Mechanism and therapeutic strategy of hepatic TM6SF2-deficient non-alcoholic fatty liver diseases via in vivo and in vitro experiments.

BACKGROUND: The lack of effective pharmacotherapies for nonalcoholic fatty liver disease (NAFLD) is mainly attributed to insufficient research on its pathogenesis. The pathogenesis of TM6SF2-efficient NAFLD remains unclear, resulting in a lack of therapeutic strategies for TM6SF2-deficient patients. AIM: To investigate the role of TM6SF2 in fatty acid metabolism in the context of fatty liver and propose possible therapeutic strategies for NAFLD caused by TM6SF2 deficiency. METHODS: Liver samples collected from both NAFLD mouse models and human participants (80 cases) were used to evaluate the expression of TM6SF2 by using western blotting, immunohistochemistry, and quantitative polymerase chain reaction. RNA-seq data retrieved from the Gene Expression Omnibus database were used to confirm the over-expression of TM6SF2. Knockdown and overexpression of TM6SF2 were performed to clarify the mechanistic basis of hepatic lipid accumulation in NAFLD. MK-4074 administration was used as a therapeutic intervention to evaluate its effect on NAFLD caused by TM6SF2 deficiency. RESULTS: Hepatic TM6SF2 levels were elevated in patients with NAFLD and NAFLD mouse models. TM6SF2 overexpression can reduce hepatic lipid accumulation, suggesting a protective role for TM6SF2 in a high-fat diet (HFD). Downregulation of TM6SF2, simulating the TM6SF2 E167K mutation condition, increases intracellular lipid deposition due to dysregulated fatty acid metabolism and is characterized by enhanced fatty acid uptake and synthesis, accompanied by impaired fatty acid oxidation. Owing to the potential effect of TM6SF2 deficiency on lipid metabolism, the application of an acetyl-CoA carboxylase inhibitor (MK-4074) could reverse the NAFLD phenotypes caused by TM6SF2 deficiency. CONCLUSION: TM6SF2 plays a protective role in the HFD condition; its deficiency enhanced hepatic lipid accumulation through dysregulated fatty acid metabolism, and MK-4074 treatment could alleviate the NAFLD phenotypes caused by TM6SF2 deficiency.

HMOX1 Attenuates the Sensitivity of Hepatocellular Carcinoma Cells to Sorafenib via Modulating the Expression of ABC Transporters.

Hepatocellular carcinoma (HCC) represents a common malignancy, and mechanisms of acquired sorafenib resistance during the treatment of HCC patients remain elusive. The present study performed integrated bioinformatics analysis and explored the potential action of heme oxygenase 1 (HMOX1) in sorafenib-resistant HCC cells. Differentially expressed genes (DEGs) of the sorafenib-resistant group as compared to the sorafenib-sensitive group from GSE140202 and GSE143233 were extracted. Fifty common DEGs between GSE140202 and GSE143233 were extracted. Ten hub genes were identified from the protein-protein interaction network based on common DEGs. Experimental results revealed the upregulation of HMOX1 in sorafenib-resistant HCC cells. HMOX1 silence promoted the sensitivity to sorafenib in sorafenib-resistant HCC cells; overexpression of HMOX1 attenuated the sensitivity. In addition, HMOX1 silence downregulated the mRNA expression of ABC transporters in sorafenib-resistant HCC cells, while HMOX1 overexpression upregulated mRNA expression of ABC transporter expression in HCC cells. Further analysis also revealed that high expression of HMOX1 was associated with shorter OS and DSS in HCC patients. In conclusion, our analysis identified ten hub genes associated with sorafenib resistance in HCC. Further validation studies demonstrated that HMOX1 promoted sorafenib resistance of HCC cells via modulating ABC transporter expression.

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.

The role of SAMM50 in non-alcoholic fatty liver disease: from genetics to mechanisms.

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation. SAMM50 encodes Sam50, a mitochondrial outer membrane protein involved in the removal of reactive oxygen species, mitochondrial morphology and regulation of mitophagy. Certain single nucleotide polymorphisms of SAMM50 have been reported to be correlated with NAFLD. However, the contribution of SAMM50 polymorphisms to the occurrence and severity of fatty liver in the Chinese Han cohort has rarely been reported. Here, we investigated the association between SAMM50 polymorphisms (rs738491 and rs2073082) and NAFLD in a Chinese Han cohort, as well as the mechanistic basis of this association. Clinical information and blood samples were collected from 380 NAFLD cases and 380 normal subjects for the detection of genotypes and biochemical parameters. Carriers of the rs738491 T allele or rs2073082 G allele of SAMM50 exhibit increased susceptibility to NAFLD [odds ratio (OR) = 1.39; 95% confidence interval (CI) = 1.14-1.71, P = 0.001; OR = 1.31; 95% CI = 1.05-1.62, P = 0.016, respectively] and are correlated with elevated serum triglyceride, alanine aminotransferase and aspartate aminotransferase levels. The presence of the T allele (TT + CT) of rs738491 (P < 0.01) or G allele (AG + GG) of rs2073082 (P = 0.03) is correlated with the severity of fatty liver in the NAFLD cohort. In vitro studies indicated that SAMM50 gene polymorphisms decrease its expression and SAMM50 deficiency results in increased lipid accumulation as a result of a decrease in fatty acid oxidation. Overexpression of SAMM50 enhances fatty acid oxidation and mitigates intracellular lipid accumulation. Our results confirm the association between the SAMM50 rs738491 and rs2073082 polymorphisms and the risk of fatty liver in a Chinese cohort. The underlying mechanism may be related to decreased fatty acid oxidation caused by SAMM50 deficiency.

Feasibility and efficacy evaluation of metallic biliary stents eluting gemcitabine and cisplatin for extrahepatic cholangiocarcinoma.

BACKGROUND: Effective endoscopic management is fundamental for the treatment of extrahepatic cholangiocarcinoma (ECC). However, current biliary stents that are widely used in clinical practice showed no antitumor effect. Drug-eluting stents (DESs) may achieve a combination of local chemotherapy and biliary drainage to prolong stent patency and improve prognosis. AIM: To develop novel DESs coated with gemcitabine (GEM) and cisplatin (CIS)-coloaded nanofilms that can maintain the continuous and long-term release of antitumor agents in the bile duct to inhibit tumor growth and reduce systemic toxicity. METHODS: Stents coated with different drug-eluting components were prepared by the mixed electrospinning method, with poly-L-lactide-caprolactone (PLCL) as the drug-loaded nanofiber membrane and GEM and/or CIS as the antitumor agents. Four different DESs were manufactured with four drug-loading ratios (5%, 10%, 15%, and 20%), including bare-loaded (PLCL-0), single-drug-loaded (PLCL-GEM and PLCL-CIS), and dual-drug-loaded (PLCL-GC) stents. The drug release property, antitumor activity, and biocompatibility were evaluated in vitro and in vivo to confirm the feasibility and efficacy of this novel DES for ECC. RESULTS: The in vitro drug release study showed the stable, continuous release of both GEM and CIS, which was sustained for over 30 d without an obvious initial burst, and a higher drug-loaded content induced a lower release rate. The drug-loading ratio of 10% was used for further experiments due to its ideal inhibitory efficiency and relatively low toxicity. All drug-loaded nanofilms effectively inhibited the growth of EGI-1 cells in vitro and the tumor xenografts of nude mice in vivo; in addition, the dual-loaded nanofilm (PLCL-GC) had a significantly better effect than the single-drug-loaded nanofilms (P < 0.05). No significant differences in the serological analysis (P > 0.05) or histopathological changes were observed between the single-loaded and drug-loaded nanofilms after stent placement in the normal porcine biliary tract. CONCLUSION: This novel PLCL-GEM and CIS-eluting stent maintains continuous, stable drug release locally and inhibits tumor growth effectively in vitro and in vivo. It can also be used safely in normal porcine bile ducts. We anticipate that it might be considered an alternative strategy for the palliative therapy of ECC patients.

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.

Additive Effects of the Risk Alleles of PNPLA3 and TM6SF2 on Non-alcoholic Fatty Liver Disease (NAFLD) in a Chinese Population.

Recent genome-wide association studies have identified that variants in or near PNPLA3, NCAN, GCKR, LYPLAL1, and TM6SF2 are significantly associated with non-alcoholic fatty liver disease (NAFLD) in multiple ethnic groups. Studies on their impact on NAFLD in Han Chinese are still limited. In this study, we examined the relevance of these variants to NAFLD in a community-based Han Chinese population and further explored their potential joint effect on NAFLD. Six single nucleotide polymorphisms (SNPs) (PNPLA3 rs738409, rs2294918, NCAN rs2228603, GCKR rs780094, LYPLAL1 rs12137855, and TM6SF2 rs58542926) previously identified in genome-wide analyses, to be associated with NAFLD were genotyped in 384 NAFLD patients and 384 age- and gender-matched healthy controls. We found two out of the six polymorphisms, PNPLA3 rs738409 (OR = 1.52, 95%CI: 1.19-1.96; P = 0.00087) and TM6SF2 rs58542926 (OR = 2.11, 95%CI: 1.34-3.39; P = 0.0016) are independently associated with NAFLD after adjustment for the effects of age, gender, and BMI. Our analysis further demonstrated the strong additive effects of the risk alleles of PNPLA3 and TM6SF2 with an overall significance between the number of risk alleles and NAFLD (OR = 1.64, 95%CI: 1.34-2.01; P = 1.4 × 10(-6)). The OR for NAFLD increased in an additive manner, with an average increase in OR of 1.52 per additional risk allele. Our results confirmed that the PNPLA3 and TM6SF2 variants were the most significant risk alleles for NAFLD in Chinese population. Therefore, genotyping these two genetic risk factors may help identify individuals with the highest risk of NAFLD.

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.

Elevated OCT1 participates in colon tumorigenesis and independently predicts poor prognoses of colorectal cancer patients.

Octamer transcription factor 1 (OCT1) was found to influence the genesis and progression of numerous cancers except for colorectal cancer (CRC). This study tried to explore the role of OCT1 in CRC and clarify the association between its expression and patients' clinical outcome. Transcriptional and post-transcriptional expression of OCT1 was detected in CRC cancerous tissues and paired normal mucosae by real-time PCR as well as immunohistochemistry. Moreover, the effect of OCT1 knockdown on CRC cell proliferation was investigated both in vitro and in vivo using Cell Counting Kit-8 assay, colony-forming assay, and mouse tumorigenicity assay. Expression of OCT1 was found to be elevated in CRC. Suppression of OCT1 significantly inhibited CRC cell proliferation both in vitro and in vivo. Furthermore, upregulated level of OCT1 was significantly associated with N stage, M stage, and American Joint Committee on Cancer (AJCC) stage (P = 0.027, 0.014, and 0.002, respectively) as well as differential degree (P = 0.022). By using multivariate Cox hazard model, OCT1 was also shown to be a factor independently predicting overall survival (OS; P = 0.013, hazard ratio = 2.747, 95 % confidence interval 1.125 to 3.715) and disease-free survival (DFS; P = 0.004, hazard ratio = 2.756, 95 % confidence interval 1.191 to 4.589) for CRC patients. Our data indicate that OCT1 carries weight in colorectal carcinogenesis and functions as a novel prognostic indicator and a promising target of anti-cancer therapy for CRC.

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.

[Effect of post-liver transplantation administration of ursodeoxycholic acid on serum liver tests and biliary complications: a randomized clinical trial].

OBJECTIVE: Endogenous hydrophobic bile acids may be a pathogenetic factor of biliary complications after orthotopic liver transplantation (OLT).This study was designed to investigate the effects of hydrophilic ursodeoxycholic acid (UDCA), when administered early after OLT, on serum liver tests and on the incidence of biliary complications. METHODS: A total of 112 adult patients undergoing OLT were randomly assigned to one of two groups for receipt of UDCA (13 to 15 mg/kg/d for 4 weeks, n=56) or a placebo (n=56). All patients underwent serum liver testing and measurement of serum bile acids during the 4 weeks following OLT.Patients with T-tube underwent measurement of biliary bile acids during the 4 weeks following OLT.Biliary complications, as well as patient and graft survival rates, were analyzed during the follow-up period (mean of 65.6 months). RESULTS: At post-OLT days 7, 21 and 28, the UDCA-treated patients showed significantly lower levels of alanine aminotransferase, aspartate aminotransferase and gamma glutamyl transpeptidase (all P less than 0.05).In addition, the UDCA-treated patients showed significantly lower incidence of biliary sludge and casts within the first year post-OLT (3.6% vs.14.3%; x2=3.953, P=0.047). However, there were no significant differences for the incidence of other biliary complications at post-OLT years 1, 3 and 5.The graft and patient survival rates were also similar between the two groups. CONCLUSION: UDCA, when administered early after OLT, improves results from serum liver tests and decreases the incidence of biliary sludge and casts within the first postoperative year.

Effect of ursodeoxycholic acid administration after liver transplantation on serum liver tests and biliary complications: a randomized clinical trial.

BACKGROUND/AIMS: Endogenous hydrophobic bile acids are suspected to be one of the pathogenetic factors of biliary complications after orthotopic liver transplantation (OLT). This study was designed to investigate the effects of hydrophilic ursodeoxycholic acid (UDCA) administration early after OLT on serum liver tests and the incidence of biliary complications. METHODS: 112 adult patients undergoing OLT from donation after cardiac death (DCD) were randomized to UDCA (13-15 mg/kg/day for 4 weeks; 56 patients) or placebo (56 patients). Serum liver tests and serum bile acids of all patients and biliary bile acids in patients with T-tube drainage were determined during the 4 weeks after OLT. Biliary complications as well as patient and graft survival were analyzed during a mean follow-up of 41.6 months. RESULTS: UDCA treatment decreased ALT, AST and GGT (p < 0.05) during the 4 weeks after OLT and the incidence of biliary sludge and casts within the 1st year (p < 0.05). However, no differences in the incidence of other biliary complications as well as 1-, 3- and 5-year graft and patient survival were observed. CONCLUSIONS: UDCA administration early after DCD-OLT improves serum liver tests and decreases the incidence of biliary sludge and casts within the 1st postoperative year but does not affect overall outcome up to 5 years after OLT.

Accumulation of mercury, selenium and their binding proteins in porcine kidney and liver from mercury-exposed areas with the investigation of their redox responses.

The subcellular localization of Se and Hg and their cytosolic binding proteins, including cellular oxidative status, in porcine liver and kidney have been studied by using samples from a chronic Hg-contaminated area and a non-Hg-contaminated area. Coaccumulation and redistribution of Se and Hg in subcellular fractions due to mercury exposure were found. The Hg and Se concentrations in tissues from Hg-exposed porcine were 80 fold and 5-20 fold higher than controls, respectively. Interestingly, the retention of both Se and Hg increased 10% in mitochondria, while decreased 10% in cytosol of Hg-exposed pig liver. Mercury was mainly in the form of MTs in the cytosol of the non-Hg-exposed porcine kidney. MT binds Hg in the cytosol with limited capacity, and the rest Hg was redistributed to the high molecular weight (MW) proteins (80-100 kDa) in the Hg-exposed group. The coaccumulation of Hg and Se was also found in high MW proteins, where their molar ratio tended to be 1:1. Moreover, the Se-containing polypeptides (3-6 kDa) increased significantly both in hepatic and renal cytosol of the Hg-exposed pigs. Se-dependent GSH-Px and SOD activity were increased to cope with Hg-induced oxidative stress. In previous studies, the roles of Se and MTs were generally taken into account separately; we discussed their combining roles in the case of high Hg exposure. The present results were beneficial to understand the existing states of Hg in vivo and evaluate the interaction of toxic and essential elements.

Expression and significance of heparanase and nm23-H1 in hepatocellular carcinoma.

AIM: To explore the relation between heparanase (HPA) and nm23-H1 in hepatocellular carcinoma (HCC), and whether they could be used as valuable markers in predicting post-operative metastasis and recurrence of HCC. METHODS: Reverse transcription-polymerase chain reaction and immunohistochemistry (S-P method) were used to measure the expressions of HPA mRNA and nm23-H1 protein in primary tumor tissue and paracancerous tissue of 33 cases of HCC. Paracancerous tissues of 9 cases of benign liver tumor were used as normal controls. The results were analyzed in combination with the results of clinicopathological examination and follow-up. RESULTS: The positive expression of HPA gene was significantly higher in primary tumor tissues of HCC (48.5%, 16/33) as compared to the paracancerous tissues of HCC and normal controls (3.03%, 1/33) (P < 0.01). HPA expression was not related with the size of tumor, envelope formation, AFP level, HBsAg state and cirrhosis of liver. The positive rates of HPA mRNA in the group with high tendency to metastasis or recurrence and in the group with metastasis or recurrence during the follow-up were significantly higher than those in the group with low tendency to metastasis or recurrence (62.5% vs 37.5%, P < 0.05) and in the group without metastasis or recurrence (78.6% vs 21.4%, P < 0.01). The poorly differentiated tumor and tumor of TNM stages III-IV had a higher positive rate of HPA gene expression than the well differentiated tumor and tumor of TNM stages I-II (66.7% vs 33.3%, P < 0.05). The positive expression rate of nm23-H1 protein in HCC tissue was significantly lower than that in corresponding non-cancerous or normal liver tissue (45.5, 72.7, 88.9%, P < 0.05). nm23-H1 expression was not related with the size of tumor, envelope formation, AFP level, HBsAg state, cirrhosis of liver, Edmondson grade, and TNM stage (P > 0.05). The positive rates of nm23-H1 in the group with high tendency to metastasis and recurrence and in patients with metastasis or recurrence during the follow-up were obviously higher than those in the group with low tendency to metastasis and recurrence (P = 0.018) and in the patients without metastasis and recurrence (P = 0.024); but no significant difference was found between HPA positive and negative groups (P = 0.082). According to the results of follow-up, the rate of accuracy in predicting metastasis of positive HPA, negative nm23-H1 and combination of positive HPA with negative nm23-H1 was 78.6% (11/14), 68.8% (11/16) and 88.9% (8/9), respectively. CONCLUSION: Expression of HPA and/or nm23-H1 is related with metastasis and recurrence of HCC. Detection of the expression rate of HPA and nm23-H1 may help increase the accuracy in predicting post-operative metastasis and recurrence of HCC.

[Preliminary study on cellular status of selenium and oxidative stress in human hepatocellular carcinoma and normal liver].

To investigate the roles of essential trace element selenium and cellular antioxidative systems in human hepatocellular carcinoma, we analyzed cellular distribution of selenium and assayed cytosolic and mitochondrial superoxide dismutase, glutathione peroxidase, thioredoxin reductase, glutathione and total protein thiols in 10 control healthy subjects, 6 cases of hepatocellular carcinoma and 2 cases of normal liver adjacent to the hepatocellular carcinoma. In hepatoma tissues, the Se contents in lysosome (P < 0.05), microsome (P < 0.05) and cytosol were higher than in the control liver. In 2 cases, normal liver adjacent to hepatocellular carcinoma had decreased Se content. In hepatoma tissues, GSH and protein thiols content and activities of SOD, GSH-Px and TrxR were all much higher than in normal liver tissue. These findings suggested the antioxidative defense-related enzymes and antioxidant were largely regulated in hepatoma cells, whereas the cause is not clear and requires further studies.

Distribution of selenium-containing proteins in human serum.

Selenium-containing proteins in human serum of four volunteers in Beijing were separated and purified by preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Selenium contents in the proteins were quantified by high-performance liquid chromatography (HPLC) coupled with a fluorescence detector (FLD) after pretreatment with a microwave digestion system and derivatization with 2,3-diaminonaphthalene (DAN). Five selenium-containing proteins with apparent molecular weights (MWs) of 68+/-3, 57.5+/-2.5, 47+/-2, 41+/-1, and 21+/-1 kDa, respectively, were detected. By comparison with known data on serum selenium-containing proteins, the 68+/-3 kDa protein should belong to albumin, which took 6.3-9.8% of the total serum Se. The 57.5+/-2.5 kDa protein should be selenoprotein P and the 47+/-2 kDa protein was believed to be an isoform of selenoprotein P. The sum of Se in selenoprotein P and its isomer took about 41.1-69.3% and was the major form of human serum selenium. The 21+/-1 kDa protein should be plasma glutathione peroxidase (p-GPx) and its Se content was about 21.1-24.3%. Also, protein of 41+/-1 kDa should be a selenium-containing protein that, to our best knowledge, was reported for the first time. The Se percentage in this protein corresponded to 12.6-20.4% of total human serum Se.

[Effect of binding pancreaticojejunotomy in prevention of post-operational anastomotic leakage: a clinical study of 200 cases].

OBJECTIVE: To explore the effect of Peng's binding pancreaticojejunotomy (PBPJ) in prevention of pancreaticojejunal anastomotic leakage. METHODS: From 1996 to 2001, 200 patients, 139 males and 61 females, aged 32 approximately 80, with carcinomas of head of pancreas, ampulla, bile duct, duodenal papilla, descending partof duodenum, gallbladder, and body of pancreas, chronic pancreatitis, polyp of lower segment of bile duct, and gastric carcinomas that invaded the head of pancreas or recurred after operation, lithiasis of pancreatic duct, and islet cell carcinoma, underwent Peng's binding pancreaticojejunotomy, devised to prevent pancreaticojejunal anastomotic leakage from the needle holes of stoma, interspace between jejunal mucosa and pancreas, high pressure of jejunum, high tension and blood circulation deficiency of pancreaticojejunal stoma, etc. The clinical data were collected and analyzed. RESULTS: While the cut end of jejunum was sutured to the pancreatic remnant the needle only penetrated the jejunal mucosa without causing a needle hole on the surface of the stoma. After the remnant of pancreas was inserted into the jejunal cavity, a piece of cat gut was bound around the entire jejunal serous muscular sheath and the pancreatic remnant so as to make them stick to each other closely. No pancreatic leakage occurred among these 200 cases after operation. CONCLUSION: The PBPJ procedure can definitively avoid anastomotic leakage following pancreatoduodenectomy.

Mercury and trace element distribution in organic tissues and regional brain of fetal rat after in utero and weaning exposure to low dose of inorganic mercury.

Since it is still absent data about the toxic risk of low dose, especially an environmentally relevant dose of mercury to fetus after their prenatal exposure, this present work was designed to investigate the metabolism of Hg and its effect on the levels of essential trace elements in the organic tissues and the brain regions of infant rats after their exposure to environmentally relevant low dose of Hg(II) during the whole pregnant and weaning period. The pregnant female rats were exposed to a very low dose of 0.2 microg Hg2+/ml (as HgCl2, 12 rats/group) in drinking water from prenatal day 0 continued to postnatal day 20. The contents of Hg and other elements (Cu, K, Mg, Mn, Na, Ca, Co, Fe, Se and Zn) in the liver, kidney, heart, spleen, pancreas and the brain regions (cerebrum, cerebellum, brain stem, hippocampus, thalamus and the remains) of the maternal and their infant rats were determined. The highest Hg contents were found in kidney of both maternal and infant rats. Considering the percentage of Hg accumulation, approximately 52.7%, 38.7%, and 1.66% were found in kidney, liver and brain for maternal rats, respectively, while 23.7%, 48.9% and 15.6% for infant rats. The important findings in this work were that the low dose of inorganic mercury appeared to accumulate in the brain of offspring and more Hg was present in infant brain than in their mother. As in the brain regions, the highest Hg content was present in infant hippocampus and cerebellum, whereas the Hg contents in maternal brains varied not so much. The imbalances of Fe/Cu, Cu/Zn, Zn/Se mass ratios and the molar ratios of Hg over other elements in the Hg-exposed rats were observed.

Hepatocellular carcinoma with bile duct thrombi: analysis of surgical treatment.

BACKGROUND/AIMS: To summarize the experience of surgical intervention for hepatocellular carcinoma with bile duct thrombi, and to evaluate the influence on prognosis. METHODOLOGY: From 1994 to 2002, 15 patients with hepatocellular carcinoma and bile duct thrombi who underwent surgical intervention were retrospectively analyzed. The operative procedures included hepatectomy with removal of bile duct thrombi (n=7), hepatectomy combined with extrahepatic bile duct resection (n=4), thrombectomy through choledochotomy (n=3), and piggyback orthotopic liver transplantation (n=1). RESULTS: The 1- and 3-year survival rates were 73.3% and 40%, respectively. Two patients survived over 5 years. There were no significant differences in the survival rates between patients with and without obstructive jaundice (P>0.05). The survival rate of patients with portal vein invasion was significantly lower than for those without portal vein invasion (P<0.05). CONCLUSIONS: Surgical intervention was effective for patients with hepatocellular carcinoma and bile duct thrombi. Operation for recurrent intrahepatic tumor can prolong the survival period. Liver transplantation is a new operative procedure worthy of investigation.

[Role and significance of extrahepatic control of hepatic vein and inferior vena cava in difficult hepatectomies for patients with liver tumors].

OBJECTIVE: To explore the role of extrahepatic control on blood flow of hepatic vein and inferior vena cava in hepatectomy, and observe its effect on minimizing hemorrhage. METHODS: From 2001 to April 2003, 33 patients who had liver tumors involving segment IV, VII, VIII or half liver underwent major hepatectomies that required exposure of the inferior vena cava and main trunks of hepatic veins, during which the major hepatic veins and inferior vena cava were isolated and taped to control blood flow when necessary. RESULTS: In 33 attempts, 32 were successful and all tumors were resected successfully. The placement of occlusion tape was unsuccessful in 1 case. 7 cases did not need blood transfusion during operation. The amount of blood transfusion for other cases were form 0 to 1 600 ml. there was no operative mortality. CONCLUSIONS: Appropriate control of main truck of hepatic vein and inferior vena cava is effective in reducing blood loss during hepatectomies. It is also very helpful for performing difficult hepatectomies.