Background In view of the fact that peripheral blood parameters have been reported as predictors of immunotherapy to various cancers, this study aimed to determine the predictors of response to anti-programmed death-1 (anti-PD-1) therapy in patients with esophageal squamous cell carcinoma (ESCC) from peripheral blood parameters. Methods A retrospective analysis was conducted to investigate the predictive value of peripheral blood parameters including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII) in the response to anti-PD-1 antibody treatment. 119 ESCC patients receiving combined treatment including anti-PD-1 antibody were enrolled in this study. Results The median progression-free survival (PFS) of all ESCC patients was 3.73 months. PFS rate in ESCC patients with low NLR at 6 weeks post treatment was higher than patients with high NLR (HR = 2.097, 95% CI 0.996–4.417, P = 0.027). However, PFS rate in ESCC patients with low NLR at baseline (HR = 1.060, 95% CI 0.524–2.146, P = 0.869) or 3 weeks post treatment (HR = 1.293, 95% CI 0.628–2.663, P = 0.459) was comparable with high NLR. And no statistically different was found in PFS rate between low PLR and high PLR at baseline (HR = 0.786, 95% CI 0.389–1.589, P = 0.469), 3 weeks post treatment (HR = 0.767, 95% CI 0.379–1.552, P = 0.452) or 6 weeks post treatment (HR = 1.272, 95% CI 0.624–2.594, P = 0.488) in ESCC patients. PFS rate was also comparable between low MLR and high MLR at baseline (HR = 0.826, 95% CI 0.408–1.670, P = 0.587), 3 weeks post treatment (HR = 1.209, 95% CI 0.590–2.475, P = 0.580) or 6 weeks post treatment (HR = 1.199, 95% CI 0.586–2.454, P = 0.596). PFS rate was similar between patients with low SII and high SII at baseline (HR = 1.120, 95% CI 0.554–2.264, P = 0.749), 3 weeks post treatment (HR = 1.022, 95% CI 0.500–2.089, P = 0.951) and 6 weeks post treatment (HR = 1.759, 95% CI 0.851–3.635, P = 0.097). Conclusions NLR at 6 weeks post treatment is a predictor of the response to anti-PD-1 treatment in patients with ESCC.

Current large animal models that could closely resemble the typical features of cirrhotic portal hypertension in human have not been well established. Thus, we aimed to develop and describe a reliable and reproducible canine cirrhosis model of portal hypertension. A total of 30 mongrel dogs were randomly divided into four groups: 1 (control; n = 5), 2 (portal vein stenosis [PVS]; n = 5], 3 (thioacetamide [TAA]; n = 5), and 4 (PVS plus TAA; n = 15). After 4-months modeling period, liver and spleen CT perfusion, abdominal CT scans, portal hemodynamics, gastroscopy, hepatic function, blood routine, the bone marrow, liver, and spleen histology were studied. The animals in group 2 (PVS) developed extrahepatic portosystemic collateral circulation, particularly esophageal varices, without hepatic cirrhosis and portal hypertension. Animals from group 3 (TAA) presented mild cirrhosis and portal hypertension without significant symptoms of esophageal varices and hypersplenism. In contrast, animals from group 4 (PVS + TAA) showed well-developed micronodular and macronodular cirrhosis, associated with significant portal hypertension and hypersplenism. The combination of PVS and TAA represents a novel, reliable, and reproducible canine cirrhosis model of portal hypertension, which is associated with the typical characteristics of portal hypertension, including hypersplenism.

Macrophages are a type of immune cells with high levels of plasticity and heterogeneity. They can polarize into M1 or M2 functional phenotypes. These two phenotypes exhibit a dynamic balance during polarization-related diseases and play opposing roles. Long noncoding RNAs (lncRNAs) play an important role in biological processes such as cell proliferation, death, and differentiation; however, how long noncoding RNAs affect the cellular functionality of macrophages remains to be studied. Long noncoding RNA Gm9866 was found to be closely related to macrophage polarization through bioinformatics analysis. In this study, by conducting real-time polymerase chain reaction analysis, it was observed that long noncoding RNA Gm9866 expression significantly increased after treatment with interleukin-4 but significantly decreased after treatment with lipopolysaccharide. Fluorescence in situ hybridization revealed that long noncoding RNA Gm9866 was expressed mainly in the nucleus. Real-time polymerase chain reaction analysis showed that overexpression of long noncoding RNA Gm9866 in RAW264.7 cells further promoted the expression of M2 markers MRC1 (macrophage mannose receptor 1) and MRC2 (macrophage mannose receptor 2). Western blotting analysis demonstrated inhibition of nuclear factor-κB (NF-κB) expression. EdU (5-ethynyl-2 ′ -deoxyuridine) and TUNEL (TdT-mediated dUTP nick-end labeling) staining assays revealed that overexpression of long noncoding RNA Gm9866 promoted cell proliferation and inhibited apoptosis. These findings thus indicated that long noncoding RNA Gm9866 promoted macrophage polarization and inhibited the nuclear factor-κB signaling pathway. Thus, long noncoding RNA Gm9866 may serve as a potential diagnostic and therapeutic target for polarization-related diseases such as infectious diseases, inflammatory diseases, liver fibrosis, and tumors.

We have evaluated the effect of early and late micro-ecological enteral nutrition on systemic inflammatory response, bacterial translocation, and immune function in patients with severe acute pancreatitis. Two weeks after treatment, experimental group receiving early nutritional intervention exhibited a significant increase in intestinal lactobacilli and bifidobacteria, fewer staphylococci, and E. coli, and lower levels of serum endotoxin, D-lactic acid, and diamine oxidase than the group receiving late intervention (control group) (P < 0.05). Also, the serum levels of CD3+ and CD4+ and CD4+/CD8+ ratio significantly increase after 2 weeks of intervention. On the other hand, the level of CD8+ and the Acute Physiology and Chronic Health Evaluation II and Modified Computed Tomography Severity Index scores significantly decreased after 2 weeks of treatment (P < 0.05). The early intervention also led to a significant shortening of time needed for abdominal pain relief, anal exhaustion, resumption of peristaltic sound, and hospitalization. Furthermore, there was a significant increase in overall response rate, and decrease in the incidence rate of complications (P < 0.05). Early micro-ecological enteral nutrition therapy can effectively relieve systemic inflammatory response, prevent intestinal bacterial translocation, restore the function of intestinal mucosal barrier, and alleviate nutritional imbalance in severe acute pancreatitis patients leading to improved immune function, mitigation of the disease, and reduced complications benefiting the recovery of patients.