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Colorectal tumorigenesis is a heterogeneous disease driven by multiple genetic and epigenetic alterations. F-box and WD repeat domain containing 11 (FBXW11) is a member of the F-box protein family that regulates the ubiquitination of key factors associated with tumor growth and aggressiveness. Our study aimed to explore the role of FBXW11 in the development and metastasis of colorectal cancer (CRC). FBXW11 was overexpressed in colorectal tumor tissues and its overexpression was associated with a poor prognosis of CRC patients. The upregulation of FBXW11 not only promoted cell proliferation, invasion, and migration, but also contributed to maintaining stem-cell features in colorectal tumor cells. Further analysis revealed that FBXW11 targeted hypermethylated in cancer 1 (HIC1) and reduced its stability in CRC cells through ubiquitination. Moreover, the expression of sirtuin 1 (SIRT1), a deacetylase in tumor cells was upregulated by FBXW11 via regulating HIC1 expression. The mouse xenograft models of CRC confirmed that FBXW11 knockdown impeded colorectal tumor growth and liver metastasis in vivo. In summary, our study identified FBXW11 as an oncogenic factor that contributed to stem-cell-like properties and liver metastasis in CRC via regulating HIC1-mediated SIRT1 expression. These results provide a rationale for the development of FBXW11-targeting drugs for CRC patients.

Pancreatic ductal adenocarcinoma (PDAC) is a common type of pancreatic cancer with one of the worst survival rate of all malignancies. Recent studies have identified that immunosuppressive B cells could employ the PD-1/PD-L1 pathway to suppress antitumour T cell responses; hence, we examined the expression and function of PD-L1 in B cells. We found that the PD-L1 expression was significantly enriched in tumour-infiltrating (TI) B cells than in peripheral blood (PB) B cells from the same patients. Additionally, the PB B cells from stage III and stage IV PDAC patients presented significantly higher PD-L1 than the PB B cells from healthy controls. High PD-L1 expression in PB B cells could be achieved by stimulation via CpG and less effectively via anti-BCR plus CD40L, but not by coculture with pancreatic cancer cell lines in vitro. Also, STAT1 and STAT3 inhibition significantly suppressed PD-L1 upregulation in stimulated B cells. CpG-stimulated PB B cells could inhibit the IFN-γ expression and proliferation of CD8 T cells in a PD-L1-dependent manner. Also, TI CD8 T cells incubated with whole TI B cells presented significantly lower IFN-γ expression and lower proliferation, than TI CD8 T cells incubated with PD-L1+ cell-depleted TI B cells, suggesting that PD-L1+ B cells could also suppress CD8 T cells in the tumour. Overall, this study identified that B cells could suppress CD8 T cells via PD-L1 expression, indicating a novel pathway of immuno-regulation in pancreatic cancer.

Colorectal cancer (CRC) is a common cancer with poor prognosis. The research was designed to explore the role of PHF20L1 in angiogenesis and liver metastasis in CRC and discuss its molecular mechanism. Expression levels of PHF20L1, HIC1 and PAX2 in CRC tissues collected from CRC patients were detected using qRT-PCR, WB and immunohistochemical staining. CRC cells were transfected with PHF20L1, HIC1 and PAX2 overexpression or knockdown vectors and the proliferation, apoptosis, EMT and angiogenesis of the cells were determined. WB was utilized to assess protein levels of PHF20L1, HIC1, PAX2 and angiogenesis factor (ANGPT2, FGF1, PDGFA and VEGFA). The role of PHF20L1 regulating tumor formation and liver metastasis in vivo was detected as well. PHF20L1 was observed to express at a high level of CRC tissues. PHF20L1 promoted CRC cell growth, EMT and angiogenesis, and inhibited cell apoptosis. Knockdown of PHF20L1 had opposite effects on CRC cells. PHF20L1 negatively regulated HIC1 expression to promote PAX2 expression, thus promoting CRC cell progression. The in vivo results showed that PHF20L1 contributed to tumor formation and liver metastasis. PHF20L1 increases PAX2 expression to promote angiogenesis in CRC by inhibiting HIC1, therefore facilitating CRC cell EMT and liver metastasis. Our finding may provide a novel insight for CRC pathogenesis.

Background: We hypothesized that Sirtuin 1 (SIRT1) might attenuate the Warburg effect in tumor cells by modulating hypoxia-induced factor-1 alpha (HIF-1α) expression. This study aimed to explore the role and the underlying mechanism of SIRT1 in protecting the mitochondrial functions in hepatocellular carcinoma (HCC) cells. Methods: Quantitative real-time PCR and western blot analysis were conducted to determine gene expression in HCC cells. Co-immunoprecipitation (co-IP), chromatin immunoprecipitation (ChIP), and luciferase reporter assays were performed to examine DNA-protein interactions. Colony formation and MTT assays were carried out to explore the role of SIRT1 in HCC cell proliferation in vitro. PLC5 and Huh7 tumor xenografts were generated in mice to investigate the role of SIRT1–HIF-1α signaling in HCC development in vivo. Results: In different HCC cell lines, overexpression of SIRT1 promoted oxidative phosphorylation-associated gene expressions, ATP production, cell proliferation, and apoptotic protein expression while attenuating VEGF expression. In mice, overexpression of SIRT1 resulted in significant reductions in the weights of PLC5 and Huh7 tumor xenografts. Knockdown of SIRT1 exhibited opposite effects. Mechanistically, overexpression of SIRT1 promoted HIF-1α deacetylation, VHL-mediated HIF-1α degradation, and AMPK expression. Furthermore, SIRT1 interfered with the HIF-1α–c-Myc interaction to stimulate the transcription of a mitochondrial biogenesis enhancer mitochondrial transcription factor A (TFAM). Overexpression of HIF-1α completely reversed the effects of SIRT1.Conclusions: SIRT1 protects the mitochondria of HCC cells via suppressing HIF-1α expression, suggesting that SIRT1 may exert antitumor activity in HCC by reducing the Warburg effect.

Hepatocellular carcinoma (HCC) is a public health problem around the world, with the molecular mechanisms being still incompletely clear. This study was carried out to explore the role and mechanism of long-noncoding RNA (lncRNA) FEZF1-AS1 in HCC progression. RNA sequencing and quantitative real time polymerase chain reaction (qRT- PCR) were applied to identify differently expressed lncRNAs in HCC tissues and adjacent normal tissues. CCK8 assay was adopted to test cell proliferation and flow cytometry was taken to detect cell apoptosis. Wound healing assay and transwell experiment were performed to determine cell migration and invasion. To validate the function of lncRNA FEZF1-AS1 in vivo, tumor-burdened models were established. The results showed that lncRNA FEZF1-AS1 level was prominently enhanced in HCC tumor specimens and overexpression of FEZF1-AS1 promoted the proliferation, migration and invasion of HCC cells. In mechanism, overexpression of FEZF1-AS1 reduced the expression of miR-107 which inhibited the activation of Wnt/β-catenin signaling. Overexpression of β-catenin promoted cell proliferation, migration and invasion which were inhibited by FEZF1-AS1 downregulation. In conclusion, our study demonstrated that FEZF1-AS1 promoted HCC progression through activating Wnt/β-catenin signaling by targeting miR-107, which provided a novel target for the therapy of HCC.

A novel Gram-staining positive, moderately halophilic, endospore-forming, motile, rod-shaped and strictly aerobic strain, designated YIM 93565T, was isolated from a salt lake in Xinjiang province of China and subjected to a polyphasic taxonomic study. Strain YIM 93565T grew in the range of pH 6.0–9.0 (optimum pH 7.0), 10–45 °C (optimum 35–40 °C) and at salinities of 2–24% (w/v) NaCl (optimum 7–10%). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain YIM 93565T clustered with members of the genera Gracilibacillus and form a clade with Gracilibacillus bigeumensis KCTC 13130T (95.6% similarity) and Gracilibacillus halophilus DSM 17856T (94.9%), which was well separated from others. The DNA G + C content of this novel strain was 36.8 mol%. The major fatty acids were anteiso-C15:0, iso-C15:0, C16:0 and anteiso-C17:0 and its polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, one unidentified glycolipid and two unidentified phospholipids. The predominant menaquinone was MK-7. The cell-wall peptidoglycan was based on meso-diaminopimelic acid. Based on the results of phylogenetic, physiological and chemotaxonomic comparative analyses, the isolate is assigned to a novel species of the genus Gracilibacillus, for which the name Gracilibacillus eburneus sp. nov. is proposed, with the type strain YIM 93565T (= DSM 23710T = CCTCC AB 2013249T).

In this study, we developed a folate (FA)-conjugated and pH-responsive active targeting micellar system for anti-cancer drug delivery. In this system, FA was attached to the terminal of the hydrophilic segment of poly(lactic acid)–poly( L -lysine) (PLA–PLL), and PLL was modified by a citric acid group. The FA receptor-mediated active targeting and electrostatic interaction between micelles and cell membrane due to a negative-to-positive charge reversal was combined in one micellar anti-cancer drug delivery system to enhance the tumour targeting and cellular internalisation of micelles. In vitro and in vivo anti-cancer studies demonstrated that the doxorubicin-loaded, FA-conjugated and pH-responsive polymeric micelles possess an enhanced and effective cancer efficiency. Statement of significance Negatively charged nano-carriers prolonged anti-cancer drugs’ blood circulation. However it is difficult to be internalised. Therefore, a negative-to-positive charged micelle surface could improve selectivity for tumour cells and increase uptake chance. In this study, we developed a folate (FA)-conjugated and pH-responsive active targeting micellar system for anti-cancer drug delivery. The FA receptor-mediated active targeting and electrostatic interaction between micelles and cell membrane due to a negative-to-positive charge reversal was combined in one micellar anti-cancer drug delivery system to enhance the tumour targeting and cellular internalisation of micelles. In vitro and in vivo anti-cancer studies demonstrated that the doxorubicin-loaded, FA-conjugated and pH-responsive polymeric micelles possess an enhanced and effective cancer efficiency.

To investigate the tensile deformation behavior of high strength anti-seismic steel with multi-phase microstructure, tensile tests with strains of 0.05, 0.12 and 0.22 were performed at room temperature. Microstructure of tested steels was observed by means of optical microscopy (OM), transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Tensile mechanical properties of tested steels were obtained, and the influence of bainite content on deformation behavior was also discussed. Meanwhile, the deformation mechanism of steel with three kinds of microstructures of bainite, pearlite and ferrite was analyzed. Results show that tested steel with high volume fraction of bainite exhibits a continuous deformation behavior, and this may be attributed to a higher bainite volume fraction and a lower mobile dislocation density. The morphology of microstructure will influence the mechanical properties of tested steels. An increasing content of bainite can improve the tensile strength, but reduce the plasticity and toughness of the tested steels. In the deformation process of 0.039Nb steel, the ferrite and bainite have priorities to deform, and the deformation exhibits co-deformation of all microstructures in the later stage of deformation. In the deformation process of 0.024Nb-0.032V steel, the ferrite and pearlite have priorities to deform, and the deformation exhibits co-deformation of all microstructures in the later stage of deformation.

Although the combination of cisplatin and gemcitabine (GEM) is considered the standard first-line chemotherapy against unresectable hilar cholangiocarcinoma (HC), its efficacy is discouraging. The present randomized open-label clinical trial aimed to evaluate the efficacy and safety of the GEM plus S-1 (GEM-S-1) combination against unresectable HC. Twenty-five patients per group were randomly assigned to receive GEM, S-1 or GEM-S-1. Neutropenia (56%) and leukopenia (40%) were the most common chemotherapy-related toxicities in the GEM-S-1 group. Median overall survival (OS) in the GEM-S-1, GEM and S-1 groups was 11, 10 and 6 months, respectively. GEM plus S-1 significantly improved OS compared to S-1 monotherapy (OR=0.68; 95%CI, 0.50–0.90; P=0.008). Median progression-free survival (PFS) times in the GEM-S-1, GEM and S-1 groups were 4.90, 3.70 and 1.60 months, respectively. GEM plus S-1 significantly improved PFS compared to S-1 monotherapy (OR=0.50; 95%CI, 0.27–0.91; P=0.024). Response rates were 36%, 24% and 8% in the GEM-S-1, GEM and S-1 groups, respectively. A statistically significant difference was found in response rates between the gemcitabine-S-1 and S-1 groups (36% vs 8%, P=0.017). Patients with CA19-9

Heme oxygenase-1 has been identified to protect allograft from ischemia/reperfusion and immunologic rejection. Activity of heme oxygenase-1 is regulated by a guanine-thymine dinucleotide length polymorphism in the heme oxygenase-1 gene promoter. In this study, we aimed to explore the impact of the heme oxygenase-1 gene promoter polymorphism of donors and recipients on the orthotopic liver graft function after transplantation. Sixty recipients and their accompanying donors of orthotopic liver allografts were included retrospectively in this study. Heme oxygenase-1 gene promoter polymorphism was assessed using genomic DNA isolated from cryopreserved splenocytes or peripheral blood mononuclear cells and analyzed by genetic analyzer. Small allele of the donor heme oxygenase-1 gene polymorphism significantly prolonged the graft survival (p = 0.017). Recipients of allografts from a class of small-allele carrier had significantly lower serum total bilirubin compared with recipients of a nonclass small-allele donor liver (p

MicroRNA-542-3p (miR-542-3p) functions as a tumor suppressor in many human cancers, but its biological roles in hepatocellular carcinoma (HCC) remains to be further explored. In our study, we revealed that miR-542-3p was frequently down-expressed in HCC cell lines and tissues using real-time quantitative reverse-transcription PCR (qRT-PCR). Overexpression of miR-542-3p inhibits the proliferation of HCC cells via induction of apoptosis and cell cycle arrest. Furthermore, we confirmed that survivin was a direct target of miR-542-3p in HCC cells, and overexpression of survivin attenuated the miR-542-3p-induced inhibition of HCC cell proliferation. A negative association between miR-542-3p and survivin mRNA levels was also found in HCC tissues. These findings showed that miR-542-3p inhibits the proliferation of HCC cells by targeting survivin, indicating that miR-542-3p/survivin signaling axis might serve as a potential therapeutic target in the treatment of HCC.

Primary biliary cholangitis (PBC) is a chronic and progressive cholestatic liver disease with unknown causes. The initiation of PBC is associated with bacterial infections and abnormal immune correlates, such as the presence of self-reactive anti-mitochondrial antibodies and shifted balance of T cell subsets. In particular, the CD4+CXCR5+ follicular helper T (Tfh) cells are highly activated in PBC patients and are significantly associated with PBC severity, but the underlying reasons are unknown. In this study, we found that the circulating CD4+CXCR5+ T cells were enriched with the interferon (IFN)-γ-secreting Th1-subtype and the interleukin (IL)-17-secreting Th17-subtype, but not the IL-4-secreting Th2 subtype. We further demonstrated that a host of microbial motifs, including Pam3CSK4, poly(I:C), LPS, imiquimod, and CpG, could significantly stimulate IFN-γ, IL-17, and/or IL-21 from circulating CD4+CXCR5+ T cells in PBC patients, especially in the presence of monocytes and B cells. Whole bacterial cells of Escherichia coli, Novosphingobium aromaticivorans, and Mycobacterium gordonae, could also potently stimulate IFN-γ, IL-17, and/or IL-21 production from circulating CD4+CXCR5+ T cells. But interestingly, while the whole cell could potently stimulate circulating CD4+CXCR5+ T cells from both healthy controls and PBC patients, the cell protein lysate could only potently stimulate circulating CD4+CXCR5+ T cells from PBC patients, but not those from healthy controls, suggesting that circulating CD4+CXCR5+ T cells in PBC patients had distinctive antigen-specificity from those in healthy individuals. Together, these data demonstrated that bacterial antigen stimulation is a potential source of aberrant Tfh cell activation in PBC patients.

A novel Gram-staining positive, moderately halophilic, endospore-forming, motile, rod-shaped and strictly aerobic strain, designated YIM 93565

Little is known about the role of antiviral therapy for patients with hepatitis B who underwent curative hepatectomy for hepatocellular carcinoma (HCC). The aim of this study was to assess whether antiviral therapy after hepatectomy improves the prognosis of HCC in preoperatively antiviral-free patients.This was a retrospective study of postoperative antiviral treatment in patients (n=87) who underwent curative hepatectomy for HCC. Clinicopathological features and disease-free survival (DFS) were assessed. Patients were followed up to monitor HCC recurrence (median of 31 months).In patients with HCC up to 3 cm (n=36), antiviral therapy reduced serum alanine transminase levels after 6 months of treatment (-26.3%, P0.01). Among these patients, there was a significant prolongation of DFS in patients who received antiviral therapy after hepatectomy compared with those who did not (P=0.006). However, in patients with HCC greater than 3 cm (n=51), antiviral therapy did not decrease alanine transminase levels (+32.8%, P0.01). In these patients, antiviral therapy had no effect on DFS (P0.05). Using multivariate analysis, postoperative antiviral therapy was found to be an independent prognostic factor that was associated with a better DFS in patients with HCC up to 3 cm (odds ratio=0.220, 95% confidence interval: 0.120-0.434, P=0.008).Antiviral therapy improved the prognosis of hepatitis B virus-related HCC up to 3 cm. Antiviral therapy should be considered a standard postoperative adjuvant therapy of hepatitis B virus-related HCC.

Infective factors cause the perpetuation of inflammation as a result of the permanent exposure of the immune system to exogenous or endogenous products of virus or bacteria. Mesenchymal stem cells (MSCs) can be exposed to this infective environment, which may change the characteristics and therapeutic potency of these MSCs. MSCs have the ability to repair damaged and inflamed tissues and regulate immune responses. In this study, we demonstrated that MSCs express functional Toll-like receptors (TLR) 3 and 4, the Toll-like receptor families that recognize the signals of viral and bacterial mimics, respectively. The specific stimulations did not affect the self-renewal and apoptosis capabilities of MSCs but instead promoted their differentiation into the adipocytes and osteoblasts with the TLR3 ligand. The reverse of these results were obtained with the TLR4 ligand. The migration of the MSCs to stimulate either of the two specific ligands was inhibited at different times, whereas the immunogenicity and immunosuppressive properties of the MSCs were not weakened unlike in the MSCs group. These results suggest that TLR3 and TLR4 stimulation affect the characterization of MSCs.

It is still uncertain whether total bilirubin per se is a risk factor for osteoporosis in postmenopausal women and no study has so far examined this important issue. This study was designed to assess the sheer effects of total bilirubin on the prevalence of osteoporosis in postmenopausal women without potential liver disease. In the present study, postmenopausal female subjects without potential liver disease (n = 918) who underwent measurement of bone mineral density were enrolled. Correlation and logistic regression analysis were used to assess the relationship between total bilirubin and other variables. As a result, subjects with osteoporosis had a significantly lower total bilirubin level (P = 0.005). A 0.1 mg/dl increase in total bilirubin was associated with reduced odds ratio of the risk by 38 % for osteoporosis [OR 0.62 (95 % CI 0.52–0.88), P = 0.012] after adjustment for several variables. Total bilirubin was independently associated with BMD [coefficient = 0.41, 95 % CI (0.35–0.47), P

Current treatment of intrahepatic cholangiocarcinoma (ICC) remains ineffective because knowledge of ICC carcinogenesis is unclear. Increasing evidence suggests that microRNAs (miRNAs), including miRNA-191, play an important role in tumorigenesis, but expression and biological functions of miRNA-191 in ICC remain to be established. This study aimed to investigate the functions and underlying mechanisms of miRNA-191 in ICC. ICC miRNA profiles were generated in 5 pairs of ICC and matched to normal bile duct tissues by next-generation sequencing technology; ICC miRNA profiles were verified in 18 pairs of ICC tissues and normal bile duct tissues by quantitative reverse transcription PCR (qRT-PCR). The miR-191-associated mechanisms in ICC were investigated in vitro and in vivo and clinical outcomes associated with miR-191 were correlated in 84 patients. Our results showed miR-191 expression was significantly increased in ICC compared with the adjacent normal bile duct tissues (p

AIMS Gamma glutamyltransferase (GGT) has attracted great interest as a potential novel marker of cardiovascular risk. However, its association with coronary artery calcification (CAC) score-determined coronary artery atherosclerosis is unknown. This study was designed to assess the association of GGT with CAC score. METHODS Participants, 311 asymptomatic men and 220 asymptomatic women who underwent evaluation of CAC by cardiac computed tomography, were retrospectively investigated. Correlation and logistic regression analysis were used to assess the association of GGT with CAC score and other variables. RESULTS Women but not men with higher GGT had a higher incidence of CAC score above 100 and a higher prevalence of metabolic syndrome (P = 0.012 and 0.007, respectively). GGT was positively correlated with C-reactive protein (CRP) in women (r = 0.336, P

Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) is one of the most common cancers in HBV-endemic regions, with irreversible progression and poor prognosis. HBV-related HCC patients lack effective antiviral/antitumor B cell antibody responses. We hypothesize that dysregulation of PD-1-expressing follicular helper T (Tfh) cell, induced by intrahepatic/intratumoral PD-L1 expression in HCC, could contribute to the defects in B cell immunity. The Tfh responses in healthy control (HC) subjects, chronic hepatitis B (HepB) patients, and HBV-related HCC patients were examined. Compared to HC and HepB individuals, HCC patients showed reduced ICOS expression, IL-10 and IL-21 secretion, and proliferation in Tfh cells. Tfh cells from stage III patients demonstrated increased impairment than those from stage I and stage II patients. Compared to Tfh cells from HC and HepB subjects, those from stage III HCC patients were significantly less effective at inducing the differentiation of naive B cells toward plasmablasts. HCC is known to upregulate hepatic PD-L1 expression, which could suppress Tfh responses. Blocking PD-1 partially rescued the Tfh functions in stage I and stage II HCC subjects but not in stage III HCC patients, while treatment with recombinant PD-L1 strongly suppressed Tfh functions in all HCC stages. Moreover, the level of IL-10 and IL-21 expression by Tfh cells was inversely correlated with the intensity of PD-L1 expression in resected tumors. Together, our results demonstrated an HCC-specific Tfh exhaustion, which might have resulted from elevated PD-1 and PD-L1 signaling.

Serum uric acid (SUA) is a potential risk factor for atherosclerosis. We assessed the relationship between SUA and subclinical atherosclerosis in Korean men (n = 3010). Multidetector computed tomography (MDCT) and ultrasonographic measurements of coronary artery calcification (CAC) and carotid intima–media thickness (cIMT), respectively, are markers of subclinical atherosclerosis. Odds ratios (ORs) of CAC score and cIMT across SUA levels were 1.101 ( P = .046) and 1.266 ( P = .002), respectively, after adjustment for several variables. The independent association between CAC and cIMT was observed (OR = 1.231, P < .001). Serum uric acid was independently associated with metabolic syndrome (MetS) with an OR of 1.415 ( P < .001). Metabolic syndrome was only independently associated with cIMT, with an OR of 2.103 ( P = .003). High-sensitivity C-reactive protein was positively correlated with SUA ( r = .125, P < .001). Serum uric acid level is independently associated with CAC, cIMT, and MetS in Korean men.

A Gram-negative, pink-coloured, rod-shaped, motile bacterium, designated YIM 93097T, was isolated from the desert soil collected from Xinjiang province of China. Strain YIM 93097T was found to grow at 20–45 °C (optimum 28–37 °C), pH 5.0–7.0 (optimum pH 7.0) and 0–8 % (w/v) NaCl (optimum 1 %, w/v). Based on 16S rRNA gene sequence similarity studies, it belongs to the genus Skermanella. The 16S rRNA gene sequence similarity was identified to be 98.7 % to Skermanella xinjiangensis CCTCC AB 207153T while the DNA–DNA hybridization value was found to be only 48.1 %. The predominant isoprenoid quinone was determined to be Q-10. The major fatty acids were identified to be C16:0, C18:1 ω7c and summed feature 4 (consisting of C17:1 anteiso B/iso I). The major polar lipids were identified as phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, two unidentified phospholipids and one unidentified aminolipid. The DNA G+C content was found to be 67.2 mol %. The analysis of the genotypic and phenotypic data indicated that strain YIM 93097T belongs to a novel species of the genus Skermanella, for which the name Skermanella rubra sp. nov. is proposed. The type strain is YIM 93097T (=DSM 21389T=CCTCC AB 2015161T).

OBJECTIVE The influence of surgical approaches on patients with gastric cancer with portal hypertension is unknown. The aim of the study was to investigate the outcomes in such patients who had undergone curative surgery for gastric cancer. PATIENTS AND METHODS The clinical data of 60 patients with portal hypertension undergoing curative surgery for gastric cancer or simultaneous surgery for portal hypertension were retrospectively analyzed. RESULTS Radical gastrectomy alone had no tremendous impact on postoperative liver function, but simultaneous surgery for portal hypertension affected patients' liver function dramatically (P

We hypothesized that the combination of APACHE II and Model for End-Stage Liver Disease systems would work satisfactorily in patients admitted to intensive care unit after living-donor liver transplant.Data were retrospectively collected from the database of our surgical team. The study included 38 patients (hepatitis B virus cirrhosis, 47.4%; hepatocellular carcinoma, 28.9%; other diseases, 23.7%). Laboratory values were obtained. Vital signs, Glasgow Coma scale scores, and urine output were abstracted. Variables included age, sex, acute physiology score, APACHE II score, APACHE II-predicted intensive care unit and hospital mortality, predicted length of intensive care unit, and hospital stay. Patients' actual length of intensive care unit and hospital stays, intensive care unit and hospital discharge status, and discharge location were recorded. Standardized mortality ratios were calculated. Discrimination and calibration of APACHE II were assessed. All patients were divided into 3 groups: Model for End-Stage Liver Disease score:25, 18 to 25, and18. Predicted hospital mortality was calculated and compared.Mean APACHE II scores of survivors and non-survivors were 13.03 and 23.67. Mean risk of death was 7.05% and 25.07%. APACHE II scores and risk of death between survivors and non-survivors was significantly different (P.001). The cutoff value of APACHE II score and Model for End-Stage Liver Disease score in the receiving operating characteristic curve was 20 and 25. Patients with APACHE II scores greater than 20 or Model for End-Stage Liver Disease scores greater than 25 had higher predicted hospital mortality after living-donor liver transplant.The modified APACHE II model provides an accurate prognosis of patients receiving a living-donor liver transplant. The combined application of Model for End-Stage Liver Disease score and APACHE II score can improve the predictive accuracy.

Background & Aims SIRT1 is a class III histone deacetylase that plays diverse roles in various cancers. However, the clinical significance of SIRT1 in hepatocellular carcinoma (HCC) remains unknown. Methods We analysed p53 mutations and the activation of SIRT1 in 252 hepatitis B virus-positive HCC cases. None of the patients had been subjected to pre-operative treatment. Results We examined 57 p53 mutations from 248 HCC tissues. Activated SIRT1 (phosphorylated form of Ser47), in the context of mutant p53 , predicted a longer relapse-free survival (RFS) but not a longer overall survival (OS) (RFS: p =0.007, OS: p =0.280) in HCC tissues harbouring mutant p53 . In multivariate analysis, activated SIRT1 remained a significant predictor of longer RFS (OR=0.307, CI: 0.143–0.660, p =0.002). Analysis of 248 paired specimens revealed a significant correlation between activated SIRT1 (Ser47) and activated AMPK (Thr172) in HCC tissues harbouring mutant p53 ( p =0.003, n=57). The combination of these 2 parameters was a powerful predictor for a good prognosis in these patients. In vitro , SIRT1 inactivation stimulated the growth of HCC cells, bearing mutated p53 , by suppressing AMPK activity and subsequently enhancing mammalian target of rapamycin (mTOR) activity, resulting in induction of p70S6K1 activation in HCC cells. Metformin, an AMPK activator, more strongly suppressed cell growth in p53 -mutant cell lines with inactive SIRT1 than in p53 -mutant cell lines with active SIRT1. Conclusions SIRT1 exerted anti-carcinogenic effects via the AMPK-mTOR pathway in HCC in the context of mutant p53 . Metformin could be a therapeutic drug for HCC in patients with mutated p53 , inactivated SIRT1, and AMPK expression.

Serum total bilirubin has been suggested to have the potential anti-inflammatory and antioxidant effects on the vasculature. This study was designed to investigate the association of bilirubin with brachial-ankle pulse wave velocity (baPWV), a marker of arterial stiffness and cardiovascular disease. Hypertensive male subjects (n = 2,361) were classified into groups according to the 50th, 75th, and 95th percentiles of baPWV value. Correlation and regression analysis were used to assess the relationship between baPWV and other variables. Hypertensive subjects with baPWV above the 50th, 75th, and 95th percentiles had a significantly lower bilirubin level than those with baPWV under them (0.97 ± 0.40 vs. 1.00 ± 0.41 mg/dl, P < 0.001; 0.95 ± 0.39 vs. 0.99 ± 0.41 mg/dl, P = 0.001; 0.92 ± 0.36 vs. 0.99 ± 0.42 mg/dl, P = 0.048, respectively). Bilirubin is inversely related to baPWV (R (2) = 0.0032, P = 0.003) and C-reactive protein (CRP) (correlation coefficient = -0.13, P < 0.001). A 0.1 mg/dl increase in bilirubin was associated with a 19, 20, and 34 % reduced odds ratio for baPWV above the 50th, 75th, and 95th percentiles, respectively [odds ratio (OR) 0.77 (95 % confidence interval (CI) 0.62-0.95), P = 0.015; OR 0.80 (95 % CI 0.64-0.99), P = 0.044; OR 0.68 (95 % CI 0.45-1.00), P = 0.048, respectively] after adjustment for several variables. This study demonstrates an independent inverse association between bilirubin and baPWV in hypertensive men. Additionally, reduced CRP may be one of mediators on the mechanisms how bilirubin reduces baPWV.

Background: Serum total bilirubin has been suggested to have potential anti-inflammatory and antioxidant effects on the vasculature, acting against plaque formation and subsequent atherosclerosis. This study was designed to assess the association of serum total bilirubin with coronary artery calcification (CAC). Hypothesis: Individuals with higher bilirubin level would be less likely to develop CAC. Methods: Male subjects (N = 3408) underwent evaluation of CAC by cardiac computed tomography. Correlation and logistic regression analysis were performed to assess the relationships between CAC score and other variables. Results: Subjects with a higher CAC score had significantly lower total bilirubin level (P = 0.001). Total bilirubin level was negatively correlated with CAC score (r = −0.052, P = 0.002). A 0.1-mg/dL increase in bilirubin was associated with a reduced odds ratio (OR) of the risk by 29.2% for a CAC score above 100 (OR: 0.708, 95% confidence interval: 0.542-0.927, P = 0.012) after adjustment for several variables. Bilirubin was inversely correlated with high-sensitivity C-reactive protein (hsCRP) (r = −0.117, P < 0.001). Conclusions: This study demonstrated an independent inverse association between serum total bilirubin and CAC score in males. Low serum bilirubin concentration would be useful as a potential risk factor for CAC in males. Additionally, reduced hsCRP may be 1 of the mechanisms for how bilirubin reduces CAC. © 2012 Wiley Periodicals, Inc. Additional Supporting Information may be found in the online version of this article. Zheng-Yun Zhang, MD, and Lu-Qin Bian, MD, contributed equally to this work. The authors have no funding, financial relationships, or conflicts of interest to disclose.

The induced expression of heme oxygenase-1 (HO-1) in donor islets improves allograft survival. Cobalt protoporphyrin (CoPP) could significantly enhance the expression of HO-1 mRNA and protein in rat islet safely. Our work was to study how to protect pancreatic islet xenograft by CoPP-induction.Islet xenografts treated with CoPP-induction and CoPP + Zinc protoporphyrin (ZnPP) in vitro and in vivo were randomly transplanted into murine subrenal capsule; then the graft survival time was compared by blood glucose level and pathological examination and meanwhile the interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), interleukin 10 (IL-10) and IL-1β level in serum and their mRNA and HO-1 mRNA and protein expression were examined.Islets with CoPP-induction under low- and high-glucose stimulation exhibited much higher insulin secretion compared with other three groups. CoPP-induction could increase higher expression of HO-1 (mRNA: 3.33- and 76.09-fold in vitro and in vivo; protein: 2.85- and 58.72-fold). The normoglycemia time in induction groups ((14.63 ± 1.19) and (16.88 ± 1.64) days) was significantly longer. The pathological examination showed less lymphocyte infiltration in induction groups. The IL-10 level and its mRNA in induction groups were significantly higher.The HO-1 induced by CoPP would significantly improve function, prolong normoglycemia time and reduce lymphocyte infiltration. Meanwhile CoPP-induction in vivo had more beneficial effects than in vitro. Its mechanism could be related to immune-modulation of IL-10.

Our work was to study the protective effect of cobalt protoporphyrin (CoPP) on islet xenograft and its mechanism. According to CoPP induction of rat pancreas islet cells in different concentration and time, the optimal CoPP dosage to induce high expression of HO-1 would be determined by examining expression of HO-1 mRNA and protein in graft and islet function. Subsequently, islet cells with untreated, CoPP-induced, and CoPP-induced with zinc protoporphyrin (ZnPP)-blocked were randomly transplanted into murine subrenal capsule, then the survival time among these different treated groups was compared by blood glucose level and pathologic examination and meanwhile the IFN-γ, TNF-α, IL-10, and IL-1β level in serum and their mRNA and protein expression would be examined in grafts. CoPP at 50 mmol/L for 36 h incubation induced the highest HO-1 mRNA and protein expression in islets. CoPP treated islets under low glucose and high glucose stimulation exhibited insulin secretion of 30.52 ± 2.04 μIU/mL and 104.60 ± 5.10 μIU/mL, respectively in comparison to control (20.35 ± 1.79 μIU/mL and 62.39 ± 2.50 μIU/mL, respectively) (P

The molecule of the title compound, C18H19N3O, displays a trans configuration with respect to the C=N double bond. There is a strong intramolecular O—H...N hydrogen-bonding interaction between the hydroxy group and imine N atom. The dihedral angle between the aromatic rings is 30.35 (8)°. The crystal packing is stabilized by O—H...N links.

In the molecule of the title compound, C28H32N2, the benzimidazole ring system is almost planar [maximum deviation = 0.0221 (15) Å] and forms dihedral angles of 85.86 (4) and 32.09 (6)° with the benzene rings. In the crystal structure, molecules are linked into chains running parallel to the a axis by intermolecular C—H...N hydrogen bonds. The methyl groups of a tert-butyl group are rotationally disordered over two positions with refined site-occupancy factors of 0.636 (4) and 0.364 (4).

The molecule of the title compound, C16H15N3, displays a trans configuration with respect to the C=N double bond. The molecule is not planar, the dihedral angle between the benzene rings being 57.83 (9)°. The crystal packing is stabilized only by van der Waals interactions.