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Background Esophageal and gastric varices bleeding (EGVB) is one of the most common and dangerous complications of liver cirrhosis. However, whether EGVB affects the one-year mortality of patients with liver cirrhosis remains unclear. Objective To explore the influence of EGVB on one-year mortality and influencing factors in patients with liver cirrhosis, providing guidance for follow-up for these patients. Methods This study selected liver cirrhosis patients who were admitted to the Affiliated Changsha Central Hospital, University of South China from January 2015 to May 2021. The patients were divided into EGVB group and non-bleeding (control group) by the prevalence of EGVB at the first consultation. One-year routine follow-up was conducted with them until the date of death from liver cirrhosis or the termination follow-up day. Logistic regression analysis was conducted for screening the factors affecting one-year mortality. Furthermore, the covariates between the two groups were matched in a 1∶2 ratio using propensity score matching (PSM) . Then, Logistic regression analyses were applied to identify and compare the influencing factors of one-year mortality in the groups. Results Among the 812 patients enrolled, 158 (19.5%) were diagnosed with EGVB, and the other 654 (80.5%) had no EGVB. The one-year mortality of the EGVB and control groups was 13.3% (21/158) and 13.9% (91/654) , respectively, showing no significant difference (P>0.05) . Before PSM, multivariate Logistic regression analysis showed that elevated serum sodium level〔OR=0.95, 95%CI (0.90, 0.99) 〕 and albumin level [OR=0.95, 95%CI (0.91, 0.99) 〕 were associated with a decreased risk of one-year mortality (P0.05) . Moreover, elevated blood urea nitrogen (BUN) 〔OR=1.15, 95%CI (1.02, 1.29) 〕 was an independent risk factor for one-year mortality in EGVB group (P

Endoplasmic reticulum stress (ERS) and Toll-like receptor 2 (TLR2) signaling play an important role in inflammatory bowel disease (IBD); however, the link between TLR2 and ERS in IBD is unclear. This study investigated whether Thapsigargin (TG) -induced ER protein expression levels contributed to TLR2-mediated inflammatory response. The THP-1 cells were treated with TLR2 agonist (Pam3CSK4), ERS inducer Thapsigargin (TG) or inhibitor (TUDCA). The mRNA expressions of TLR1-TLR10 were detected by qPCR. The production and secretion of inflammatory factors were detected by PCR and ELISA. Immunohistochemistry was used to detect the expressions of GRP78 and TLR2 in the intestinal mucosa of patients with Crohn's disease (CD). The IBD mouse model was established by TNBS in the modeling group. ERS inhibitor (TUDCA) was used in the treatment group. The expression of TLRs was detected via polymerase chain reaction (PCR) in THP-1 cells treated by ERS agonist Thapsigargin (TG). According to the findings, TG could promote TLR2 and TLR5 expression. Subsequently, in TLR2 agonist Pam3CSK4 induced THP-1 cells, TG could lead to increased expression of the inflammatory factors such as TNF-α, IL-1β and IL-8, and ERS inhibitor (TUDCA) could block this effect. However, Pam3CSK4 did not significantly impact the GRP78 and CHOP expression. Based upon the immunohistochemical results, TLR2 and GRP78 expression were significantly increased in the intestinal mucosa of patients with Crohn's disease (CD). For in vivo experiments, TUDCA displayed the ability to inhibit intestinal mucosal inflammation and reduce GRP78 and TLR2 proteins. ERS and TLR2 is upregulated in inflammatory bowel disease, ERS may promote TLR2 pathway-mediated inflammatory response. Moreover, ERS and TLR2 signaling could be novel therapeutic targets for IBD. [ABSTRACT FROM AUTHOR]

In the present study, the effects of copper and zinc addition on the microstructure and indentation creep behaviors of SnSb8Cu4 Babbitt alloy were systematically investigated. An indentation creep testing device with a flat tip indenter was used to characterize the creep behaviors of the Babbitt alloys at ~100°C with different loads. By increasing the copper content from 4wt% to 8wt%, coarser and shorter Cu6Sn5 dendrites with larger volume fraction were observed. The corresponding Brinell hardness increased from 21.9 to 28.1 at room temperature. However, the improvement in creep resistance was not obvious. After adding 0.72 wt% zinc, large number of small-sized SnSb particles precipitated along the grain boundaries of tin matrix. The total volume fraction of intermetallics, i.e., Cu6Sn5 and SnSb particles, increased from 15.1% to 20.9%. Although, the increment of Brinell hardness was not remarkable at room temperature, dramatic improvement in creep resistance was observed. The addition of zinc caused the decrement of the solid solubility of Sb in tin matrix, while more network-like SnSb particles precipitating in tin matrix were found, giving rise to the pinning effect against grain boundary sliding during creep deformation. However, increment of copper content showed no obvious effect on the solid solubility of Sb in tin matrix. Meanwhile, an exponential relationship between indentation creep rate and indentation stress at the steady creep stage was found. Based on the measured data, the indentation stress exponent of SnSb8Cu4, SnSb8Cu8 and SnSb8Cu4Zn was deduced to be 2.949, 2.865 and 2.743, respectively. [ABSTRACT FROM AUTHOR]

The nucleotide binding oligomerization domain containing 2 (NOD2) protein and its ligand N-acetyl muramyl dipeptide (MDP) are crucially involved in Crohn's disease (CD). However, the mechanism by which NOD2 signaling is regulated in CD patients remains unclear. Ubiquitin specific protease (USP14) is a deubiquitylase that plays an important role in immunity. This study aimed to investigate the mechanism by which UPS14 regulates NOD2 induced inflammatory response in CD and inflammatory bowel diseases (IBD). Our results showed that USP14 protein and mRNA levels in intestinal tissues of CD patients were significantly higher than those in healthy controls. In addition, USP14 was upregulated in IBD mouse model. While treatment with MDP, TNF-α or the Toll-like receptor 1/2 agonist Pam3CSK4 all led to significantly higher mRNA levels of TNF-α, IL-8 and IL-1β in THP-1 cells, pretreatment with USP14 inhibitor IU1 could stimulate further upregulation of TNF-α, IL-8 and IL-1β. In particular, MDP promoted the activation of JNK, ERK1/2 and p38 as well as NF-kB in THP-1 cells, and IU1 significantly enhanced the MDP-induced activation of these proteins without effects on USP14 protein level. Furthermore, the JNK inhibitor sp600125, ERK1/2 inhibitor U0126 or P38 MAPK inhibitor PD169316 significantly decreased the mRNA levels of TNF-α, IL-8 and IL-1β in THP-1 cells stimulated by both IU1 and MDP. In conclusion, our findings suggest that USP14 could inhibit MDP-induced activation of MAPK signaling and the inflammation response involved in IBD, and that USP14 is a potential therapeutic target for IBD.

Objective: To explore the role of Pim-1 in the pathology of inflammatory bowel disease and the potential effect of Pim-1 inhibitor on treating such disease.
 Methods: Forty-five BALB/c mice were randomly divided into 5 groups (n=9): A normal control group, a inflammatory bowel disease group, two different dose of Pim-1 inhibitor treatment groups, and steroidhormone treatment group. The model of inflammatory bowel disease was induced by intracolonic administration of 2, 4, 6-trinitrobenzenestdfonic acid (TNBS) and ethanol mixture. Mice were treated with Pim-1 inhibitor [intraperitoneal inject, 5 or 10 mg/(kg.d)] for 5 days and prednisone (intragastric administration, 0.1 mg/d) for 5 days. The DAI, colon length, gross score and pathological grade were evaluated. The expressions of T cell master transcription factors T-box expressed in T cells (T-bet), GATA binding protein 3 (GATA-3), RA orphan receptorγ (RORγt) and forkhead box P3 (Foxp3) were measured by Real-time PCR and Western blot, respectively.
 Results: Pim-1 inhibitor and prednisone showed therapeutic effect on acute TNBS colitis in vivo. GATA3 and RORγt were significantly up-regulated in acute TNBS colitis (P<0.05). In contrast, the expression of Foxp3 was suppressed in the inflammatory bowel disease group, whereas it did not cause any significant change in T-bet expression (P>0.05). Administration of Pim-1 inhibitor and prednisone resulted in suppression of GATA3, RORγt expression, and the increase of Foxp3 expression (P<0.05). Administration of Pim-1 inhibitor and prednisone resulted in inhibition of T-bet mRNA expression (P<0.05), but only prednisone could inhibit T-bet protein expression (P>0.05).
 Conclusion: Pim-1 inhibitor significantly suppresses Th2- and Th17-type immune responses. Furthermore, Pim-1 inhibitor could induce T-cell differentiation towards a Treg phenotype. Pim-1 inhibitor has therapeutic effect on acute TNBS colitis.