Role of CD56-expressing immature biliary epithelial cells in biliary atresia

AIM: To analyze the clinical and pathological parameters and expression of the neural cell adhesion molecule(CD56) in patients with biliary atresia(BA).METHODS: Established clinical laboratory markers of hepatic function, including enzyme activity, protein synthesis, and bilirubin metabolism, were evaluated in patients with BA and compared with those in patients with choledochal cysts and neonatal hepatitis. Pathological changes in tissue morphology and fibrosis were examined by histological and tissue collagen staining. Immunohistochemical staining for the biliary epithelial cell markers CD56 and CK19 together with the Notch signaling related molecules Notch1 and Notch2 was performed in the context of alterations in the structure of intrahepatic biliary ducts.RESULTS: Differences in some clinical laboratoryparameters among the three diseases examined were observed, but they did not correlate with the pathological classification of fibrosis in BA. Immunohistochemical staining showed the presence of CD56-positive immature bile ducts in most patients(74.5%) with BA but not in patients with choledochal cysts or neonatal hepatitis. The number of CD56-expressing cells correlated with disease severity, with more positive cells present in the later stages of liver damage(81.8% vs 18.2%). Furthermore, bile plugs were mainly found in CD56-positive immature biliary ducts. Notch signaling was a key regulatory pathway in biliary duct formation and played a role in tissue fibrosis. Notch1 was co-expressed in CD56-positive cells, whereas Notch2 was found exclusively in blood vessels in the portal area of patients with BA. CONCLUSION: The maturation of biliary epithelial cells and the expression of Notch may play a role in the pathogenesis of BA.

Stability of a rat model of prehepatic portal hypertension caused by partial ligation of the portal vein

AIM:To study the stability of portal hypertension (PHT) caused by partial ligation of the portal vein ligation (PVL) in a rat model.METHODS: Thirty male adult Wistar rats were divided into two groups: 10 in Group received a sham operation; and 20 in Group measured at four time periods: before ligation, 2 wk, 6 wk and 10 wk post-surgery. Portal venography, blood sampling and liver and spleen pathological examinations were conducted at 10 wk after surgery.RESULTS:The PVP was 9.15±0.58 cmH2O before ligation, and increased to 17.32±0.63 cmH2O 2 wk after PVL. By repeat measurement of the PVP in each rat, it was shown to remain elevated for 10 wk. There were no signif icant differences in the pressure measurements at 2 wk, 6 wk and 10 wk. Varices were found mainly in the mesenteric vein 2 wk after PVL, which were more obvious later, while these manifestations were similar at week 6 and week 10. Portal venography demonstrated the varices and collaterals. There was no significant change in liver pathology. The volume of the spleen was enlarged 2-fold after ligation, and the sinus of the spleen was enlarged due to congestion. Significant sinus endothelial cell proliferation was observed, but no evidence of hypersplenia was found on hemogram and biochemical examination.CONCLUSION: These findings suggest that a satisfactory prehepatic PHT rat model can be obtained by partial ligation of the portal vein, and this PHT rat model was stable for at least 10 wk.

Downregulation of Hes1 expression in experimental biliary atresia and its effects on bile duct structure

AIM To analyze the expression and function of the notchsignaling target gene Hes1 in a rhesus rotavirusinduced mouse biliary atresia model. METHODS The morphologies of biliary epithelial cells in biliary atresia patients and in a mouse model were examined by immunohistochemical staining. Then, the differential expression of Notch signaling pathway-related molecules was investigated. Further, the effects of the si RNAmediated inhibition of Hes1 expression were examined using a biliary epithelial cell 3 D culture system.RESULTS Both immature(Ep CAM+) and mature(CK19+) biliary epithelial cells were detected in the livers of biliary atresia patients without a ductile structure and in the mouse model with a distorted bile duct structure. The hepatic expression of transcripts for most Notch signaling molecules were significantly reduced on day 7 but recovered to normal levels by day 14, except for the target molecule Hes1, which still exhibited lower m RNA and protein levels. Expression of the Hes1 transcriptional co-regulator, RBP-Jκ was also reduced. A 3 D gel culture system promoted the maturation of immature biliary epithelial cells, with increased expression of CK19+ cells and the formation of a duct-like structure. The administration of Hes1 si RNA blocked this process. As a result, the cells remained in an immature state, and no duct-like structure was observed.CONCLUSION Our data indicated that Hes1 might contribute to the maturation and the cellular structure organization of biliary epithelial cells, which provides new insight into understanding the pathology of biliary atresia.

Mechanical properties of graphene nanoplatelets reinforced 7075 aluminum alloy composite fabricated by spark plasma sintering

A 0.3wt%graphene nanoplatelets(GNPs)reinforced 7075 aluminum alloy matrix(7075 Al)composite was fabricated by spark plasma sintering and its strength and wear resistance were investigated.The microstructures of the internal structure,the friction surface,and the wear debris were characterized by scanning electron microscopy,X-ray diffraction,and Raman spectroscopy.Compared with the original 7075 aluminum alloy,the hardness and elastic modulus of the 7075 Al/GNPs composite were found to have increased by 29%and 36%,respectively.The results of tribological experiments indicated that the composite also exhibited a lower wear rate than the original 7075 aluminum alloy.

Family socioeconomic position and abnormal birth weight:evidence from a Chinese birth cohort

Background Birth weight is a strong determinant of infant short-and long-term health outcomes.Family socioeconomic position(SEP)is usually positively associated with birth weight.Whether this association extends to abnormal birth weight or there exists potential mediator is unclear.Methods We analyzed data from 14,984 mother-infant dyads from the Born in Guangzhou Cohort Study.We used multi-variable logistic regression to assess the associations of a composite family SEP score quartile with macrosomia and low birth weight(LBW),and examined the potential mediation effect of maternal pre-pregnancy body mass index(BMI)using causal mediation analysis.Results The prevalence of macrosomia and LBW was 2.62%(n=392)and 4.26%(n=638).Higher family SEP was associated with a higher risk of macrosomia(OR 1.30,95%CI 0.93-1.82;OR 1.53,95%CI 1.11-2.11;and OR 1.59,95%CI 1.15-2.20 for the 2nd,3rd,and 4th SEP quartile respectively)and a lower risk of LBW(OR 0.69,95%CI 0.55-0.86;OR 0.76,95%CI 0.61-0.94;and OR 0.61,95%CI 0.48-0.77 for the 2nd,3rd,and 4th SEP quartile respectively),compared to the 1st SEP quartile.We found that pre-pregnancy BMI did not mediate the associations of SEP with macrosomia and LBW.Conclusions Socioeconomic disparities in fetal macrosomia and LBW exist in Southern China.Whether the results can be applied to other populations should be further investigated.