Patient-related factors are as important as procedure-related factors in determining high-risk predictors for post-ERCP overall complications and pancreatitis. However, the risk factors for asymptomatic hyperamylasemia may be mostly procedure related.

Immune checkpoint blockade has become a promising therapeutic approach to reverse immune cell exhaustion. Coinhibitory CD96 and T‐cell immunoglobulin and ITIM domain (TIGIT), together with costimulatory CD226, bind to common ligand CD155. The balancing between three receptors fine‐tunes immune responses against tumors. In this study, we investigated the expression of CD96, TIGIT, and CD226 in 55 fresh human hepatocellular carcinoma (HCC) samples, 236 paraffin‐embedded HCC samples, and 20 normal human livers. The cumulative percentage, absolute count, and mean fluorescence intensity (MFI) of CD96+ NK cells are significantly increased in the intratumoral tissues of HCC and break the balance between three receptors. Human CD96+ NK cells are functionally exhausted with impaired interferon‐gamma (IFN‐γ) and tumor necrosis factor‐alpha (TNF‐α) production, high gene expression of interleukin (IL)‐10 and transforming growth factor‐beta 1 (TGF‐β1), and low gene expression of T‐bet, IL‐15, perforin, and granzyme B. In addition, blocking CD96‐CD155 interaction specifically increases lysis of HepG2 cells by NK cells. HCC patients with a high level of CD96 or CD155 expression within tumor are strongly associated with deteriorating disease condition and shorter disease‐free survival (DFS) and overall survival times. Patients with a higher cumulative percentage of CD96+ NK cells within tumor also exhibit shorter DFS. High plasma level of TGF‐β1 in HCC patients up‐regulates CD96 expression and dynamically shifts the balance between CD96, TIGIT, and CD226 in NK cells. Blocking TGF‐β1 specifically restores normal CD96 expression and reverses the dysfunction of NK cells. Conclusion: These findings indicate that human intratumoral CD96+ NK cells are functionally exhausted and patients with higher intratumoral CD96 expression exhibit poorer clinical outcomes. Blocking CD96‐CD155 interaction or TGF‐β1 restores NK cell immunity against tumors by reversing NK cell exhaustion, suggesting a possible therapeutic role of CD96 in fighting liver cancer.

: As the predominant lymphocyte subset in the liver, natural killer (NK) cells have been shown to be highly associated with the outcomes of patients with chronic hepatitis B virus infection (CHB) and hepatocellular carcinoma (HCC). Previously, we reported that NKG2A, a checkpoint candidate, mediates human and murine NK cell dysfunction in CHB. However, NK cell exhaustion and, particularly, the level of NKG2A expression within liver tumors have not been reported. : In this study, we analyzed NKG2A expression and the related dysfunction of NK cells located in intra- or peritumor regions of liver tissue samples from 207 HCC patients, in addition to analyzing disease outcomes.: The expression of NKG2A in NK cells and the NKG2A ligand, HLA-E, in intratumor HCC tissues was observed to be increased. These NK cells, and particularly CD56 NK cells, with higher NKG2A expression showed features of functional exhaustion and were associated with a poor prognosis. The increase in NKG2A expression might be induced by IL-10, which was present at a high level in the plasma of HCC patients. Blocking IL-10 could specifically inhibit NKG2A expression in NK cells. : These findings indicate that NKG2A expression is influenced by factors from cancer nests and contributes to NK cell exhaustion, suggesting that NKG2A blockade has the potential to restore immunity against liver tumors by reversing NK cell exhaustion.

This study aimed to investigate the supplemental effects of probiotic Bacillus subtilis fmbJ (BS fmbJ) on growth performance, antioxidant capacity, and meat quality of broiler chickens. A total of 240 day-old male Arbor Acres (AA) broiler chickens were randomly allotted to 4 treatments and raised for 6 wk. Each treatment had 6 replicate pens with ten birds per replicate. Birds in the control group (CON) were fed diets without BS fmbJ and antibiotics. The BS groups were fed the basal diets with BS fmbJ at 2 × 10 cfu/kg (BS-1 group), BS fmbJ at 3 × 10 cfu/kg (BS-2 group), BS fmbJ at 4 × 10 cfu/kg (BS-3 group) without antibiotics for 42 d. In the study, dietary supplementation with BS fmbJ significantly improved (P < 0.05) the average daily gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR) of broilers from 21 to 42 d and 1 to 42 d. At 42 d, the final body weight was increased (P < 0.05) in BS-2 group compared with that in CON. Dietary BS fmbJ significantly increased (P < 0.05) serum IgA and IgG concentrations of broilers after 42 days raising. The glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activity of serum and liver were increased (P < 0.05), and methane dicarboxylic aldehyde (MDA) contents in serum and liver were decreased (P < 0.05) by BS fmbJ added into the broiler diets. Dietary supplementation with BS fmbJ significantly decreased (P < 0.05) reactive oxygen species (ROS) contents in liver mitochondria of broilers. Additionally, the expression of antioxidant enzyme gene including nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were improved (P < 0.05) by BS fmbJ added into the broiler diets. Among measuring items of chicken breast meat quality, the drip loss, cooking loss, shear force, L*, a* b* and b* values were influenced (P < 0.05) by BS fmbJ provided in the diet. Based on these results, Bacillus subtilis fmbJ could be acted as a beneficial feed additive with antioxidant capacity in broiler diets.