A Rare Case of Benign Recurrent Intrahepatic Cholestasis Initially Diagnosed in Middle-age.

Background: Repeated episodes of jaundice and pruritus are common in a group of autosomal recessive liver diseases known as benign recurrent intrahepatic cholestasis. Benign recurrent intrahepatic cholestasis (BRIC) is divided into two types, type 1 and type 2, and is caused by mutations in the ATP8B1 and ABCB11 genes. Here, we report a rare case of BRIC type 2 mutation. Case presentation: A 45-year-old Chinese man had three frequent episodes of jaundice marked by extensive excoriation and severe pruritis, although he had no prior history of jaundice. Laboratory investigations showed no evidence of liver damage caused by viral, autoimmune, or acquired metabolic etiologies. The CT scan revealed an enlarged gallbladder with numerous punctate high-density shadows, while no wall thickening was observed. Endoscopic ultrasonography showed no evidence of dilation of the intrahepatic and extrahepatic bile duct, as well as the absence of gallstone. Diagnostic evaluation: Immunohistochemical examinations of liver biopsy samples showed cytokeratin-7 positive hepatocytes, suggesting chronic intrahepatic cholestasis. The reticulin fiberstaining demonstrated that the portions of the hepatic plate in the center of the lobule were asymmetrically organized,and somewhat enlarged, with collapsed areas indicating intralobular inflammation. Moreover, there were areas of collapse that indicated the presence of intralobular inflammation. Whole exome sequencing revealed mutations in the ABCB11 gene; c.3084A>G, p.A1028A homozygous mutation (chr2-169789016), and c.2594C>T, p.A865V heterozygous mutation (chr2-169801131). Based on these findings, the final diagnosis of the patient was metabolism-related jaundice. Treatment: Apart from receiving tapering dosage of prednisone to lower bilirubin levels, the patient received no extra care. Conclusion: The comprehensive diagnosis of a middle-aged male patient with BRIC-2, which involved extensive radiological, hematological, and genetic investigations, informed a tailored tapering prednisone regimen, highlighting the importance of personalized medicine in managing atypical presentations of this rare cholestatic disorder.

Long Non-coding RNA Signature for Liver Metastasis of Colorectal Cancers.

Colorectal cancer ranks within the top three cancers both in terms of incidence as well as deaths. Metastasis is often the major cause of mortality and liver is the primary and most common site to which colorectal cancers metastasize. We tested the prognostic ability of a long non-coding RNA (lncRNA) signature in liver metastatic colorectal cancers. We first evaluated expression levels of several lncRNAs in eight excised liver metastases from primary colorectal cancers and found significantly upregulated lncRNAs HOTAIR and MALAT1 along with significantly downregulated LOC285194. We further compared the expression levels of HOTAIR, MALAT1 and LOC285194 in primary colorectal tumors at the time of initial diagnosis and correlated them with disease progression and liver metastasis. HOTAIR and MALAT1 were significantly upregulated and LOC285194 was significantly downregulated in twelve patients who were diagnosed with liver metastasis within 5 years of initial diagnosis, compared to the five patients with no metastasis. A positive signature comprising of high HOTAIR/MALAT1 and low LOC285194 also correlated with progression to higher grade tumors. Thus, the lncRNA signature comprising of high HOTAIR/MALAT1 and low LOC285194 could be a prognostic signature for liver metastasis as well as overall poor survival.

CTGF-mediated ERK signaling pathway influences the inflammatory factors and intestinal flora in ulcerative colitis.

OBJECTIVE: To examine the effect of connective tissue growth factor (CTGF)-mediated ERK signaling pathway on the inflammatory response and intestinal flora in ulcerative colitis (UC). METHODS: CTGF expression was determined through immunohistochemistry in UC and colon polyp patients. Dextran sulfate sodium (DSS) was used to construct UC models. Wild-type (WT) and CTGF-deficient (CTGF-/-) mice were randomly divided into WT/CTGF-/- + saline, WT/CTGF-/- + DSS, and WT/CTGF-/- + DSS + U0126 (ERK pathway inhibitor) groups. HE staining was conducted to observe the pathological changes in intestinal mucosa. The quantity of intestinal flora was tested in the feces. ELISA, qRT-PCR, and Western blotting were used to detect related-molecules expressions. RESULTS: CTGF was up-regulated in the intestinal mucosa of UC patients in relation to the severity and grade. Moreover, UC patients showed enhanced the expressions of p-ERK/ERK and pro-inflammatory factors (IL-1ß, IL-6, TNF-α, MPO), increased the quantity of Bacteriodes fragilis (B. fragilis) and Escherichia coli (E. coli), and decreased Bifidobacterium and Lactobacillus. CTGF and pERK/ERK expressions were increased in DSS-induced WT mice, but the pERK expression was lower in CTGF-/- + DSS group than that in the WT + DSS group. U0126 decreased the expressions of pro-inflammatory factors and improved the intestinal flora in WT mice induced with DSS. No significant differences were found in the above indexes between CTGF-/- + DSS group and WT + DSS + U0126 group. CONCLUSION: Inhibiting CTGF could improve inflammatory response and intestinal flora to partially reverse DSS-induced UC via blocking ERK signaling pathway.

The human plasma proteome: analysis of Chinese serum using shotgun strategy.

We have investigated the serum proteome of Han-nationality Chinese by using shotgun strategy. A complete proteomics analysis was performed on two reference specimens from a total of 20 healthy donors, in which each sample was made from ten-pooled male or female serum, respectively. The methodology used encompassed (1) removal of six high-abundant proteins; (2) tryptic digestion of low- and high-abundant proteins of serum; (3) separation of peptide mixture by RP-HPLC followed by ESI-MS/MS identification. A total of 944 nonredundant proteins were identified under a stringent filter condition (X(corr) > or = 1.9, > or = 2.2, and > or = 3.75, < or = C(n) > or = 0.1, and R(sp) > or = 4.0) in both pooled male and female samples, in which 594 and 622 entire proteins were found, respectively. Compared with the total 3020 protein identifications confirmed by more than one laboratory or more than one specimen in HUPO Plasma Proteome Project (PPP) participating laboratories recently, 206 proteins were identified with at least two distinct peptides per protein and 185 proteins were considered as high-confidence identification. Moreover, some lower abundance serum proteins (ng/mL range) were detected, such as complement C5 and CA125, routinely used as an ovarian cancer marker in plasma and serum. The resulting nonredundant list of serum proteins would add significant information to the knowledge base of human plasma proteome and facilitate disease markers discovery.

Alterations in expression, proteolysis and intracellular localizations of clusterin in esophageal squamous cell carcinoma.

AIM: To investigate biogenesis and intracellular localizations of clusterin to elucidate the potential molecular mechanisms implicated in tumorigenesis of esophageal mucosa. METHODS: Semi-quantitative RT-PCR for multi-region alteration analysis, Western blot for different transcriptional forms and immunohistochemical staining for intracellular localizations of clusterin were carried out in both tissues and cell lines of ESCC. RESULTS: The N-terminal deletions of the clusterin gene and the appearance of a 50-53 ku nuclear clusterin, an uncleaved, nonglycosylated, and disulfide-linked isoform, were the major alterations in cancer cells of esophagus. Naturally the 40 ku clusterin was located in the connective tissue of the lamina propria of epithelial mucosa and right under the basal membrane of epithelia, but it was disappeared in stromal mucosa of esophagus and the pre-matured clusterin was found positive in cancerous epithelia. CONCLUSION: The N-terminal deletion of clusterin may be essential for its alterations of biogenesis in ESCC.