Segregation analysis of hepatocellular carcinoma in a moderately high-incidence area of East China

AIM: To explore the mode of inheritance of hepatocellular carcinoma (HCC) in a moderately high-incidence area of East China.METHODS: A pedigree survey was conducted in 210 families (3315 individuals) ascertained through 210 HCC probands in Haimen, Jiangsu Province. Simple segregation analysis was conducted using SEGRANB software. The probability of ascertainment (π), segregation ratio (p), and the proportion of sporadic cases (x) were estimated. Complex segregation analysis was performed using the REGTL program of S.A.G.E.Models were fitted on the data of 3212 individuals that allowed for personal HBsAg status and variable age of onset in REGTL program.RESULTS: The estimate of segregation ratio was 0.191 by SEGRANB. The probability of ascertainment was 0.0266, and the proportion of sporadic cases was 0.465. The results of complex segregation analysis showed that Mendelian autosomal recessive inheritance of a major gene that influenced the age of onset distribution of HCC, provided the best fit to the data. In the best-fitting recessive model,the frequency of the disease allele was 0.11138. HBsAg seropositive status would significantly increase the risk of developing HCC.CONCLUSION: These results suggest that at least one major gene is involved in the genetic predisposition to develop HCC at an earlier age of onset. The seropositive HBsAg status can significantly increase the risk of developing HCC, which provides strong support for the interaction between genetic and environmental risk factors.

Modified technique for combined liver-small bowel transplantation in pigs

AIM: As the conventional combined liver-small bowel transplantation is complicated with many postoperative complications, the aim of this study was to describe a modified technique for the combined liver-small bowel transplantation with preservation of the duodenum, partial head of pancreas and hepatic biliary system in pigs.METHODS: Composite liver/small bowel allotransplantations were undertaken in 30 long-white pigs. The graft included liver, about 3 to 4 m proximal jejunum, duodenum and partial pancreatic head. Vessels reconstructions included subhepatic vena cava-vena cava anastomosis, aorta-aorta anastomosis and portal-splenic vein anastomosis.RESULTS: Without immunosuppressive treatment, the median survival time of the animals was 6 days (2 to 12days), and about 76.9 % (20/26) of the animals survived for more than 4 days after operation.CONCLUSION: The modified technique is feasible and safe for the composite liver/small bowel transplantation with duodenum and pancreas preserved in pigs. And also this technique can simplify the operation and decrease possible postoperative complications.

Auxiliary en-bloc liver-small bowel transplantation with partial pancreas preservation in pigs

AIM: The aim of this study was to describe an auxiliary combined liver-small bowel transplantation model with the preservation of duodenum, head of pancreas and hepatic biliary system in pigs. The technique, feasibility, security and immunosuppression were commented.METHODS- Forty outbred long-white pigs were randomized into two groups, and the auxiliary composite liver/small bowel allotransplantations were undertaken in 10 longwhite pigs in each group with the recipient liver preserved.Group A was not treated with immunosuppressive drugs while group B was treated with cyclosporine A and methylprednisolone after operation. The hemodynamic changes and amylase of body fluid (including blood, urine and abdominal drain) were analyzed.RESULTS: The average survival time of the animals was 10±1.929 d (6 to 25 d) in group A while more than 30 d in group B. The pigs could tolerate the hemodynamic fluctuation during operation and the hemodynamic parameters recovered to normal 2 h after blood reperfusion. The transient high amylase level was decreased to normal one week after operation and autopsy showed no pancreatitis.CONCLUSION: Auxiliary en-b/oc liver-small bowel transplantation with partial pancreas preservation is a feasible and safe model with simplified surgical techniques for composite liver/small bowel transplantation. This model may be used as a preclinical training model for clinical transplantation method, clinical liver-small bowel transplantation related complication research, basic research including immunosuppressive treatment, organ preservation, acute rejection, chronic rejection, immuno-tolerance and xenotransplantation.

Are polymorphisms of N-acetyltransferase genes susceptible to primary liver cancer in Luoyang, China?

AIM: To identify whether the polymorphisms of the Nacetyltransferase (NAT) genes are susceptible to primary liver cancer (PLC) in Luoyang, a PLC low-incidence area of China.METHODS: The NAT1 and NAT2 genotypes of 96 PLC cases and 173 controls were determined by PCR-RFLP.Both interaction between NAT1 or NAT2 and environmental risk factors were analyzed based on case control study.RESULTS: Compared to the control group, the frequencies of alleles NAT1*3, NAT1*4, NAT1*10, NAT1*14B and alleles NAT2*4, NAT2*6, NAT2*7 in PLC group showed no statistically significant difference (x2 = 2.61 and 4.16,respectively, both P＞0.05). The frequencies of NAT1 genotypes NAT1*3/*3, NAT1*3/*4, NAT1*3/*10,NAT1*3/*14B, NAT1*4/*4, NAT1*4/*10, NAT1*4/*14B,NAT1*10/*10, NAT1*10/*14B, and NAT2 genotypes NAT2*4/*4, NAT2*4/*6, NAT2*4/*7, NAT2*6/*6,NAT2*6/*7 and NAT2*7/*7 also had no statistically significant difference between the two groups (x2 = 11.86 and 2.94respectively both, P＞0.05). Neither the frequencies of rapid and slow NAT1 acetylators nor the frequencies of rapid and slow NAT2 acetylators were significantly different between the two groups (x2 = 0.598 and 0.44,respectively, both P＞0.05). The interaction betweenNAT1*10 and occupational exposures was found significant with an odds ratio of 3.40 (x2 = 8.42, P = 0.004,OR 95%CI:1.03-11.22). But no interaction was found between NAT2 and any environmental risk factors.CONCLUSION: The polymorphisms of NAT1 and NAT2are not susceptible to PLC in Luoyang. Allele NAT1*10interacts with occupational exposures.

Modifications in combined liver-small bowel transplantation in pigs

AIM: To introduce combined liver-small bowel transplantation in pigs.METHODS: Eighteen transplantations in 36 large white pigs were performed. Three modifications in combined liver-small bowel transplantation model were applied: Veno-venous bypass was not used. Preservation of the donor duodenum and head of pancreas in continuity with the combined graft to avoid biliary reconstruction. The splenic vein of donor was anastomosed end-to-end with the portal vein of recipients by the formation of a 'cuff'.RESULTS: Without immunosuppressive therapy, 72-hour survival rate of the transplanted animals was 72% (13/18).Five of 18 pigs operated died of respiratory failure (3 cases)and bleeding during hepatectomy (2 cases). The longest survival time of animals was 6 days.CONCLUSION: Our surgical modifications are feasible and reliable, which have made the transplantation in pigs simpler and less aggressive, and thus these can be used for preclinical study.

医学细胞生物学实验课教学改革需求的现状分析

目的:对细胞生物学实验教学改革需求进行问卷调查。方法:应用“医学生对医学细胞生物学实验课程教学评估问卷”进行问卷调查。结果:71.2%的学生支持实验课教学改革,实验课程设置分值(t=2.518,P=0.012)和学生学习效果分值(t=2.108,P=0.036)是教学改革的影响因素。结论:学生具有较强的实验课教学改革意愿和需求。

The M Protein of SARS-CoV: Basic Structural and Immunological Properties

We studied structural and immunological properties of the SARS-CoV M (membrane) protein, based on comparative analyses of sequence features, phylogenetic investigation, and experimental results. The M protein is predicted to contain a triple-spanning transmembrane (TM) region, a single N-glycosylation site near its N-terminus that is in the exterior of the virion, and a long C-terminal region in the interior. The M protein harbors a higher substitution rate (0.6% correlated to its size) among viral open reading frames (ORFs) from published data. The four substitutions detected in the M protein, which cause non-synonymous changes, can be classified into three types. One of them results in changes of pI (isoelectric point) and charge, affecting antigenicity. The second changes hydrophobicity of the TM region, and the third one relates to hydrophilicity of the interior structure. Phylogenetic tree building based on the variations of the M protein appears to support the non-human origin of SARS-CoV. To investigate its immunogenicity, we synthesized eight oligopeptides covering 69.2% of the entire ORF and screened them by using ELISA (enzyme-linked immunosorbent assay) with sera from SARS patients. The results confirmed our predictions on antigenic sites.