peptide showed specific binding to FRα expressing cells by cell ELISA and flow cytometry. Tumor targeting ability of C7 was proved in vivo by both phage homing experiment and fluorescence imaging. C7 can be internalized by SKOV3 cells and its affinity to FRα was determined by MST. The molecular recognition was revealed by structure modeling, suggesting its binding mode with FRα.