Field demonstration of on-site immobilization of arsenic and lead in soil using a ternary amending agent.

Soil contamination by heavy metals and metalloids has been a major environmental challenge. While various remediation technologies have been reported, field data on the remediation effectiveness have been limited. We tested a new remediation technology for on-site immobilization of As(III) and Pb(II) in a contaminated soil at an abandoned chemical plant site. A novel ternary amending agent consisting of Fe2O3, MnO2, and Mg(OH)2 (molar ratio = 1.0:5.5:5.5) was used to amend the soil on-site. Field monitoring data indicated that the amendment severed as a pH buffer and a long-term sequester for both As and Pb in the soil. At a dosage of 3 wt%, the acid-leachable As and Pb were lowered from 0.042-0.077 mg/L and 0.013-0.022 mg/L to 0.0062-0.0093 mg/L and 0.0030-0.0080 mg/L, respectively, after one day of the amendment, and to 0.0020-0.0050 mg/L and 0.0020-0.0054 mg/L after 240 days of aging. As(III) was oxidized to As(V) and subsequently immobilized via complexation and precipitation, whereas Pb(II) was sequestered via electrostatic attraction and chemical precipitation. The treatment cost was estimated at $31.5/m3. The results indicate that complex contaminants in soil can be effectively immobilized using combined amending agents that can interact with the target chemicals and induce synergistic immobilization reactions.

CCND1 rs9344 polymorphism is associated with the risk of hepatocellular carcinoma in Caucasian population.

AIMS: Some studies investigated the association between CCND1 rs9344 polymorphism and hepatocellular carcinoma (HCC) risk. However, the results were inconclusive. Thus, we did a meta-analysis to determine this relationship. MATERIALS AND METHODS: Relevant studies were systematically searched using the PubMed, CNKI, and EMBASE databases. The strength of the association was calculated with the odds ratio (OR) and respective 95% confidence intervals (Cis). RESULTS: We investigated the association between CCND1 rs9344 polymorphism and HCC risk in the dominant models. The result of this meta-analysis showed that CCND1 rs9344 polymorphism did not significantly associated with HCC risk (OR = 1.09; 95% CI 0.88-1.34). In the stratified analysis by ethnicity, we found that this polymorphism was significantly associated with HCC risk in Caucasians (OR = 1.55; 95% CI, 1.05-2.29). However, we did not find any significant association between this polymorphism and HCC risk in Asians (OR = 0.91; 95% CI, 0.71-1.18). CONCLUSIONS: This meta-analysis suggested that CCND1 rs9344 polymorphism might be associated with the risk of HCC among Caucasians.

Identfication of key miRNAs in pancreatitis using bioinformatics analysis of microarray data.

Pancreatitis is a type of inflammation in the pancreas, which frequently occurs due to alcohol and gallstones. The present study aimed to identify pancreatitis­associated microRNAs (miRNAs) by analyzing the microarray of GSE24279. GSE24279 was downloaded from the Gene Expression Omnibus, composed of a collective of 27 pancreatitis and 22 normal control samples. The differentially expressed miRNAs (DE­miRNAs) in pancreatitis samples were screened using the Limma package in Bioconductor. Subsequently, target genes of the DE­miRNAs were predicted using the miRecords and miRWalk databases. Their potential functions were analyzed by functional and pathway enrichment analysis using the Database for Annotation, Visualization and Integrated Discovery online tool. Finally, pancreatitis­associated genes among the target genes identified were searched using the Comparative Toxicogenomics Database, and a regulatory network of pancreatitis­associated genes and their target miRNAs were constructed using Cytoscape software. A total 14 upregulated and 39 downregulated miRNAs were identified in pancreatitis samples compared with control samples and 290 target genes of DE­miRNAs were determined. Cyclin D1 (CCND1), v­akt murine thymoma viral oncogene homolog 2 (AKT2), cyclin­dependent kinase 6 (CDK6) and SMAD family member 2 (SMAD2) were involved in the pathway of pancreatic cancer. Among the target genes, 279 genes were pancreatitis­associated genes, which in turn were targeted by 37 miRNAs in the regulatory network. Hsa­miR­15a, hsa­miR­16, hsa­miR­155, hsa­miR­375 and hsa­miR­429 in particular may be involved in pancreatitis by targeting genes in the regulatory network, including hsa­miR­15a→CCND1, hsa­miR­16→CCND1, hsa­miR­155→CCND1/SMAD2, hsa­miR­375→AKT2/CDK6 and hsa­miR­429→CCND1. The above miRNAs and their targets may contribute to the pathogenesis of pancreatitis; therefore, they may be potential therapeutic targets.

The ubiquitin ligase RNF43 downregulation increases membrane expression of frizzled receptor in pancreatic ductal adenocarcinoma.

RNF43 is a novel tumor suppressor protein and known to be expressed in a multitude of tissue and dysregulated in cancers of these organs including ovarian and colorectal tissues. RNF43 expression has been shown to be expressed in mutated forms in several pancreatic cell lines. RNF43, by virtue of being an ubiquitin ligase, has the potential to ubiquitinylate membrane receptors like frizzled that subserves sensing Wnt soluble signals at the cell membrane. Thus, normally, RNF43 downregulates Wnt signaling by removing frizzled receptor from the membrane. In the present study, the expression of the tumor suppressor RNF43 was examined in human patient samples of pancreatic ductal adenocarcinoma (PDAC). Reduced levels of expression of RNF43 in PDAC were demonstrated by Western blotting. We incorporated membrane biotinylation assay to examine the expression of frizzled6 receptor in the membrane and demonstrated that it is significantly increased in PDAC tissues. This may be responsible for enhanced Wnt/beta-catenin signaling and provides the first level of evidence of a possible role of this well-known pathway in pancreatic exocrine carcinogenesis. We have utilized appropriate controls to ensure the true positivity of the findings of the present study. The contribution of Wnt/beta-catenin/RNF43 pathway in pancreatic carcinogenesis may provide for utilization of pharmacologic resources for precision-based approaches to treat pancreatic ductal adenocarcinoma.

Identification of MicroRNAs and target genes involvement in hepatocellular carcinoma with microarray data.

The aim of the study is to identify the differentially expressed microRNAs (miRNAs) between hepatocellular carcinoma (HCC) samples and controls and provide new diagnostic potential miRNAs for HCC. The miRNAs expression profile data GSE20077 included 7 HCC samples, 1 HeLa sample and 3 controls. Differentially expressed miRNAs (DE-miRNAs) were identified by t-test and wilcox test. The miRNA with significantly differential expression was chosen for further analysis. Target genes for this miRNA were selected using TargetScan and miRbase database. STRING software was applied to construct the target genes interaction network and topology analysis was carried out to identify the hub gene in the network. And we identified the mechanism for affecting miRNA function. A total of 54 differentially expressed miRNAs were identified, in which there were 13 miRNAs published to be related to HCC. The differentially expressed hsa-miR-106b was chosen for further analysis and PTPRT (Receptor-type tyrosine-protein phosphatase T) was its potential target gene. The target genes interaction network was constructed among 33 genes, in which PTPRT was the hub gene. We got the conclusion that the differentially expressed hsa-miR-106b may play an important role in the development of HCC by regulating the expression of its potential target gene PT-PRT.

Should temporary extracorporeal continuous portal diversion replace meso/porta-caval shunts in "small-for-size" syndrome in porcine hepatectomy?

AIM: To investigate the feasibility of temporary extracorporeal continuous porta-caval diversion (ECPD) to relieve portal hyperperfusion in "small-for-size" syndrome following massive hepatectomy in pigs. METHODS: Fourteen pigs underwent 85%-90% liver resection and were then randomly divided into the control group (n = 7) and diversion group (n = 7). In the diversion group, portal venous blood was aspirated through the portal catheter and into a tube connected to a centrifugal pump. After filtration, the blood was returned to the pig through a double-lumen catheter inserted into the internal jugular or subclavian vein. With the conversion pump, portal venous inflow was partially diverted to the inferior vena cava through a catheter inserted via the gastroduodenal vein at 100-130 mL/min. Portal hemodynamics, injury, and regeneration in the liver remnant were compared between the two groups. RESULTS: Compared to the control group, porta-caval diversion via ECPD significantly mitigated excessive portal venous flow and portal vein pressure (PVP); the portal vein flow (PVF), hepatic artery flow (HAF), and PVP in the two groups were not significantly different at baseline; however, the PVF (431.8 ± 36.6 vs 238.8 ± 29.3, P < 0.01; 210.3 ± 23.4 vs 122.3 ± 20.6, P < 0.01) and PVP (13.8 ± 2.6 vs 8.7 ± 1.4, P < 0.01; 15.6 ± 2.1 vs 10.1 ± 1.3, P < 0.05) in the control group were significantly higher than those in the diversion group, respectively. The HAF in the control group was significantly lower than that in the diversion group at 2 h and 48 h post hepatectomy, and ECPD significantly attenuated injury to the sinusoidal lining and hepatocytes, increased the regeneration index of the liver remnant, and relieved damage that the liver remnant suffered due to endotoxin and bacterial translocation. CONCLUSION: ECPD, which can dynamically modulate portal inflow, can reduce injury to the liver remnant and facilitate liver regeneration, and therefore should replace permanent meso/porta-caval shunts in "small-for-size" syndrome.

Comparison analysis in synchronous and metachronous metastatic colorectal cancer based on microarray expression profile.

BACKGROUND/AIMS: Colorectal cancer (CRC) is one of the most common malignancies, and liver metastasis is one of the major causes of death of CRC. This study aimed to compare the genetic difference between metachronous lesions (MC) and synchronous lesions (SC) and explore the molecular pathology of CRC metastasis. METHODOLOGY: Microarray expression profile data (GSE10961) including 8 MC and 10 SC was downloaded from Gene Expression Omnibus. The differentially expressed genes (DEGs) between the two groups were identified based on T test. Furthermore, GO enrichment analysis was performed for the down-regulated DEGs using DAVID. Finally, Classify validation of known CRC genes based on previous studies between MC and SC samples was conducted. RESULTS: Total of 36 DEGs including 35 down-regulated DEGs and 1 up-regulated DEGs were identified. The expressional differences of the 5 informative oncogenes: EGFr, PIK3R1, PTGS2 (COX-2), PTGS1 (COX1), and ALOX5AP between SC and MC were really tiny. CONCLUSIONS: Some DEGs, such as NFAT5, OLR1, ERAP2, HOXC6 and TWIST1 might play crucial roles in the regulation of CRC metastasis (both SC and MC) and by disrupting some pathways. However, our results indeed demand further research and experiment.

Prognostic significance of microRNA-141 expression and its tumor suppressor function in human pancreatic ductal adenocarcinoma.

Increasing evidence shows that dysregulation of microRNAs is correlated with tumor development. This study was performed to determine the expression of miR-141 and investigate its clinical significance in pancreatic ductal adenocarcinoma (PDAC). Taqman quantitative RT-PCR was used to detect miR-141 expressions in 94 PDAC tissues and 16 nontumorous pancreatic tissues. Correlations between miR-141 expression and clinicopathologic features and prognosis of patients were statistically analyzed. The effects of miR-141 expression on growth and apoptosis of PDAC cell line (PANC-1) were determined by MTT, colony formation, and flow cytometry assays. Potential target genes were identified by luciferase reporter and Western blot assays. The expression level of miR-141 in PDAC tissues was significantly lower than that in corresponding nontumorous tissues. Downregulation of miR-141 correlated with poorer pT and pN status, advanced clinical stage, and lymphatic invasion. Also, low miR-141 expression in PDAC tissues was significantly correlated with shorter overall survival, and multivariate analysis showed that miR-141 was an independent prognostic factor for PDAC patients. Further, functional researches suggested that miR-141 inhibits growth and colony formation, and enhances caspase-3-dependent apoptosis in PANC-1 cells by targeting Yes-associated protein-1 (YAP1). Therefore, miR-141 is an independent prognostic factor for PDAC patients, and functions as a tumor suppressor gene by targeting YAP1.

Extracorporeal continuous portal diversion plus temporal plasmapheresis for "small-for-size" syndrome.

AIM: To investigate the effect of plasmapheresis via the portal vein for "small-for-size" syndrome (SFSS) aided by extracorporeal continuous portal diversion (ECPD). METHODS: Extensive or total hepatectomy in the pig is usually adopted as a postoperative liver failure (PLF) or SFSS model. In this study, animals which underwent 85%-90% hepatectomy were randomized into either the Systemic group (n = 7) or the Portal group (n = 7). In the Systemic group, all pigs received temporal plasmapheresis (PP) via the extracorporeal catheter circuit (systemic to systemic circulation) from 24 to 30 h post-hepatectomy (PH); in the Portal group, all pigs received ECPD to divert partial portal vein flow (PVF) to the systemic circulation after hepatectomy, then converted to temporal PP from 24 to 30 h PH, and subsequently converted to ECPD again until 48 h PH. In the Portal group, the PVF was preserved at 3.0-3.3 times that of the baseline value, similar to that following 70% hepatectomy, which was regarded as the optimal PVF to the hypertrophic liver remnant. At 48 h PH, all pigs were re-opened and the portal vein pressure (PVP), PVF, and HAF (hepatic artery flow) were measured, and then diversion of the portal venous flow was terminated. After 1 h the PVP, PVF, and HAF were re-measured. The portal hemodynamic changes, liver injury, liver regeneration and bacterial/lipopolysaccharide (LPS) translocation were evaluated in the two groups. RESULTS: The PVP in the Portal group was significantly lower than that in the Systemic group during the time period from 2 to 49 h PH (P < 0.05). Serum alanine aminotransferase (ALT), total bilirubin (TB) and ammonia were significantly reduced in the Portal group compared with the Systemic group from 24 to 48 h PH (P < 0.05). The Portal group may have attenuated sinusoidal endothelial injury and decreased the level of HA compared with the Systemic group. In the Systemic group, there was significant sinusoidal dilation, hydropic changes in hepatocytes and hemorrhage into the hepatic parenchyma, and the sinusoidal endothelial lining was partially destroyed and detached into the sinusoidal space. CD31 immunostaining revealed significant destruction of the endothelial lining. In the Portal group, there was no intraparenchymal hemorrhage and the sinusoidal endothelial cells and hepatocytes were well preserved. CD31 immunostaining was mild which indicated less destruction of the endothelial lining. HA was significantly decreased in the Portal group compared with the Systemic group from 2 to 48 h PH. The rate of liver remnant regeneration was elevated, while apoptosis was attenuated in the Portal group compared with the Systemic group. Thymidine kinase activity was much higher in the Portal group than in the Systemic group at 48 h PH. The PCNA index was significantly increased and the apoptotic index was significantly decreased in the Portal group compared with the Systemic group. Bacterial translocation and endotoxin, as well as the inflammatory response, were significantly attenuated in the Portal group compared with the Systemic group. LPS, tumor necrosis factor-α and interleukin-6 levels were all significantly decreased in the Portal group compared with the Systemic group from 24 to 48 h PH, while bacterial DNA level was significantly decreased from 2 to 48 h PH. CONCLUSION: PP plus ECPD via the portal vein can attenuate toxic load and hyperperfusion injury, and should be undertaken instead of PP via the systemic circulation in SFSS or PLF.

Impact of mesocaval shunt on safe minimal liver remnant: porcine model.

AIM: To investigate the capacity of shunts to relieve portal hypertension and decrease the safe minimal liver remnant in pigs. METHODS: A subtotal hepatectomy with < 60 mL blood loss and without hepatic pedicle occlusion was performed. The mesenteric venous inflow was diverted through a mesocaval shunt (MCS) constructed using the prepared left renal vein with an end-to-side running suture of 5-0 proline. All 21 animals that underwent subtotal hepatectomy and/or MCS were divided into three groups. In the 15% group, the residual volume was 14%-19% of total liver volume (TLV); in the 15%+ S group, the residual volume was also 14%-19% of TLV with a mesocaval shunt (MCS); and in the 10%+ S group, the residual volume was 8%-13% of TLV with an MCS. In the three groups, the intraoperative portal vein pressure (PVP) and portal vein flow (PVF) were monitored and compared at laparotomy and 1 h post-hepatectomy. The survival rate, sinusoidal endothelial damage, tissue analysis, and serum analysis were investigated among the three groups. RESULTS: The percentage residual liver volume was 15.9%, 16.1% and 11.8% in the 15%, 15%+ S, 10%+ S groups, respectively. After hepatectomy, PVF and portal-to-arterial flow ratio in the 15%+ S group significantly decreased and hepatic artery flow (HAF) per unit volume significantly increased, compared to those in the 15% group. The PVP in the 15%+ S group and 10%+ S group increased slightly from that measured at laparotomy; however, in the 15% group, the PVP increased immediately and significantly above that observed in the other two groups. The 14-d survival rates were 28.5%, 85.6%, and 14.2% in the 15%, 15%+ S, and 10%+ S groups, respectively. In the 15%+ S group, the shunts effectively attenuated injury to the sinusoidal endothelium, and the changes in the serum and tissue analysis results were significantly reduced compared to those in the 15% and 10%+ S groups. CONCLUSION: MCS can decompress the portal vein and so attenuate liver injury from hyperperfusion, and make extreme or marginal hepatectomy safer.

Retroperitoneal laparoscopic debridement and drainage of infected retroperitoneal necrosis in severe acute pancreatitis.

OBJECTIVE: To explore the effect of retroperitoneal laparoscopic debridement and drainage on infected necrosis in severe acute pancreatitis. MATERIALS AND METHODS: This retrospective study included 18 patients with severe acute pancreatitis (SAP) undergoing retroperitoneal laparoscopic debridement and drainage from May 2006 to April 2012 in our hospital. All patients had infected retroperitoneal necrosis and single or multiple peritoneal abscesses. Eleven patients transferred to our hospital were treated with the retroperitoneal laparoscopic debridement and drainage within 24-72 hours after admission. Conservative treatments were given to eight patients. Retroperitoneal laparoscopic debridement and drainage were applied 3-11 days after admission. RESULTS: All patients had infection of necrotic pancreas or peripancreatic tissues. Twelve patients had organ failure. Three patients underwent secondary surgery. Laparotomy with debridement and drainage were applied to one patient who had a huge lesser sac abscess 7 days after first surgery. The other two patients were given secondary retroperitoneal laparoscopic debridement and drainage. One case was complicated by retroperitoneal hemorrhage, four cases had pancreatic leakage, and no intestinal fistula was found. The patients' heart rate, respiration, temperature, and white blood cell count were significantly improved 48 hours after surgery compared with those prior to surgery (p<0.05). The average length of stay in hospitals was 40.8 days (range, 6-121 days), and the drainage tube indwelling time was 44.4 days (range, 2-182 days). CONCLUSION: Retroperitoneal laparoscopic debridement and drainage is an SAP surgical treatment with a minimally invasive procedure and a good effect, and can be applied for infected retroperitoneal necrosis in early SAP.

Laparotomy versus retroperitoneal laparoscopy in debridement and drainage of retroperitoneal infected necrosis in severe acute pancreatitis.

BACKGROUND: The aim of this study was to compare laparotomy and retroperitoneal laparoscopy in debridement and drainage of retroperitoneal infected necrosis of severe acute pancreatitis (SAP), and to evaluate the curative efficacy and the timing of retroperitoneal laparoscopic debridement drainage (RLDD) for SAP patients. METHODS: We performed a retrospective analysis of 50 SAP cases, including 18 patients in the RLDD group and 32 patients in the laparotomy group. Observed indices included gender, age, CT severity index, Ranson score, APACHE II score, preoperative course, length of stay, operation time, mortality, postoperative complications, drainage tube indwelling time, and change of body temperature and peripheral white blood cell (PWBC) count between the time before the operation and at 48 h after surgery. RESULTS: Between the RLDD group and the laparotomy group, there was a significant difference in operation time (130 ± 15 vs. 148 ± 25 h; P = 0.007), length of stay [40.8 (6-121) vs. 55.9 (28-133) days; P = 0.053], and preoperative course [14.7 (5-31) vs. 18.3 (6-31) days; P = 0.05], but no significant difference in average drainage tube indwelling time [44.4 (2-182) vs. 49.8 (2-175) days; P = 0.663]. More improvement in body temperature and PWBC count was observed in the patients of the RLDD group. There was one death (1/18) in the RLDD group and four (4/32) in the laparotomy group. Fourteen cases (14/32) in the laparotomy group had postoperative complications, including pancreatic fistula (n = 11), intestinal fistula (n = 2), retroperitoneal hemorrhage (n = 2), infection of incision (n = 9), and 5 cases (5/18) in the RLDD group, including pancreatic fistula (n = 4) and retroperitoneal hemorrhage (n = 1). CONCLUSIONS: RLDD, as minimally invasive surgery, is technically feasible, safe, and effective in the treatment of retroperitoneal infected necrosis in SAP patients, in contrast to the laparotomy technique, and can be performed in the early phase of SAP to prevent the deterioration of the disease.

MTHFR gene polymorphisms are not involved in pancreatic cancer risk: a meta-analysis.

PURPOSE: Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported to be associated with pancreatic cancer, but the published studies have yielded inconsistent results. This study assessed the relationship between MTHFR gene polymorphisms and the risk for pancreatic cancer using a meta-analysis approach. METHODS: A search of Google scholar, PubMed, Cochrane Library and CNKI databases before April 2012 was performed, and then associations of the MTHFR polymorphisms with pancreatic cancer risk were summarized. The association was assessed by odds ratios (ORs) with 95% confidence intervals (CIs). Publication bias was also calculated. RESULTS: Four relative studies on MTHFR gene polymorphisms (C667T and A1298C) were included in this meta-analysis. Overall, C667T (TT vs. CC:OR=1.61,95%CI=0.78-3.34; TT vs. CT: OR=1.41,95%CI=0.88-2.25; Dominant model:OR=0.68,95%CI=0.40-1.17; Recessive model: OR=0.82,95%CI=0.52-1.30) and A1298C (CC vs. AA:OR=1.01,95%CI=0.47-2.17; CC vs. AC: OR=0.99,95%CI=0.46-2.14; Dominant model:OR=1.01, 95%CI=0.47-2.20; Recessive model: OR=1.01,95%CI=0.80-1.26) did not increase pancreatic cancer risk. CONCLUSIONS: This meta-analysis indicated that MTHFR polymorphisms (C667T and A1298C) are not associated with pancreatic cancer risk.