The NPC1L1 Polymorphism 1679C>G Is Associated with Gallstone Disease in Chinese Patients.

Niemann Pick Type C1 Like 1 (NPC1L1) protein plays a key role in intestinal and hepatic cholesterol metabolism in humans. Genetic variation in NPC1L1 has been widely studied in recent years. We analyzed NPC1L1 single nucleotide polymorphisms in Chinese gallstone disease patients to investigate their association with gallstone disease. NPC1L1 mRNA expression was also measured in liver biopsies from patients with cholesterol gallstone disease and compared between genotypes. The G allele of the g1679C>G (rs2072183) polymorphism was significantly more prevalent in patients with gallstones compared with gallstone-free subjects. Moreover, patients carrying the G allele had lower hepatic NPC1L1 mRNA expression and higher biliary cholesterol (molar percentages) and cholesterol saturation index. Our study suggests that the G allele of the NPC1L1 polymorphism g1679C>G may be a positive marker of gallstone formation risk.

Clinical features and outcomes of patients with severe acute pancreatitis complicated with gangrenous cholecystitis.

BACKGROUND: The effects of gangrenous cholecystitis (GC) and consequent surgical interventions on the clinical outcomes and prognosis of patients with severe acute pancreatitis are not clear. The present study was to characterize the clinical outcomes of patients with severe acute pancreatitis complicated with GC. METHODS: We retrospectively analyzed 253 consecutive patients hospitalized for acute pancreatitis in intensive care unit. Among them, 68 were diagnosed as having severe acute pancreatitis; 10 out of the 68 patients had GC. We compared these 10 patients with GC and 58 patients without GC. The indices analyzed included sepsis/septic shock, pancreatic encephalopathy, acute respiratory distress syndrome, acute renal failure, multiple organ dysfunction syndrome, and death. RESULTS: Specific CT images of GC in patients with severe acute pancreatitis included enlarged and high-tensioned gallbladder, wall thickening, lumenal emphysema, discontinuous and/or irregular enhancement of mucosa, and pericholecystic effusion. The rates of severe sepsis/septic shock (70.0% vs 24.1%, P<0.01), pancreatic encephalopathy (50.0% vs 17.2%, P<0.05), acute respiratory distress syndrome (90.0% vs 41.4%, P<0.01), multiple organ dysfunction syndrome (70.0% vs 24.1%, P<0.01), acute renal failure (40.0% vs 27.6%, P<0.05), and death (40.0% vs 13.8%, P<0.05) were significantly higher in patients with GC than in those without GC. CONCLUSION: CT scans can help to identify early GC in patients with severe acute pancreatitis; early diagnosis and intervention for patients with GC can reduce morbidity and mortality.

Single nucleotide polymorphism rs3732860 in the 3'-untranslated region of CYP8B1 gene is associated with gallstone disease in Han Chinese.

BACKGROUND AND AIMS: Gallstone disease (GD) is a common disease of multigenetic origin; however, the major susceptibility loci for GD in human populations remain unidentified. This study aimed to identify the genetic factors contributing to gallstone development in Chinese. METHODS: A genome-wide scan was conducted in 12 Han Chinese GD families to identify linkage loci. The linkage region showing the highest logarithm of odds score encompasses the sterol 12α-hydroxylase gene (CYP8B1). Replication analysis with an independent sample of 192 GD patients and 192 unrelated, matched controls was carried out to verify the associations between CYP8B1 polymorphisms and GD. RESULTS: Three loci (D3S1266, D4S406, and D9S1682) showed suggestive or nominal evidence of linkage in all 12 GD families. The logarithm of odds score of D3S1266 reached 2.71 in the families with late-onset patients. The single nucleotide polymorphism rs3732860 in the 3'-untranslated region of CYP8B1 showed significant association to GD (P = 0.022), and carriers of the A allele had lower risk of GD (odds ratio = 1.46, 95% confidence interval: 1.055-2.034) compared with carriers of the G allele. CONCLUSIONS: The single nucleotide polymorphism rs3732860 in the 3'-untranslated region of the CYP8B1 gene is associated with risk of GD in Chinese Han and appears to be responsible for the observed linkage with D3S1266.

[Association of single nucleotide polymorphism in human CYP8B1 gene with gallstone disease].

OBJECTIVE: To identify the single nucleotide polymorphisms of human CYP8B1gene and explore the association of some of these SNPs with gallstone disease in Chinese population. METHODS: The exon and part of promoter were sequenced by a fluorescent labeling automatic method to identify and characterize the SNPs in Chinese population. For SNPs with an allelic frequency of over 10%, a case-control study was performed in patients and controls. RESULTS: Eleven SNPs were found within a 5119 bp region. Among them, 1 was in coding region, 5 in promoter and 5 in 3'-UTR. There were 3 novel SNPs and 12 SNPs in SNP database were not found. The allelic frequency of rs3732860 polymorphism showed a significant difference (P = 0.022) in the association study. The subjects with A allele had a significantly lower frequency of gallstone disease than those with G allele (OR = 1.465, 95%CI 1.055 - 2.034, P = 0.023). CONCLUSION: SNP rs3732860 of CYP8B1 gene is associated with gallstone disease in Chinese population. And A allele may play a protective role in the pathogenesis of gallstone.

Rapid hemodilution is associated with increased sepsis and mortality among patients with severe acute pancreatitis.

BACKGROUND: Hemoconcentration may be an important factor that determines the progression of severe acute pancreatitis (SAP). In addition, it has been proposed that biomarkers may be useful in predicting subsequent necrosis in SAP. However, it is still uncertain whether hemodilution in a short term can improve outcome. We aimed to investigate the effect of rapid hemodilution on the outcome of patients with SAP. METHODS: One hundred and fifteen patients were admitted prospectively according to the criteria within 24 hours of SAP onset. Patients were randomly assigned to either rapid hemodilution (hematocrit (HCT) < 35%, n = 56) or slow hemodilution (HCT > or = 35%, n = 59) within 48 hours of onset. Balthazar CT scores were calculated on admission, day 7, and day 14, after onset of the disease. Time interval for sepsis presented, incidence of sepsis within 28 days and in-hospital survival rate were determined. RESULTS: The amount of fluid used in rapid hemodilution was significantly more than that used in slow hemodilution (P < 0.05) on the admission day, the first day, and the second day. There were significant differences between the rapid and slow hemodilution group in terms of hematocrit, oxygenation index, pH values, APACHE II scores and organ dysfunction at different time during the first week. There were significant differences in the time interval to sepsis in rapid hemodilution ((7.4 +/- 1.9) days) compared with the slow hemodilution group ((10.2 +/- 2.3) days), and the incidence of sepsis (78.6%) was higher in the rapid group compared to the slow (57.6%) in the first 28 days. The survival rate of the slow hemodilution group (84.7%) was better than the rapid hemodilution (66.1%. P < 0.05). CONCLUSIONS: Rapid hemodilution can increase the incidence of sepsis within 28 days and in-hospital mortality. Hematocrit should be maintained between 30%-40% in the acute response stage.

[Investigation of distribution of bacteria and fungi in severe acute pancreatitis].

OBJECTIVE: To investigate the spectrum of bacteria and fungi in different sites in severe acute pancreatitis (SAP). METHODS: The prospective study was performed in 205 patients with SAP treated from January 2000 to December 2008. The Infection rate of bacteria and fungi was observed prospectively in pancreatic necrosis and(or) pus form abdomen, body fluids and deep vein catheter in SAP. Body fluids and pancreatic necrosis were cultured twice a week. Central venous catheter was cultured when it had been placed for two weeks. Blood was cultured for bacteria and fungi when body temperature was more than 39 degrees C. Constituent ratio of bacteria and fungi was observed in different sites and in all sites within 28 days after onset of SAP. RESULTS: There were 937 pathogens, among which infection rates of gram-negative bacteria was higher than gram-positive bacteria and fungi (P < 0.05), the infection rates of gam-positive bacteria and fungi were similar. Infection rates of gram-negative bacteria in pancreatic necrosis (55.2%), bile (55.4%), blood (68.1%) and central venous catheter (44.4%) were increased significantly (P < 0.05) compared with gram-positive bacteria and (30.2%, 33.9%, 23.4%, 38.9%) and fungi (14.6%, 10.7%, 8.5%, 16.7%); however, infection rate of fungi (59.6%) was increased significantly (P < 0.05) compared with gram-negative bacteria (24.0%) and gram-positive bacteria (16.3%) in urine; infection rate of gram-negative bacteria (53.2%) was significantly higher (P < 0.05) than that of fungi (27.1%) and gram-positive bacteria (19.7%) in sputum. Infection rate of non-zymogenic bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia) in gram-negative bacteria in pancreatic necrosis, bile, blood, central venous catheter and sputum was significantly higher than that of zymogenic bacteria (Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae) (P < 0.01); infection rate of zymogenic bacteria (Klebsiella pneumoniae, Escherichia coli) was higher significantly (P < 0.01) than that of non-zymogenic bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii). Infection rate of staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus was significantly higher (P < 0.05) than that of Enterococcus faecalis and Enterococcus faecium in pancreatic necrosis and sputum;but infection rate of Enterococcus faecium in bile and urine was significantly higher than other gram-positive bacteria (P < 0.05). There was not difference among gram-positive bacteria;however, infection rate of Staphylococcus epidermidis in central venous catheter was increased significantly (P < 0.05). Infection rate of candida mycoderma in pancreatic necrosis, bile, urine and sputum was significantly higher than that of tricho bacteria (P < 0.05). The peak of infection rate of microbes in body fluid was within 2 to 3 weeks. CONCLUSIONS: Constituent ratio in gram-negative, gram-positive bacteria and fungi as well as their species in different sites is diverse. The peak of infection rate of microbes is 2 to 3 weeks after onset of the disease.

HNF1alpha and SREBP2 are important regulators of NPC1L1 in human liver.

Niemann-Pick C1-like 1 (NPC1L1), a key regulator of intestinal cholesterol absorption, is highly expressed in human liver. Here, we aimed to gain more insight into mechanisms participating in its hepatic regulation in humans. Correlation analysis in livers from Chinese patients with and without gallstone disease revealed strong positive correlations between NPC1L1 and sterol regulatory element binding protein 2 (SREBP2) (r = 0.74, P < 0.05) and between NPC1L1 and hepatic nuclear factor alpha (HNF4alpha) (r = 0.53, P < 0.05) mRNA expression. HNF4alpha is an upstream regulator of HNF1alpha; thus, we also tested whether HNF1alpha participates in the regulation of NPC1L1. We showed a dose-dependent regulation by SREBP2 on the NPC1L1 promoter activity and mRNA expression in HuH7 cells. Chromatin immunoprecipitation assay confirmed the binding of SREBP2 to the promoter in vivo. Surprisingly, HNF4alpha slightly decreased the NPC1L1 promoter activity but had no effect on its gene expression. By contrast, HNF1alpha increased the promoter activity and the gene expression, and an important HNF1 binding site was identified within the human NPC1L1 promoter. ChIP assays confirmed that HNF1alpha can bind to the NPC1L1 promoter in vivo.

Decreased NPC1L1 expression in the liver from Chinese female gallstone patients.

BACKGROUND: Cholesterol gallstone disease is a very common disease in both industrialized and developing countries. Many studies have found that cholesterol gallstones are more common in women than men. The molecular mechanisms underlying the relationship between female gallstone disease and hepatic sterol transporters are still undergoing definition and have not been evaluated in humans. AIMS: The aim of this study is to probe for underlying hepatic molecular defects associated with development of gallstones in female. METHODS/RESULTS: Fifty-seven nonobese, normolipidemic Chinese female gallstone patients (GS) were investigated with 12 age- and body mass index-matched female gallstone-free controls (GSF). The bile from the female GS had higher cholesterol saturation than that from the female GSF. The hepatic NPC1L1 mRNA levels were lower in female GS, correlated with SREBP2 mRNA. NPC1L1 downregulation was confirmed at protein levels. Consistently, immunohistochemistry showed decreased NPC1L1 expression in female GS. CONCLUSIONS: The decreased hepatic NPC1L1 levels in female GS might indicate a downregulated reabsorption of biliary cholesterol in the liver, which, in turn, leads to the cholesterol supersaturation of bile. Our data are consistent with the possibility that hepatic NPC1L1 may be mediated by SREBP2.

[Expression and regulation of megalin in gallbladder mucosa associated with cholesterol gallstone disease].

OBJECTIVE: To explore the relationship between expression and regulation of Megalin in gallbladder mucosa and cholesterol gallstone disease. METHODS: Gallbladder mucosa, gallbladder wall, bile, gallstone were collected from 29 patients with cholesterol gallstone disease (GS) and 12 patients with gallstone free (GSF). Lipids of bile and stone were measured by kits. Expression of Megalin and Cubilin was analyzed by Real-time PCR. GBC-SD cell line were treated with T0901317, 9-cis retinoic acid, chenodeoxycholic acid (CDCA), the agonists of LXR, RXR, FXR, respectively. Gene expressions were detected. RESULTS: Biliary cholesterol % molar and CSI increased significantly in GS group [(7.98 +/- 0.44) mol% vs (4.87 +/- 0.39) mol%, P < 0.01]. Megalin expression in GS group was significantly higher than that in GSF group (P < 0.05) and cubilin expression was similar between two groups. In vitro experiments showed that CDCA markedly increased expression of megalin. CONCLUSION: This study shows that the increased expression Megalin may help to increase cholesterol uptake in gallbladder and play a compensative role in GS. FXR may participate in the transcription regulating of Megalin.

ACAT2 and human hepatic cholesterol metabolism: identification of important gender-related differences in normolipidemic, non-obese Chinese patients.

OBJECTIVE: ACAT2 is a major cholesterol esterification enzyme specifically expressed in hepatocytes and may control the amount of hepatic free (unesterified) cholesterol available for secretion into bile or into HDL. This study aims to further elucidate physiologic roles of ACAT2 in human hepatic cholesterol metabolism. METHODS AND RESULTS: Liver biopsies from 40 normolipidemic, non-obese gallstone patients including some gallstone-free patients (female/male, 18/22) were collected and analyzed for microsomal ACAT2 activity, protein and mRNA expression. Plasma HDL-cholesterol (HDL-C) was significantly higher in females than in males, while triglycerides were significantly lower. ACAT2 activity in females was significantly lower than observed in males, regardless of the presence of gallstone disease. Moreover, the activity of ACAT2 correlated negatively with plasma levels of HDL-C (r=-0.57, P<0.05) and with Apo AI (r=-0.49, P<0.05). CONCLUSION: This is the first description of a gender-related difference in hepatic ACAT2 activity in normolipidemic non-obese Chinese patients suggesting a possible role for ACAT2 in the regulation of cholesterol metabolism in humans. The negative correlation between ACAT2 activity and HDL-C or Apo AI may reflect this regulation. Since ACAT2 activity generally has been found to be pro-atherogenic in animal models, the observed sex-related difference may contribute to female protection from complications of coronary heart disease (CHD).

[A study on increased permeability and morphological changes in actin cytoskeleton and tight junction of vascular endothelial cells induced by tumor necrosis factor-alpha].

OBJECTIVE: To study the effect of human tumor necrosis factor-alpha (TNF-alpha) on permeability of human vascular endothelial cell (EA.hy926) monolayer and its mechanism. METHODS: 5, 10, 20 microg/L TNF-alpha was respectively added to the cultured endothelial cell monolayer for 24 hours, or 10 microg/L TNF-alpha for 6, 12, 24 hours. Human vascular endothelial cell (EA.hy926) monolayer permeability was measured by detecting fluorescence intensity of fluorescein isothiocyanate (FITC) labeled dextran. Immunofluorescence and laser confocal microscopy were used to assess vascular endothelial actin cytoskeleton (F-actin) and tight junction protein (ZO-1) distribution. Western blotting was used to assess ZO-1 expression. RESULTS: Compared with control group, TNF-alpha significantly increased endothelial permeability and induced F-actin redistribution and stress fiber formation with ZO-1 derangement. Gaps increased obviously between endothelial cells. Furthermore, Western blotting showed that TNF-alpha reduced ZO-1 expression in a dose- and time-dependent manner. CONCLUSION: TNF-alpha increased endothelial cell permeability by damaging integrity of endothelial barrier function.

Effects of gut barrier dysfunction and NF-kappaB activation on aggravating mechanism of severe acute pancreatitis.

OBJECTIVE: To study the effects of gut-derived endotoxin translocation and NF-kappaB activation on the aggravating mechanism of severe acute pancreatitis (SAP) and of treatment with pyrrolidine dithiocarbamate (PDTC) on rats with SAP. METHODS: SD rats were randomly divided into sham operation group (SO), SAP group, SAP + lipopolysaccharide(LPS) group, pyrrolidine dithiocarbamate (PDTC) treatment group and LPS group. Biochemical parameters and cytokines were examined in the serum. Multiple organs pathological slices were examined. Expression of NF-kappaB mRNA in the liver tissue was detected by RT-PCR. Activation of NF-kappaB by the method of streptomycin avidin-peroxidase (SP) and expression of NF-kappaB p65 protein and its binding activity were analyzed by Western blot and electrophoretic mobidity shift assay (EMSA). RESULTS: Compared with sham operation group, the concentration of TNF-alpha, alanine aminotransferase (ALT), and diamine oxidase (DAO) in serum significantly increased in SAP + LPS group (P < 0.05). Pathological changes were markedly observed in tissues and the expression of NF-kappaB mRNA in the liver significantly increased (P < 0.05) also, the activation of NF-kappaB and binding activity of NF-kappaB p65 protein in the liver markedly increased (P < 0.01) in SAP + LPS group. Treatment with PDTC markedly reduced concentration of ALT, DAO and TNF-alpha, and the expression of NF-kappaB, and the pathologic scores, as well as significantly decreased the expression of NF-kappaB p65 protein. CONCLUSION: The activation and overexpression of NF-kappaB may participate in the aggravating mechanism of SAP. Treatment with PDTC has a protective effect on multiple organs damage in SAP.

Fluid therapy for severe acute pancreatitis in acute response stage.

BACKGROUND: Fluid therapy for severe acute pancreatitis (SAP) should not only resolve deficiency of blood volume, but also prevent fluid sequestration in acute response stage. Up to date, there has not a strategy for fluid therapy dedicated to SAP. So, this study was aimed to investigate the effects of fluid therapy treatment on prognosis of SAP. METHODS: Seventy-six patients were admitted prospectively according to the criteria within 72 hours of SAP onset. They were randomly assigned to a rapid fluid expansion group (Group I, n = 36) and a controlled fluid expansion group (Group II, n = 40). Hemodynamic disorders were either quickly (fluid infusion rate was 10 - 15 ml x kg(-1) x h(-1), Group I) or gradually improved (fluid infusion rate was 5 - 10 ml x kg(-1) x h(-1), Group II) through controlling the rate of fluid infusion. Parameters of fluid expansion, blood lactate concentration were obtained when meeting the criteria for fluid expansion. And APACHE II scores were obtained serially for 72 hours. Rate of mechanical ventilation, incidence of abdominal compartment syndrome (ACS), sepsis, and survival rate were obtained. RESULTS: The two groups had statistically different (P < 0.05) time intervals to meet fluid expansion criteria (Group I, 13.5 +/- 6.6 hours; Group II, (24.0 +/- 5.4) hours). Blood lactate concentrations were both remarkably lower as compared to the level upon admission (P < 0.05) and reached the normal level in both groups upon treatment. It was only at day 1 that hematocrit was significantly lower in Group I (35.6% +/- 6.8%) than in Group II (38.5% +/- 5.4%) (P < 0.01). Amount of crystalloid and colloid in group I ((4028 +/- 1980) ml and (1336 +/- 816) ml) on admission day was more than those of group II ((2472 +/- 1871) ml and (970 +/- 633) ml). No significant difference was found in the total amount of fluids within four days of admission between the two groups (P > 0.05). Total amount of fluid sequestration within 4 days was higher in Group I ((5378 +/- 2751) ml) than in Group II ((4215 +/- 1998) ml, P < 0.05). APACHE II scores were higher in Group I on days 1, 2, and 3 (P < 0.05). Rate of mechanical ventilation was higher in group I (94.4%) than in group II (65%, P < 0.05). The incidences of abdominal compartment syndrome (ACS) and sepsis were significantly lower in Group II (P < 0.05). Survival rate was remarkably lower in Group I (69.4%) than in Group II (90%, P < 0.05). CONCLUSIONS: Controlled fluid resuscitation offers better prognosis in patients with severe volume deficit within 72 hours of SAP onset.

[Studies on the cell markers of endothelial function in sepsis].

OBJECTIVE: To study the phasic changes of the number of circulating endothelial cells (CEC) and endothelial microparticles (EMP) during the process of sepsis. METHODS: Thirty-one patients with sepsis were divided into mild group (<9), moderate group (9-15) and severe group (>15) according to the acute physiology and chronic health evaluation II (APACHE II) scores after onset, and each group was further divided into survivors and non-survivors.The level of CEC, EMP and pro-inflammatory cytokines were determined on 1, 2, 3, 7, 14 days after onset. RESULTS: (1)The level of EMP, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in the severe group were significantly higher than the mild group and moderate group (P<0.05 or P<0.01). The number of CEC in the severe group was significantly lower than the mild group and moderate group (P<0.05 or P<0.01). (2)The levels of CEC, EMP in the non-survivor and the survivor group were significantly higher with sepsis increased significantly; and the levels of EMP, pro-inflammatory in the non-survivor group were significantly higher than those of the survivor group (P<0.05 or P<0.01), but the levels of CEC, IL-4 and IL-10 in non-survivors were significantly lower than the survivors (P<0.05 or P<0.01). CONCLUSION: The levels of CEC and EMP in patients with sepsis increased significantly. They can not only serve as an index to reflect the severity of sepsis, but also have a prognostic value in patients with sepsis.

Increased NPC1L1 and ACAT2 expression in the jejunal mucosa from Chinese gallstone patients.

The incidence of cholesterol gallstones is a very common disease. The aim of this study is to probe for underlying intestinal molecular defects associated with development of gallstones. Twelve Chinese patients with cholesterol gallstone disease (GS) and 31 gallstone-free (GSF) patients were investigated. Quantitation of mRNA levels for individual genes in mucosal biopsies from jejunum was carried out with real-time PCR. The frequency of two SNPs in the ABCG8 gene (Y54C and T400K) was determined by allelic discrimination. The intestinal mRNA expression of NPC1L1 and ACAT2 were significantly higher in GS than GSF (P<0.05). No differences were observed concerning the levels for plasma lipids, plant sterols and 7alpha-hydroxy-4-cholesten-3-one between GS and GSF. No correlations were observed between patients carrying the different genotypes for Y54C or T400K and their mRNA levels for ABCG5 or ABCG8. The increased NPC1L1 and ACAT2 mRNA levels in gallstone patients might indicate an upregulated absorption and esterification of cholesterol in the small intestine.

[Detection of early organ dysfunction for the selection of treatment strategy on severe acute pancreatitis.].

OBJECTIVE: To investigate the severity related influencing factor and treatment strategy of severe acute pancreatitis with early organ dysfunction. METHODS: From July 2007 to December 2008, 167 patients with severe acute pancreatitis were treated in the Surgical Department of Ruijin Hospital. The relationships between the happening of early organ dysfunction and outcome of the patients were observed, with operative or nonoperative treatment strategy. RESULTS: Among 167 patients, 68 patients have early organ dysfunction, in which 39 with single organ dysfunction and 29 with multiple organ dysfunction. The early organ dysfunction were involved in 47.1% in cardiovascular system, 35.3% in lung and 29.4% in kidney. Aging (P < 0.05) and higher APACHE II score (P < 0.05) predicted a poor prognosis, which were benefit from early operation. CONCLUSIONS: The mortality of the patients with SAP is related to age, and the degree of organ dysfunction as well. In the first phase of the disease, the selection of operation depends on the trends and the degree of early organ dysfunction before infected necrosis happens, with the aid of SOFA score as a scale.

[Strategy of treatment with high-volume hemofiltration on severe acute pancreatitis and fulminant acute pancreatitis.].

OBJECTIVE: To investigate strategy of treatment of hemofiltration on severe acute pancreatitis (SAP) and fulminant acute pancreatitis (FAP). METHODS: One hundred and thirty patients with SAP and eighty-one patients with FAP treated with hemofiltration (HF) were prospectively observed from March 1997 to December 2008. Indications for HF, variables (time interval for hemofiltration), mode, therapeutic dosage, blood rate, heparin dosage and components of hemofiltration, therapeutic efficacy (time of disapearance of abdominal pain, intra-abdominal pressure and survival rate) and complications (incidence of bleeding and blood infection). RESULTS: All patients underwent high volume hemofiltration (HVHF) or hemodialysis-filtration (HDF) within 72 hours after onset of the disease. Dose of SAP and FAP was (53 +/- 6) mlxkg(-1)xh(-1) and (59 +/- 10) mlxkg(-1)xh(-1) (P < 0.05), respectively. Rate of short veno-venous hemofiltration in SAP (76.9%) was higher than that of FAP (38.3%) (P < 0.05); however, rate of continuous veno-venous hemofiltration (23.1%) was lower than that of FAP (37.0%) (P < 0.05). Rate of HDF was much higher in FAP than that of SAP. Low molecular weight heparin and heparin were both available to anticoagualte;but dosage required in patients with FAP was much higher than that of SAP (P < 0.05). Time intervals for amelioration of abdominal pain in SAP and FAP were (9 +/- 6) h and (15 +/- 10) h, respectively. Itra-abdominal pressure was decreased significantly at the end of hemofiltration compared to prior to hemofiltration in SAP and FAP (P < 0.05). Level of serum triglyceride decreased abruptly after adsorption (P < 0.05). Rate of operation within 28 days in SAP (73.8%) was lower than FAP (87.7%). The in-hospital survival rates in SAP and FAP were 88.5% and 67.9%, respectively. Amount of platelet decreased in patients with blood flow rate less than 240 ml/min was higher than that of more than 240 ml/min (P < 0.05). And incidence of blood stream infection and bleeding increased significantly (P < 0.05). CONCLUSIONS: HVHF and HDF used in SAP and FAP patients underwent conservative treatment within 72 hours, respectively, can increase survival rate significantly.

Increased expression of LXR alpha, ABCG5, ABCG8, and SR-BI in the liver from normolipidemic, nonobese Chinese gallstone patients.

Cholesterol supersaturation of bile is one prerequisite for gallstone formation. In the present study of Chinese patients with gallstones, we investigated whether this phenomenon was correlated with the hepatic expression of genes participating in the metabolism of cholesterol and bile acids. Twenty-two nonobese, normolipidemic patients (female-male, 11:11) with gallstones were investigated with 13 age- and body mass index-matched gallstone-free controls (female-male, 10:3). The bile from the gallstone patients had higher cholesterol saturation than that from the controls. The mRNA levels of ABCG5, ABCG8, and liver X receptor alpha (LXRalpha) in the gallstone patients were increased by 51, 59, and 102%, respectively, and significantly correlated with the molar percentage of biliary cholesterol and cholesterol saturation index (CSI). The mRNA and protein levels of the hepatic scavenger receptor class B type I (SR-BI) were increased, and a significant correlation was found between the protein levels and the CSI. No differences were recorded between the two groups concerning the hepatic synthesis of cholesterol, bile acids, and esterification of cholesterol. Our results suggest that the upregulation of ABCG5/ABCG8 in gallstone patients, possibly mediated by increased LXRalpha, may contribute to the cholesterol supersaturation of bile. Our data are consistent with the possibility that increased amounts of biliary cholesterol may originate from plasma HDL cholesterol by enhanced transfer via SR-BI.