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Recently, nonalcoholic fatty liver disease (NAFLD) has been renamed metabolic-associated fatty liver disease (MAFLD). Based on the definition for MAFLD, a group of non-obese and metabolically healthy individuals with fatty liver are excluded from the newly proposed nomenclature.To analyze the histologic features in the MAFLD and non-MAFLD subgroups of NAFLD.Eighty-three patients with biopsy-proven NAFLD were separated into MAFLD and non-MAFLD groups. The diagnosis of MAFLD was established as hepatic steatosis along with obesity/diabetes or evidence of metabolic dysfunction. The histologic features were compared according to different metabolic disorders and liver enzyme levels.MAFLD individuals had a higher NAFLD activity score (Metabolic dysfunction is associated with hepatic steatosis but no other histologic features in NAFLD. Further research is needed to assess the dynamic histologic characteristics in NAFLD based on the presence or absence of metabolic disorders.

Background: Concurrent non-alcoholic fatty liver disease (NAFLD) is common in patients with chronic hepatitis B (CHB). But the impact of fatty liver on the histologic progression of CHB remains controversial.Methods: Consecutive CHB patients who underwent liver biopsy between 2016 and 2021 were included. Alcohol consumption and other types of viral hepatitis were excluded. All biopsies were scored for grading and staging by Scheuer’s score, and the steatosis was scored as an estimate of the percentage of liver parenchyma replaced by fat. Logistic regression analyses were applied to assess the associated factors for significant liver inflammation (G≥2) and significant fibrosis (S≥2). Results: Among the 873 CHB patients, hepatic steatosis was prevalent in 255 patients (29.21%). Significant liver inflammation was present in 461 patients (52.81%), while significant fibrosis was observed in 527 patients (60.37%). Fatty liver was an independent risk factor for significant liver inflammation (OR: 2.117, 95% CI: 1.500-2.988), but it could not predict significant fibrosis. We developed a predictive model for significant liver inflammation with the area under receiver operating characteristic curve (AUROC) of 0.825, and a model for significant fibrosis with the AUROC of 0.760.Conclusions: NAFLD is independently associated with significant liver inflammation, but does not increase the fibrosis severity.

BACKGROUND It is well known that nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR). LB100, a serine/threonine protein phosphatase 2A (PP2A) inhibitor, is closely related to IR. However, there is little data regarding its direct influence on NAFLD. AIM To elucidate the effect and underlying mechanism of LB100 in NAFLD. METHODS After 10 wk of high fat diet (HFD) feeding, male C57BL/6 mice were injected intraperitoneally with vehicle or LB100 for an additional 6 wk (three times a week). The L02 cell line was treated with LB100 and free fatty acids (FFAs) for 24 h. Hematoxylin and eosin and oil red O staining were performed for histological examination. Western blot analysis was used to detect the protein expression of Sirtuin 1 (Sirt1), total and phosphorylated AMP-activated protein kinase α (AMPKα), and the proteins involved in lipogenesis and fatty acid oxidation. The mRNA levels were determined by qPCR. Pharmacological inhibition of AMPK was performed to further examine the exact mechanism of LB100 in NAFLD. RESULTS LB100 significantly ameliorated HFD-induced obesity, hepatic lipid accumulation and hepatic injury in mice. In addition, LB100 significantly downregulated the protein levels of acetyl-CoA carboxylase, sterol regulatory element-binding protein 1 and its lipogenesis target genes, including stearoyl-CoA desaturase-1 and fatty acid synthase, and upregulated the levels of proteins involved in fatty acid β-oxidation, such as peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), carnitine palmitoyltransferase 1α, acyl-CoA oxidase 1 and uncoupling protein 2, as well as the upstream mediators Sirt1 and AMPKα in the livers of HFD-fed mice. In vitro, LB100 alleviated FFA-induced lipid accumulation in L02 cells through the AMPK/Sirt1 signaling pathway. Further studies showed that the curative effect of LB100 on lipid accumulation was abolished by inhibiting AMPKα in L02 cells. CONCLUSION PP2A inhibition by LB100 significantly ameliorates hepatic steatosis by regulating hepatic lipogenesis and fatty acid oxidation via the AMPK/Sirt1 pathway. LB100 may be a potential therapeutic agent for NAFLD.

OBJECTIVE The inflammatory bowel disease disability index (IBD-DI) has been used to evaluate functional status for patients with inflammatory bowel diseases (IBD). The study aimed to develop a reliable Chinese version of IBD-DI (C-IBD-DI). METHODS Consecutive patients with IBD and healthy controls were recruited from June 2016 to July 2017 in the First Affiliated Hospital, College of Medicine, Zhejiang University (Hangzhou, Zhejiang Province, China) to complete an inflammatory bowel disease questionnaire-32 (IBDQ-32), Hamilton's anxiety rating scale (HAMA) and Hamilton's depression rating scale-24 items (HAMD-24). The validation process included item reduction, reliability and validity tests. RESULTS Altogether 122 patients with IBD completed the validation process. Factor analysis reduced the C-IBD-DI to 13 items. Cronbach's α coefficient was 0.90. The C-IBD-DI scores were correlated with IBDQ-32 score (r = -0.79, P

BACKGROUND Allyl isothiocyanate (AITC), a classic anti-inflammatory and antitumorigenic agent, was recently identified as a potential treatment for obesity and insulin resistance. However, little is known about its direct impact on the liver. AIM To investigate the effect and underlying mechanism of AITC in nonalcoholic fatty liver disease (commonly referred to as NAFLD). METHODS To establish a mouse and cellular model of NAFLD, C57BL/6 mice were fed a high fat diet (HFD) for 8 wk, and AML-12 cells were treated with 200 μM palmitate acid for 24 h. For AITC treatment, mice were administered AITC (100 mg/kg/d) orally and AML-12 cells were treated with AITC (20 μmol/L). RESULTS AITC significantly ameliorated HFD-induced weight gain, hepatic lipid accumulation and inflammation in vivo. Furthermore, serum alanine aminotransferase and aspartate aminotransferase levels were markedly reduced in AITC-treated mice. Mechanistically, AITC significantly downregulated the protein levels of sterol regulatory element­binding protein 1 (SREBP1) and its lipogenesis target genes and upregulated the levels of proteins involved in fatty acid β-oxidation, as well as the upstream mediators Sirtuin 1 (Sirt1) and AMP-activated protein kinase α (AMPKα), in the livers of HFD-fed mice. AITC also attenuated the nuclear factor kappa B (NF-κB) signaling pathway. Consistently, AITC relieved palmitate acid-induced lipid accumulation and inflammation in AML-12 cells in vitro through the Sirt1/AMPK and NF-κB signaling pathways. Importantly, further studies showed that the curative effect of AITC on lipid accumulation was abolished by siRNA-mediated knockdown of either Sirt1 or AMPKα in AML-12 cells. CONCLUSION AITC significantly ameliorates hepatic steatosis and inflammation by activating the Sirt1/AMPK pathway and inhibiting the NF-κB pathway. Therefore, AITC is a potential therapeutic agent for NAFLD.

OBJECTIVE Recent genome-wide association studies have demonstrated that rs2236379 in PRKCQ is a novel significant locus for Crohn's disease (CD). However, the association has not been replicated in any populations. We therefore aimed to investigate the prevalence of the PRKCQ rs2236379 variant in the Chinese Han population and evaluate whether the genetic variant of PRKCQ confers susceptibility to CD and is associated with its clinical characteristics. METHODS A total of 283 patients with CD and 381 healthy controls were enrolled. Genomic DNA was extracted from their whole blood samples and polymerase chain reaction-restriction fragment length polymorphism was used for genotyping. The association between PRKCQ polymorphisms and susceptibility to CD, and between genotypes and clinical phenotypes was analyzed. RESULTS A higher frequency of the T allele was discovered in CD patients than in healthy controls (P = 0.027). A significant difference in the distribution of the TT and CT/CC genotypes was observed between CD patients and controls (P = 0.024). The TT genotype showed a significant association with susceptibility to CD (odds ratio 1.647, 95% confidence interval: 1.088-2.574, P = 0.019). Patients with CD with the rs2236379 TT mutant risk genotype were most likely to exhibit perianal disease (P = 0.044). CONCLUSIONS Our research revealed an association between the PRKCQ rs2236379 (C>T) and CD. The TT homozygous mutation increased the risk of developing CD and may contribute to perianal disease.

Background: The role of specific IgE (sIgE) against Der p 1 and Der p 2 in Chinese patients with house dust mite (HDM) allergy has not yet been well investigated. Methods: One hundred patients were enrolled, based on sensitization and doctor-diagnosed allergy to HDM. Questionnaires were administered to document demographic and clinical characteristics. Serum IgE reactivity to Dermatophagoides pteronyssinus (Dp) extract, Der p 1, Der p 2 and Der p 10 was measured by ImmunoCAP. Results: Almost all patients were sensitized to Der p 1 (95%) and Der p 2 (93%), with both allergens together being largely responsible for the total anti-HDM IgE response. No evidence for a significant role of Der p 10 was found. Overall, IgE responses to HDM and its 2 major allergens were higher in children than in adults in this cross-sectional study. With increasing age, IgE responses to Der p 2 become more important. A positive correlation was observed between the reaction of sIgE against Dp, Der p 1 and Der p 2 and the number of organs (including the eyes, nose, lungs and skin) that were affected in patients. Conclusions: In China, Der p 1 and Der p 2 are the dominant allergens in patients with HDM allergy. The relative importance of Der p 1 and Der p 2 changes with age, in favor of Der p 2. Overall, sIgE titers were positively associated with the number of organs affected.

Background and study aims Owing to the indistinctive endoscopic appearance of gastric intestinal metaplasia (GIM), gastric intraepithelial neoplasia (GIN), and early gastric cancer (EGC), a significant number of such lesions may be missed during surveillance endoscopy. The aim of this clinical trial was to assess the value of combined computed virtual chromoendoscopy (flexible spectral imaging color enhancement [FICE]) and probe-based confocal laser endomicroscopy (pCLE) for in vivo detection of GIM, GIN, and EGC. Patients and methods This was a multicenter, randomized controlled trial performed in 238 patients at four tertiary centers. Patients were randomized to FICE-guided pCLE with targeted biopsies (group A) or FICE with standard biopsies (group B). The diagnostic yield of GIM, GIN, or EGC was compared between the two groups. Results On a per-patient assessment, the diagnostic yield for GIM/GIN/EGC was 73.3 % (88/120) in group A and 63.6 % (75/118) in group B (P = 0.09). On a per-biopsy analysis, FICE-guided pCLE with targeted biopsies significantly increased the diagnostic yield of GIM/GIN/EGC vs. FICE with standard biopsies, from 31.5 % (252/800) to 75.1 % (313/417) (P Conclusions Real-time pCLE and targeted biopsies after FICE improved the diagnostic yield for the detection of GIM, GIN, and EGC, and only required about half the number of biopsies vs. FICE with standard biopsies. This may allow a better regimen for endoscopic surveillance and subsequent treatment of patients with premalignant and malignant gastric abnormalities.Trial registered at ClinicalTrials.gov (NCT02515721).

Replenishing the insulin-producing β-cell mass is considered to be a potential cure for diabetes. A recent study identified a secreted protein, known as betatrophin, which potently induces pancreatic β-cell proliferation. Notably, a number of studies reportedly identified betatrophin, which is also known as lipasin, atypical angiopoietin-like 8 and refeeding-induced fat and liver protein, and considered to be a novel regulator in lipid metabolism according to the studies. The identification of betatrophin was considered to create novel opportunities for potential diabetes therapy. In the present study, the current knowledge of betatrophin is reviewed, with regards to its character and function in lipid homeostasis and pancreatic β-cell proliferation.

We develop a novel system for temporal-spatial simulation and dynamic regulation of water quality in water pollution accidents by introducing GIS to traditional one-dimensional system dynamics water quality model. We apply this system to the Songhua River water pollution accident which happened in 2005 and achieve good performance in simulating pollution zone migration and transformation in temporal and spatial dimensions.

Summary Objectives To characterize the application of traditional Chinese medicine (TCM) among children with idiopathic precocious puberty (IPP). Design and setting This study examined data sets from patients diagnosed with IPP at Chang Gung Memorial Hospital between 2010 and 2012. The patients were allocated into three groups according their voluntary choice of treatment modalities: TCM users (received TCM treatment only), Western medicine (WM) users (received WM treatment only), and “no treatment” group (received no medical treatment at all). Main outcome measures The demographic data of children with IPP were characterized. The prescription patterns and frequencies of TCM for IPP patients were analyzed. The patients’ bone maturation rates and the change of predicted height after different approaches were measured as outcomes. Results There were 3390 patients enrolled in the study. Zhi-Bai-Di-Huang-Wan (70.62%) was the most common herbal formula and Mai-Ya (Hordei Fructus Germinatus) (51.58%) was the most common single herb prescribed for IPP in all of the 2784 prescriptions. The bone maturation rates of TCM users (0.95 ± 0.20) and WM users (0.69 ± 0.05) were both decelerated but the “no treatment” group had an accelerated bone maturation rate of 1.33 ± 0.04. TCM and WM users also had higher predicted height after treatment (1.15 ± 1.19 cm versus 1.73 ± 0.29 cm), while the “no treatment” group had a decreased predicted height (−0.52 ± 0.23 cm). Conclusions Our study revealed a comprehensive list of TCM prescriptions for IPP patients. Future well-designed, randomized, double-blinded, and placebo-controlled clinical trials are warranted to evaluate the efficacy and safety of TCM for precocity.

Objective To evaluate the state of oral tolerance and its therapeutic role in mice with dextran sulfate sodium (DSS)-induced colitis. Methods Delayed-type hypersensitivity (DTH) was determined 7 and 14 days after DSS-induced colitis and control mice. Disease activity index (DAI) score and colonic histopathological score were measured 7 days after colonic extracted protein (CEP) or bovine serum albumin (BSA) (control) was administrated, with the evaluation of Th1–Th2 balance in the spleen, Peyer's patch and γδ T cells in intraepithelial lymphocytes and lamina proper lymphocytes in the intestine. Results After fed with 250 μg ovalbumin oral tolerance was induced in 7 days in both DSS-induced colitis and control mice, while oral tolerance persisted in the control mice but vanished in DSS-induced colitis 14 days after ovalbumin challenge. DAI and colonic histopathological scores were decreased significantly after the ingestion of CEP (controlled by BSA) in DSS-induced colitis with significant reduction of Th1 and the ratio of Th1 to Th2 in Peyer's patch as well as the γδ T cells in lamina proper lymphocytes in the intestine. No significant difference in Th1–Th2 balance in the spleen and γδ T cells in intraepithelial lymphocytes in the intestine were observed. Conclusions There is a defect in oral tolerance at day 7 in DSS-induced colitis. If taken orally, CEP may have a protective role in DSS-induced colitis, which may be related to the deflection from Th1 to Th2 in Peyer's patch and the reduction of γδ T cells in lamina proper lymphocytes in the intestine.

Haematopoietic stem cells (HSCs) can differentiate into cells of all lineages in the blood. However, the mechanisms by which cytokines in the blood affect HSC homeostasis remain largely unknown. Here we show that leukocyte cell-derived chemotaxin 2 (LECT2), a multifunctional cytokine, induces HSC expansion and mobilization. Recombinant LECT2 administration results in HSC expansion in the bone marrow and mobilization to the blood via CD209a. The effect of LECT2 on HSCs is reduced after specific depletion of macrophages or reduction of osteolineage cells. LECT2 treatment reduces the tumour necrosis factor (TNF) expression in macrophages and osteolineage cells. In TNF knockout mice, the effect of LECT2 on HSCs is reduced. Moreover, LECT2 induces HSC mobilization in irradiated mice, while granulocyte colony-stimulating factor does not. Our results illustrate that LECT2 is an extramedullar cytokine that contributes to HSC homeostasis and may be useful to induce HSC mobilization., How extramedullar cytokines regulate hematopoietic stem cell (HSC) homeostasis is unclear. Here, the authors show that the cytokine leukocyte cell-derived chemotaxin 2 regulates HSC expansion and mobilisation via tumour necrosis factor and interaction with CD209a in macrophages.

la betatrofina es una novedosa adipoquina que provoca la proliferación de células β pancreáticas e interviene en el metabolismo de los lípidos. Objetivos: el propósito de este estudio es evaluar el papel de la betatrofina en el síndrome metabólico.se llevó a cabo un estudio hospitalario de casos y controles según sexo y edad. El nivel de betatrofina en suero fue evaluado mediante ensayo por inmunoabsorción ligado a enzimas. Se midieron las concentraciones en suero de 12 adipoquinas para evaluar las asociaciones con la betatrofina usando los kits comerciales Adipokine Magnetic Bead Panel. Los análisis estadísticos incluyeron correlación bivariada, análisis de curva ROC y análisis de regresión lineal multivariable.el nivel de betatrofina en suero fue más elevado en pacientes con síndrome metabólico (997,36 ± 475,92 pg/ml, p = 0,001) que en los controles (735,35 ± 526,51 pg/ml). Frente al tercil más bajo, el tercil más alto del nivel de betatrofina mostró una asociación con mayor riesgo de síndrome metabólico (odds ratio ajustado = 3,521, intervalo de confianza [IC] 95% [1,191-10,413], p = 0,023). Se desarrolló la curva ROC de betatrofina para pronosticar la presencia de síndrome metabólico (área bajo la curva ROC = 0,682 [95% IC, 0,597-0,767], p0,001). Además, la betatrofina mostró correlación con distintos parámetros, como edad (r = 0,286, p0,001), índice de masa corporal (r = 0,160, p = 0,046), índice cintura-cadera (r = 0,241, p = 0,002), lipoproteína de alta densidad (r = -0,167, p = 0,037), lipoproteína de baja densidad (r = -0,195, p = 0,015), glucosa plasmática en ayunas (r = 0,266, p = 0,001), hemoglobina A1C (r = 0,314, p0,001), índice de resistencia a la insulina mediante HOMA (r = 0,272, p = 0,001) y diversas adipoquinas, entre ellas resistina (r = 0,571, p0,001), interleucina-8 (r = 0,435, p0,001), factor de necrosis tumoral alfa (r = 0,295, p = 0,011) y lipocalina-2 (r = 0,346, p = 0,003).este estudio demuestra que la betatrofina en suero desempeña una importante labor en el síndrome metabólico, implicando la regulación del metabolismo de la glucosa y los lípidos y la inflamación.

Background: Betatrophin is a novel adipokine that provokes pancreatic β-cell proliferation and is involved in lipid metabolism. Aims: This study aims to evaluate the role of serum betatrophin in metabolic syndrome (MetS). Methods: A hospital-based, age-/gender-matched case control study was conducted. The serum betatrophin level was evaluated by enzyme-linked immunosorbent assay. Serum concentrations of 12 adipokines were measured to assess their associations with serum betatrophin, using commercial Adipokine Magnetic Bead Panel kits. Statistical analyses included bivariate correlation, receiver operating characteristic (ROC) curve, and multivariate stepwise linear regression. Results: Serum betatrophin showed a higher level in MetS patients (997.36 ± 475.92 pg/ml, p = 0.001) compared with controls (735.35 ± 526.51 pg/ml). Compared with the lowest tertile, the highest tertile of serum betatrophin level indicated an association with higher risk of MetS (adjusted odds ratio = 3.521, 95% confidence interval [CI] [1.191-10.413], p = 0.023). ROC curve of betatrophin was developed to predict the presence of MetS (area under ROC = 0.682 [95% CI, 0.597-0.767], p < 0.001). Furthermore, betatrophin correlated with several parameters, e.g. age (r = 0.286, p < 0.001), body mass index (r = 0.160, p = 0.046), waist-to-hip ratio (r = 0.241, p = 0.002), high-density lipoprotein cholesterol (r = -0.167, p = 0.037), low-density lipoprotein cholesterol (r = -0.195, p = 0.015), fasting plasma glucose (r = 0.266, p = 0.001), hemoglobin A1C (r = 0.314, p < 0.001), homeostasis model assessment of insulin resistance (r = 0.272, p = 0.001), and various adipokines, e.g. resistin (r = 0. 571, p < 0.001), interleukin-8 (r = 0.435, p < 0.001), tumor necrosis factor-α (r = 0.295, p = 0.011) and lipocalin-2 (r = 0.346, p = 0.003). Conclusions: This study supports that serum betatrophin plays an important role in MetS, involving the regulations of glucose and lipid metabolism and inflammation. Introducción: la betatrofina es una novedosa adipoquina que provoca la proliferación de células β pancreáticas e interviene en el metabolismo de los lípidos. Objetivos: el propósito de este estudio es evaluar el papel de la betatrofina en el síndrome metabólico. Método: se llevó a cabo un estudio hospitalario de casos y controles según sexo y edad. El nivel de betatrofina en suero fue evaluado mediante ensayo por inmunoabsorción ligado a enzimas. Se midieron las concentraciones en suero de 12 adipoquinas para evaluar las asociaciones con la betatrofina usando los kits comerciales Adipokine Magnetic Bead Panel. Los análisis estadísticos incluyeron correlación bivariada, análisis de curva ROC y análisis de regresión lineal multivariable. Resultados: el nivel de betatrofina en suero fue más elevado en pacientes con síndrome metabólico (997,36 ± 475,92 pg/ml, p = 0,001) que en los controles (735,35 ± 526,51 pg/ml). Frente al tercil más bajo, el tercil más alto del nivel de betatrofina mostró una asociación con mayor riesgo de síndrome metabólico (odds ratio ajustado = 3,521, intervalo de confianza [IC] 95% [1,191-10,413], p = 0,023). Se desarrolló la curva ROC de betatrofina para pronosticar la presencia de síndrome metabólico (área bajo la curva ROC = 0,682 [95% IC, 0,597-0,767], p < 0,001). Además, la betatrofina mostró correlación con distintos parámetros, como edad (r = 0,286, p < 0,001), índice de masa corporal (r = 0,160, p = 0,046), índice cintura-cadera (r = 0,241, p = 0,002), lipoproteína de alta densidad (r = -0,167, p = 0,037), lipoproteína de baja densidad (r = -0,195, p = 0,015), glucosa plasmática en ayunas (r = 0,266, p = 0,001), hemoglobina A1C (r = 0,314, p < 0,001), índice de resistencia a la insulina mediante HOMA (r = 0,272, p = 0,001) y diversas adipoquinas, entre ellas resistina (r = 0,571, p < 0,001), interleucina-8 (r = 0,435, p < 0,001), factor de necrosis tumoral alfa (r = 0,295, p = 0,011) y lipocalina-2 (r = 0,346, p = 0,003). Conclusiones: este estudio demuestra que la betatrofina en suero desempeña una importante labor en el síndrome metabólico, implicando la regulación del metabolismo de la glucosa y los lípidos y la inflamación.

Leukocyte cell–derived chemotaxin 2 enhances phagocytosis and bacterial killing of macrophages to improve the outcome of bacterial-induced sepsis., Leukocyte cell–derived chemotaxin 2 (LECT2) is a multifunctional cytokine and reduced plasma levels were found in patients with sepsis. However, precise functions and mechanisms of LECT2 remain unclear. The aim of the present study was to determine the role of LECT2 in modulating immune responses using mouse sepsis models. We found that LECT2 treatment improved outcome in mice with bacterial sepsis. Macrophages (MΦ), but not polymorphonuclear neutrophils, mediated the beneficial effect of LECT2 on bacterial sepsis. LECT2 treatment could alter gene expression and enhance phagocytosis and bacterial killing of MΦ in vitro. CD209a was identified to specifically interact with LECT2 and mediate LECT2-induced MΦ activation. CD209a-expressing MΦ was further confirmed to mediate the effect of LECT2 on sepsis in vivo. Our data demonstrate that LECT2 improves protective immunity in bacterial sepsis, possibly as a result of enhanced MΦ functions via the CD209a receptor. The modulation of MΦ functions by LECT2 may serve as a novel potential treatment for sepsis.

Distinguishing ulcerative colitis (UC) from Crohn’s disease (CD) is sometimes difficult in a clinical setting. The purpose of this study was to identify a series of independent serum markers capable of distinguishing between UC and CD. 140 UC and 174 CD patients hospitalized at The First Affiliated Hospital, College of Medicine, Zhejiang University were recruited into this study. A panel of serum markers was quantified for each patient and the Bayesian information criterion (BIC) was used to determine a discrimination model. The receiver operating characteristic (ROC) was used to evaluate the performance of the model, and the area under the ROC curve (AUC) was used to evaluate the accuracy of the model. Serum albumin (Alb), total cholesterol (TC), total calcium (TCa), platelet (Plt), glycyl proline dipeptidyl aminopeptidase (GPDA) and their ratios (Alb: Plt, Alb: GPDA, TCa: TC, and Plt: GPDA) were selected into the diagnosis model using BIC. The resulting CD/UC Index (CUI) is CUI = 1.901 + 0.425 Alb - 3.324 TC - 7.444 TCa + 0.018 Plt + 0.087 GPDA - 0.0007 Alb: Plt - 0.004 Alb: GPDA + 1.839 TC: TCa + 0.003 Plt: GPDA, with CUI > 0 incrementally favored a diagnosis of UC, while CUI < 0 corresponded to a higher likelihood of a diagnosis of CD. An average value of the AUC for the CUI model is 0.73 (95% confidence interval: 0.67-0.80). The CUI, derived from commonly available serum biomarkers, could try to differentiate UC from CD in patients with unclear clinical features as a new approach to diagnosis.

There are a multitude of cross-sectional surveys that provide the prevalence of irritable bowel syndrome (IBS) in the community. However, the data regarding the influence of socioeconomic status on prevalence of IBS were sparse. This study is to investigate the possible relation between human development and prevalence of IBS, at national level.EMBASE Classic, EMBASE, and MEDLINE were searched (until October 2013) to identify population-based studies that reported prevalence of IBS. Human Development Index (HDI) was chosen to assess socioeconomic status at national level.Firstly, no correlation was observed between prevalence of IBS and national HDI (P = 0.848). Specifically, there was no statistical significance in prevalence between developing and developed countries (P = 0.319). Moreover, prevalence of IBS failed to witness a downtrend in worldwide over the past two decades. Interestingly, the ratio of female/male prevalence was correlated with national HDI according to linear regression analysis (r = 0.395), and the ratio in the developing was significant lower than that in the developed (P = 0.0394). Lastly, except methods of data collection (P0.000), it shows no difference between developing and developed countries in diagnostic criteria, IBS subtypes, and age distribution (P = 0.119, 0.327, and 0.845 respectively).This study is the first time to investigate the relation between IBS prevalence and national socioeconomic status, with consideration of years, gender, and other factors. It demonstrates that national development is not a direct indicator for prevalence of IBS.

Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of liver diseases, with markedly increased prevalence. However, its mechanisms are not clear. The present study was undertaken to illustrate the role of caveolin-1 (cav1) and the scavenger receptor class B type 1 (SR-B1) in NAFLD.Adult male C57BL/6 mice were fed with a normal diet or high fat and cholesterol (HFC) diet for 14 weeks. The mice were sacrificed to collect plasma and harvest the liver; their plasma lipid concentration was measured. Hepatic cav1 and SR-B1 mRNA and protein expression were determined by real-time quantitative polymerase chain reaction (qPCR) and Western blotting, respectively. In order to study cav1 and SR-B1 distribution and change in hepatocytes, immunohistochemical analysis was performed.HFC diet increased plasma lipids, induced NAFLD and increased the liver/body weight ratio. Compared to the control mice (n=6), the mRNA and protein levels of cav1 and SR-B1 in liver tissue of the NAFLD mice (n=12) increased significantly (cav1 mRNA: 1.536+/-0.226 vs 0.980+/-0.272, P0.05; protein: 0.643+/-0.240 vs 0.100+/-0.130, P0.01; SR-B1 mRNA: 1.377+/-0.125 vs 0.956+/-0.151, P0.01; protein: 2.156+/-0.507 vs 0.211+/-0.211, P0.01). Furthermore, both cav1 and SR-B1 immunoreactivity increased and their distribution was also changed, mainly in the plasma membrane of hepatocytes, cytoplasm and membrane of lipid droplets and around.NAFLD is associated with increased concentration of plasma lipids and upregulation of hepatic cav1 and SR-B1 gene and protein expressions, which indicate that cav1 and SR-B1 might play crucial roles in the pathogenesis of NAFLD.

To evaluate the state of oral tolerance and its therapeutic role in mice with dextran sulfate sodium (DSS)-induced colitis.Delayed-type hypersensitivity (DTH) was determined 7 and 14 days after DSS-induced colitis and control mice. Disease activity index (DAI) score and colonic histopathological score were measured 7 days after colonic extracted protein (CEP) or bovine serum albumin (BSA) (control) was administrated, with the evaluation of Th1-Th2 balance in the spleen, Peyer's patch and γδ T cells in intraepithelial lymphocytes and lamina proper lymphocytes in the intestine.After fed with 250 μg ovalbumin oral tolerance was induced in 7 days in both DSS-induced colitis and control mice, while oral tolerance persisted in the control mice but vanished in DSS-induced colitis 14 days after ovalbumin challenge. DAI and colonic histopathological scores were decreased significantly after the ingestion of CEP (controlled by BSA) in DSS-induced colitis with significant reduction of Th1 and the ratio of Th1 to Th2 in Peyer's patch as well as the γδ T cells in lamina proper lymphocytes in the intestine. No significant difference in Th1-Th2 balance in the spleen and γδ T cells in intraepithelial lymphocytes in the intestine were observed.There is a defect in oral tolerance at day 7 in DSS-induced colitis. If taken orally, CEP may have a protective role in DSS-induced colitis, which may be related to the deflection from Th1 to Th2 in Peyer's patch and the reduction of γδ T cells in lamina proper lymphocytes in the intestine.

The aim of the present study is to elucidate whether endoplasmic reticulum stress involved in the course of lipogenesis in fatty acids induced hepatic steatosis and the potential effect of metformin on endoplasmic reticulum stress.HepG2 cells were exposed to different types of culture media. After incubation for 24 h, cells were harvested to evaluate cell survival rate and lipid level among different groups. Moreover, reverse transcriptase polymerase chain reaction and western blot for glucose-regulated protein-78 (GRP78), sterol response element-binding protein-1c (SREBP1c) and fatty acid synthase (FAS) were applied.The levels of triglyceride (TG), mRNA of FAS, mRNA and protein of GRP78 and SREBP1c significantly increased in the free fatty acids (FFA)-induced hepatic steatosis group. Then, HepG2 cells with hepatic steatosis induced by FFA were treated by metformin, levels of TG, GRP78 mRNA, SREBP1c mRNA and FAS mRNA as well as GRP78 and SREBP1 protein levels were partially decreased but without significant differences.Endoplasmic reticulum stress might be involved in lipogenesis in fatty acids-induced hepatic steatosis. Therefore, endoplasmic reticulum stress might serve as a novel target in the pathogenesis and therapy of non-alcoholic fatty liver disease.

OBJECTIVE: The aim of this study was to obtain a comprehensive survey on the expression of p53, p16 and cyclooxygenase-2 (COX-2) in esophageal cancer progression and their clinical significance. METHODS: A tissue microarray containing 86 specimens from esophageal cancer and 40 specimens from adjacent non-cancer tissue was constructed to survey the expression of p53, p16 and COX-2 by immunohistochemistry. The influence of each biomarker on the histotype of esophageal lesion was assessed by logistic regression analysis. RESULTS: The expression of p53 and COX-2 was significantly higher in tumorous tissue than in non-tumorous tissue. As to p16, no significant difference was detected between tumorous and non-tumorous tissue. A significant correlation was observed among p53, COX-2 and p16 expression. Logistic regression analysis revealed that the risk factors of a tumorous histotype were the positive expression of p53 (odds ratio [OR] = 18.214) or COX-2 (OR = 42.703), and no reciprocal relationship to neoplastic progression was recognized with p53, p16 and COX-2. CONCLUSIONS: p53 and COX-2 were independent predictors in esophageal carcinogenesis. Esophageal tissue with a positive expression of p53 or COX-2 was more likely to develop esophageal cancer.

To explore the relationship between dihydropyrimidine dehydrogenase (DPYD) gene polymorphism and metabolism as well as chemotherapeutic toxicity of 5-FU in gastric and colonic carcinoma.Chemotherapy scheme based on 5-FU was used for the treatment of 75 patients with gastrointestinal carcinoma. Serum drug concentration and DPYD gene polymorphism (DPYD*2, *3, *4, *5, *9, *12) were detected with high performance liquid chromatography (HPLC) and gene chip technique respectively.It was found that there was no DPYD*2, *3, *4, *12 type mutation in all the patients. Of the DPYD*9 gene polymorphism loci in the 75 patients, there were 7 with heterozygote (9.3%) and 68 with wide type (90.7%). Of the DPYD*5 gene polymorphism loci in the 75 patients, there were 11 with mutation (14.67%) and 23 heterozygote (30.67%) and 41 with wide type (54.67%). Ke value of DPYD*5 mutation was statistically lower than that of wild type (P=0.022). The incidence of middle-severe nausea and vomiting and white blood cell decrease in DPYD*5 gene type could be arranged from the highest to lowest as follows: mutation, heterozygote, wide type (P0.05). The incidence of middle-severe nausea and vomiting was significantly higher in DPYD*9 heterozygous genotype than in DPYD*9 wild genotype (P0.05).DPYD*5 gene mutation contributes to reduced DPYD enzyme activity and 5-FU dyes metabolism, which is associated with accumulation of 5-FU and chemotherapeutic toxicity in patients with gastric and colonic carcinoma.

To investigate the diagnosis and treatment of sinusoidal obstruction syndrome (SOS).The data of 8 patients with SOS, including clinical manifestations, laboratory results, imaging, pathology, and the course of diagnosis and treatment were reviewed. All cases were followed up.The main clinical manifestations included abdominal distention, hepatalgia and signs of ascites and hepatomegaly. There were mild or moderate hepatocellular injury in 6 patients and heavy injury in 2. All patients' serum-ascites albumin gradient exceeded 11.1 g/L. The levels of CA125 in both serum and ascites elevated significantly. All patients' ultrasonography showed hepatomegaly, appearance of portal hypertension and attenuated hepatic veins. Reverse blood flow in portal vein was observed in 5 cases. Magnetic resonance imaging showed that contrast agent accumulated unevenly in liver in both portal period and lag period, but filled poorly in hepatic veins. Per cutsem liver biopsy showed that all patients' hepatic sinusoids were congested, but venular occlusion was observed in only 3 cases. Five cases had been misdiagnosed. One patient healed after liver transplantation, 4 patients recovered gradually by treatment with heparin and so on and 3 patients died.Signs of outstanding portal hypertension with mild hepatocellular injury is the main clinical feature of SOS. Both serum and ascites CA125 levels in SOS patients are elevated significantly. The misdiagnosis rate of SOS is quite high, ultrasonography and magnetic resonance imaging have significant value in diagnosis and differential diagnosis, while the value of per cutsem liver biopsy is limited. Combination of imaging and pathology should contribute to correct diagnosis of SOS. Application of anticoagulant in early course is vital, liver transplantation should be considered in severe cases.

Excessive alcohol consumption can result in multiple organ injury, of which alcoholic liver disease (ALD) is the most common. With economic development and improvement of living standards, the incidence of diseases caused by alcohol abuse has been increasing in China, although its pathogenesis remains obscure. The aim of this study was to investigate the role of hypoxia in chronic ALD.Twenty-eight male Sprague-Dawley rats were randomized into a control group (n=12) with a normal history and an experimental group (n=16) fed with 10 ml/kg of 56% (vol/vol) ethanol once per day by gastric lavage for 24 weeks. At 24 weeks, blood samples were collected and then the rats were killed. Liver samples were frozen at -80 degrees C and used for RT-PCR; other liver samples were obtained for immunohistochemical staining.When the period of alcohol consumption increased, the positive rate of expression of hypoxia-inducible factor-1 alpha (HIF-1alpha) mRNA was more significantly elevated in the liver of the alcohol group than in the control group (Por = 0.05). The HIF-1alpha protein located in the cytoplasm was seldom expressed in the control group, but significantly in the alcohol group (Por = 0.01).HIF-1alpha mRNA expression was activated by ethanol-induced injury in this study, suggesting that hypoxia is involved in the underlying mechanism of ALD.

To constructed tissue microarray containing specimens from gastric cancer and adjacent non-cancer tissue to survey the expression of p53, p16 and cyclooxygenase-2 (COX-2), and to obtain a comprehensive survey on the expression of three proteins in gastric cancer progression and their clinical significance.We constructed a tissue microarray containing 50 specimens from gastric cancer and 78 specimens from adjacent non-cancer tissue, and assayed three different proteins (p53, p16 and COX-2) by immunohistochemistry to consecutive formalin-fixed tissue microarray sections.In non-cancer tissue, p53, p16 and COX-2 positive staining were 19%, 15% and 74% respectively. In gastric cancer tissue, p53, p16 and COX-2 positive staining were 50%, 54% and 94% respectively. There were a significant difference between two different tissues (P0.05). 52% (66/128) cases were COX-2+/p53-, only 1 case were COX-2-/p53+. There was a significant association between COX-2 and p53 (P0.05). COX-2 negative expression tissues were found significantly more often in p53-negative than in p53-positive cases. 52% (67/128) cases were COX-2+/p16-, only 1 case were COX-2-/p16+. A significant correlation was recognized between expression of COX-2 and p16 (P0.05). Logistic regression analysis revealed that the risk factors of tumorous histotype were p53, p16 and COX-2 positive expression together, determined by Wald chi2 test (P0.05; odds ratio, 18.889). There was reciprocal relationship among p53, p16 and COX-2.Combination analysis of p53, p16 and COX-2 may be useful for the prediction of gastric carcinogenesis.

Hepatic veno-occlusive disease (VOD) or sinusoidal obstruction syndrome is associated with a high mortality because of its severity. Gymura segetum, a Chinese herbal medicine, is always used to cure injury and bleeding in rural areas in China. This study was undertaken to better understand VOD and its relations to the effect of Gymura segetum.Between 2000 and 2002, two patients were admitted to our department because of VOD. Before admission, both of them had been injured and taken oral decoction of patent drug Gymura segetum. We analyzed the clinical manifestations, diagnosis and therapy of the two patients.Pyrrolizidine in Panax notginseng was proved to induce VOD. The diagnosis of VOD depended on hepatic biopsy.Gymura segetum can induce VOD. More attention should be paid to its unsuscepted side effects.

To investigate whether leptin receptor Lys109Arg polymorphism influences non-alcoholic fatty liver disease.Genomic DNA samples were extracted from blood of subjects who had received a physical examination. Genotyping was performed using oligonucleotide microarray and these fluorescence labeled PCR-amplified fragments were hybridized to allele-specific oligonucleotide probes. The relevant mutation was confirmed by sequencing analysis.A total of 180 subjects (109 males and 71 females) were included in the study, 117 of them had fatty liver disease and the other 63 had no liver problems and served as healthy controls. There were 144 (80%) subjects with GG genotype (Arg109Arg), 33 (18.3%) with GA genotype (Lys109Arg) and 3 (1.7%) with AA genotype (Lys109Lys). The distribution of leptin receptor Lys109Arg polymorphism had no significant difference (P0.05) between the fatty liver disease patients (95GG, 21GA and 1AA) and the healthy control subjects (49GG, 12GA and 2AA). The abdominal wall fat was significantly thicker in AA genotype subjects (4.1+/-0.4) cm than that in GA (2.8+/-0.6) cm and GG genotype subjects (2.7+/-0.7) cm (F = 5.197, P = 0.006). The serum cholesterol levels in AA genotype subjects (5.1+/-0.4) mmol/L was significantly lower than that in AG (25.5+/-6.9) mmol/L and GG genotype (27.2+/-8.4) mmol/L subjects (F = 8.164, P = 0.005). There were no significant differences in age, body mass index, hip circumference, waist circumference, blood pressure (BP), percentage of body fat, blood protein, triglyceride, HDL and fasting blood glucose between AA, GG and GA genotype subjects.Leptin receptor Lys109Arg polymorphism may be involved in the regulation of distribution of abdominal wall fat thickness and cholesterol metabolism. Whether leptin receptor Lys109Arg polymorphism is in any way related to fatty liver disease is still not known.

Oxidative stress plays a pathogenetic role in initiation and progression of hepatic damage caused by alcohol. Recently, antioxidants have received considerable attention. Green tea polyphenols have both antioxidant and antiinflammatory properties. This study was designed to evaluate the effect of tea polyphenol (TP) on alcohol-induced liver injury in rats.The rats were divided randomly into 3 groups: group A gastrically infused with alcohol for 12 weeks, group B fed with alcohol plus TP (250 mg/kg.d) simultaneously, and group C (control group) gastrically infused with normal saline. At the end of 12 weeks, the rats were sacrificed. The liver specimen of each rat was taken for histological examination. All data were statistically analyzed in quantum and semi-quantum. Gene expression of cytokines of each group was determined.At the end of 12 weeks, hepatic injury of different degrees developed in group A and group B compared to group C. The degree of hepatic injury was attenuated in group B, with slight steatosis, liver cellular swelling in small areas; less spot and focal necrosis, no bridging necrosis, less mega-bubble steatosis and less collagen deposition in contrast to group A. Gene expressions of IL-3, IL-4, IL-1R2, IL-6R, IL-7R2 were up-regulated in group B compared with group A, but those of IL-3Ra, IL-1R1 were down-regulated. Gene expressions of IL-13, IL-1R1, IL-7R2, EPO-R, LIFR were up-regulated in group A compared with group C, but those of IL-1R2, IL-5R2, CSF1, CD27, IL-6R were down-regulated.TP is able to attenuate alcoholic liver damage. Cytokine may contribute to alcoholic liver disease.

In the organs that mediate alcohol effects on the human body and its health, the liver plays a particular important role. This study was designed to detect the changes of hepatic enzymes after alcohol intake and evaluate the corresponding damage to the human body.Fifteen volunteers were included according to the criteria. After the intake of 80 g ethanol containing beverage, alcohol levels were detected and blood samples were collected at 0.5- to 3-hour interval to detect the levels of hepatic enzymes simultaneously.After the intake of 80 g ethanol, various symptoms occurred in volunteers while the concentration of blood alcohol peaked at 1 hour and normalized within 24 hours. The ratio of alanine aminotransferase (ALT) to aspartate aminotransferase (AST) increased significantly when the venous alcoholic concentration increased from 0 g/L to 1.2 g/L and the levels of alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (gamma-GT) were elevated when the alcoholic concentration reached 0.4 g/L. No significant changes were noticed in ALT, AST or cholinesterase (CHE).Acute alcohol intoxication may cause the changes of hepatic enzymes and prove the existence of reversible hepatic injury.

Pancreatic cancer development and progression is driven by the accumulation of genetic changes. In this study we constructed tissue microarray containing specimens from pancreatic cancer, adjacent non-cancer tissue and normal tissue to survey the expression of p53, p16 and cyclooxygenase-2 (COX-2).Tissue microarray containing 337 specimens from different stages of pancreatic cancer, adjacent non-cancer tissue and normal tissues was constructed, and the expression of p53, p16 and COX-2 was assayed by immunohistochemistry to consecutive formalin-fixed tissue microarray sections.The expression of p53, p16 and COX-2 was significantly higher in tumorous tissues than in non-tumorous ones. A significant relationship was observed between p53 and COX-2, or p16 and COX-2. But no obvious correlation was seen between p53 and p16 expressions. Logistic regression analysis showed p53 and COX-2 as dependent predictors in pancreatic carcinogenesis, and a reciprocal relationship to neoplastic progression between p53 and COX-2.Combination analysis of p53 and COX-2 may be useful in predicting pancreatic carcinogenesis.

Interstitial collagenase has been considered as an essential enzyme for collagenolysis in liver fibrosis, because type I and III collagens increase predominantly in liver fibrosis. The present study aimed to demonstrate the gene expression of matrix metalloproteinases-13 (MMP-13) in the progressive phases of ethanol induced experimental liver fibrosis in rats.Thirty-four Sprague-Dawley rats were randomly divided into two groups. The experimental group (24 rats) was given ethanol (44%, 7 g/kg) every day and the control group (10) was given normal saline. Liver samples were harvested from experimental rats at 4, 12 and 24 weeks respectively. The kinetics of MMP-13 mRNA expression was assayed by semi-quantity reverse transcriptase-polymerase chain reaction (RT-PCR).In normal rat liver, a faint band for MMP-13 mRNA was observed by RT-PCR (0.24+/-0.41). The gene expression of MMP-13 was increased in the liver of the rats treated with ethanol for 4 weeks (0.62+/-0.54), but it was not considered statistically significant (P0.05). And the livers from 12-week-treated rats showed a marked mRNA expression (1.65+/-0.47, P0.01). Once fibrosis became prominent (24 weeks), a faint band of MMP-13 mRNA was observed (0.39+/-0.25).MMP-13 participates in the degradation of newly-formed matrix in the early phase of rat liver fibrosis induced by ethanol, and it was induced in a distinct time frame.

To evaluate the effect of tea polyphenol(TP) on the rat with alcoholic liver damage.Rats were divided into 3 groups, in which 2 groups were stomach perfused with alcohol to result in ALD, and 1 group of them stomach perfused with TP simultaneously. Another group was normal control groups (stomach perfused with drinking water). In the end of 12 weeks, the liver specimen of each rat was observed by anglicizing its tissue damage, and all data collected was performed by statistical analysis in quantum and semi-quantum. Meanwhile cytokines gene express of each group is determined.In the end of 12 weeks, alcoholic hepatitis appeared in rat liver. Hepatic injury in alcohol group and TP group were found, but could not be found in normal group. Compared with pure alcohol group, alcoholic liver damage mainly showing with steatosis in TP group were slight, in addition showing liver cellular swelling with small area, with less spot and focal necrosis, none bridging necrosis. Steatosis were slight relatively, mega-bubble steatosis were less found. Collagen deposition of TP group were less than those of pure alcohol group. Gene expression of. cytokine have diversity statistically such as IL-3, IL-4, IL-1R2, IL-6R, IL-7R2, IL-3Ra, IL-R1, IL-13, IL-1R1, IL-7R2, EPO-R, LIFR, IL-1R2, IL-5R2, CSF1, CD27, IL-6R.TP is able to attenuate alcoholic liver damage. It's mechanism is possibly due to modulating cytokines gene expression of cytokine.

Nonalcoholic fatty liver disease (NAFLDéis a common chronic liver disease in China, of which diabetic fatty liver (DFLéaccounts for a large proportion in clinic. DFL is a disease without specific clinical features and lacking of confirmatory laboratory tests, and the etiology of hepatic steatosis remains poorly understood. The aim of this paper was to explore the clinical characteristics and to determine associated risk factors in type 2 diabetes patients with fatty liver.A total of 166 patients, 53 in DFL group and 113 in NDFL (diabetes without fatty liverégroup participated in this study. Serum fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphate (AKP), gamma glutamyl transpeptidase (GGT), total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C)were measured in both groups. And these variables were analyzed by using Student's t test and logistic regression model.A progressive increase in the level of FBG, ALT, AST, AKP, GGT, TG (P0.05) and a decrease of HDL-C (P0.01) were observed from DFL group to NDFL group. And there was no statistical difference in the level of TC between the two groups.Dyslipidemia, dysglycemia and elevation of liver enzyme can be seen more frequently in the DFL patients than in the NDFL patients. The successive escalation of serum ALT and TG levels and the lower HDL-C level are the independent risk factors of DFL.

Endoscopic retrograde cholangiopancreatography (ERCP) is the most complex gastrointestinal procedure, which needs patients' cooperation. The aim of this study was to observe the quality and safety of sedation with propofol in patients undergoing therapeutic ERCP.Seventy patients who had undergone therapeutic ERCP were randomly divided into two groups. One group,given intravenously propofol,and the other sedated with routine method,served as the control. Blood pressure,heart rate, oxygen saturation were monitored and cardiorespiratory event was observed. Patient cooperation, performance, recovery time and amnesia served as variables postoperation.Blood pressure elevated in four patients in the propofol group, less than in the control group (P0.01). Seven patients showed decreased blood pressure after administration of propofol, but none in the control group (P0.01). Twelve patients in the control group showed mild or significant resistance, but none in the propofol group (P0.01). The time for performance in the propofol group (P0.05) was shorter than in the control group. Patient recovery was quicker in the propofol group than in the control group (P0.01). The degree of amnesia better in the propofol group than in the control group (P0.01). The degree of amnesia was also better in the propofol group than in the control group (P0.01).Propofol proves to be an excellent sedative for therapeutic ERCP. Being effective and safe, it shows a shorter ERCP duration but quick recovery and better amnesia. It is better than other routine sedatives.