The intestinal microbiome is essential in humans to maintain physiological balance and nutrition metabolism. Laparoscopic cholecystectomy due to gallstone disease and cholecystitis can cause intestinal microbial dysbiosis, and following bile acid metabolism dysfunction, positions the patient at high risk of colorectal cancer. However, little is known regarding intestinal microbiota characteristics in post-cholecystectomy patients. Here, we compared the microbial composition of cholecystectomy patients with that of a healthy population. We determined that cholecystectomy eliminated aging-associated fecal commensal microbiota and further identified several bile acid metabolism-related bacteria as contributors of colorectal cancer incidence via elevation of secondary bile acids.Significance statementWe identified aging-associated fecal microbiota in a healthy population, which was lost in cholecystectomy patients. Absent intestinal bacteria, such as Bacteroides, were negatively related to secondary bile acids and may be a leading cause of colorectal cancer incidence in cholecystectomy patients. Our study provides novel insight into the connection between cholecystectomy-altered gut microbiota and colorectal carcinoma, which is of value for colorectal cancer diagnosis and management.

BackgroundCDCA5 plays an important role in the development of various human cancers, but the associated mechanisms have not been investigated in hepatocellular carcinoma (HCC).Materials and methodsWe evaluated expression levels and functions of CDCA5 in HCC and showed that CDCA5 is upregulated in HCC tissues compared with paired or unpaired normal liver tissues.ResultsIncreased CDCA5 expression in HCCs was significantly associated with shorter survival of patients. Knockdown of CDCA5 using lentivirus-mediated shRNA significantly inhibited cell proliferation and suppressed cell survival, as well as induced cell cycle arrest at the G2/M phase and cell apoptosis of HCC cells. The tumor suppression effects of CDCA5 knockdown were mediated by decreased expression of cyclin-dependent kinase 1 (CDK1) and CyclinB1, which were increased in HCC tissues comparing with adjacent normal liver tissues. Moreover, upregulation of CDCA5 was positively associated with increased CDK1 and CyclinB1 expression in HCC tissues.ConclusionThe present data warrant consideration of CDCA5 as a prognostic biomarker and therapeutic target for HCC.

The proinflammatory cytokines transforming growth factor beta 1 (TGF-β1) and interleukin (IL)-31 have been implicated in tissue injury. However, whether TGF-β1/IL-31 are stimulated and elevated in response to liver injury that leads to fibrogenesis in hepatitis B virus-related liver cirrhosis (HBV-LC) remains unclear. To investigate the association between TGF-β1/IL-31 and stages of chronic HBV infection, serum TGF-β1, IL-9, IL-10,IL-17, IL-22, IL-23, IL-31, IL-33, and IL-35 were determined among patients with chronic hepatitis B (CHB; n=19), HBV-LC (n=20), and a normal control population (NC; n=18). Disease severity in patients with HBV-LC was assessed using model for end-stage liver disease (MELD) scores. Serum TGF-β1 and IL-31 levels were strongly positively linked in all subjects, and both correlated positively with IL-22, IL-33, and IL-17. TGF-β1 and IL-31 levels in the blood were both significantly higher in CHB and HBV-LC patients than in NC subjects. Elevated serum TGF-β1 and IL-31 levels were positively associated with albumin, alpha-fetoprotein, creatinine, white blood cell count, and platelet levels. Serum TGF-β1 and IL-31 were markedly higher in HBV-LC patients who did not have esophageal varices, and IL-31 had the highest sensitivity and specificity (90.9% and 66.7%, respectively) for indicating the absence of this complication. In summary, TGF-β1 and IL-31 were linked to progression from CHB to LC, and correlated well with the severity of HBV-LC. These findings suggest possible roles of the TGF-β1/IL-31 pathway in the pathogenesis of liver fibrosis during chronic HBV infection.

The transforming growth factor ␤1/interleukin-31 (TGF-␤1/IL-31) pathway plays an important role in the process of cell injury and inflammation. The purpose of this work was to explore the role of the TGF-␤1/IL-31 pathway in the cytopathic process of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). The quantitative serum levels of TGF-␤1, IL-9, IL-10, IL-17, IL-22, IL-23, IL-31, IL-33, and IL-35 were analyzed among chronic hepatitis B (CHB) patients (n ‫؍‬ 17), ACLF patients (n ‫؍‬ 18), and normal control (NC) subjects (n ‫؍‬ 18). Disease severity in patients with ACLF was assessed using the model for endstage liver disease (MELD) and Child-Pugh scores. Serum TGF-␤1 levels were strongly positively correlated with IL-31 in all subjects, and both of them were positively correlated with IL-17, IL-22, and IL-33. In CHB and ACLF patients, serum levels of TGF-␤1 and IL-31 were both increased significantly compared with those in NC subjects and positively correlated with total bilirubin (TBil) and alpha-fetoprotein (AFP) levels. ACLF patients showed the highest levels of TGF-␤1 and IL-31, which were positively correlated with Child-Pugh scores. Furthermore, the recovery from the liver injury in CHB was accompanied by decreased TGF-␤1 and IL-31 levels. More importantly, serum levels of TGF-␤1 and IL-31 were markedly upregulated in ACLF nonsurvivors, and IL-31 displayed the highest sensitivity and specificity (85.7% and 100.0%, respectively) in predicting nonsurvival of ACLF patients. Increasing activity of the TGF-␤1/IL-31 pathway is well correlated with the extent of liver injury, disease severity, and nonsurvival of ACLF patients, while reducing activity is detected along the recovery from liver injury in CHB, suggesting its potential role in the pathogenesis of liver injury during chronic HBV infection. Hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) is triggered mainly by severe extensive liver injury, and the exact mechanisms of massive destruction of HBV-infected hepatocytes remain unclear. However, one of the current assumptions is that the imbalance of the cytokine network, the so-called cytokine storm theory (1), points to potential involvement of inflammatory cytokines in destroying the HBV-infected cells, which may provide an explanation for the aggravation of liver injury.Transforming growth factor-␤1 (TGF-␤1) is a 25-kDa homodimeric protein composed of two subunits linked by a disulfide bond and is a powerful inhibitor of DNA synthesis and cellular proliferation (2). It also mediates formation of extracellular matrix and facilitates cell differentiation (3). Previous studies have shown that TGF-␤1 plays a role in developing liver failure (LF). Miwa et al. found that the mRNA and protein expression of TGF-␤1 were significantly upregulated in both the plasma and liver tissue in patients with fulminant liver failure (FLF) (4). Yoshimoto et al. found that the overexpression of TGF-␤1 delayed liver regeneration and promoted perisinusoidal fibrosis and hepatocyte apoptos...

CD4+ T helper (Th) cells are reported to be essential for initiating and maintaining an effective immune response to hepatitis B virus (HBV) infection. Th9 cells are a new subset of CD4+ Th cells that produce interleukin (IL)-9 and IL-10. The present study aimed to investigate the percentage of Th9 cells relative to the number of CD4+ cells in peripheral blood.We also measured serum IL-9 and IL-10 levels in different stages of HBV infection and their relationship with progress and prognosis of liver disease. Whole blood samples from 111 patients with HBV infection, including 39 chronic hepatitis B (CHB), 25 HBV-liver cirrhosis (HBV-LC), 21 acute-on-chronic liver failure (ACLF) patients, and 26 healthy controls were collected.The percentage of Th9 cells and serum IL-9 and IL-10 levels were determined. There was no significant difference in the percentage of Th9 cells and serum IL-9 and IL-10 levels among different groups, nor were these related to hepatitis B e antigen status, complications of cirrhosis, inflammation index, or prognosis indexes. There was no change in the percentage of Th9 cells before and after antiviral treatment in CHB patients. There was no correlation of Th9 cells with survival of ACLF patients. However, IL-9 and IL-10 levels were significantly higher in the nonsurvived ACLF patients compared to survived ACLF patients. Furthermore, baseline IL-9 level predicted the prognosis of ACLF patients with 87.5% sensitivity and 61.5% specificity.Thus, our data indicate that Th9 cells were unlikely involved in the pathogenesis of HBV infection, but elevation in IL-9 and IL-10 may signal poor prognosis for ACLF.