[Research Progress of Antibacterial Biliary Stent].

Biliary stent has been widely used in the treatment of biliary stricture and obstruction, it can relieve the pain of patients effectively, but bacterial infection and stent obstruction are still troublesome after surgery. We introduce the mechanism of infection and stent blockage caused by bacterial invasion after biliary stent implantation, and expound the formation mechanism of bacterial biofilm and bile sludge in this review. Antibacterial biliary stent is an effective way to inhibit biliary tract infection, the literatures on antibacterial modification of biliary stent with different antibacterial methods in domestic and abroad are reviewed, and the research prospect of antibacterial biliary stent is summarized and prospected.

Associations between methylenetetrahydrofolate reductase polymorphisms and hepatocellular carcinoma risk in Chinese population.

Genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene are considered to have some influence on both folate metabolism and cancer risk. Previous studies on the associations of MTHFR genetic polymorphisms with hepatocellular carcinoma (HCC) risk in Chinese population reported inconsistent results. We performed this meta-analysis to comprehensively assess the associations. Finally, 12 individual case-control studies were included into the meta-analysis. There were seven studies (6,384 subjects) on the MTHFR C677T polymorphism and five studies (4,502 subjects) on the MTHFR A1298C polymorphism. Overall, MTHFR C677T polymorphism was significantly associated with susceptibility to HCC in Chinese population (T versus C, odds ratio (OR) = 1.09, 95 % confidence interval (95% CI) 1.01-1.17; TT versus CC, OR = 1.17, 95% CI 1.00-1.38; TT/CT versus CC, OR = 1.12, 95% CI 1.00-1.26). MTHFR A1298C polymorphism was conversely associated with HCC risk in Chinese population (CC versus AA, OR = 0.65, 95% CI 0.46-0.91; CC versus AA/AC, OR = 0.64, 95% CI 0.46-0.90). The sensitivity analysis confirmed the reliability and stability of the meta-analysis. Thus, the findings from our meta-analysis support the associations of MTHFR C677T and A1298C polymorphisms with HCC risk in Chinese population.

Low expression of KIF20A suppresses cell proliferation, promotes chemosensitivity and is associated with better prognosis in HCC.

This study analysed the microarray datasets from Gene Expression Omnibus (GEO) database, and aimed to identify novel potential hub genes associated with the progression of HCC via bioinformatics analysis and experimental validation. The common differentially expressed genes (DEGs) from five GEO datasets were screened using GEO2R tool. The expression and survival analysis of hub genes in HCC were performed using Gene Expression Profiling Interactive Analysis, UALCAN and Kaplan-Meier plotter tools. In vitro functional assays were used to determine the caspase-3, -9, cell proliferation and chemo-sensitivity of HCC cells. A total of 177 common DEGs were identified between normal liver and HCC tissues among these datasets. Functional enrichment and PPI network analysis identified 22 hub genes from the common DEGs. The mRNA expression of 22 hub genes was all significantly up-regulated in HCC tissues compared to that in normal liver tissues. Further survival analysis showed that 10 hub genes predicted poor prognosis of patients with HCC. More importantly, the in vitro functional studies demonstrated that KIF20A knockdown suppressed the HCC cell proliferation and promoted the chemosensitivity of HCC cells to cisplatin and sorafenib. In conclusion, the present study identified a total of 177 common DEGs among 5 GEO microarray datasets and found that 10 hub genes could predict the poor prognosis of patients with HCC using the comprehensive bioinformatics analysis. Furthermore, KIF20A silence suppressed cell proliferation and enhanced chemosensitivity in HCC cells. Further studies may be required to determine the mechanistic role of these hub genes in HCC progression.

Long non-coding RNA MINCR aggravates colon cancer via regulating miR-708-5p-mediated Wnt/ß-catenin pathway.

BACKGROUND: Increasing evidence has found that the dysregulation of long non-coding RNAs (lncRNAs) may be important indicators in tumorigenesis. MYC-induced long non-coding RNA (MINCR) has been found to be related with some cancers, such as non-small cell lung cancer and gallbladder cancer. Besides, MINCR has potentially prognostic value for colon cancer (CC) patients' prognosis, yet its function and molecular mechanism in CC are not explored. METHODS: qRT-PCR evaluated gene expression, and western blot detected protein level. In vitro and in vivo experiments were adopted to understand the biological role of MINCR in CC. TOP/FOP Flash assay was performed to measure the activity of Wnt/ß-catenin pathway. RNA pull down, luciferase reporter and RIP assays were utilized to analyze the relationship among genes. Immunohistochemistry and HE staining techniques were utilized to evaluate Ki67 staining in xenografts. RESULTS: MINCR was up-regulated in CC cells. Knockdown of MINCR suppressed cell proliferation and migration. MINCR could up-regulate CTNNB1 via sequestering miR-708-5p, resulting in activated Wnt/ß-catenin pathway. The addition of LiCl treatment, miR-708-5p inhibitor or pcDNA3.1/CTNNB1 abolished the inhibitory impacts induced by MINCR silence in CC progression. CONCLUSION: MINCR sponges miR-708-5p to up-regulate CTNNB1 and activate Wnt/ß-catenin pathway, thus promoting the development CC. Targeting MINCR might shed new light on the therapeutic strategies of CC.

Expert consensus on management of metabolic disease in Chinese liver transplant recipients.

Metabolic disease, including diabetes mellitus, hypertension, dyslipidemia, obesity, and hyperuricemia, is a common complication after liver transplantation and a risk factor for cardiovascular disease and death. The development of metabolic disease is closely related to the side effects of immunosuppressants. Therefore, optimization of the immunosuppressive regimen is very important for the prevention and treatment of metabolic disease. The Chinese Society of Organ Transplantation has developed an expert consensus on the management of metabolic diseases in Chinese liver transplant recipients based on recent studies. Emphasis is placed on the risk factors of metabolic diseases, the effect of immunosuppressants on metabolic disease, and the prevention and treatment of metabolic diseases.

Drug-eluting fully covered self-expanding metal stent for dissolution of bile duct stones in vitro.

BACKGROUND: The treatment of difficult common bile duct stones (CBDS) remains a big challenge around the world. Biliary stenting is a widely accepted rescue method in patients with failed stone extraction under endoscopic retrograde cholangiopancreatography. Fully covered self-expanding metal stent (FCSEMS) has gained increasing attention in the management of difficult CBDS. AIM: To manufacture a drug-eluting FCSEMS, which can achieve controlled release of stone-dissolving agents and speed up the dissolution of CBDS. METHODS: Customized covered nitinol stents were adopted. Sodium cholate (SC) and disodium ethylene diamine tetraacetic acid (EDTA disodium, EDTA for short) were used as stone-dissolving agents. Three different types of drug-eluting stents were manufactured by dip coating (Stent I), coaxial electrospinning (Stent II), and dip coating combined with electrospinning (Stent III), respectively. The drug-release behavior and stone-dissolving efficacy of these stents were evaluated in vitro to sort out the best manufacturing method. And the selected stone-dissolving stents were further put into porcine CBD to evaluate their biosecurity. RESULTS: Stent I and Stent II had obvious burst release of drugs in the first 5 d while Stent III presented controlled and sustainable drug release for 30 d. In still buffer, the final stone mass-loss rate of each group was 5.19% ± 0.69% for naked FCSEMS, 20.37% ± 2.13% for Stent I, 24.57% ± 1.45% for Stent II, and 33.72% ± 0.67% for Stent III. In flowing bile, the final stone mass-loss rate of each group was 5.87% ± 0.25% for naked FCSEMS, 6.36% ± 0.48% for Stent I, 6.38% ± 0.37% for Stent II, and 8.15% ± 0.27% for Stent III. Stent III caused the most stone mass-loss no matter in still buffer or in flowing bile, which was significantly higher than those of other groups (P < 0.05). In vivo, Stent III made no difference from naked FCSEMS in serological analysis (P > 0.05) and histopathological examination (P > 0.05). CONCLUSION: The novel SC and EDTA-eluting FCSEMS is efficient in diminishing CBDS in vitro. When conventional endoscopic techniques fail to remove difficult CBDS, SC and EDTA-eluting FCSEMS implantation may be considered a promising alternative.

Association of patatin-like phospholipase domain-containing protein 3 gene polymorphisms with susceptibility of nonalcoholic fatty liver disease in a Han Chinese population.

Gene polymorphisms had been found to be associated with increased risk of nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to assess the association between rs2896019 and rs3810622 in PNPLA3 with the susceptibility to NAFLD in Han Chinese population.A total of 384 NAFLD patients and 384 controls were enrolled in the study. Blood samples collected from each subject were used for biochemical index analysis and DNA extraction. Genotyping analyses of PNPLA3 rs2896019 and rs3810622 were performed by real-time PCR methods.Results showed that patients with genotype GG of rs2896019 had a higher incidence of NAFLD than patients with genotypes GT and TT (62.4% vs 52.0% and 43.3%, respectively, P = 0.002), and a higher risk of moderate to severe NAFLD than patients with genotypes GT and TT (60.3% vs 46.2% and 40.2%, respectively, P = 0.03). Furthermore, patients with genotype GG of rs2896019 had higher levels of low-density lipoprotein (LDL, P < 0.001), ALT (P = 0.003), and AST (P = 0.002). Patients with genotype TT of rs3810622 had a higher incidence of NAFLD than patients with genotypes CT and CC (56.7% vs 48.4% and 41.5%, respectively, P = 0.013). Likewise, patients with genotype TT of rs3810622 had higher levels of ALT (P = 0.021) and blood glucose (GLU) (P = 0.034). Haplotype association analysis showed that GT haplotype conferred a statistically significant increased risk for NAFLD (OR = 1.49; 95% CI = 1.20-1.84, P < 0.01).These results suggest that PNPLA3 rs2896019 and rs3810622 polymorphisms significantly contribute to increased NAFLD risk in Han Chinese population.

Decreased MALL expression negatively impacts colorectal cancer patient survival.

The aim of the present study was to determine whether MALL expression is associated with colon cancer progression and patient survival. MALL mRNA expression was reduced in the tumor tissues of 70% of the colon cancer patients and 75% of the rectal cancer patients as compared to their normal tissues. MALL protein was also significantly reduced in the tumor tissues of colon cancer patients (P < 0.001). Increased LOH and methylation of MALL was observed in tumor tissues as compared to normal tissues. Reduced MALL expression was associated with vessin invasion, disease recurrence and metastasis or death (P ≤ 0.027). Furthermore, patients with MALL-negative tumors had significantly decreased overall survival (OS) and disease-free survival (DFS) (P < 0.008 and P < 0.011, respectively). Univariate analysis indicated that MALL expression was significantly associated with OS and DFS. Finally, overexpression of MALL suppressed HCT116 and SW480 cell proliferation and inhibited HCT116 migration. MALL may play a role in colorectal cancer progression as suppression of its expression in tumor tissues negatively impacts colorectal cancer patient survival. Further analyses are required to determine if reduced MALL expression is due to LOH and/or methylation.

The Relationship Between Serum Interleukin-6 and the Recurrence of Hepatitis B Virus Related Hepatocellular Carcinoma after Curative Resection.

The aim of this study is to assess whether preoperative serum interleukin-6 (IL-6) can predict recurrence of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC). The association between preoperative IL-6 levels and HCC recurrence following curative hepatectomy in 146 patients with chronic HBV infection was determined. Patients were divided into groups based on the presence or absence of HCC recurrence. Serum IL-6 levels were compared between groups, and the association between serum IL-6 level and greatest tumor dimension was also analyzed. Receiver operating characteristics (ROC) curve was used to define the optimal cutoff value for predicting recurrence-free survival (RFS) and overall survival (OS) rates. The OS and RFS rates were calculated using the Kaplan-Meier method. Out of 146 patients, 80 (54.8%) patients were documented as having HCC recurrence during the follow-up period. After adjusting for potential confounders, serum IL-6 levels were significantly associated with HCC recurrence, and a saturation effect existed with serum IL-6 levels up to 3.7 pg/mL. In addition, patients with preoperative serum IL-6 levels over 3.1 pg/mL had lower RFS and OS rates (P < 0.01). There was no significant correlation between preoperative serum IL-6 levels and maximal tumor dimension (r = 0.0003, P = 0.84). Elevated serum levels of IL-6 were significantly associated with an increased risk of HBV-associated HCC recurrence suggesting that preoperative IL-6 serum level is potential biomarker for early prediction of HBV-associated HCC recurrence.

Adenovirus-mediated combined P16 gene and GM-CSF gene therapy for the treatment of established tumor and induction of antitumor immunity.

Antitumor effects of combined transfer of P16 and cytokine genes were investigated in this study. The adenovirus harboring the P16 gene (AdP16) and murine granulocyte-macrophage colony-stimulating factor gene (AdGM-CSF) were utilized for the treatment of established tumors. The mice were inoculated subcutaneously with Renca cells and, 6 days later, received an intratumoral injection of AdP16 in the presence or absence of AdGM-CSF. The results demonstrated that tumor-bearing mice treated with AdP16 in combination with AdGM-CSF showed more potent inhibition of tumor growth and survived much longer than did mice treated with AdP16, AdGM-CSF, adenovirus expressing beta-galactosidase, or phosphate-buffered saline alone (P<.01). The tumor mass showed obvious necrosis and inflammatory cell infiltration, and more CD(4)(+) and CD(8)(+) T cells infiltrating the tumor after combined therapy. After combined therapy, the expression of MHC-1 (H-2K(d)) and Fas molecules on freshly isolated tumor cells increased greatly. The activity of specific cytotoxic T lymphocytes was also found to be induced more significantly after the combined therapy (P<.01). Our results demonstrated that combined therapy with P16 and GM-CSF genes can inhibit the growth of established tumors in mice significantly and induce antitumor immunity of the host efficiently.