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Liver diseases significantly affect human health. Classic research models cannot maintain hepatocyte polarity for a long time and have a different genetic background from normal human hepatocytes, which limits the research on the physiological functions of hepatocytes and the mechanisms of related diseases. The latest liver organoid technology can obtain liver organoids with partial liver structure by reprogrammed induced pluripotent stem cells or in vitro culture of liver biopsy tissue and maintain long-term proliferation and genetic stability, and therefore, it is expected to become a powerful tool for disease modelling, drug screening, and cell therapy. This article mainly reviews the research and application of liver organoids in recent years.
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The advancement and popularization of molecular diagnostic techniques has challenged and redefined the traditional concept of genetic metabolic disease. Regardless of disease origin, all genetic defects that lead to hepatobiliary dysfunction or structural abnormalities are termed as genetic liver disorders. Online Mendelian Inheritance in Man (OMIM) is a database consisting 693 genetic diseases with clear molecular mechanism of liver related phenotypes. Moreover, the effective measures to control infectious liver disease have strengthened the importance of research in the field of (adult and children) genetic liver disorders at home and abroad by well-recognized hepatologists. Notably, all patients with unexplained hepatopathy and multiple system diseases involving liver and gallbladder needs screening for genetic liver disorders, except for factors such as infection, immunity, drug-related, and anatomical abnormalities. We hope more patients with complicated liver disorders will benefit from definitive diagnosis and effective treatment in the near future with clear explanation of clinical phenotype, genotype, and metabolomics.
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Objective@#To summarize and review the clinical and genetic features of neonatal sclerosing cholangitis (NSC) caused by DCDC2 variations.@*Methods@#Whole exome sequencing was performed to identify DCDC2 variants in two Chinese siblings with NSC who were diagnosed in Children's Hospital of Fudan University in May 2017. Clinical, laboratory and genetic data of the two cases were summarized. Key words of "DCDC2" "neonatal sclerosing cholangitis" were searched in Chinese databases and PubMed for articles published until April 2018, and all the relevant literature were reviewed.@*Results@#Patient 1 was a 3-year-and-2-month-old boy. He was admitted to our hospital due to cholestasis for 3 years. Laboratory findings showed elevated levels of gamma-glutamyl transpeptidase (161-1 092 U/L) and total cholesterol (5.4-7.7 mmol/L). Magnetic resonance cholangiopancreatography showed multiple dilations of intrahepatic bile ducts and bilateral hydronephrosis. Patient 2, the older brother of patient 1, was a 9-year-and-9-month-old boy. He was admitted to our hospital due to "cholestasis for 9 years" . CT angiography showed hydrocephalus and left internal carotid artery aneurysms with vascular malformations. A homozygous variant c.529dupA (NM_001195610) in DCDC2 gene was identified in patient 1 by whole exome sequencing. Patient 2 was a homozygote and his parents were heterozygotes with the variation. There has been 2 relevant articles published (Chinese 0, English 2), which reported 11 cases of DCDC2-related NSC in total. All the 13 patients, including the 2 cases reported here, had an onset of symptoms at 0 to 6 months of age. The most common clinical manifestation was cholestasis with high gamma-glutamyl transpeptidase levels, acholic stool, and progression to portal hypertension. Renal and neurological abnormalities were also frequently present. Hypercholesterolemia was observed in one case. Radiological findings revealed the characteristic strictures and dilatations of the intrahepatic and (or) extrahepatic biliary tree. Liver histological examination showed peripheral ductopenia, ductal plate malformation, fibrosis, and cirrhosis. Among the 13 patients, 10 patients required liver transplantation. A total of 7 types of DCDC2 variants were detected in 13 patients.@*Conclusions@#DCDC2-related NSC is characterized by the onset of cholestasis with high gamma-glutamyl transpeptidase level and acholic stool in early infancy, which was likely to progress to cirrhosis in early childhood. Renal and neurological abnormalities are also frequently present.Cholangiography or magnetic resonance cholangiopancreatography show strictures and dilatations of the intrahepatic or (and) extrahepatic biliary tree. Identification of pathogenic DCDC2 variants would aid the diagnosis of NSC.
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Objective: To observe the treatment effect of acupoint sticking at Shenque (CV 8) with ginger-preparedBan Xia (Rhizoma Pinelliae) on nausea and vomiting induced by Amifostine for myelodysplastic syndromes (MDS). Methods: Totally 124 eligible subjects intervened by Amifostine were randomized into 2 groups by the visiting order,an observation group and a control group,62 in each group. The control group was intervened by conventional treatment, while the observation group was by acupoint sticking at Shenque (CV 8) with ginger-preparedBan Xia (Rhizoma Pinelliae) in addition to the same conventional treatment. The occurrence rate of nausea and vomiting in the two groups were observed. Results: After intervention, the occurrence rate of nausea and vomiting in the observation group was significantly lower than that in the control group (P Conclusion: Acupoint sticking at Shenque (CV 8) with ginger-prepared Ban Xia (Rhizoma Pinelliae)can produce a content effect on nausea and vomiting induced by Amifostine for MDS.