Objective To investigate the predictive value of lymphocyte count(LYM),interleukin-6(IL-6)and D-dimer(DD)combined detection on the 28 day prognosis of patients with sepsis.Methods Patients with sepsis 3.0 admitted to the People's Hospital of Xinjiang Uygur Autonomous Region from January 2023 to November 2023 were retrospectively selected.The clinical data of pa-tients were collected and divided into groups according to their survival at 28 days,and the levels of LYM,IL-6 and DD were compared.Draw the receiver operating characteristic(ROC)curve and calculate the area under the curve(AUC),the 28 days Kaplan-Meier sur-vival curve was plotted according to the cut-off value determined by the ROC curve.Results Finally,107 patients with sepsis were in-cluded,of which 66survived and 41 died within 28days.The levels of DD and IL-6 in the death group were significantly higher than those in the survival group,and the level of LYM was significantly lower than that in the survival group,and the difference between groups was statistically significant(P＜0.05).The results of multivariate COX regression analysis showed that LYM,IL-6 and DD were all risk factors for 28days death(P＜0.05).The results of ROC curve analysis showed that the AUC of LYM,IL-6 and DD combined detection was greater than that of single detection(0.909 vs 0.821,0.788,0.807).The results of Kaplan-Meier survival curve analysis showed that the 28days survival rate of patients with LYM≤0.52 × 109/L was significantly lower than that of patients with LYM＞0.52 × 109/L.The 28 days survival rate of patients with IL-6 ≥551.45pg/ml was significantly lower than that of patients with IL-6＜551.45pg/ml.The 28 days survival rate of patients with DD≥3.25mg/L was significantly lower than that of patients with DD＜3.25mg/L.Conclusion DD,IL-6 and LYM are all valuable in predicting the 28d prognosis of sepsis,and the combined detection of the three indicators is better than the single detection,which is expected to provide help for clinicians in the diagnosis and treatment of sepsis.

Objective: To prepare the fusion protein mGM-CSF-GnRH3 (mGGn) of mouse granulocyte-macrophage colony stimulating factor (mGM-CSF) combining with gonadotropin releasing hormone (GnRH) and the fusion protein mGM-CSF-GRP6 (mG6) of mGM-CSF combining with gastrin-releasing peptide (GRP), and to investigate the inhibitory effect of the above two fusion proteins on B16F10 melanoma in vitro as well as to preliminarily predict their isoelectric point, relative molecular weight, hydrophobicity, stability, subcellular localization, signal peptide, spatial structure and potential epitopes. Methods:After the successful preparation of mGGn and mG6, the effects of different concentrations of fusion proteins on tumor cell morphology, migration, proliferation and cell cycle were detected by microscopic observation, scratch test, CCK-8 method and flow cytometry, respectively. The protein online analysis systems EXPASY, GOR4, SWISS MODEL were used to predict the basic properties and secondary/tertiary structure of recombinant fusion proteins. The B cell epitopes were predicted by IEDB and ABCpred software, the CTL epitopes were comprehensively predicted by SYFPEITHI, BlMAS and NetCTL software, and the Th epitopes were predicted by NetMHCIIpan 3.1 Server and IEDB software. Results:Both mGGn and mG6 inhibited the migration and proliferation of tumor cells. mGGn could block B16F10 cell cycle at G1 phase while mG6 could block B16F10 cell cycle at S phase, all of which prevented cells entering into G2 phase to inhibit tumor cell growth. The mGGn and mG6 fusion proteins got diverse structures and had multiple potential B epitopes, CTL epitopes and Th epitopes. Conclusion: mGGn and mG6 have inhibitory effect on B16F10 melanoma in vitro, and bioinformatics predictions have laid a foundation for further study of the biological functions and immunological activities of these fusion proteins.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by severe synovial inflammation and cartilage damage. Despite great progress in RA therapy, there still lacks the drugs to completely cure RA patients. Herein, we propose a reprogrammed neutrophil cytopharmaceuticals loading with TNFα-targeting-siRNA (siTNFα) as an alternative anti-inflammatory approach for RA treatment. The loaded siTNFα act as not only the gene therapeutics to inhibit TNFα production by macrophages in inflamed synovium, but also the editors to reprogram neutrophils to anti-inflammatory phenotypes. Leveraging the active tendency of neutrophils to inflammation, the reprogrammed siTNFα/neutrophil cytopharmaceuticals (siTNFα/TP/NEs) can rapidly migrate to the inflamed synovium, transfer the loaded siTNFα to macrophages followed by the significant reduction of TNFα expression, and circumvent the pro-inflammatory activity of neutrophils, thus leading to the alleviated synovial inflammation and improved cartilage protection. Our work provides a promising cytopharmaceutical for RA treatment, and puts forward a living neutrophil-based gene delivery platform.