Reliability and validity of the Chinese version of chronic liver disease questionnaire-nonalcoholic fatty liver disease in patients with nonalcoholic fatty liver disease: a multicenter cross-sectional survey in China.

PURPOSE: The Chronic Liver Disease Questionnaire (CLDQ)-Nonalcoholic Fatty Liver Disease (NAFLD) is a disease-specific instrument to assess the health-related quality of life (HRQL) of patients with NAFLD. In order to provide further evidence for the cross-cultural utility of this instrument in the Chinese population, we translated the CLDQ-NAFLD into Chinese and examined its reliability and validity. METHODS: Patients with NAFLD in 90 hospitals across China were enrolled in this multicenter cross-sectional survey. Eligible patients completed the Chinese version of CLDQ-NAFLD at enrollment to assess HRQL. Internal consistency of the questionnaire was assessed using Cronbach's alpha coefficient and split-half reliability. Convergent and discriminant validity were assessed using Spearman correlation coefficient. Factor analysis was used to test the construct validity. RESULTS: Between March and August 2019, 5181 patients with a mean age of 43.8 ± 13.3 years were enrolled. All domains exhibited good internal consistency, with Cronbach's alpha and split-half reliability greater than 0.70. The scaling success rate of all domains was 100% for convergent validity and 99.4% (179/180) for discriminant validity. The inter-scale correlations indicated a significant correlation between all CLDQ-NAFLD domains (r = 0.608 to 0.832, all p < 0.001). Factor analysis of 36 items extracted 6 factors, which explained 69.14% of the total variance. CONCLUSION: The Chinese version of CLDQ-NAFLD is a reliable and valid instrument for assessing the HRQL of Chinese patients with NAFLD.

Health-related quality of life in Chinese population with non-alcoholic fatty liver disease: a national multicenter survey.

BACKGROUND: Health Related Quality of Life (HRQL) is a multi-dimensional construct that can comprehensively evaluate the patient's health status, including physical, emotional, mental and social well-being. In this study, we aimed to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on HRQL in a Chinese population. METHODS: In this national multicenter cross-sectional survey, patients with NAFLD were enrolled. Chronic Liver Disease Questionnaire (CLDQ)-NAFLD was used to qualify HRQL. Univariate and multivariate analysis were used to identify independent risk factors of HRQL. RESULTS: A total of 5181 patients with NAFLD from 90 centers were enrolled in this study (mean age, 43.8 ± 13.3 years; male, 65.8%). The overall CLDQ score was 5.66 ± 0.89. Multivariate logistic regression analysis showed that body mass index (BMI: HR, 1.642; 95% CI, 1.330-2.026), alanine transaminase (ALT: HR, 1.006; 95% CI, 1.001-1.011), triglyceride (HR, 1.184; 95% CI, 1.074-1.305), disease severity (HR, 3.203; 95% CI, 1.418-7.232) and cardiovascular disease (HR, 4.305; 95% CI, 2.074-8.939) were independent risk factors for overall CLDQ score. In the logistic analyses of individual domain, BMI and triglyceride were independent risk factors of all domains. ALT, disease severity, diabetes, depression and cardiovascular disease were influencing factors for the CLDQ score of several domains. CONCLUSIONS: This national multicenter cross-sectional survey in China indicated that the HRQL in patients with NAFLD was impaired. HRQL was found to be significantly associated with sociodemographic and clinical factors. Attention should be paid to the optimally managing care of patients with NAFLD to improve their HRQL.

Investigation of key microRNAs associated with hepatocellular carcinoma using small RNA-seq data.

To identify key microRNAs (miRNAs) associated with hepatocellular carcinoma (HCC) using small RNA-seq data. Small RNA-seq data for two HCC samples and two normal samples were downloaded from NCBI Gene Expression Omnibus. MiRNAs were identified through database search. Differentially expressed miRNAs were screened out with t test and their target genes were retrieved. Functional enrichment analysis was performed to uncover their biological functions. Regulatory networks and core metabolic networks were also constructed to present the global patterns. In addition, new miRNAs and their target genes were predicted. A total of 59 differentially expressed miRNAs were obtained, 12 up-regulated and 47 down-regulated. A total of 3,306 target genes were retrieved for eight miRNAs. Pathway enrichment analysis for the target genes showed that "pathways in cancer" and "MAPK signaling pathway" were significantly over-represented. Functional enrichment analysis found that "biological regulation" and "macromolecule modification" were significantly related to the target genes. Two regulatory networks were constructed for up- and down-regulated differentially expressed miRNAs with information from Ingenuity Pathway Analysis database. Two metabolic networks were also established based upon "pathways in cancer" and "MAPK signaling pathway", consisting of miRNAs, target genes, compounds and others genes. Moreover, a number of new miRNAs and relevant target genes were predicted. Our study discloses a number of miRNAs as well as genes which may be involved in the development of HCC and these findings are beneficial in guiding future researches.

Identifying candidate genes for discrimination of ulcerative colitis and Crohn's disease.

In this study we aimed to screen effective biomarkers for differential diagnosis of ulcerative colitis (UC) and Crohn's disease (CD). By using the gene expression profile dataset GSE24287 including 47 ileal CD, 27 UC and 25 non-inflammatory bowel diseases control downloaded from Gene Expression Omnibus database, we identified the differentially expressed genes (DEGs) between UC patients and controls as well as between CD patients and controls (|log2FC(fold change)| > 1 and p < 0.05). Then Gene Ontology (GO) functional enrichment analyses were performed for these DEGs in two groups, followed by the construction of weight PPI (protein-protein interaction) networks. Subnets enriched for the PPIs and differentially expressed genes were constructed based on the weight PPI networks. The overlapping genes between the genes in the top 10 subnets with smallest p value and the DEGs were selected as the candidate genes of disease. A total of 75 DEGs were identified in UC group and 87 ones in CD group. There were 69 and 57 specific DEGs in CD group and UC group, respectively. The DEGs in CD group were mainly enriched in "inflammatory response" and "defense response", while the most significantly enriched GO terms in UC group were "anion transport" and "chemotaxis". FOS and SOCS3 were identified as candidate genes for CD and other three genes HELB, ZBTB16 and FAM107A were candidate genes for UC. In conclusion, there were distinct genetic alterations between UC and CD. The candidate genes identified in current study may be used as biomarkers for differential diagnosis of CD and UC.

LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior.

This study aimed to clarify the role of la-related protein 1 (LARP1) in cell cycle progression and metastatic behavior of cultured gastric carcinoma (GC) cells. To do that, LARP1 expression was detected in clinical GC tissues and cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. The cell viability, apoptosis, cell cycle, migration, invasion, and cell growth were examined using a Cell Counting Kit-8, Annexin V-FITC staining, propidium iodide staining, Transwell migration and invasion assays, and colony formation assays after LARP1 knockdown. Phosphatidyl inositol 3-kinase (PI3K) and AKT1 mRNA and protein expression levels of PI3K, p-AKT1, AKT1, p-BAD, p-mTOR, and p21 in si-LARP1 transfected GC cells were determined using qRT-PCR and western blotting. Here, we've shown that LARP1 expression was upregulated in human GC tissues and KATO III cells. LARP1 knockdown inhibited GC cell proliferation, cell cycle progression, migration, invasion, and colony formation and promoted apoptosis. In si-LARP1-transfected KATO III cells, the mRNA expression levels of PI3K and AKT1, PI3K protein expression, and the p-AKT1/AKT1 ratio were significantly suppressed. p-mTOR and p-BAD were significantly decreased, whereas p21 was significantly increased in si-LARP1-transfected KATO III cells. In conclusion LARP1 knockdown induces apoptosis and inhibits cell cycle progression and metastatic behavior via PI3K/AKT1 signaling in GC cells.

Ossicular Reconstruction With Various Degrees of Malleus Preservation in Patients With Chronic Otitis Media.

Objective: We examined the relationship between factors of middle ear conditions and the outcome of ossiculoplasty in chronic otitis media (COM) by measuring the improvement in the air-bone gap (ABG) and air conduction threshold (TAC). Methods: This retrospective study analyzed 76 patients (77 ears) who underwent ossiculoplasty from among 520 COM patients who underwent tympanoplasty based on the maximum preservation of the original ossicles. The reconstructed ossicular chain was performed by preserving or utilizing the remaining malleus in all cases with the presence of the malleus manubrium. Patients with eardrum adhesion, cholesteatoma, and cholesterol granuloma were defined as having a compromised middle ear condition (Group A), and those without as having an uncompromised middle ear condition (Group B). In each group, pure-tone audiometry was performed preoperatively and postoperatively, and improvements in the ABG and TAC were compared. The effects of the types of tympanoplasty and the method of ossiculoplasty (columella versus incus interposition) on postoperative ABG and TAC were also compared. Results: The postoperative ABG improvement in Group B was significantly higher than that in Group A [ß = 7.31, 95% confidence interval (CI) = 1.93-12.69, P < .05]. Type III minor columella tympanoplasty yielded significantly better results than type III major and type Vb tympanoplasty (ß = 11.42, 95% CI = 5.16-17.68, P < .01). There were no significant differences in the postoperative ABG or TAC between the reconstruction groups with and without preservation of malleus. Conclusions: Our results indicate that complex cases compromised by adhesions, cholesteatoma, and cholesterol granuloma have worse outcomes regarding hearing improvement and success rates, while those with intact stapes suprastructure have better outcomes. Malleus was maximally preserved in the patients of this study; however, this showed no significant prognostic benefit in hearing.

Stages of psychological change among patients with non-alcoholic fatty liver disease in China: a national cross-sectional study.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is becoming the leading cause of chronic liver disease worldwide. However, treatment of NAFLD is potentially influenced by psychological conditions. Using the simplified version of the University of Rhode Island Change Assessment (URICA-SV) scale, this study aimed to evaluate the stage of psychological change as a prerequisite to refining implementation strategies for psychological change. DESIGN: A multicentre cross-sectional survey. SETTING: Ninety hospitals in China. PARTICIPANTS: 5181 patients with NAFLD were included in this study. OUTCOME MEASURES: All patients completed the URICA-SV questionnaire and were assigned to one of the three stages of change (precontemplation, contemplation or action) according to their readiness scores. A stepwise multivariate logistic regression analysis was used to identify independent factors associated with the stage of psychological change. RESULTS: A total of 4832 (93.3%) patients were included in the precontemplation stage and only 349 (6.7%) considered making a change or preparing to make one. There were significant differences in gender (Cohen's d=0.039, p=0.005), age (Cohen's d=-0.327, p<0.001), waist circumference (Cohen's d=0.143, p=0.003), alanine transaminase (Cohen's d=0.347, p=0.001), triglyceride (Cohen's d=0.351, p=0.002), body mass index (BMI; Cohen's d=0.056, p<0.001), proportion of hyperlipidaemia (Cohen's d=0.068, p<0.001) and cardiovascular disease (Cohen's d=0.032, p=0.029), therapeutic regimen (Cohen's d=0.136, p<0.001), and Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease overall score (Cohen's d=-0.420, p<0.001) between patients with NAFLD in the precontemplation stage and those in the contemplation/action stage. Logistic regression identified BMI (HR 0.659, 95% CI 0.469 to 0.928, p=0.017), cardiovascular disease (HR 2.161, 95% CI 1.089 to 4.287, p=0.027) and triglyceride (HR 0.751, 95% CI 0.591 to 0.955, p=0.020) as independent factors predicting psychological change. CONCLUSIONS: The results demonstrated that very few patients with NAFLD presented psychological condition in the stage of action. Psychological condition was found to be significantly related to BMI, cardiovascular disease and triglyceride factors. Integrated diversity considerations for evaluating psychological change are necessary.

Cytokine expression and the role of Thl7 cells in mice colitis.

BACKGROUND/AIMS: To explore the expression and mechanism of Thl7 cells and cytokines in mice model with 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced inflammatory bowel disease (IBD). METHODOLOGY: ELISA assay was used to detect the expression of Th17 cytokine IL-17 and Thl cytokines IFN-y in colon tissues. Western blot assay was applied to detect IL-17 expression in peripheral blood mononuclear cells (PBMC), spleen mononuclear cells (SMC), mesenteric lymph node cells and colon tissue of colitic mice. RT-PCR assay was used to detect the effect of anti-IL-17 antibody application on TNF-a, IFN-y and IL-6 mRNA levels in SMCs from colitic mice. RESULTS: Th17 cytokine IL-17 and Thl cytokines IFN-y were both expressed at high level in TNBS-induced colitic mice. In addition, the expression of Thl7 cytokine appeared earlier than the Thl cytokine. IL-17 levels in SMCs, mesenteric lymph node cells and colon tissue of the disease model group had significant differences compared with normal control group (p<0.01), while the IL-17 level in PBMCs of the disease model group had no significant difference (p>0.05) to control group. After application of 10 ug/mL anti-IL-7 antibody, the TNF-ct, IL-6 and IFN-y mRNA levels in SMCs of the model group showed no significant difference from that of no antibody group (p>0.05). CONCLUSIONS: Both Th17 cells and Thl cells involved in TNBS-induced IBD and the role of Thl17 cells may be through inducing the secretion of pro-inflammatory cytokines.

Optimal N-acetylcysteine concentration for intratympanic injection to prevent cisplatin-induced ototoxicity in guinea pigs.

BACKGROUND: Cisplatin is a chemotherapy drug that can induce sensorineural hearing loss. At present, no otoprotective agent is approved for use. OBJECTIVES: This study investigated the optimal concentration of intratympanic N-acetylcysteine (NAC) to prevent cisplatin-induced ototoxicity in a guinea pig model. MATERIALS AND METHODS: Guinea pigs (n = 64) were treated with a single intratympanic injection containing different NAC concentrations or saline (control) 3 days prior to intraperitoneal injection with cisplatin. The threshold change in the auditory brainstem response was assessed. RESULTS: Four weeks after intraperitoneal cisplatin injection, only the group that received 2% NAC exhibited significant otoprotection (p < .05) compared with the control. Otoprotection was observed at all the frequencies tested (1k, 2k, 4k, and 8k Hz). The 2% NAC group also exhibited significant otoprotection (p < .05) compared with the other NAC groups (at 1k, 2k, 4k, and 8k Hz). The 4% NAC group exhibited significantly reduced hearing capacity (p < .05) in the fourth week compared with controls. CONCLUSIONS AND SIGNIFICANCE: Intratympanic NAC administration is an efficient and safe means of preventing cisplatin-induced ototoxicity. In our animal model, the optimal intratympanic NAC concentration was 2%; concentrations of 4% loss of otoprotection.

Integrated analysis of copy number alterations and loss of heterozygosity in human pancreatic cancer using a high-resolution, single nucleotide polymorphism array.

OBJECTIVE: To chart molecular genetic events in pancreatic cancer. METHODS: We analyzed genome-wide copy number alterations and loss of heterozygosity (LOH) in 25 established pancreatic cancer cell lines using a high-density single nucleotide polymorphism (SNP) array. We verified the data using genomic PCR and applied them to clinical samples. RESULTS: Twenty-six homozygous deletion regions were detected in at least 1 cell line and LOH was found at 9p, 18q, 17p, 8p, 13q, 6q, 3p, 6p, 22q, 9q and 12q with high frequency (>50%), consistent with a previous study. Moreover, we found 23 amplified regions in at least 2 cell lines, including 8 unreported loci. We then examined representative genes at the 8 amplified loci in matched pairs of pancreatic cancer and normal tissues. The amplification was detected in 1 (7.1%) to 5 (35.7%) of 14 microdissected tissue specimens. CONCLUSION: Using high-resolution SNP arrays, we studied genome-wide copy number alterations and LOH simultaneously. We identified several novel and minute genomic amplifications, which contained candidate oncogenes in human pancreatic cancers.

Meta-analysis of the effectiveness and safety of vedolizumab for ulcerative colitis.

AIM: To conduct a meta-analysis examining the effectiveness and safety of vedolizumab for the treatment of ulcerative colitis (UC). METHODS: A search was conducted of MEDLINE, Cochrane, EMBASE, and Google Scholar on July 31, 2013. Inclusion criteria were: (1) Randomized controlled trial (RCT); (2) Patients treated for UC; and (3) Intervention was vedolizumab. The following information/data were extracted from studies that met the inclusion criteria: the name of the first author, year of publication, study design, patient demographic information, response rate, remission rate, and adverse events. The primary outcome was clinical response rate, and the secondary outcomes were clinical remission rate and serious adverse events. Odds ratio (OR) with 95%CI were calculated for each outcome. RESULTS: Of 224 studies initially identified, three RCTs examining the use of vedolizumab meeting the inclusion criteria were included in the meta-analysis. All studies examined the use of vedolizumab at dosages ranging from 0.5 to 10 mg/kg body weight (one study used a standard dose of 300 mg). The follow-up periods were approximately 6 wk. The total number of patients in the intervention groups was 901, and in the control groups was 221. The mean age of the patients was approximately 41 years, and approximately half were males. The follow-up periods ranged from 43 d to 6 wk. The clinical response and remission rates were significantly higher for patients who received vedolizumab as compared to control patients (clinical response: OR = 2.69; 95%CI: 1.94-3.74, P < 0.001 and remission rate: OR = 2.72; 95%CI: 1.76-4.19, P < 0.001). Serious adverse events were not higher in patients that received vedolizumab. CONCLUSION: This analysis supports the use of vedolizumab for the treatment of UC.

Gingko biloba extract (Ginaton) ameliorates dextran sulfate sodium (DSS)-induced acute experimental colitis in mice via reducing IL-6/STAT3 and IL-23/IL-17.

This study explored the underlying mechanism of Gingko biloba extract (Ginaton) on dextran sulfate sodium (DSS)-induced acute experimental colitis in mice. 40 male C57BL/6 mice were randomly divided into four groups: normal control group, Ginaton group, Ginaton treatment group, and DSS group. After 7 days administration, mice were sacrificed and colons were collected for H-E staining, immunohistochemistry, real-time PCR and Western blot. By observing clinical disease activity and histological damage, we assessed the effect of Ginaton on DSS-induced acute experimental colitis in mice and observed the effect of Ginaton on normal mice. We also explored the specific mechanism of Ginaton on DSS-induced acute experimental colitis in mice through examining the expression of inflammatory related mediators (gp130, STAT3, p-STAT3, ROR-γt) and cytokines (IL-6, IL-17, IL-23). Ginaton-treated DSS mice showed significant improvement over untreated DSS mice. Specifically, Ginaton improved clinical disease activity (DAI score, weight closs, colon shortening, and bloody stool) and histological damage, and reduced the expression of inflammatory-related mediators (p-STAT3, gp130, ROR-γt) and cytokines (IL-6, IL-17, IL-23). In addition, clinical disease activity, histological damage, the expression of inflammatory related mediators (STAT3, p-STAT3, gp130, ROR-t) and cytokines (IL-6, IL-17, IL-23) in mice of Ginaton group were similar to normal control group. In conclusion, Ginaton ameliorates DSS-induced acute experimental colitis in mice by reducing IL-17 production, which is at least partly involved in inhibiting IL-6/STAT3 signaling pathway and IL-23/IL-17 axis. Moreover, Ginaton itself does not cause inflammatory change in normal mice. These results support that Ginaton can be as a potential clinical treatment for ulcerative colitis (UC).

Adipose-Derived Mesenchymal Stem Cells Ameliorate Ulcerative Colitis Through miR-1236 Negatively Regulating the Expression of Retinoid-Related Orphan Receptor Gamma.

Mesenchymal stem cells (MSCs) were reported to accelerate the curing of ulcerative colitis (UC). Altered expression of microRNAs (miRNAs) has recently revealed association with UC. However, the effect of adipose-derived MSCs (ASCs) on UC and the mechanism of how miRNAs regulate UC remain unclear. We investigated the effect of ASCs on 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced UC in rat colon tissues. qRT-PCR and immunofluorescence analyses were performed to monitor the expression of miR-1236 and its target molecule, retinoid-related orphan receptor γ (RORγ). Regulation of the expression of RORγ by miR-1236 was assessed using luciferase reporter construct assays and miR-1236 mimic transfection. The relationship between miR-1236 and RORγ was further investigated in HT29 cells induced by TNF-α. ASCs highly ameliorated UC and decreased the inflammation markers in rats with TNBS-induced UC. In addition, ASCs upregulated the expression of miR-1236 and decreased the expression of RORγ in the TNBS-induced rat model of UC. The luciferase reporter assay and bioinformatic analysis demonstrated that the expression of RORγ was directly targeted and regulated by miR-1236. Specifically, the expression of RORγ was suppressed by miR-1236 mimic and enhanced by miR-1236 inhibitor. Furthermore, we demonstrated that exogenous miR-1236 mimic could inhibit the expression of RORγ in HT29 cell induced by TNF-α. ASCs effectively alleviated UC in rats with the expression of miR-1236 alteration, and miR-1236 may play important roles in UC by downregulating the expression of RORγ.

Correlation between serum levels of high mobility group box-1 protein and pancreatitis: a meta-analysis.

BACKGROUND: Aberrant expression of high mobility group box-1 protein (HMGB1) contributes to the progression of various inflammatory diseases. This meta-analysis focused on the clinical significance of serum HMGB1 levels in pancreatitis patients, with the goal of building a novel diagnostic score model. METHOD: We conducted a meta-analysis by searching in the PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases without any language restrictions. Studies were pooled and standard mean difference (SMD) and its corresponding 95% confidence intervals (95% CIs) were calculated. Version 12.0 STATA software was used for statistical analysis. RESULTS: We performed a final analysis of 841 subjects from 12 clinical case-control studies. The meta-analysis results showed a positive association between serum HMGB1 levels and the progression of pancreatitis. In the subgroup analysis by country, high serum level of HMGB1 may be related to pancreatitis progression in China, Korea, Hungary, and Japan populations (all P < 0.05). CONCLUSION: The present meta-analysis indicated that serum HMGB1 level was statistically elevated in patients with pancreatitis, and thus serum levels of HMGB1 could be determined to be a useful biomarker for pancreatitis patients.

Expression of survivin protein in human colorectal carcinogenesis.

AIM: To identify the role of survivin in colorectal carcinogenesis and the relationship between Survivin and histological differentiation grade of colorectal carcinoma. METHODS: Immunohistochemical staining of survivin by using the monoclonal antibody was performed by the standard streptavidin-peroxidase (SP) technique for the 188 paraffin sections which included 30 normal colorectal mucosas, 41 adenomas with low grade dysplasia, 30 adenomas with high grade dysplasia, and 87 colorectal carcinomas which were classified as high, middle and low differentiated subgroups which included 33, 28, 26 cases respectively. RESULTS: Expression of survivin was observed in the cytoplasm of adenoma with dysplasia and colorectal carcinoma cells. No immunoreactivity of survivin was seen in normal mucosas. The positive rate of survivin increased in the transition from normal mucosas to adenomas with low grade dysplasia to high grade dysplasia/ carcinomas (0.0 %, 31.7 %, 56.7 % and 63.2% respectively). But the difference between high grade dysplasia and carcinomas had no statistical significance. Positive rate was not related to histological differentiation grade of colorectal carcinoma. Moreover, there was no correlation between histological differentiation grade of colorectal carcinoma and immunoreactive intensity of survivin. CONCLUSION: The expression of survivin is the essential event in the early stage of colorectal carcinogenesis and plays an important role in the transition sequence and it is not related to histological differentiation grade of colorectal carcinoma. It thus may provide a new diagnostic and therapeutic target in colorectal cancer.

Progress in searching for susceptibility gene for inflammatory bowel disease by positional cloning.

Inflammatory bowel disease (IBD) includes two clinical subtypes: Crohn disease (CD) and ulcerative colitis (UC). The general prevalence is about 1.0-2.0 % in Western countries. It is predominantly regarded as a multifactorial disorder involving environmental factors and polygenic defects. The view was confirmed by a lot of evidences from clinical attributions and animal models, especially from epidemiological investigations. So the etiological study of IBD has been focused on searching for susceptibility genes by positional cloning, which consists of two steps: linkage analysis and association analysis. Linkage analysis has been an important method of searching for susceptibility genes to polygenic diseases as well as single-gene disorders. IBD, as a polygenic disease, has been widely investigated by linkage analysis for susceptibility gene since 1996. The paper reviewed 38 articles, which covered almost all original researches in relation to IBD and linkage analysis. So far, several loci, such as 16q, 12q, 6p and 3p, have been identified by the studies. The most striking is 16q12 (IBD1), which linked only with CD not UC in the majority of studies. Association analysis, as one essential step for positional cloning, is usually carried out by genotyping candidate genes selected by means of linkage analysis or other methods, for figuring out the frequencies of alleles and comparing the frequencies between IBD group and healthy control group to identify the specific allele. It has been established that IBD is implicated in immune disorder. So the studies were centered on the genes of NOD2/CARD15, HLA-II, cytokine, cytokine receptor and adhesion molecule. This paper reviewed 14 original articles on association between NOD2 and IBD that have been published since 2001. All results, with the exception of one report from a Japanese group, provide evidences that the three kinds of variants of NOD2 are susceptibility factors for IBD. This article also comprehensively analyzed 18 original researches of HLA gene polymorphism in IBD. We found extensive discrepancy among the conclusions and a novel hypothesis was put forward to explain the discordance. Most studies published recently on association between IBD and cytokine gene polymorphism were reviewed.

Dairy product consumption and gastric cancer risk: a meta-analysis.

AIM: To investigate whether dairy product consumption is a risk factor for gastric cancer. METHODS: We searched the PubMed and Web of Science databases for English-language studies on dairy product consumption and gastric cancer risk that were published between October 1980 and September 2013. One author independently extracted data and assessed study quality. Based on the heterogeneity results, we used either the fixed effects model or the random effects model to compute the summary relative risks and 95% confidence intervals (CIs). We also analyzed subgroups according to the study design, geographic region, sex, and whether there were adjustments for confounders (smoking and drinking) with respect to the sources of heterogeneity. RESULTS: We found 39 studies that were potentially eligible for inclusion in this meta-analysis, including 10 cohort studies and 29 case-control studies. The summary relative risk for gastric cancer, comparing the highest and lowest dairy product consumption categories, was 1.06 (95%CI: 0.95-1.18). Specific analyses for milk, butter, and margarine yielded similar results, but the results for cheese and yogurt were different. There was significant heterogeneity for all studies (Q = 112.61; P = 0.000; I (2) = 67.1%). No publication bias was observed (Egger's test: P = 0.135; Begg's test: P = 0.365). There was a nonsignificant association between dairy product consumption and gastric cancer risk in the subgroup analysis for the study design, sex, geographic region, and whether there were adjustments for confounders (smoking and drinking). CONCLUSION: In our meta-analysis, dairy product consumption was associated with a nonsignificantly increased risk of gastric cancer. However, this result should be verified using large, well-designed prospective studies.

Comprehensive analysis on clinical features of Wilson's disease: an experience over 28 years with 133 cases.

OBJECTIVES: Here, we reported our experience over 28 years with 133 cases of patients with Wilson's disease (WD) in order to illustrate the diverse clinical presentation and to improve understanding and early diagnosis of WD. METHODS: We reviewed the medical records of patients with WD at Shengjing Hospital of China Medical University from 1993 to 2011. The clinical manifestations and laboratory findings were analyzed. The diagnosis was based on the presence of Kayser-Fleisher (K-F) rings, low serum copper levels, low serum ceruloplasmin levels, increased urinary copper concentrations before or after penicillamine challenge. RESULTS: Among them, 93 patients mainly presented with hepatic manifestations, 27 with neural abnormalities, and 13 presented with others. Age range at diagnosis was wide (3-74 years, average 13·2 years), and five patients were over 40 years. The oldest one was aged 74 years and presented with neuropsychiatric disorder. The positive rate of K-F rings was 93·0%. The serum ceruloplasmin decreased in 83·6% patients, 24-hour urinary copper increased in 88·1% patients, and serum copper decreased in 68·9% patients. About 79·7% of patients were diagnosed within 6 months, but only 33·1% were diagnosed at their initial medical consultation. There was a substantial delay of up to 15 years. CONCLUSIONS: The clinical manifestation of WD is very diverse and no one feature is completely reliable. Doctors in many fields have opportunities to encounter this disease, and the most important thing is to be aware of the possibility of WD.

Candidate agents for pancreatic ductal adenocarcinoma identified by a sub-pathway based method.

AIM: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer death worldwide. This study aims to explore the molecular mechanism of PDAC and identify biologically active small molecules capable of targeting the sub-pathways which were dysregulated in the development of PDAC. METHODS: The gene expression profile of GSE28735 microarray data (including 45 matching pairs of pancreatic tumor and adjacent non-tumor tissues) was downloaded from GEO (Gene Expression Omnibus) database. Differentially expressed genes (DEGs) between pancreatic tumor tissues and non-tumor tissues were identified, and then the sub-pathway enrichment analysis was performed. Moreover, an approach based on targeting sub-pathways was used to reveal potential agents for PDAC. RESULTS: A total of 5315 DEGs were identified between pancreatic tumor tissues and non-tumor tissues with a false discovery rate of 0.01. Genes of collagen family and integrin receptor family which were involved in pathways of focal adhesion and ECM-receptor interaction respectively were differentially expressed in the pancreatic tumor tissue. Besides, a total of 85 small molecules including fludrocortisone, latamoxef and metronidazole were revealed by bioinformatics analysis. CONCLUSION: This study proposed the use of an approach based on targeting sub-pathways to identify potential agents for PDAC. The sub-pathways and small molecules discovered in this study were not only related to PDAC but also play a role in perturbing the development of PDAC.