Polymorphism rs738409 in PNPLA3 is associated with inherited susceptibility to non-alcoholic fatty liver disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the relationship between the patatin-like phospholipase domain-containing protein 3 (PNPLA3) gene and hereditary susceptibility to non-alcoholic fatty liver disease (NAFLD) by detecting single nucleotide polymorphisms (SNPs).</p><p><b>METHODS</b>Peripheral blood DNA from 315 patients diagnosed with NAFLD (including the spectrum of simple steatosis (SS) and non-alcoholic steatosis (NASH)) and 336 control subjects was used to determine the PNPLA3 genotype by polymerase chain reaction (PCR) and direct sequencing. The relationship of SNPs and NAFLD-related markers of liver function were assessed by correlation analysis.</p><p><b>RESULTS</b>The SNP rs738409 was identified in more of the NAFLD patients (allele variant frequencies: NAFLD, 65.40%; NASH: 71.87%; SS, 56.47%) than in the controls (33.18%). Case-control analysis revealed that carriers of the 148GG genotype were at 3.81-fold (95% CI: 3.03 ~ 4.79) higher risk of developing NAFLD and at 1.97-fold (95% CI: 1.41 ~ 2.75) higher risk of progressing from SS to NASH, compared with non-carriers. rs738409 was also found to be associated with serum levels of alanine aminotransferase (ALT) and y-glutamyltransferase (y-GT) (both P less than 0.05). Carriers of the 148GG genotype had significantly higher body mass index, ALT, and fasting insulin than carriers of the 148CC genotype (all P less than 0.05), and significantly higher level of serum HDL than carriers of either the 148CC genotype or the 148GC genotype (both P less than 0.05).</p><p><b>CONCLUSION</b>Polymorphisms in the PNPLA3 gene may play an important role in mediating susceptibility to developing NAFLD in the Chinese population. The rs738409 polymorphism, in particular, is related to development and progression of NAFLD and may play a role in the contribution of PNPLA3 to NAFLD pathogenesis.</p>

Study of inhibiting and killing effects of transgenic LIGHT human umbilical cord blood mesenchymal stem cells on stomach cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the inhibition and killing effect of transgenic LIGHT umbilical cord blood mesenchymal stem cells (UCBMSCs) on stomach carcinoma.</p><p><b>METHODS</b>The LIGHT gene was recombined to construct the transfer plasmid pGC-FU-LIGHT by infusion technique. The 293T cells were co-transfected with the transfer plasmid pGC-FU-LIGHT, the construction plasmid Helper 1.0 and the envelope plasmid Helper 2.0 with the help of lipofectamine 2000 to produce lentiviral particles. Transgenic UCBMSCs(MSC-LIGHT) and empty carrier UCBMSCs (MSC) were obtained. Human gastric cancer cell SGC-7901 was injected into nude mice subcutaneously groin. The model of transplanted human gastric cancer cell SGC-7901 in nude mice was established. Tumorigenesis nude mice were separated into three groups randomly with 5 in each group: MSC-LIGHT group, MSC group, and NS group. Three groups of nude mice were injected around the tumor with MSC-LIGHT, MSC and NS every other day for 3 times. Four weeks later, the transplanted gastric cancer volume was measured. The expressions of LIGHT in the three groups were determined by RT-PCR and ELISA method. The necrosis area in the tumors was calculated under pathological examination.</p><p><b>RESULTS</b>The average volume of transplanted tumor was(0.45±0.25) cm(3) in MSG-LIGHT group, (0.64±0.36) cm(3) in MSG group, and(1.21±0.79) cm(3) in NS group, and the difference was statistically significant(P<0.05). The LIGHT mRNA was 2.96±0.27, 1.23±0.47, and 0.73±0.10 respectively. The LIGHT protein was(167.89±2.31), (73.22±5.74), and (49.66±5.25) ng/L. The differences were all statistically significant among the three groups(both P<0.01). Pathological examination showed that the necrosis area was largest in MSC-LIGHT group.</p><p><b>CONCLUSION</b>Transgenic UCBMSCs secret LIGHT in a paracrine manner, which has inhibition and killing effects on stomach carcinoma.</p>

General characteristics and clinical practices of Chinese patients with non-alcoholic fatty liver disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To assess the characteristics and daily treatment compliance of non-alcoholic fatty liver disease (NAFLD) patients in China.</p><p><b>METHODS</b>NAFLD adult patients from 21 clinics of 12 cities in China were enrolled in this registry. Physical examination such as demographic characteristics (height, weight, waist circumference measurement), blood pressure and clinical laboratory and ultrasonographic examination of liver were undertaken. Daily practice including life style and medication were recorded and assessed in accordance with 2006 Chinese NAFLD treatment guidelines.</p><p><b>RESULTS</b>A total of 1656 patients were enrolled (1146 male and 510 female), mean of 45.8 ± 12.6 years old, mean duration of NAFLD history was (47.2 ± 47.7) months. 44.9% of NAFLD were suffering from metabolic syndromes. Patients with central obesity have higher incidence of hypertension and lower level of high-density lipoprotein cholesterol (HDL-C) than those without central obesity, P < 0.05. Body mass index (BMI), waist circumference, triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in ALT abnormal group were higher than those in ALT normal group (P < 0.05), HDL-C was lower in ALT abnormal group (P < 0.05). Significant differences existed between the BMI, female waist circumference, TG, fast insulin, HOMA index, ALT, AST and HDL-C among subgroups with mild, moderate and severe steatosis. Majority of the patients did not follow recommendations of NAFLD treatment guidelines. Among targeted population only 15.3% of patients used insulin sensitizers and 23.8% took lipid lowering medicine according to the guideline.</p><p><b>CONCLUSION</b>Data indicated that nearly half of NAFLD patients co-morbid with metabolic disorders. Therapy compliance was unsatisfactory and the gap between current practice and Chinese NAFLD treatment guidelines was not optimal.</p>

Study on the correlations between HBsAg and hepatitis C virus expression as well as fibrotic staging in hepatocellular carcinoma and pericarcinomatous tissues / 中华流行病学杂志

<p><b>OBJECTIVE</b>To study the correlation between hepatitis B virus surface antigen (HBsAg) and hepatitis C virus (HCV) expression as well as fibrosis staging in hepatocellular carcinoma (HCC) and pericarcinomatous tissues.</p><p><b>METHODS</b>The patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied on paraffin-embeded sections with immunohistochemistry technique, and liver tissues were also staged.</p><p><b>RESULTS</b>HBV, HCV virus infection were positively correlated with the fibrotic staging (r(s) = 0.32, P = 0.001). HBsAg and HCV were detected both in HCC and pericarcinomatous tissues. The positive rate of HBsAg in Pericarcinomatous Tissues (79%) was higher than that of in HCC tissues (23%). HCV expressions in HCC (15%) and pericarcinomatous tissues (23%) showed no significant differences.</p><p><b>CONCLUSION</b>The fibrotic degree in the tissues of liver cancer with previous virus infection was obviously higher than that without virus infection. Viral infection seemed to be one of the reasons causing liver cancer while perennial virusemia would aggravate pathological changes of the liver tissue.</p>

Study on Helicobacter infection in liver tissue from hepatocellular carcinoma / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between Helicobacter species and hepatocellular carcinoma(HCC).</p><p><b>METHODS</b>Liver samples resected during operation from 34 patients with HCC diagnosed by histopathology and 20 without primary liver carcinoma as controls were studied. The two groups of sample were cranked out pathologic slice for in situ hybridization of Helicobacter, Helicobacter pylori and Helicobacter hepaticus. Qualitative and quantitative studies were used to assess the correlation of liver tissue Helicobacter infection with HCC.</p><p><b>RESULTS</b>64.71% (22/34). of the samples of HCC showed positive for Helicobacter specific 16S rRNA-mRNA gene by in situ hybridization, while none was positive in controls (P < 0.01).</p><p><b>CONCLUSION</b>Helicobacter pylori were found in the liver of patients with HCC.</p>

Correlation between HBsAg, HCV expression in cancerous and pericancer tissues of hepatocellular carcinoma and liver fibrosis markers in serum / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the correlation between HBsAg and HCV in hepatocellular carcinoma (HCC) pericarcinomatous tissues and serum liver fibrosis markers.</p><p><b>METHODS</b>The patterns of HBsAg and HCV in 100 cases of HCC and their surrounding liver tissues were studied with paraffin sections using immunohistochemistry techniques. Hyaluronic acid (HA), procollagen III peptide (PIIIP), collagen IV (CIV), and laminin (LN) were detected by radioimmunoassay.</p><p><b>RESULTS</b>The levels of HA, PIIIP, CIV and LN in the HBV and HCV coinfection group were the highest among the four groups. The levels of HA, PIIIP, CIV and LN in the groups not infected by HBV and HCV were the lowest among the four groups. HBV and HCV expressions were positively correlated with HA, LN and CIV and their Spearman's rank correlation coefficients were 0.60, 0.45, 0.46, respectively (P < 0.01).</p><p><b>CONCLUSION</b>Liver cancer development follows a sequential trend of chronic hepatitis, liver cirrhosis, and liver cancer. In the tissues of liver cancer with virus infection background, the serum marker level of hepatic fibrosis is obviously higher than those without virus infection background. On the one hand, virus infection is one of the reasons causing liver cancer; and on the other hand, longstanding viremia will aggravate pathological changes of liver tissues. Therefore antivirus treatment of hepatitis is of significance for the prognosis of liver cancer.</p>