Dermoscopy and reflection confocal microscope features of pigmented prurigo.

BACKGROUND: Pigmented prurigo (PP) is a chronic and recurrent inflammatory skin disease. PP is not common clinically, but it is easily misdiagnosed because of its diversified clinical manifestations in different stages. MATERIALS AND METHODS: We retrospectively analyzed the clinical, histopathological, dermoscopy, and reflectance confocal microscopy (RCM) features of 20 patients diagnosed as PP. RESULTS: The female predominance ratio was revealed with male to female of 1:4. Seven female patients were on a diet (without staple food) and one patient had a history of diabetes. Eight cases were suffered in spring, six cases in winter, three cases in summer, and three cases in autumn. Multiple sites were involved in 13 cases. Four patients had urticarial papules and plaques. Nineteen patients had erythematous papules with reticular distribution, of which 14 cases accompanied reticulate hyperpigmentation, four cases with papulovesicle, and two cases accompanied with pustules. One patient only showed reticulate hyperpigmentation. In the early lesions, dermatoscopy showed pink oval lesions, punctate or linear vessels, and pale yellow rings around the skin lesions. RCM is characterized by spongiosis, spongy vesicle, neutrophils scattered in the epidermis, which was consistent with epidermis spongiosis, neutrophils infiltrating into the upper epidermis and necrotic keratinocytes in histopathology. In the fully developed lesions, dermatoscopy showed pink lesions with brown pigment granules in the center and linear vessels in the edge. RCM showed that demarcation of epidermis and dermis is not clear, and inflammatory cells can be seen in the upper dermis and histopathologically lesions assumed a patchy lichenoid pattern, and the inflammatory cells infiltrating the dermis were dominated by lymphocytes. In the late lesions, dermatoscopy showed grainy grayish-brown or yellowish-brown pigmentation surrounding the hair follicle merging with each other. RCM showed that pigment granules were increased on the ring of basal cells, inflammatory cells were sparsely infiltrated in the dermal papilla and superficial layer, and epidermis slightly hyperplastic, with melanophages and a few lymphocytes infiltrating the superficial dermis in histopathology. CONCLUSION: PP is easily misdiagnosed and not always occurs in those on a restrictive diet. A combination of dermatoscopy and RCM is helpful for its diagnosis of PP.

Repression of TXNIP-NLRP3 axis restores intestinal barrier function via inhibition of myeloperoxidase activity and oxidative stress in nonalcoholic steatohepatitis.

Dysfunction of the intestinal barrier function occurs in hepatic injury, but the specific mechanisms responsible are largely unknown. Recently, NOD-like receptor 3 (NLRP3) inflammasome functions in impairing endothelial barrier function. In this study, we test the hypothesis that TXNIP-NLRP3 axis repression prevents against intestinal barrier function disruption in nonalcoholic steatohepatitis (NASH). First, lipopolysaccharide (LPS)-induced alterations in expression of ZO-1 and occludin, myeloperoxidase (MPO) activity, reactive oxygen species (ROS) level, and transepithelial electric resistance (TEER) in intestinal epithelial cells (IECs) isolated from C57BL/6 wild-type (WT) and TXNIP-/- mice were evaluated. The underlying regulatory mechanisms of TXNIP knockout in vivo were investigated with the detection of expressions of TXNIP, NLRP3 and ZO-1, and occludin, the interaction of TXNIP-NLRP3, MPO activity, ROS level, permeability of intestinal mucosa, levels of inflammatory factors in serum, and LPS concentration. We identified that TXNIP knockout promoted ZO-1 and occludin expression, yet reduced MPO activity, ROS level, and cell permeability in IECs, indicating restored the intestinal barrier function. However, LPS upregulated TXNIP and NLRP3 expression, as well as contributed to the interaction between TXNIP and NLRP3 in vitro. Furthermore, TXNIP was significantly upregulated in the intestinal mucosa of NASH mice and its knockout repaired the intestinal barrier disrupt, inhibited expression of inflammatory factors, and reduced LPS concentration as well as hepatic injury in vivo. Taken together, our findings demonstrated that inhibited the activation of the TXNIP-NLRP3 axis reduced MPO activity and oxidative stress and thus restoring the intestinal barrier function in NASH. TXNIP-NLRP3 axis may be a promising therapeutic strategy for the NASH treatment.

Novel hypolipidemic conjugates of fatty acid and bile acid with lysine for linkage.

Novel fatty acid-bile acid conjugates (1a-1k) were designed and synthesized by coupling of the fatty acids to the 3-OH of bile acids using lysine for linkage. In the conjugates, the 24-COOH of the bile acids was kept intact to preserve liver-specific recognition. The ability of the newly synthesized conjugates (at 100 mg/kg dosage) to reduce total cholesterol (TC) and triglyceride (TG) levels in mice fed with high-fat diet (HFD) was evaluated. Conjugates of stearic acid with cholic acid and palmitic acid with ursodeoxycholic acid (at dosages of 50, 100, and 200 mg/kg) were further evaluated to determine their ability to reduce aspartate aminotransferase (AST), alanine aminotransferase (ALT), TC, and TG levels in mice fed with HFD. All conjugates showed potent hypolipidemic activity. Further investigation revealed that compounds 1c and 1 g not only dose-dependently reduced serum levels of TC and TG, but also inhibited the elevation of serum AST and ALT levels in mice fed with HFD. Thus, compounds 1c and 1 g are promising hypolipidemic agents with hepatocyte protective effects against HFD-induced liver damage.

Plasma exchange-centered artificial liver support system in hepatitis B virus-related acute-on-chronic liver failure: a nationwide prospective multicenter study in China.

BACKGROUND: Plasma exchange (PE)-centered artificial liver support system reduced the high mortality rate of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). But the data were diverse in different medical centers. The present prospective nationwide study was to evaluate the effects of PE on patients with HBV-ACLF at different stages. METHODS: From December 2009 to December 2011, we evaluated 250 patients at different stages of HBV-ACLF from 10 major medical centers in China. All the laboratory parameters were collected at admission, before and after PE. RESULTS: Among the 250 patients who underwent 661 rounds of PE, one-month survival rate was 61.6%; 141 (56.4%) showed improvement after PE. Variables such as age (P=0.000), levels of total bilirubin (TB, P=0.000), direct bilirubin (P=0.000), total triglycerides (P=0.000), low-density lipoprotein (P=0.022), Na+ (P=0.014), Cl- (P=0.038), creatinine (Cr, P=0.007), fibrinogen (P=0.000), prothrombin time (PT, P=0.000), white blood cell (P=0.000), platelet (P=0.003) and MELD (P=0.000) were significantly related to prognosis. Multivariate logistic regression analysis showed that age, disease stage, TB, Cr and PT levels were independent risk factors of mortality among HBV-ACLF patients. CONCLUSIONS: PE can improve the clinical outcome of patients with HBV-ACLF. Levels of TB, Cr and PT, age and disease stage help to predict prognosis.

Results of a phase III clinical trial with an HBsAg-HBIG immunogenic complex therapeutic vaccine for chronic hepatitis B patients: experiences and findings.

BACKGROUND & AIMS: Even though various experimental therapeutic approaches for chronic hepatitis B infection have been reported, few of them have been verified by clinical trials. We have developed an antigen-antibody (HBsAg-HBIG) immunogenic complex therapeutic vaccine candidate with alum as adjuvant (YIC), aimed at breaking immune tolerance to HBV by modulating viral antigen processing and presentation. A double-blind, placebo-controlled, phase II B clinical trial of YIC has been reported previously, and herein we present the results of the phase III clinical trial of 450 patients. METHODS: Twelve doses of either YIC or alum alone as placebo were administered randomly to 450 CHB patients and they were followed for 24weeks after the completion of immunization. The primary end point was HBeAg seroconversion, and the secondary end points were decrease in viral load, improvement of liver function, and histology. RESULTS: In contrast to the previous phase II B trial using six doses of YIC and alum as placebo, six more injections of YIC or alum resulted in a decrease of the HBeAg seroconversion rate from 21.8% to 14.0% in the YIC group, but an increase from 9% to 21.9% in the alum group. Decrease in serum HBV DNA and normalization of liver function were similar in both groups (p>0.05). CONCLUSIONS: Overstimulation with YIC did not increase but decreased its efficacy due to immune fatigue in hosts. An appropriate immunization protocol should be explored and is crucial for therapeutic vaccination. Multiple injections of alum alone could have stimulated potent inflammatory and innate immune responses contributing to its therapeutic efficacy, and needs further investigation.

A New Assessment Method of Vitiligo by Combination of Dermoscopy and Reflectance Confocal Microscopy.

Purpose: The aim is to investigate the application value of dermoscopy combined with reflectance confocal microscopy (RCM) in assessing vitiligo disease activity and treatment response. Patients and Methods: We enrolled 279 patients with vitiligo and evaluated the disease activity by Vitiligo Disease Activity (VIDA) score, dermoscopy, RCM and dermoscopy combined with RCM respectively. The sensitivity and specificity of different assessment techniques were compared with VIDA score by the differences and consistency. The different characteristics of dermoscopy and RCM with different treatment responses were also analyzed. Results: The results showed that the sensitivity and specificity of dermoscopy combined RCM were higher than RCM or dermoscopy alone (P values less than 0.05). In the repigmentation process, leukotrichia, pigment network absent and perilesional hyperpigmentation under dermoscopy at the baseline suggested a poor treatment response, while the incompletely disappearing pigment rings under RCM and perifollicular hyperpigmentation under dermoscopy indicated a good treatment response. We also found the proportion of patients with telangiectasia, increased pigment at the lesions and around the hair follicles was significantly higher in the good treatment response group than that in the poor one by dermoscopy (χ2 = 4.423, 32.471, 4.348, P = 0.035 0.000, 0.037) and by RCM the proportion of patients with both increased pigment granules and dendritic melanocytes in the good treatment response group was higher than that in the poor one (χ2 = 38.215, 5.283, P = 0.000, 0.022, respectively). Conclusion: With the higher sensitivity and specificity than dermoscopy or RCM alone, a combination of dermoscopy and RCM may be a new more accurate measure to assess the vitiligo disease activity and the treatment response.

Baicalin confers hepatoprotective effect against alcohol-associated liver disease by upregulating microRNA-205.

Recently, baicalin refers to flavonoid compound extracted from Scutellaria baicalensis Georgi has been indicated to hold promising therapeutic effects in alcohol-associated liver disease (ALD). However, knowledge of the molecular mechanisms for its hepatoprotective effect is still very limited. Evidence exists suggesting potential association between miR-205 and baicalin's function. Bioinformatic analysis and dual luciferase reporter assay were conducted to determine the binding affinity between miR-205 and importinα5. Our findings revealed that baicalin could alleviate ALD by raising the expression of miR-205. Additionally, miR-205 repressed NF-κB signaling pathway activation by binding to importinα5 to relieve ALD. Baicalin inhibited importinα5-mediated NF-κB signaling pathway to protect the liver against alcohol-induced injury, inflammation, oxidative stress and hepatocyte apoptosis. Taken conjointly, baicalin confers hepatoprotective effect against ALD through miR-205-mediated importinα5 inhibition via the NF-κB signaling pathway, highlighting a promising therapeutic target for ALD treatment with the help of traditional Chinese medicine.

Intestinal mucosal barrier in functional constipation: Dose it change?

BACKGROUND: The intestinal mucosal barrier is the first line of defense against numerous harmful substances, and it contributes to the maintenance of intestinal homeostasis. Recent studies reported that structural and functional changes in the intestinal mucosal barrier were involved in the pathogenesis of several intestinal diseases. However, no study thoroughly evaluated this barrier in patients with functional constipation (FC). AIM: To investigate the intestinal mucosal barrier in FC, including the mucus barrier, intercellular junctions, mucosal immunity and gut permeability. METHODS: Forty FC patients who fulfilled the Rome IV criteria and 24 healthy controls were recruited in the Department of Gastroenterology of China-Japan Friendship Hospital. The colonic mucus barrier, intercellular junctions in the colonic epithelium, mucosal immune state and gut permeability in FC patients were comprehensively examined. Goblet cells were stained with Alcian Blue/Periodic acid Schiff (AB/PAS) and counted. The ultrastructure of intercellular junctional complexes was observed under an electron microscope. Occludin and zonula occludens-1 (ZO-1) in the colonic mucosa were located and quantified using immunohistochemistry and quantitative real-time polymerase chain reaction. Colonic CD3+ intraepithelial lymphocytes (IELs) and CD3+ lymphocytes in the lamina propria were identified and counted using immunofluorescence. The serum levels of D-lactic acid and zonulin were detected using enzyme-linked immunosorbent assay. RESULTS: Compared to healthy controls, the staining of mucus secreted by goblet cells was darker in FC patients, and the number of goblet cells per upper crypt in the colonic mucosa was significantly increased in FC patients (control, 18.67 ± 2.99; FC, 22.42 ± 4.09; P = 0.001). The intercellular junctional complexes in the colonic epithelium were integral in FC patients. The distribution of mucosal occludin and ZO-1 was not altered in FC patients. No significant differences were found in occludin (control, 5.76E-2 ± 1.62E-2; FC, 5.17E-2 ± 1.80E-2; P = 0.240) and ZO-1 (control, 2.29E-2 ± 0.93E-2; FC, 2.68E-2 ± 1.60E-2; P = 0.333) protein expression between the two groups. The mRNA levels in occludin and ZO-1 were not modified in FC patients compared to healthy controls (P = 0.145, P = 0.451, respectively). No significant differences were observed in the number of CD3+ IELs per 100 epithelial cells (control, 5.62 ± 2.06; FC, 4.50 ± 2.16; P = 0.070) and CD3+ lamina propria lymphocytes (control, 19.69 ± 6.04/mm2; FC, 22.70 ± 11.38/mm2; P = 0.273). There were no significant differences in serum D-lactic acid [control, 5.21 (4.46, 5.49) mmol/L; FC, 4.63 (4.31, 5.42) mmol/L; P = 0.112] or zonulin [control, 1.36 (0.53, 2.15) ng/mL; FC, 0.94 (0.47, 1.56) ng/mL; P = 0.185] levels between FC patients and healthy controls. CONCLUSION: The intestinal mucosal barrier in FC patients exhibits a compensatory increase in goblet cells and integral intercellular junctions without activation of mucosal immunity or increased gut permeability.

Interleukin-17-producing CD4(+) T cells increase with severity of liver damage in patients with chronic hepatitis B.

UNLABELLED: Interleukin-17 (IL-17)-producing CD4(+) T cells (Th17)-mediated immune response has been demonstrated to play a critical role in inflammation-associated disease; however, its role in chronic hepatitis B virus (HBV) infection remains unknown. Here we characterized peripheral and intrahepatic Th17 cells and analyzed their association with liver injury in a cohort of HBV-infected patients including 66 with chronic hepatitis B (CHB), 23 with HBV-associated acute-on-chronic liver failure (ACLF), and 30 healthy subjects as controls. The frequency of circulating Th17 cells increased with disease progression from CHB (mean, 4.34%) to ACLF (mean, 5.62%) patients versus healthy controls (mean, 2.42%). Th17 cells were also found to be largely accumulated in the livers of CHB patients. The increases in circulating and intrahepatic Th17 cells positively correlated with plasma viral load, serum alanine aminotransferase levels, and histological activity index. In vitro, IL-17 can promote the activation of myeloid dendritic cells and monocytes and enhance the capacity to produce proinflammatory cytokines IL-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and IL-23 in both CHB patients and healthy subjects. In addition, the concentration of serum Th17-associated cytokines was also increased in CHB and ACLF patients. CONCLUSION: Th17 cells are highly enriched in both peripheral blood and liver of CHB patients, and exhibit a potential to exacerbate liver damage during chronic HBV infection.

[Comparison of MELD-Na versus MELDNa in the prediction of short-term prognosis for acute-on-chronic hepatitis B liver failure].

OBJECTIVE: To evaluate the short-term prognostic values for the model of end-stage liver disease-sodium (MELD-Na), end-stage liver disease sodium (MELDNa) and their dynamic changes in patients with acute-on-chronic hepatitis B liver failure (ACLF-HBV). METHODS: A total of 172 patients diagnosed with ACLF-HBV, admitted between January 2007 to February 2009 and hospitalized for over 2 weeks, were retrospectively recruited. The predictive accuracy of MELD-Na, MELDNa and their dynamic change (Δ) was compared by the method of the area under the receiver operating characteristic curve. RESULTS: The 3-month mortality rate was 43.6%. The largest concordance (c) statistic predicting 3-month mortality was MELDNa score after a 2-week treatment (0.790), followed by MELD-Na (0.728) score, ΔMELDNa (0.713) and ΔMELD-Na (0.646). The average MELD-Na, MELDNa scores after a 2-week treatment and ΔMELD-Na, ΔMELDNa of survival group were 27.7 ± 8.9, 25.9 ± 5.0, -2.1 ± 10.0 and -1.9 ± 4.2 while those of dead group 34.6 ± 8.7, 31.5 ± 5.0, 2.4 ± 10.3 and 2.4 ± 10.3. There was significant difference in MELD-Na, MELDNa, ΔMELD-Na and ΔMELDNa between two groups. The 3-month mortality of the MELD-Na scores group < 25, 25 - 30, 30 - 35 and > 35 were 18.9%, 37.8%, 57.6% and 65.3% while the MELDNa scores group 14.6%, 33.3%, 72.5% and 84.2% respectively. There was significant difference in the 3-month mortality between four groups. The 3-month mortality of the ΔMELD-Na > 0 group was 58.5% while that of the ΔMELD-Na ≤ 0 group 30%; the 3-month mortality of the ΔMELDNa > 0 group was 61.3% while that of the ΔMELDNa ≤ 0 group 29.9%. There was significant difference between two groups. CONCLUSION: MELDNa score after a 2-week treatment is a promising and useful predictor for 3-month mortality in ACLF-HBV patients. The predictive value may further improve if in conjunctions with dynamic changes.

Overexpressed sFRP3 exerts an inhibitory effect on hepatocellular carcinoma via inactivation of the Wnt/ß-catenin signaling pathway.

Hepatocellular carcinoma (HCC) is recognized as the most common malignancy of the liver in adults. Many human cancers have been associated with the oncogenic activation of the Wnt/ß-catenin signaling pathway. The secreted frizzled-related proteins (sFRPs) function as negative regulators of the Wnt signaling and have important implications in carcinogenesis. This study aims to investigate the possible regulatory effects of sFRP3 on the Wnt/ß-catenin signaling pathway and their interactions in HCC occurrence. Firstly, sFRP3 expression was quantified in the collected cancer and adjacent normal tissue samples from HCC patients. The lowly expressed sFRP3 in HCC tissues was found to be correlated with HCC development. The expression of sFRP3 was regulated by a lentivirus-based packaging system, and the Wnt/ß-catenin signaling pathway was inactivated by DDK-1 in HepG2 cells. The expressions of Wnt1, ß-catenin and the nuclear translocation of ß-catenin were determined, both of which were down-regulated by sFRP3 overexpression. CCK8 assay, EdU staining, Colony formation assay, flow cytometry, scratch test and Transwell assay were employed to test cell viability, proliferation, cell cycle, apoptosis, migration and invasion, respectively. Overexpressed levels of sFRP3 were found to produce a reduction in MMP-2, MMP-7, MMP-9, PCNA, Ki67, and Bcl-2 expressions but an increase in the expressions of caspase-3 and Bax. In addition, overexpression of sFRP3 inhibited cell proliferation, migration, invasion, and colony formation, but promoted cell cycle arrest and cell apoptosis in HCC cells. The addition of the Wnt/ß-catenin signaling pathway inhibitor, DKK-1, reversed the contributory effect of sFRP3 silencing on HCC development. Lastly, in vivo tumor formation was inhibited by enforced sFRP3 expressions. The obtained results suggested that sFRP3 acts as an anti-oncogene in HCC by inhibiting the activation of the Wnt/ß-catenin signaling pathway.

[Clinical features and prognostic analysis of 51 drug-induced case of liver failure].

OBJECTIVE: To enhance the understanding of drug-induced liver failure by analyzing the etiology, clinical features and prognosis associated factors of patients with drug-induced liver failure. METHODS: Fifty-one cases of drug-induced liver failure admitted to our hospital from 2002 - 2007 were reviewed according to their drug history, clinical features, Laboratory tests, complications and prognosis associated factors. RESULTS: The predominant etiological drugs were the traditional Chinese medicine (54.9%) and antitubercular agent (25.5%). Two predominant types of liver failure were acute liver failure (13.7%) and subacute liver failure (78.4%). The common complications were electrolyte disturbance, ascites and hepatic encephalopathy. The total improvement rate in patients was 29.4%. The incidences of hepatic encephalopathy, electrolyte disturbance and PTA value had statistical difference between improvement group and ineffective group. CONCLUSION: The etiologies of drugs-induced liver failure are traditional Chinese medicine and antitubercular agent in China. The prognosis of drug-induced liver failure remains poor. During the therapy of these drugs treatment, liver function test should be monitored.

[Study on gene delivery via the bile duct to rat liver using naked DNA particles].

OBJECTIVE: To evaluate the efficacy of gene delivery to the right lateral lobe of the rat liver via a branch of the bile duct using naked DNA. METHODS: We evaluated regional gene delivery to the right lateral lobe of the rat liver via a branch of the bile duct, using naked DNA, including pGL3, pCMV beta and Cy3 labeled CMV beta. RESULTS: Gene expression was observed in right lateral lobe of both the damaged and the normal rats liver. The gene delivery efficiency was similar in two groups (P > 0.05). Gene expression was found in the right lateral lobe of damaged and normal livers. Fluorescence was observed in the region of the portal triads, and occasionally, in the lobule. CONCLUSION: Retrograde infusion of naked DNA via the bile duct is an effective way to deliver genes to in both damaged and normal rat liver.

[The short-term efficacy of nucleoside analogue on the treatment of acute-on-chronic liver failure].

OBJECTIVE: To discuss the short-term efficacy of nucleoside analogue on the treatment of hepatitis B virus induced acute-on-chronic liver failure (HBV-ACLF). METHODS: 348 patients with HBV-ACLF in our hospital from January 2006 to June 2008 were selected. According to the stages of patient's condition and whether or not with nucleoside analogue administration, The patients were divided into early stage therapy group, early stage control group, middle stage therapy group and middle stage control group. Groups were compared on the basis of stages. The clinical data were analyzed using chisquare test and independent-Samples T Test. RESULTS: After 2 weeks of therapy no significant difference found between the therapy group and the control group. the total bilirubin (TBil) and alanine transaminase (ALT) showed no significant difference between the middle stage therapy group and the control group in 4 weeks of therapy. However significant differences existed in the HBV DNA negative rate, PTA, the model for end-stage liver disease (MELD) score and the improvement rate between the two groups (P<0.05, P<0.01). Only the 4 week survival rate and HBV DNA negative rate showed significant difference in patients who received anti-virus therapy on the early stage as compared to the control group. CONCLUSION: Anti-virus therapy with nucleoside analogue is an effective way for the treatment of those patients with HBV-ACLF and can increase the survival rate.

[The clinical characteristics of hepatic failure with aspergillosis].

OBJECTIVES: To study the clinical characteristics of hepatic failure with aspergillosis. METHODS: The data of hepatic failure patients with fungal infection hospitalized in our hospital form January 1985 to June 2006 were collected. This research mainly focused on the clinical characteristics of the patients co-infected with aspergillosis. RESULTS: The occurrence of aspergillosis was 20.5% (104 cases) among 507 hepatic failure patients with fungal infection. Compared with other fungal infection in hepatic failure patients, the effective rate of antifungal therapy and the improvement rate of underlying disease were worse in patients with aspergillus infection (36.5% vs 57.8%, P = 0.000; 26.0% vs 36.7%, P = 0.049). Aspergillus fumigatus was the most common species among 108 fungal species. The species next to Aspergillus fumigatus were Aspergillus niger and Aspergillus flavus. The mainly infected organ was lung and its clinical manifestation was atypical. Liver function could be improved with effective anti-fungus therapy. CONCLUSIONS: Diagnosis and treatment of aspergillosis is difficult in hepatic failure patients co-infected with aspergillosis. Early and effective antifungal therapy is helpful to the recovery of liver function in the hepatic failure patients suspected with aspergillosis co-infection.

Altered metabolism of bile acids correlates with clinical parameters and the gut microbiota in patients with diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Bile acids (BAs) have attracted attention in the research of irritable bowel syndrome with predominant diarrhea (IBS-D) due to their ability to modulate bowel function and their tight connection with the gut microbiota. The composition of the fecal BA pool in IBS-D patients is reportedly different from that in healthy populations. We hypothesized that BAs may participate in the pathogenesis of IBS-D and the altered BA profile may be correlated with the gut microbiome. AIM: To investigate the role of BAs in the pathogenesis of IBS-D and the correlation between fecal BAs and gut microbiota. METHODS: Fifty-five IBS-D patients diagnosed according to the Rome IV criteria and twenty-eight age-, sex-, and body mass index-matched healthy controls (HCs) were enrolled in this study at the gastroenterology department of China-Japan Friendship Hospital. First, clinical manifestations were assessed with standardized questionnaires, and visceral sensitivity was evaluated via the rectal distension test using a high-resolution manometry system. Fecal primary BAs including cholic acid (CA) and chenodeoxycholic acid (CDCA), secondary BAs including deoxycholic acid (DCA), lithocholic acid (LCA), and ursodeoxycholic acid (UDCA) as well as the corresponding tauro- and glyco-BAs were examined by ultraperformance liquid chromatography coupled to tandem mass spectrometry. The gut microbiota was analyzed using 16S rRNA gene sequencing. Correlations between fecal BAs with clinical features and gut microbiota were explored. RESULTS: Fecal CA (IBS-D: 3037.66 [282.82, 6917.47] nmol/g, HC: 20.19 [5.03, 1304.28] nmol/g; P < 0.001) and CDCA (IBS-D: 1721.86 [352.80, 2613.83] nmol/g, HC: 57.16 [13.76, 1639.92] nmol/g; P < 0.001) were significantly increased, while LCA (IBS-D: 1621.65 [58.99, 2396.49] nmol/g, HC: 2339.24 [1737.09, 2782.40]; P = 0.002] and UDCA (IBS-D: 8.92 [2.33, 23.93] nmol/g, HC: 17.21 [8.76, 33.48] nmol/g; P = 0.025) were significantly decreased in IBS-D patients compared to HCs. Defecation frequency was positively associated with CA (r = 0.294, P = 0.030) and CDCA (r = 0.290, P = 0.032) and negatively associated with DCA (r = -0.332, P = 0.013) and LCA (r = -0.326, P = 0.015) in IBS-D patients. In total, 23 of 55 IBS-D patients and 15 of 28 HCs participated in the visceral sensitivity test. The first sensation threshold was negatively correlated with CDCA (r = -0.459, P = 0.028) in IBS-D patients. Furthermore, the relative abundance of the family Ruminococcaceae was significantly decreased in IBS-D patients (P < 0.001), and 12 genera were significantly lower in IBS-D patients than in HCs (P < 0.05), with 6 belonging to Ruminococcaceae. Eleven of these genera were negatively correlated with primary BAs and positively correlated with secondary BAs in all subjects. CONCLUSION: The altered metabolism of BAs in the gut of IBS-D patients was associated with diarrhea and visceral hypersensitivity and might be ascribed to dysbiosis, especially the reduction of genera in Ruminococcaceae.

Withdrawal Notice: Therapeutic Effect of Prdx1 on NAFLD Mice May be Related to the Activation of Nrf-2/HO-1 Pathway

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[Analysis of prognostic factors for patients with acute-on-chronic liver failure].

OBJECTIVE: To analyze the prognostic factors for patients with acute-on-chronic liver failure, and to build a scoring system for assessment of the prognosis of liver failure. METHODS: 480 patients with acute-on-chronic liver failure in our hospital from January 2006 to June 2008 were enrolled in this study. The patients were divided into improved group and deteriorated group. The clinical data were analyzed by using chi square test, independent-Samples T Test and Binary logistic regression. RESULTS: The factors that significantly affected the prognosis of Acute-on-chronic Liver Failure included age, hepatitis or liver cirrhosis, Staging, Hyponatremias, alpha-fetoprotein (AFP), the prothrombin time activity (PTA), total bilirubin (TBil), creatinine (Cr), albumin (ALB) and Hepatic encephalopathy, ascites, alimentary tract hemorrhage (P less than 0.05, P less than 0.01). PTA, Hyponatremias, hepatitis or liver cirrhosis, Hepatic encephalopathy and alimentary tract hemorrhage were independent risk factors of prognosis. CONCLUSION: PTA, Hyponatremias, hepatitis or liver cirrhosis, Hepatic encephalopathy and alimentary tract hemorrhage are important to build a scoring system to assess the prognosis of Acute-on-chronic Liver Failure and may be useful to guide clinical treatment.

[Regional gene delivery via the bile duct to damaged liver using peptide/DNA particles: experiment with rats].

OBJECTIVE: To evaluate the efficacy of gene delivery to the right lateral lobe of liver via a branch of the bile duct. METHODS: Twenty LEW rats underwent intraperitoneal injection of D-galactosamine to establish acute liver damage models and were randomly divided into 5 groups to undergo ligation of the common bile duct and left bile duct 4, 5, 6, or 7 days after the acute liver damage. Non-viral vector gene compound, polylysine-molossin/pGL3 containing firefly luciferin gene or CMVbeta containing beta-galactosidase of Escherichia coli/fusogenic) was injected in to the right lateral lobes 2 and 3 via the branch of right bile duct. Four rats without injection of D-galactosamine but undergoing injection of polylysine-molossin/pGL3 or CMVbeta/fusogenic were used as normal controls. Twenty-four hours after the regional gene delivery the rats were killed. The expressions of luciferin and beta-galactosidase in different lobes were detected. Pathological examination of liver was conducted. RESULTS: All rats survived after the operation. The expression levels of luciferin in the liver on the days 4, 5, and 6 were all significantly higher than that of the normal control rats (all P < 0.05). The expression levels of luciferin in the liver on the day 7 was the highest compared with the normal control rats (P = 0.01). However, the level of luciferin in the liver on the day 9 was lower and not significantly different from that of the normal rats (P > 0.05). Scattered distribution of beta-galactosidase was seen in the lobe 2 of the rats with acute liver damage. The levels of alanine transaminase and aspartate aminotransferase were slightly increased and the albumin level was slightly decreased in the rats with acute liver damage on the days 4 and 7, however, these biochemical indexes were not significantly correlated with the gene expression. There was no obvious histological difference between the lobes 2 and 3 and lobe 1. CONCLUSION: Gene delivery with peptide/DNA complexes shows a good expression in the acute damaged liver without aggravating the liver damage, thus providing a technical platform for the experimental research of liver gene therapy.

[Etiological analysis of 1977 patients with acute liver failure, subacute liver failure and acute-on-chronic liver failure].

OBJECTIVE: To investigate the etiology of 1977 patients from northern China with acute (ALF), sub-acute (SALF) or acute-on-chronic liver (ACLF) failures. METHOD: The age, gender, etiology, pathogenesis, and prognosis of the 1977 patients with liver failures were retrospectively analyzed. RESULTS: Of the 1977 cases, the three most common causes of ALF were HEV (33.96%) or HBV (13.21%) infections or those caused by medicines (9.43%). The three predominant causes of SALF were medicines (31.53%), HEV (16.22%) or HBV (9.91%) infections, but those of the ACLF were HBV (90.29%) infection, alcoholic hepatopathy (2.65%), and HBV super infected with HEV (2.26%) infections. 90.09% (1781) patients were infected by hepatotropic viruses. Of these 1781 patients, the most common cause of their liver failures was HBV infection (92.93%). In these HBV infected patients, 77.10% were from 26 to 55 years old. From 2005 to 2007, there were 39 patients with alcoholic liver failure. In the past two years, there were 23 patients with drug induced liver failure. The improvement rate of the 1977 patients after their treatments was 35.56%. The improvement rate of HEV infected liver failure was higher than drug induced liver failure (P less than 0.05); no statistical significance was found between other groups (P more than 0.05). CONCLUSION: Different types of liver failure have different predominant causes. HBV infection is the most common cause in our 1977 patients. In the past two years, the number of drug induced liver failures and alcoholic liver failures have been increasing.