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 a (LXRa) 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 LXRa, 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

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Objective: In order to improve the prognosis of pancreatic cancer patients, it is crucial to explore novel tools for its early diagnosis. Here, we attempted to screen serum biomarkers to distinguish pancreatic cancer from non-cancer individuals. Methods: 47 serum samples from pancreatic cancer patients, 39 of whom had small surgically resectable cancers, were collected before surgery, and an additional 53 serum samples from age- and sex-matched individuals without cancer were used as controls. The surface-enhanced laser desorption/ionization (SELDI) ProteinChip was applied to analyze serum protein profiling. 54 samples (27 with pancreatic cancer and 27 controls) were analyzed in the training set by a decision tree algorithm to be able to separate pancreatic cancer from controls. A double-blind test was used to determine the sensitivity and specificity of the classification model. Results: A panel of six biomarkers was selected to set up a decision tree as the classification model. The model separated effectively pancreatic cancer from control samples, achieving a sensitivity of 88.9% and a specificity of 74.1%. The double-blind test challenged the model with a sensitivity of 80% and a specificity of 84.6%. Conclusion: The SELDI ProteinChip combined with an artificial intelligence classification algorithm shows great potential for the diagnosis of pancreatic cancer.

The apolipoprotein (apo) B gene Xba I polymorphism is associated with alterations in serum lipids. Disturbances in serum lipids may be a risk factor for cholesterol gallstone disease. However, the relation between the Xba I polymorphism and cholesterol gallstones is unknown. This study was aimed at characterizing the polymorphism of the apo B gene Xba I in patients with gallbladder stones and the association of Xba I polymorphism with serum lipids. Xba I genotypes were measured by PCR-RFLP, and serum lipids assayed in 190 patients with gallbladder stones and 441 control subjects. The frequency of the X+/- genotype (20.63 vs. 7.94%) and X+ allele (10.79 vs. 3.97%) was significantly higher in the patient group than in the control group. Patients with the X+/- genotype had a significantly higher concentration of total cholesterol, low-density lipoprotein (LDL)-cholesterol, and apo B in serum than patients with the X-/- genotype. The X+ allele of the apo B gene is characterized by a higher cholesterol concentration and a higher LDL-cholesterol concentration in serum, and it may be a marker for increased risk of cholesterol gallstone disease.

AIM: To investigate the relationship between gallbladder stone disease (GSD) and single nucleotide polymorphisms of cholesterol 7α-hydroxylase (CYP7A) gene promoter, apolipoprotein (APO) B gene exon 26, APOE gene exon 4 or microsatellite polymorphism of low density lipoprotein receptor (LDLR) gene exon 18. METHODS:Genotypes of CYP7A, APOB, APOE and LDLR genes were determined in 105 patients with GSD diagnosed by B-mode ultrasonography and 274 control subjects. Serum lipids were analyzed with HITACHI 7060 automaic biochemical analyzer. RESULTS:Body mass index (BMI) was significantly higher in patients with GSD (24.47±3.09) than in controls (23.50±2.16). Plasma total cholesterol was lower in patients with GSD (4.66±0.92 mmol/L) than in controls (4.91±0.96 mmol/L), P<0.01 after adjusted for age, sex and BMI. The significantly higher frequency of A allele of CYP7A gene polymorphism and X+ allele of APOB gene polymorphism was seen in GSD patients. Percentages of A allele in patients and controls were 62.86% and 54.38% (P <0.05) and those of X+ allele 8.57% and 4.01% (P<0.01). Subjects with A allele had significantly lower plasma total cholesterol and LDL cholesterol than subjects with CC homozygote. In a multiple variable logistic regression model, the BMI (OR=1.13, 95% CI: 1.05-1.22), A allele (OR=1.48, 95% CI: 1.05-2.09) and X+ allele (OR=2.28, 95% CI: 1.14-4.59) were positively associated with GSD (P <0.05). Plasma total cholesterol (OR=0.69, 95% CI: 0.64-0.74) was negatively related to GSD (P<0.05). CONCLUSION:With an association analysis, it was determined that A allele of CYP7A gene and X+ allele of APOB gene might be considered as risk genes for GSD. These alleles are related with differences of serum lipids among subjects. Multiple-variable logistic regression model analysis showed that besides BMI, GSD was affected by polygenetic factors. But the mechanism for these two alleles responsible for GSD requires further investigations.