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.

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.

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.

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.

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.

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

Since the authors are not responding to the editor's requests to fulfill the editorial requirement, therefore, the article has been withdrawn.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

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.

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.

Polymorphism of IFN-γ +874T/A associated with production of IFN-γ affects human papillomavirus susceptibility in rural women from Luohe, Henan, China.

PURPOSE: In this paper, the association between polymorphisms of IFN-γ +874T/A (rs2430561), IFN-γR1 -56 T/C (rs2234711), IFN-γR1 +95 C/T (rs7749390), and IFN-γR1 -611A/G (rs 1327474) and human papillomavirus (HPV) susceptibility was investigated in rural women from Luohe, Henan, China. PATIENTS AND METHODS: A total of 520 rural women were enrolled from Luohe, including 260 with HPV infection and mild dysplasia or less and 260 without HPV infection. Single-nucleotide polymorphisms (SNPs) of IFN-γ +874T/A, IFN-γR1 -56 T/C, IFN-γR1 +95 C/T and IFN-γR1 -611A/G were genotyped using TaqMan Pre-Designed SNP Genotyping Assays. Serum IFN-γ levels were measured using Human IFN-γ Quantikine ELISA Kit. Multivariate logistic regression analysis was performed to identify the SNPs associated with HPV susceptibility. Serum IFN-γ levels were compared between different genotypes. RESULTS: The polymorphism of IFN-γ +874T/A was associated with HPV susceptibility and +874A carriers had an increased risk. Moreover, the odds ratio was higher in +874 AA carriers than in +874 AT carriers (1.672 vs 2.874). Serum IFN-γ levels were highest in IFN-γ +874 TT carriers, intermediate in AT carriers, and lowest in AA carriers (2.86±1.14 vs 1.57±0.79 vs 0.41±0.22 pg/mL, all P<0.05). CONCLUSION: The polymorphism of IFN-γ +874T/A was associated with HPV susceptibility in rural women from Luohe, Henan, China, and +874A carriers had an increased risk. The possible mechanism was that +874A carriers had a low production of IFN-γ.

Time-Dependent Effects of Acute Exercise on University Students' Cognitive Performance in Temperate and Cold Environments.

Background: Few studies have examined the acute exercise-induced changes in cognitive performance in different thermal environments and the time course effects. Objective: Investigate the time-dependent effects of acute exercise on university students' processing speed, working memory and cognitive flexibility in temperate and cold environments. Method: Twenty male university students (age 23.5 ± 2.0 years) with moderate physical activity level participated in a repeated-measures within-subjects design. Processing speed, working memory and cognitive flexibility were assessed using CogState test battery at baseline (BASE), followed by a 45-min rest (REST), immediately after (EX) and 30 min after (POST-EX) 30-min moderate-intensity treadmill running in both temperate (TEMP; 25°C) and cold (COLD; 10°C) environments. Mean skin temperature (MST) and thermal sensation (TS) were also recorded. Two-way repeated measures ANOVA was performed to analyze each variable. Spearman's rho was used to identify the correlations between MST, TS and cognitive performance. Results: Reaction time (RT) of processing speed and working memory decreased immediately after exercise in both conditions (processing speed: p = 0.003; working memory: p = 0.007). The facilitating effects on processing speed disappeared within 30 min after exercise in TEMP (p = 0.163) and COLD (p = 0.667), while improvements on working memory remained 30 min after exercise in TEMP (p = 0.047), but not in COLD (p = 0.663). Though RT of cognitive flexibility reduced in both conditions (p = 0.003), no significance was found between EX and REST (p = 0.135). Increased MST and TS were significantly associated with reductions in processing speed RT (MST: r = -0.341, p < 0.001; TS: r = -0.262, p = 0.001) and working memory RT (MST: r = -0.282, p < 0.001; TS: r = -0.2229, p = 0.005), and improvements in working memory accuracy (MST: r = 0.249, p = 0.002; TS: r = 0.255, p = 0.001). Conclusion: The results demonstrate different time-dependent effects of acute exercise on cognition in TEMP and COLD. Our study reveals facilitating effects of exercise on university students' processing speed and working memory in both environments. However, in contrast to TEMP, effects on working memory in COLD are transient.

Fusaric acid (FA) protects heart failure induced by isoproterenol (ISP) in mice through fibrosis prevention via TGF-ß1/SMADs and PI3K/AKT signaling pathways.

Fusaric acid (FA) is a novel compound derived from a class of nicotinic acid derivatives, exhibiting activity against cancers. However, its role in regulating cardiac injury is limited. Our study was aimed to investigate the role and the underlying molecular mechanism of FA in heart fibrosis and hypertrophy. Isoproterenol (ISP) was used to induce cardiac fibrosis and hypertrophy in vitro and in vivo. FA administration ameliorated hypertrophy by reducing atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and ß -myosin heavy chain (ß-MHC) in vitro and in vivo. Additionally, FA reduced collagen accumulation and fibrosis-related signals, including α- smooth muscle actin (α-SMA), Collagen type I and Collagen type III. Transforming growth factor-ß1 (TGF-ß1)/SMADs and mitogen-activated protein kinases (MAPKs), including p38, extracellular signal regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), signalling pathways were highly activated for ISP induction, which were prevented due to FA administration. Further, FA suppressed ISP-induced PI3K/AKT activity in a dose dependent manner. Of note, FA-reduced MAPKs phosphorylation was associated with phosphoinositide 3-Kinase (PI3K)/Protein kinase B (AKT) activity caused by ISP. However, PI3K/AKT activation showed no effects on TGF-ß1/SMADs expression in FA-treated cells after ISP exposure. Together, FA might be an effective candidate agent for preventing cardiac fibrosis by modulating TGF-ß1/SMADs and PI3K/AKT signalling pathways.

[Application of key contact point management in health education at ICU for oral and maxillofacial cancer patients].

PURPOSE: To explore the effect of key contact point management in health education at ICU for oral and maxillofacial cancer patients. METHODS: Key contact point checklist was constructed by literature review, brain storm, patients review and expert consultation. The patients in the control group accepted routine health education, while patients in the experimental group accepted health education based on key contact point theory. The data were analyzed by nonparametric rank sum test using SPSS 17.0 software package. RESULTS: The key contact point checklist for oral and maxillofacial cancer patients consisted of 11 items. After intervention, the understanding rate and the satisfaction rate of patients in the experimental group were improved significantly than those in the control group. CONCLUSIONS: Health education model based on key contact point theory can effectively improve the quality of health education and patients' satisfaction.

[Establishment of an evidence-based protocol for tracheotomy care in adult patients].

PURPOSE: To establish a clinical practice protocol for tracheotomy care of adult patients. METHODS: Though constructive document retrieval, personnel interview and brain-storming, protocol draft was constructed. Delphi method was used in the study, and the final protocol was based on two rounds of consultation among 15 experts from 10 tertiary general hospitals. SPSS 16.0 software package was used for statistical analysis. RESULTS: The effective rates of two rounds of questionnaire were 100% and 93.3%, the authority coefficient was 0.83, and the P value of expert coordination coefficients W was less than 0.05. The final evidence-based protocol for tracheotomy care in adult patients consists of 5 sections, 16 dimensions and 61 items. CONCLUSIONS: The evidence-based tracheotomy care protocol was combined with Chinese clinical status and experts' opinion. The protocol was scientific and credible, which may play an important role in clinical practice.

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.

Cytokine IL-6 is required in Citrobacter rodentium infection-induced intestinal Th17 responses and promotes IL-22 expression in inflammatory bowel disease.

Citrobacter rodentium (C. rodentium) infection is a widely used murine model to mimic human enteric bacteria infection and inflammatory bowel disease (IBD). In this model, interleukin (IL)­17A plays critical roles in increasing chemokine and cytokine production in various tissues to recruit innate cells, including monocytes and neutrophils, to the local site of infection. However, the source of IL­17A remains unclear, as the majority of cell types produce IL­17A, including intestinal endothelium cells, innate immune cells and CD4+ T cells in disease development. In the current study, wild­type B6 mice were treated with C. rodentium and the CD4+ Th17 cell subset was observed as being specifically increased in Peyer's patches (PP), but not in mesenteric draining lymph nodes. Furthermore, the research suggested that the differentiation and activation of Th17 cells in PP were dependent on the inflammatory cytokine IL­6, as blocking IL­6 signaling with neutralizing antibodies decreased Th17 cells and resulted in the mice being more susceptible to C. rodentium infection. These results confirmed that the Th17 cell subset was specifically activated in PP and demonstrated that IL­6 is required in Th17 cell activation, which are important to the clinical treatment of IBD.

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.

Comparison of four prognostic models and a new Logistic regression model to predict short-term prognosis of acute-on-chronic hepatitis B liver failure.

BACKGROUND: Acute-on-chronic hepatitis B liver failure (ACLF-HBV) is a clinically severe disease associated with major life-threatening complications including hepatic encephalopathy and hepatorenal syndrome. The aim of this study was to evaluate the short-term prognostic predictability of the model for end-stage liver disease (MELD), MELD-based indices, and their dynamic changes in patients with ACLF-HBV, and to establish a new model for predicting the prognosis of ACLF-HBV. METHODS: A total of 172 patients with ACLF-HBV who stayed in the hospital for more than 2 weeks were retrospectively recruited. The predictive accuracy of MELD, MELD-based indices, and their dynamic change (D) were compared using the area under the receiver operating characteristic curve method. The associations between mortality and patient characteristics were studied by univariate and multivariate analyses. RESULTS: The 3-month mortality was 43.6%. The largest concordance (c) statistic predicting 3-month mortality was the MELD score at the end of 2 weeks of admission (0.8), followed by the MELD: sodium ratio (MESO) (0.796) and integrated MELD (iMELD) (0.758) scores, DMELD (0.752), DMESO (0.729), and MELD plus sodium (MELD-Na) (0.728) scores. In multivariate Logistic regression analysis, the independent factors predicting prognosis were hepatic encephalopathy (OR = 3.466), serum creatinine, international normalized ratio (INR), and total bilirubin at the end of 2 weeks of admission (OR = 10.302, 6.063, 5.208, respectively), and cholinesterase on admission (OR = 0.255). This regression model had a greater prognostic value (c = 0.85, 95%CI 0.791 - 0.909) compared to the MELD score at the end of 2 weeks of admission (Z = 4.9851, P = 0.0256). CONCLUSIONS: MELD score at the end of 2 weeks of admission is a useful predictor for 3-month mortality in ACLF-HBV patients. Hepatic encephalopathy, serum creatinine, international normalized ratio, and total bilirubin at the end of 2 weeks of admission and cholinesterase on admission are independent predictors of 3-month mortality.

Survival and prognostic factors in hepatitis B virus-related acute-on-chronic liver failure.

AIM: To investigate the survival rates and prognostic factors in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: Clinical data in hospitalized patients with HBV-ACLF admitted from 2006 to 2009 were retrospectively analyzed. Their general conditions and survival were analyzed by survival analysis and Cox regression analysis. RESULTS: A total of 190 patients were included in this study. The overall 1-year survival rate was 57.6%. Patients not treated with antiviral drugs had a significantly higher mortality [relative risk (RR) = 0.609, P = 0.014]. The highest risk of death in patients with ACLF was associated with hepatorenal syndrome (HRS) (RR = 2.084, P =0.026), while other significant factors were electrolyte disturbances (RR = 2.062, P = 0.010), and hepatic encephalopathy (HE) (RR = 1.879, P < 0.001). CONCLUSION: Antiviral therapy has a strong effect on the prognosis of the patients with HBV-ACLF by improving their 1-year survival rate. HRS, electrolyte disturbances, and HE also affect patient survival.