TLR4 Knockout Attenuates BDL-induced Liver Cholestatic Injury through Amino Acid and Choline Metabolic Pathways

The exact mechanism by which knockout of Toll-like receptor 4(TLR4)attenuates the liver injury remains unclear.The present study aimed to examine the role of TLR4 in the pathogenesis of bile duct ligation(BDL)-induced liver cholestatic injury and the underlying mechanism.Wild type(WT)mice and TLR4 knockout(TLR4-KO)mice were used for the establishment of the BDL model.Metabolomics were applied to analyze the changes of small molecular metabolites in the serum and liver of the two groups.The serum biochemical indexes and the HE staining results of liver tissue showed that liver damage was significantly reduced in TLR4-KO mice after BDL when compared with that in WT mice.The metabolite analysis results showed that TLR4 KO could maintain the metabolisms of amino acids-and choline-related metabolites.After BDL,the amino acids-and choline-related metabolites,especially choline and 3-hydroxybutyrate,were significantly increased in WT mice(both in serum and liver),but these metabolites in the liver of TLR4-KO mice after BLD were not significant different from those before BLD.In conclusion,TLR4 KO could attenuate BDL-induced liver cholestatic injury through regulating amino acid and choline metabolic pathways.

Clinicopathological Study of Sporadic Burkitt Lymphoma in Children

Background：Non-Hodgkin lymphoma is the fourth most common malignant tumors in children,Burkitt lymphoma （BL） accounts for 30-50％ of all pediatric lymphomas.The aim of this study was to investigate the clinicopathologic features,immunophenotype,Epstein-Barr virus （EBV） infection and c-myc gene rearrangement of sporadic BL in children.Methods：Ninety-two cases of pediatric BL were retrospectively analyzed for clinical features,immunohistochemistry,EBV-encoded RNA （EBER） status by in situ hybridization and c-myc gene rearrangement by fluorescence in situ hybridization.Results：In the 92 cases,male is predominant in sex distribution （M：F =3.38：1）.The average age at diagnosis was 4.97 years.Polypoid BL showed a lower clinical stage （P =0.002）,and advanced clinical stage and low serum albumin level at diagnosis were associated with poor outcome （P =0.024 and 0.053,respectively）.The positive expression of CD10,B-cell lymphoma-6,MUM1 and EBER were 95.7％ （88 cases）,92.4％ （85 cases）,22.8％ （21 cases）,41.3％ （38 cases）,respectively.The expression of MUM1 were not associated with EBV infection status （P =1.000）.c-myc gene rearrangement was detected in 94.6％ （87/92）.Clinical treatment information for 54 cases was collected,21 patients died of tumor after surgery alone,33 patients received surgery and chemotherapy,and of which six patients died shortly afterwords （MUM 1 positive expression in 3 cases,P =0.076）.Conclusions：The anatomical location,growth pattern and serum albumin level of BL were associated with biological behavior.MUM1 may be a potential adverse prognostic marker,and not associated with EBV infection status.