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.

Chromatin-Remodelling ATPases ISWI and BRM Are Essential for Reproduction in the Destructive Pest Tuta absoluta.

The tomato leaf miner (Tuta absoluta) is one of the top 20 plant pests worldwide. We cloned and identified the chromatin-remodelling ATPase genes ISWI and BRM by RACE and bioinformatic analysis, respectively; used RT-qPCR to examine their expression patterns during different life cycle stages; and elucidated their roles in insect reproduction using double-stranded RNA injections. The full-length cDNA of TaISWI was 3428 bp and it encoded a 1025-aa polypeptide. The partial-length cDNA of TaBRM was 3457 bp and it encoded a 1030-aa polypeptide. TaISWI and TaBRM were upregulated at the egg stage. Injection of TaISWI or TaBRM dsRNA at the late pupa stage significantly inhibited adult ovary development and reduced fecundity, hatchability, and longevity in the adult females. To the best of our knowledge, the present study was the first to perform molecular characterisations of two chromatin-remodelling ATPase genes and clarify their roles in T. absoluta fecundity. Chromatin-remodelling ATPases are potential RNAi targets for the control of T. absoluta and other insect pests. The present study was also the first to demonstrate the feasibility of reproductive inhibitory RNAi as a putative approach for the suppression of T. absoluta and other Lepidopteran insect populations.

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.

Chromoendoscopy with targeted biopsies is superior to white-light endoscopy for the long-term follow-up detection of dysplasia in ulcerative colitis patients: a multicenter randomized-controlled trial.

BACKGROUND: Data from single-center experience or small sample-sized studies have shown that chromoendoscopy (CE) might be superior to white-light endoscopy (WLE) for dysplasia surveillance in ulcerative colitis (UC) patients. We performed a prospective randomized trial with a long-term follow-up to compare the detection rate of dysplasia among WLE with targeted biopsies (WLT), WLE with random biopsies (WLR), and dye-based CE with targeted biopsies (CET) in UC patients. METHODS: Patients with long-standing UC were enrolled from 11 medical centers from March 2012 to December 2013 and randomized into three arms (WLT, WLR, and CET). Only high-definition endoscopy was used in all three groups. The patients were followed up by annual endoscopy with biopsies through December 2017. RESULTS: With a median follow-up time of 55 months, a total of 122 patients with 447 colonoscopies were finally analysed in the per-protocol set: WLT (n = 43), WLR (n = 40), and CET (n = 39). A total of 34 dysplastic lesions were found in 29 colonoscopies of 21 patients. WLR and CET could identify more colonoscopies that diagnosed dysplasia than WLT (8.1% and 9.7% vs 1.9%; P = 0.014 and 0.004, respectively). WLR obtained more biopsied samples than WLT and CET (16.4 ± 5.1 vs 4.3 ± 1.4 and 4.3 ± 1.4; both P < 0.001). During the second half of the follow-up (37 - 69 months), CET could identify more colonoscopies that diagnosed dysplasia than WLT (13.3% vs 1.6%, P = 0.015) and showed a trend for increasing the detection rate compared with WLR (13.3% vs 4.9%, P = 0.107). CONCLUSIONS: For a better outcome of cancer/dysplasia surveillance in patients with long-standing UC, CET appeared to be more effective than WLT and less tedious than WLR. CET was found to be particularly useful when a long-term (>3 years) follow-up was conducted for dysplasia surveillance. The trial was registered on www.chictr.org.cn (ChiCTR1900023689).

Production of gold/silver doped carbon nanocomposites for effective photothermal therapy of colon cancer.

Surgery followed by adjuvant chemotherapy is a reliable therapy for colon cancer, but is associated with side effects and risks. Recent advancements in nanobioengineering in the form of targeted nanoparticles, cubosomes, liposomes, nanosheets, nanorods, quantum dots have generated substantial advancements in theranostics of colon cancer decreasing the cytotoxic drugs' side effects. We describe a facile mechanism of preparation of hybrid nanocomposite encompassing Au and Ag. Preparation of hybrid nanocomposite is one step process which may be easily escalated. The nanocomposite was characterized using transmission eleactron microscopy, energy dispersive X-Ray spectroscopy, X-ray photoelectron spectroscopy, Fourier transform infra-red spectroscopy, UV-Vis spectroscopy, photoluminescence and cytotoxic studies. In-vivo studies were carried out in Balb/c mice. Photothermal heating experiments in HeLa cells were promising and the characterization studies clearly indicated the formation of hybrid nanocomposite. In-vivo experiments confirmed the efficacy of treatment, along with involvement of epigenetic regulation, which may be helpful in translation from research to clinical applications.

Prognostic Value of D-Dimer in Patients with Diffuse Large B-cell Lymphoma: A Retrospective Study.

This study evaluated the significance of serum D-Dimer for predicting survival of patients with diffuse large B-cell lymphoma (DLBCL). We analyzed the clinical data from 113 patients who were newly diagnosed with DLBCL at Tongji Hospital from January 2012 to January 2016. The results indicated that there were higher levels of D-Dimer in DLBCL patients with the following characteristics: stage III/IV, lymphocyte monocyte ratio (LMR) <2.27, lactate dehydrogenase (LDH) > upper limit of normal (ULN), albumin (ALB) < 35 g/L, and anemia. After the first chemotherapeutic regimen, D-Dimer was significantly decreased concomitantly with LDH. Cox univariate regression analysis showed that the overall survival (OS) was negatively affected by the following factors: age > 60 years, stage III/W, LDH > ULN, LMR < 2.27, anemia and D-Dimer > 0.92. Multivariate analysis showed that only LDH > ULN (P=0.038) and age > 60 years (P=0.047) were independent adverse prognostic factors. However, it was suggested that D-Dimer could be regarded as a marker of high tumor burden and a potential prognostic screening tool for patients with DLBCL, not otherwise specified (NOS).

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.

A N-doped graphene-cobalt nickel sulfide aerogel as a sulfur host for lithium-sulfur batteries.

Herein, three-dimensional (3D) N-doped reduced graphene oxide (N-rGO) nanosheets were decorated with a uniform distribution of Co-Ni-S (CNS) nanoparticles to form the CNS/N-rGO composite as a sulfur host material for lithium-sulfur batteries. The CNS nanoparticles and N in CNS/N-rGO strongly interact with polysulfides, whereas graphene, as a conductive network, can improve its electrical conductivity. A CNS/N-rGO/sulfur composite cathode was prepared via the sulfur melting diffusion method. The electrochemical study showed that the CNS/N-rGO/sulfur cathode delivered an initial discharge capacity of 1430 mA h g-1 at a current density of 0.1C. Moreover, it retained a specific capacity of 685 mA h g-1 after 300 cycles at 0.5C with a coulombic efficiency of 98%, which was better than that of commercial rGO. This composite was used as a sulfur cathode for a lithium-sulfur battery, exhibiting excellent rate capability and remarkable performance in terms of long cycling stability.

[Pollution Characteristics and Ecological Risk Assessment of PAHs in Water and Fishes from Daqing Lakes].

The concentrations of 16 polycyclic aromatic hydrocarbons (PAHs) in 30 water samples and 5 tissues (gill, liver, brain, kidney and muscle) of 36 fishes which were collected from 18 typical lakes of the Daqing lakes group, China were measured between February and April 2012. The results of PAHs concentrations in the water showed that the range of total concentrations was 0.2-1.21 µg x L(-1) and the highest concentration was found in the Yueliangpao Lake. Clustering analysis of statistical method was used to classify the concentrations of PAHs in the water of 18 lakes, and PAHs source and evaluation of ecological risk in different lake groups were obtained respectively based on the analysis of PAHs ratio and the species sensitivity distributions method. The results of cluster analysis about PAHs concentrations in the water of 18 lakes showed that all the lakes were divided into 4 lake groups. Yueliangpao (YLP) and dongdahai (DDH) lakes were respectively divided into a separate group and the other 14 lakes were divided into two groups named XHH group and DQSK group. PAHs in the water of lakes were mainly from wood and coal burning except that the PAHs of the water in YLP group was caused by oil contamination. According to the surface water quality standard of the world and China, the concentrations of PAHs in the water of 4 lake groups all exceeded the standard variously. The PAHs concentrations of most water samples in YLP group and XHH group exceeded the 16 PAHs limit value of Environmental Protection Agency (US EPA) standard, especially, the concentration of Benz[a] pyrene with the strongest carcinogenicity of YLP group exceeded Chinese surface water quality standard. While in the DQSK lake group and the DDH lake group, several PAHs contaminations of water samples exceeded the standard. The tested and statistical results of 16 PAHs concentrations in 5 tissues of Cyprinus carpio and Hypophthalmichthys molitrix fish species in Daqing lakes showed the concentrations of anthracene in the gill tissue of Cyprinus carpio were significantly greater than those in the Hypophthalmichthys molitrix, while other 15 PAHs concentrations had no difference between the two species. Among the different tissues of Hypophthalmichthys molitrix or Cyprinus carpio, the concentrations of PAHs in the liver and kidney tissues which are the important tissues of PAHs accumulation were significantly greater than those in the muscle, gill and brain tissues of fish because of their pervasion ability of pollutants. The results of ecological risks of PAHs in water samples to different aquatic organism species and health risk of PAHs to human through the consumption of fish showed that low ecological risk to aquatic organism species and health risk of PAHs in the muscle of Hypophthalmichthys molitrix and Cyprinus carpio to human were observed in the 4 lake groups.

Pre-endurance training prevents acute alcoholic liver injury in rats through the regulation of damaged mitochondria accumulation and mitophagy balance.

AIM: The aim of this study is to investigate the effect of pre-endurance training on the prevention of alcohol-induced acute hepatic injury and on hepatic mitophagy. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into four groups: (1) control group, (2) 12-week exercise training group, (3) 5-day alcohol intake group, and (4) 12-week exercise training plus 5-day alcohol intake group. The rats were examined to determine the following: BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), hypoxia-inducible factor-1α (HIF-1α), cytochrome P450 2E1 (CYP2E1), alcohol dehydrogenase (ADH), microtubule-associated protein 1 light chain 3 (LC3II), Beclin1 mRNA and protein expressions, mitochondrial reactive oxygen species (ROS) production, mitochondrial thiobarbituric acid-reactive substances (TBARS) level, aconitase and ATP synthase activities, mitochondrial inner membrane potential, NADH/NAD(+) ratio, triglyceride (TG), the number of mtDNA and mitochondrial respiration functions in liver tissue, and serum ALT and AST. RESULTS: Pre-endurance training attenuated acute alcohol treatment-induced increase in mitochondrial TBARS, ROS production, NADH/NAD(+) ratio, state 4 respiration rate, TG, serum ALT and AST, as well as BNIP3, HIF-1α, LC3II, and Beclin 1 mRNA and protein levels, however, CYP2E1 and ADH mRNA and protein levels unchanged. Meanwhile, it attenuated the acute alcohol intake-induced decrease in aconitase activity, inner mitochondrial membrane potential (Δψ), ATP synthase activity, state 3 respiration rate, respiratory control ratio, and the number of mtDNA. CONCLUSION: Pre-endurance training can decrease acute alcohol intake-induced damaged mitochondria accumulation and reduced acute alcohol intake-induced mitophagy, which built a new balance between mitophagy and damaged mitochondria accumulation.

[Expression and localization of vascular endothelial growth factor in the radial artery of the coronary artery bypass grafting patients with diabetes].

OBJECTIVE: To evaluate the quality of the radial artery for coronary artery bypass grafting (CABG) from patients with diabetes by observing the morphology of the radial artery and detecting the expression of vascular endothelial growth factor (VEGF) which may attribute to the long-term patency rate of the coronary artery bypass grafting. METHODS: Samples from 20 cases of diabetic and non-diabetic patients were prospective collected from June 2009 to December 2010. HE staining technique was used to test the morphology of radial artery through the observation of 20 cases of diabetic and 20 cases of non-diabetic patients who undergone CABG. The intimal thicken of the radial artery in the two groups of patients was compared. Western blot and immunofluorescence were then used to test the expression and location of VEGF in the two groups of patients. RESULTS: The radial artery endothelial thickening index and intima/media ratio were significantly higher in the diabetic patients when compared with non-diabetic patients (0.90 ± 0.28 vs. 0.29 ± 0.25, t = 7.27, P < 0.01; 0.90 ± 0.21 vs. 0.37 ± 0.18, t = 8.57, P < 0.01). The expression of VEGF in diabetic patients was significantly higher than non-diabetic patients as revealed by Western blot (1.20 ± 0.21 vs. 0.67 ± 0.15, t = 6.49, P < 0.01). Immunofluorescence showed that VEGF distributed in the cytoplasm of the endothelial cells of diabetic patients radial artery. CONCLUSIONS: Diabetic patient's radial artery intimal thickness is significantly higher than non-diabetic patient's. VEGF may be an important inflammatory cytokine which is leading the radial artery intima thickening in the diabetic patients. The choice of the radial artery grafts in diabetic patients for CABG should be careful.

Multicenter case-control study of the risk factors for ulcerative colitis in China.

AIM: To evaluate potential risk factors in the development of ulcerative colitis (UC) in China. METHODS: A total of 1308 patients with UC and 1308 age-matched and sex-matched controls were prospectively studied in China. The UC cases were collected from 17 hospitals in China from April 2007 to April 2010. Uniform questionnaires were designed to investigate risk factors including smoking, appendectomy, stress, socio-economic conditions, nonsteroidal anti-inflammatory drugs (NSAIDs), oral contraceptives, diet, breastfeeding, infections and family sanitary conditions. Group comparisons by each factor were done using simple logistic regression analysis. Conditional logistic regression was used for multivariate analysis. RESULTS: By univariate analysis, the variables predictive of UC included feeling stress, light and heavy alcoholic drinking, spicy food, sugar consumption and infectious diarrhea, while heavy tea intake and tap water consumption were protective against UC. On multivariate analysis, the protective factor for UC was tap water consumption [odds ratios (OR) = 0.424, 95%CI: 0.302-0.594, P < 0.001]; while the potential risk factors for UC were heavy sugar consumption (OR = 1.632, 95%CI: 1.156-2.305, P < 0.001), spicy food (light intake: OR = 3.329, 95%CI: 2.282-4.857, P < 0.001; heavy intake: OR = 3.979, 95%CI: 2.700-5.863, P < 0.001), and often feeling stress (OR = 1.981, 95%CI: 1.447-2.711, P < 0.001). Other factors, such as smoking habit, appendectomy, breastfeeding, a history of measles, rural or urban residence, education, oral contraceptives, and NSAID use have not been found to have a significant association with the development of UC in the present study. CONCLUSION: Our study showed tap water consumption was a protective factor for UC, while spicy food, heavy sugar consumption and often feeling stress were risk factors for UC in this Chinese population.

[Prokaryotic expression of pig nuclear transcription factor-kappaB p65/p50 and its impacts on PRRSV proliferation].

This study aims to express pig nuclear transcription factor-kappaB (NF-kappaB) p65/p50 fusion protein in E. coli Rosetta, and study its impacts on PRRSV proliferation in vitro. The p65 ORF and mature p50 encoding gene were amplified by RT-PCR, the products were cloned into the pET-21a(+) vector, then transformed into Escherichia coli Rosetta, recombinant fusion protein was expressed by IPTG induction, the expressed product was identified by SDS-PAGE and Western-Blot. The purified and re-folded p65/p50 was added to the 2% FBS DMEM, and the cytotoxicity on Marc145 was observed to select the optimum concentration. The effects of optimum concentration of p65/p50 on PRRSV proliferation activity were investigated by detecting PRRSV infection phase in the culture supernatant using real-time FQ-PCR method and drawing PRRSV one-step growth curve. The results showed the p65/p50-pET21a(+) prokaryotic expression vector were successfully constructed , recombinant p50 and p65 fusion protein was expressed abundantly in the form of inclusion body with molecular weight of 70kD, Western-Blot results showed that the rabbit anti-human p50 polyclonal serum, rabbit anti-human p65 purified antibody could bind specifically to p50 and p65 respectively. The optimum concentration of p65/p50 was 0.4 microg/mL. The real-time FQ-PCR results indicated that NF-kappaB p65/p50 could promote CPE appearance and PRRSV proliferation before CPE appeared, and suppress PRRSV proliferation after CPE appeared, and lower the virus titer levels significantly(P < 0.05). These results will provide some new insight of the pathogenic mechanism and treatment strategies of PRRS.

[The role of OX40 in CD4+ T cells cytokines production in ulcerative colitis].

OBJECTIVE: To investigate the expression of OX40 on CD(4)(+) T cells in patients with ulcerative colitis (UC) and the role of OX40/OX40L interaction for the cytokine production of lamina propria (LP)-CD(4)(+) T cells from UC. METHODS: LP-CD(4)(+) T cells were purified. The expression of OX40 molecule was measured with FACS. LP-CD(4)(+) T cells were cultured with different stimuli and proliferation was assessed. The cytokines concentrations of the culture supernatant were detected. RESULTS: No difference of the OX40 expression was observed among the CD(4)(+) T cells from peripheral blood (PB) of UC patients, LP of non-inflammatory colonic tissue in UC patients and control PB. However, the expression of OX40 was significantly higher on LP-CD(4)(+) T cells from inflammatory colonic tissue in UC patients. In vitro culture with antigen presenting cells, the levels of IFNgamma and TNFalpha secreted by LP-CD(4)(+) T cells from the inflammatory colonic tissue were significantly higher than those from the non-inflammatory colonic tissue (both P < 0.01). The levels of IFNgamma and TNFalpha secreted by LP-CD(4)(+) T cells from the inflammatory colonic tissue were further increased by anti-OX40 MoAb stimulation, but suppressed significantly by adding anti-OX40L MoAb (compared with non stimulation, P < 0.01, respectively). The IFNgamma and TNFalpha secretion of the LP-CD(4)(+) T cells from the non-inflammatory colonic tissue were not significantly different with and without anti-OX40 or anti-OX40L MoAbs stimulation. IL-4 and IL-10 produced by LP-CD(4)(+) T cells from the inflammatory or non-inflammatory colonic tissue were not significantly changed when adding different stimuli. CONCLUSIONS: OX40 is highly expressed on LP-CD(4)(+) T cells from inflammatory colonic tissue in patients with UC. Anti-OX40L MoAb can inhibit the proinflammatory cytokines secreted by these cells. It is indicated that OX40(+) T cells are involved in the immunopathological process in UC and blockage of the interaction of OX40 and OX40L is a new strategy to be considered for the treatment of the disease.