Deletion of the PPARδ gene exacerbates high-fat diet-induced nonalcoholic fatty liver disease in mice through the gut-liver axis.

Gut microbiota dysbiosis is an essential factor contributing to non-alcoholic fatty liver disease (NAFLD), in which the gut-liver axis plays a crucial role. Peroxisome proliferator-activated receptor δ (PPARδ) is considered a new direction for the research on NAFLD due to its positive regulation of glucose and lipid metabolism. Our experiment aimed to investigate the effect of PPARδ gene deletion on gut microbiota and NAFLD through the gut-liver axis. PPARδ-/- mice and wild-type mice were randomly divided into high-fat diet(HFD) groups and normal diet groups. In each group, six mice were sacrificed at weeks 4, 8, and 12. Metabolic indicators and inflammation indicators were measured, and the degree of liver steatosis and the ileum mucosa integrity were evaluated. Additionally, fecal samples were subjected to 16S rDNA gene sequencing and analysis of gut microbiota. Deletion of the PPARδ gene exhibited exacerbated effects on HFD-induced NAFLD and displayed more severe liver inflammation and intestinal mucosal barrier injuries. The HFD reduced the abundance of short-chain fatty acid (SCFA)-producing bacteria and increased the abundance of intestinal endotoxin-rich bacteria in mice. Deletion of the PPARδ gene exacerbated this trend, resulting in decreased abundances of norank_f__Eubacterium_coprostanoligenes_group and Alloprevotella and increased abundances of Acidibacter, unclassified_f__Comamonadaceae, unclassified_c__Alphaproteobacteria, unclassified_f__Beijerinckiaceae, unclassified_f__Caulobacteraceae, unclassified_c__Bacteroidia and Bosea. Spearman's correlation analysis found Lachnoclostridium, unclassified_f__Rhizobiaceae, Allobaculum, Acinetobacter, Romboutsia, norank_f__Muribaculaceae and Dubosiella showed some correlations with metabolic indicators, inflammation indicators, NAS and occludin. Deletion of the PPARδ gene exacerbated HFD-induced gut microbiota dysbiosis and affected NAFLD through the gut-liver axis.

Cyclin-Dependent Kinase Inhibitor p21WAF1/CIP1 Facilitates the Development of Cardiac Hypertrophy.

BACKGROUND/AIMS: Adult cardiomyocytes can re-enter cell cycle as stimulated by prohypertrophic factors although they withdraw from cell cycle soon after birth. p21WAF1/CIP1, a cyclin-dependent kinase inhibitor, has been implicated in cardiac hypertrophy, however, its precise contribution to this process remains largely unclear. METHODS: The gene expression profile in left ventricle (LV) of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was determined using quantitative PCR array and verified by real-time PCR and Western blotting. Hypertrophic response of H9c2 cells and neonatal rat ventricular myocytes (NRVM) were induced by angiotensin II (1 µmol/L). Cardiac hypertrophy of mice was elicited by isoproterenol (ISO) infusion (40 mg/kg per day for 14 days). p21-adenovirus and p21-siRNA were employed to transfect NRVM, and sterigmatocystin (STE, 3 mg/kg, ip, qd) was used to inhibit p21 activity. mRNA and protein expression levels of α- and ß-myosin heavy chain (MHC), p21WAF1/CIP1, calcineurin (CaN) and atrial natriuretic peptide (ANP) were assayed by realtime PCR and WB, respectively. RESULTS: Sixteen genes showed two-fold or greater changes between SHR and WKY rats, in which the expression of p21WAF1/CIP1 was upregulated by 4.15-fold (P=0.002) and reversed by losartan. Surface area, protein content, mRNA and protein expressions of ß-MHC, ANP and p21WAF1/CIP1 in H9c2 cells treated with AngII elevated significantly compared with control group. p21-Ad transfection markedly increased the surface area and ß-MHC mRNA expression of normal NRVMs, and p21-siRNA transfection decreased them in AngII-treated NRVMs. STE treatment decreased HW/BW and cross-sectional area, expression levels of ß-MHC, ANP and p21 significantly in ISO-treated mice. CONCLUSION: Our findings suggest that p21 facilitates the development of cardiac hypertrophy, and regulating the expression of p21 may be an approach to attenuate hypertrophic growth of cardiomyocytes.

[Expression of CXCR7 in Gastric Cancer Cells and Its Effect on the Migration and Invasion of SGC-7901 Cells].

OBJECTIVES: To determine the expression of chemokine (C-X-C motif) receptor 7 (CXCR7) in five gastric cancer cell lines with various degrees of differentiation, and the effect of silencing CXCR7 on the migration and invasion of SGC-7901 cells. METHODS: The expression of CXCR7 in gastric cell lines (HGC-27, MGC-803, SGC-7901, BGC-823 and MKN-28) was detected by Western bolt and RT-PCR. The SGC-7901 cells were transfected with liposome of CXCR7 siRNA to silence CXCR7 gene, and then treated with stromal-derived factor-1 (SDF-1)-the ligand of CXCR7. Transwell assay was used for determining the migratory and invasive ability of SGC-7901 cells in the four groups: NC siRNA, NC siRNA+SDF-1, CXCR7 siRNA and CXCR7 siRNA+SDF-1. RESULTS: CXCR7 was expressed in the five gastric cancer cell lines, with the highest intensity in SGC-7901. The migrated and invasive cells increased in the NC siRNA+SDF-1 group and reduced in the CXCR7-siRNA group compared with the NC siRNA group (P<0.05). The CXCR7-siRNA+SDF-1 group had less migrated and invasive cells than the NC siRNA+SDF-1 group (P<0.05). CONCLUSIONS: CXCR7 is highly expressed in SGC-7901. SDF-1 promotes the migratory and invasive capability of SGC-7901 cells, but such an effect can be inhibited by silencing it with CXCR7siRNA.

Absorption and Fluorescence Properties of Chromophoric Dissolved Organic Matter Produced by Algae.

Four kinds of diatom (Chaetoceros curvisetus, Phaeodactylum tricornutum, Nitzschia closterium f. minutissima and Navicula halophile) and two kinds of dinoflagellates (Prorocentrum donghaiense and Gymnodinium) were cultured under laboratory conditions. Variations of optical properties of chromophoric dissolved organic matter (CDOM) were studied with absorption and fluorescence excitation-emission matrix spectroscopy(EEM) during growth of marine microalgae in incubation experiment. Absorption spectrum revealed absorption coefficient a(355) (CDOM absorption coefficients at 355 nm) of 6 kinds of marine microalgae above increased by 64.8%, 242.3%, 535.1%, 903.2%, 836% and 196.4%, respectively. Simultaneously, the absorption spectral slope (Sg), determined between 270 and 350 nm, representing the size of molecular weight of CDOM and humic-like composition, decreased by 8.7%, 34.6%, 39.4%, 53.1%, 46.7%, and 35.7%, respectively. Applying parallel factor analysis (PARAFAC) together with EEM got four components of CDOM: C1(Ex/Em=350(260) nm/450 nm), C2 (Ex/Em=260(430) nm/525 nm), C3 (Ex/Em=325 nm/400 nm) and C4(Ex/Em=275 nm/325 nm), which were relative to three humic-like and one protein-like fluorescent components of Nitzschia closterium f. minutissima and Navicula halophile. In incubation experiment, fluorescence intensity of these four components during growth of Nitzschia closterium f. minutissima increased by, respectively, 8.68, 24.9, 7.19 and 39.8 times, and those of Navicula halophile increased by 2.64, 0.07, 4.39 and 12.4 times, respectively. Significant relationships were found between the fluorescence intensity of four components of CDOM, a(355) and Sg. All results demonstrated that both content and molecular weight of CDOM produced by diatom and dinoflagellate studied in incubation experiment increased, but these two parameters changed more obviously of the diatom than those of dinoflagellate; the proportion of humic-like components in the composition of CDOM also increased clearly with the growth of marine microalgae, but protein-like fluorescent component had only a slow growth. Furthermore, the absorption spectrum of CDOM produced by different species of algae changed obviously and the relative composition fluorescence intensity of CDOM produced by different microalgae were found to vary among different composition from EEM, which suggested CDOM produced by different microalgae make quite different contributions to CDOM in natural seawater.

Gene-gene interaction of BLK, TNFSF4, TRAF1, TNFAIP3, and REL in systemic lupus erythematosus.

OBJECTIVE: Although the number of convincingly established genetic associations with systemic lupus erythematosus (SLE) has increased sharply over the last few years, refinement of these associations is required, and their potential roles in gene-gene interactions need to be further investigated. Recent genome-wide association studies (GWAS) in SLE have produced renewed interest in B cell/T cell responses and the NF-κB signaling pathway. The aim of this study was to search for possible gene-gene interactions based on identified single-nucleotide polymorphisms (SNPs), in using an approach based on the role of signaling pathways. METHODS: The SNPs in BLK, TNFSF4, TRAF1, TNFAIP3, and REL were replicated in order to evaluate genetic associations with SLE. TaqMan genotyping was conducted in 804 Chinese patients with SLE and 722 matched control subjects. A multiple logistic regression model was used to estimate the multiplicative interaction effect of the SNPs, and additive interactions were analyzed by 2×2 factorial designs. Data from a previously published GWAS conducted by the International Consortium on the Genetics of Systemic Lupus Erythematosus were derived for comparison and validation. RESULTS: Single-marker analysis validated the association of BLK rs2736340 (P=4.25×10(-6)) as well as TNFSF4 rs2205960 (P=2.82×10(-5)) and TNFAIP3 rs5029939 (P=1.92×10(-3)) with SLE susceptibility in Chinese. Multiplicative interaction analysis indicated that BLK had an interactive effect with TNFSF4 in Chinese patients with SLE (P=6.57×10(-4)). Additive interaction analysis revealed interactions between TRAF1 and TNFAIP3 in both Chinese (P=2.18×10(-3)) and Caucasians (P=2.86×10(-4)). In addition, multiple tendencies toward interactions were observed, and an additive effect was observed as the number of risk genotypes increased. CONCLUSION: The results of this study provide evidence of the possible gene-gene interactions of BLK, TNFSF4, TRAF1, TNFAIP3, and REL in SLE, which may represent a synergic effect of T cells and B cells through the NF-κB pathway in determining immunologic aberration.

Epidemiology of eight common rheumatic diseases in China: a large-scale cross-sectional survey in Beijing.

OBJECTIVE: To investigate the prevalence of eight common rheumatic diseases in a large Chinese population. METHODS: A population-based epidemiological investigation of the prevalence of eight common rheumatic diseases in a suburb of Beijing was conducted in 14 642 individuals. A community-based survey was carried out using a screening questionnaire. Positive responders were included in a clinical and laboratory examination. Diagnosis was based on the criteria of ACR or those used widely in literature. RESULTS: A total of 10 556 inhabitants were interviewed. Forty-three cases of RA were identified with an age-adjusted prevalence of 0.28% (95% CI 0.19%, 0.41%). Gout was diagnosed with a crude prevalence of 0.09% (95% CI 0.05%, 0.17%). Psoriasis was reported in 28 individuals with a prevalence of 0.27% (95% CI 0.18%, 0.38%). This included two cases diagnosed with PsA, resulting in a prevalence of 7.14% (95% CI 0.88%, 23.5%) in psoriasis patients and 0.02% (95% CI 0%, 0.07%) in the general population. Three individuals were identified with SLE, with a prevalence of 0.03% (95% CI 0%, 0.06%). One individual was identified with SSc and the calculated prevalence was 0.01% (95% CI 0%, 0.05%). One case of Behçet's disease was identified, giving a prevalence of 0.01% (95% CI 0%, 0.05%). CONCLUSION: This large-scale epidemiological survey provides an estimate of the burden of rheumatic diseases in China.

[Effects of pretreatment of lipid, midazolam and propofol on ropivacaine-induced convulsion and LD50 in rats].

OBJECTIVE: To assess the effects of lipid on ropivacaine-induced convulsion and LD50 in rats and compare with those of the traditional anticonvulsants midazolam and propofol. METHODS: Protocol 1: A total of 120 SD rats (60 males, 60 females), weighing 200-300 g, were randomly assigned into 4 groups with equal males and females: lipid (L), midazolam (M) and propofol (P) and control (C). Rats were pretreated with 10 ml/kg lipid intravenously in group L, saline and 0.23 mg/kg midazolam (10 ml/kg in volume) sequentially in group M, saline and 4 mg/kg propofol (10 ml/kg in volume) in group P and saline 10 ml/kg in group C. Then ropivacaine 44 mg/kg (0.75%) was injected intraperitoneally into each rat. The convulsion rate in each group and the time of convulsion after ropivacaine injection were observed. Meanwhile, the plasma concentration of ropivacaine at the time of convulsion was measured. Protocol 2: Additional 100 male SD rats were used for the measurements of ropivacaine LD50 with different pretreatments including lipid, midazolam, propofol and saline through the up-and-down method. Rats were randomly assigned into 4 groups similarly as protocol 1. The doses of ropivacaine in each group were determined according to our pilot study and 6 dosage levels with the same interval ratio 8.5 was applied in each group. The doses of these pretreatment drugs and administration methods were similarly as protocol 1. RESULTS: The convulsion rate after 44 mg/kg ropivacaine ip injection was 43.3% in group C, 0% in group M, 13.3% in group P and 70% in group L. Lipid increased the convulsion rate significantly. The plasma concentration of ropivacaine at the time of convulsion was 1.65 ± 0.30 µg/kg in group C, 1.73 ± 0.14 µg/kg in group P and 3.45 ± 0.26 µg/kg in group L. The LD50 of ropivacaine in group C was 64.39 mg/kg, 88.40 mg/kg in group M and 90.20 mg/kg in group P and 55.45 mg/kg in group L. CONCLUSIONS: Midazolam and propofol not only decrease the convulsion rate of ropivacaine, but also increase its LD50. Lipid not only increases the convulsion rate of ropivacaine, but also decreases its LD50. The application of lipid for the prevention of local anesthetic toxicity has potential risks.

[Changes in the intestinal microenvironment during development of alcoholic fatty liver disease and related effects of probiotic therapy].

OBJECTIVE: To investigate the initial changes in the gut microenvironment that accompany intestinal endotoxemia related to alcoholic fatty liver disease (ALD) in order to explore the potential initiating factors and to observe the effect of probiotic therapy on these factors. METHODS: Fifty Sprague-Dawley male rats were randomly divided into an ALD model group (alcoholic intragastric administration), an intervention group (ALD with probiotic intragastric administration), and a control group (physiological saline intragastric administration). Histological changes of the liver were evaluated using hematoxylin-eosin staining and light microscopy. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and triglycerides (TG), and plasma endotoxin and coli bacillus were determined. The structural integrity of intestinal mucosa and tight junctions were observed by transmission electron microscopy. Occludin protein expression in intestinal epithelial cells was detected by immunohistochemistry. RESULTS: After four weeks, the three groups showed significant differences in the plasma endotoxin levels [control: (0.67+/-0.14) pg/ml, model: (4.42+/-1.28) pg/ml, and intervention: (2.88+/-0.83) pg/ml; F = 27.288, P = 0.000] and numbers of Escherichia coli [control: (2.31+/-0.39) lg3/ml, model: (3.23+/-0.41) lg3/ml, and intervention: (2.24+/-0.44) lg3/ml; F = 10.692, P = 0.001]. The plasma endotoxin level and E. coli number were significantly higher in the model group than in the control group and the intervention group (all P less than 0.05). The three groups showed no significant differences in the levels of ALT, AST, and TG at four weeks. After eight weeks, however, all three serum markers were significantly different between the three groups [ALT: control: (62.33+/-7.12) U/L, model: (95.50+/-8.73) U/L, and intervention: (81.33+/-6.19) U/L; F = 18.051, P = 0.000]; [AST: control: (90.50+/-10.67) U/L, model: (130.00+/-14.91) U/L, and intervention: (110.33+/-7.26) U/L; F = 30.170, P = 0.000]; [TG: control: (0.84+/-0.84) mmol/L, model: (1.40+/-0.17) mmol/L, and intervention: (1.10+/-0.17) mmol/L; F = 10.592, P = 0.001]. In addition, the three groups showed significant differences in E. coli number [control: (2.23+/-0.46) lg3/ml, model: (4.81+/-0.29) lg3/ml, and intervention: (3.61+/-0.50) lg3/ml; F = 23.579, P = 0.000] and plasma endotoxin level [control: (0.52+/-0.21) pg/ml, model: (12.46+/-2.61) pg/ml, intervention: (6.83+/-1.74) pg/ml; F = 30.731, P = 0.000]. The levels of ALT, AST, TG and endotoxin, and the number of E. coli were all significantly higher in the model group than in the control group and the intervention group (all P less than 0.05). Small intestinal epithelial cell structural failure was more apparent and intercellular gaps more broad after eight weeks than after four weeks for all three groups. However, the intervention group showed clearer cell connection structures and less extensive cell gap broadening than the model group at eight weeks. After eight weeks, the occludin protein had become significantly down-regulated and distributed in a non-continuous pattern in the model group, as compared with the control group. However, the occludin protein expression was higher in intervention group than in the model group. CONCLUSION: Intestinal endotoxemia related to perturbations in the microenvironment occurs in the early phase of ALD, and the increased intestinal permeability appears to be the initial factor of elevated plasma endotoxin, which may lead to liver damage. Probiotic therapy can reduced plasma endotoxin levels and postpone ALD progression by altering the composition of the gut microbiota and up-regulating expression of the occludin protein in intestinal epithelial cells.

Prediction model using readily available clinical data for colorectal cancer in a chinese population.

BACKGROUND: In China, health screening has become common, although colonoscopy is not always available or acceptable. We sought to develop a prediction model of colorectal cancer (CRC) for health screening population based on readily available clinical data to reduce labor and economic costs. METHODS: We conducted a cross-sectional study based on a health screening population in Karamay Central Hospital. By collecting clinical data and basic information from participants, we identified independent risk factors and established a prediction model of CRC. Internal and external validation, calibration plot, and decision curve analysis were employed to test discriminating ability, calibration ability, and clinical practicability. RESULTS: Independent risk factors of CRC, which were readily available in primary public health institutions, included high-density lipoprotein cholesterol, male sex, total cholesterol, advanced age, and hemoglobin. These factors were successfully incorporated into the prediction model (AUC 0.740, 95% CI 0.713-0.767). The model demonstrated a high degree of discrimination and calibration, in addition to a high degree of clinical practicability in high-risk people. CONCLUSIONS: The prediction model exhibits good discrimination and calibration and is pragmatic for CRC screening in rural areas and primary public health institutions.

Genetic association of PRDM1-ATG5 intergenic region and autophagy with systemic lupus erythematosus in a Chinese population.

OBJECTIVE: Recent genome-wide association studies suggested the PRDM1-ATG5 gene region as a systemic lupus erythematosus (SLE)-associated locus both in Caucasian and Chinese populations; however, the candidate gene was still obscure and the possible functional significance needed to be determined. METHODS: In this study, by a multistage integrative strategy, the authors first performed a case-control association study involving 1745 individuals in the Chinese population by genotyping nine single nucleotide polymorphisms within this region, and a meta-analysis was conducted. Correlation between associated genotypes and expression levels of messenger RNA in B-cell lines from 210 unrelated HapMap data was examined, and was validated in vitro. To determine the biological significance, a genetic association study was also checked in a pathway-based manner and the significant associations were validated in a second 844 Chinese cohort. RESULTS: A peak of association was found in the intergenic region (p=0.036-3.26×10(-4)). Meta-analysis consolidated the association between rs548234 and SLE (OR 1.254, p=1.28×10(-16)). Significant positive correlations with ATG5 expression were identified, suggesting ATG5 as a candidate gene in the region. Epstein-Barr virus B-cell-based downstream gene expression analysis supported a functional effect of rs548234 and rs6937876, and in-vitro experiments confirmed the regulatory effect of rs6937876 in B-cell populations. Finally, an autophagy pathway-based genetic association study identified ATG7 (p=1.12×10(-4)) and IRGM (p=0.015) as novel candidate genes, and gene-gene interactions were observed between ATG5, ATG7 and IRGM. CONCLUSION: These data may demonstrate that autophagy is involved in the pathogenesis of SLE and imply a common biological pathway in autoimmunity.

Appropriate body mass index cutoffs for type 2 diabetes in Xinjiang population: defining the influence of liver aminotransferase.

BACKGROUND/PURPOSE: Recent study suggested that type 2 diabetes (T2DM) attributed to body mass index (BMI) could be influenced by liver aminotransferase. We aim to ascertain the cut-off point of BMI associated with T2DM and the influence of both elevated aminotransferase (AST) and alanine aminotransferase (ALT). MATERIALS AND METHODS: In our retrospective cohort study, T2DM was diagnosed when FBS ≥ 7.0 mmol/L, BMI of participants with baseline fasting (FBS) < 7.0 mmol/L was divided by percentiles and by aminotransferanse (ALT and AST ≥ 20 U/L, ALT or AST < 20 U/L). Hazard ratios and the turning point of BMI of high T2DM risk was estimated in totality and different aminotransferanse groups. RESULTS: During an average follow-up time of 3.71 years of 33346 participants, 1486 developed T2DM, and the average baseline BMI of participants who developed T2DM was 26.22 kg/m2. Cumulative incidence of T2DM was more than 5% when ALT and AST ≥ 20U/L, age over 44, male sex or BMI over 25.39 kg/m2; The risk of T2DM incidence increased as the BMI grow. The turning point of BMI at high risk of T2DM was 25.0 kg/m2 in totality, 25.1 kg/m2 when ALT or AST < 20 U/L and 26.1 kg/m2 when ALT and AST ≥ 20U/L. CONCLUSIONS: BMI of 25.0 kg/m2 was the cutoff point for T2DM development, and there is greater association between BMI and T2DM when ALT or AST < 20 U/L.

[Light energy utilization and distribution characteristics of flag leaf 13C assimilate in different spike-type wheat varieties and their responses to supplementary irrigation]. / ä¸åŒç©—åž‹å°éº¦å ‰èƒ½åˆ©ç”¨å’Œæ——å¶13CåŒåŒ–ç‰©åˆ†é ç‰¹æ€§åŠå¯¹è¡¥çŒæ°´å¹³çš„å“åº”.

To clarify the differences in light energy utilization and distribution characteristics of flag leaf 13C assimilate in different spike-type wheat varieties and their responses to supplementary irrigation, we set three water treatments in a field experiment, including no irrigation during growth duration of wheat (W0), water-saving irrigation (W1, irrigating at jointing and anthesis of wheat to keep the relative moisture of 0-40 cm soil to 65% and 70%), full irrigation (W2, irrigating at jointing and anthesis of wheat to keep the relative moisture of 0-40 cm soil to 85% and 90%) with the medium-spike wheat cultivars Jimai 22 and Qingnong 2, large-spike wheat cultivars Shannong 23 and Shannong 30 as test materials. The effects of different water treatments on canopy light energy utilization and 13C assimilate distribution characteristics of two spike-type wheat varieties were examined. The results showed that leaf area index, canopy light interception rate, and light energy utilization rate of the two varieties at 2, 11, 20 and 31 days after anthesis were significantly higher than W0 treatment, but there was no significant change in each index when the irrigation increased to W2 treatment. The distribution of flag leaf 13C assimilates of Jimai 22 and Shannong 23 of W1 in grain was 159.34 and 171.1 g·hm-2 higher than W0, respectively, and the distribution ratio was 6.5% and 6.5%, with no significant difference compared with W2. The grain yields of both varieties under W1 were significantly higher than that under W0, but with no significant difference with W2. Under water-saving irrigation, the medium-spike cultivars had higher canopy photosynthetically active radiation interception and utilization ability at 2 and 11 days after anthesis and large-spike cultivars at 20 and 31 days after anthesis. The distribution amount and ratio of 13C assimilates in the grain of medium-spike variety Jimai 22 flag leaf were 6.8% and 2.7% lower than that of the large-spike variety Shannong 23.

Diagnostic value of gamma-glutamyltransferase/aspartate aminotransferase ratio, protein induced by vitamin K absence or antagonist II, and alpha-fetoprotein in hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Researchers have investigated the diagnostic value of protein induced by vitamin K absence or antagonist II (PIVKA-II) and alpha-fetoprotein (AFP) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), and obtained abundant clinical diagnostic data. However, PIVKA-II and AFP have unsatisfactory specificity and sensitivity in the diagnosis of early-stage HBV-related HCC. Gamma-glutamyltransferase (γ-GT) and aspartate aminotransferase (AST) are common biomarkers for evaluating liver function, and we hypothesized that the γ-GT/AST ratio in combination with PIVKA-II and AFP would improve the diagnosis of early-stage HBV-related HCC. AIM: To evaluate the diagnostic value of γ-GT/AST ratio alone or in combination with PIVKA-II and AFP in HBV-related HCC. METHODS: Serum levels of γ-GT, AST, PIVKA-II, and AFP were detected and analysed in 176 patients with HBV-related HCC and in 359 patients with chronic hepatitis B. According to tumour size and serum level of HBV DNA, HBV-related HCC patients were divided into the following categories: Early-stage HCC patients, HCC patients, HBV DNA positive (HBV DNA+) HCC patients, and HBV DNA negative (HBV DNA-) HCC patients. Receiver-operating characteristic (ROC) curves were used to analyse and compare the diagnostic value of the single and combined detection of various biomarkers in different types of HBV-related HCC. RESULTS: Tumour size was positively correlated with serum levels of PIVKA-II and AFP in HCC patients (r = 0.529, a P < 0.001 and r = 0.270, b P < 0.001, respectively), but there was no correlation between tumour size and the γ-GT/AST ratio (r = 0.073, P = 0.336). The areas under the receiver-operating characteristic curves (AUROCs) of the γ-GT/AST ratio in early-stage HCC patients, HBV DNA+ HCC patients and HBV DNA- HCC patients were not significantly different from that in the total HCC patients (0.754, 0.802, and 0.705 vs 0.779, respectively; P > 0.05). When PIVKA-II was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, and HBV DNA+ HCC, the AUROCs of PIVKA-II increased, with values of 0.857 vs 0.835, 0.925 vs 0.913, and 0.958 vs 0.954, respectively. When AFP was combined with the γ-GT/AST ratio in the diagnosis of early-stage HCC, HCC, HBV DNA+ HCC, and HBV DNA- HCC, the AUROCs of AFP increased, with values of 0.757 vs 0.621, 0.837 vs 0.744, 0.868 vs 0.757, and 0.840 vs 0.828, respectively. CONCLUSION: The γ-GT/AST ratio may be better than PIVKA-II and AFP in the diagnosis of early-stage HBV-related HCC, and its combination with PIVKA-II and AFP can improve the diagnostic value for HBV-related HCC.

Decreased expression of serotonin in the jejunum and increased numbers of mast cells in the terminal ileum in patients with irritable bowel syndrome.

AIM: To investigate if there are changes in serotonin (5-HT) levels, enterochromaffin (EC) cells and mast cells in small intestinal mucosa of patients with irritable bowel syndrome (IBS). METHODS: Diarrhea-predominant (IBS-D, n = 20), or constipation-predominant (IBS-C, n = 18) IBS patients and healthy controls (n = 20) underwent colonoscopy and peroral small intestinal endoscopy, and mucosal samples were obtained at the descending part of the duodenum, proximal end of jejunum and terminal ileum. High-performance liquid chromatography-electrochemistry and immunohistochemical methods were used to detect 5-HT content, EC cells and mast cells. RESULTS: (1) There were no differences in the number and distribution of EC cells between IBS patients and the normal group. (2) The mucosal 5-HT contents at the duodenum, jejunum and ileum in IBS-C patients were 182 +/- 90, 122 +/- 54, 61 +/- 35 ng/mg protein, respectively, which were all lower than those in the normal group (256 +/- 84, 188 +/- 91, and 93 +/- 45 ng/mg protein, respectively), with a significant difference at the jejunum (P < 0.05). There were no differences in the small intestinal mucosal 5-HT contents between IBS-D patients and the normal group. The mucosal 5-HT contents at the duodenum were significantly higher than those at the ileum in the three groups (P < 0.001). (3) The numbers of mast cells in patients with IBS-C and IBS-D at the ileum were 38.7 +/- 9.4 and 35.8 +/- 5.5/high power field (hpf), respectively, which were significantly more than that in the normal group (29.8 +/- 4.4/hpf) (P < 0.001). There was no significant difference in the numbers of mast cells at the other two parts between IBS patients and the normal group. The numbers of mast cells in IBS-C, IBS-D, and normal groups were all significantly higher at the ileum (38.7 +/- 9.4, 35.8 +/- 5.5, 29.8 +/- 4.4/hpf, respectively) than at the duodenum (19.6 +/- 4.7, 18.5 +/- 6.3, 19.2 +/- 3.3/hpf, respectively, P < 0.001). CONCLUSION: The changes in the 5-HT signaling pathway at the jejunum of IBS-C patients and the increase in mast cells in patients with IBS at the terminal ileum may offer evidence to explain the pathogenesis of IBS.

[Synthesis and DNA binding spectroscopic studies of Cu(II)-HAsp-Im complexes].

Two novel complexes of [Cu(HAsp)ImH2O]SO4 x 4 H2O and [Cu(Asp)Im(OH)] x 4 H2O (HAsp = Aspartic acid molecule, Asp = Aspartic acid ion, Im = Imidazole) were synthesized and characterized by elemental analysis, IR spectroscopy and TG-DTA. The interactions of the complexes with sperm DNA were studied by electronic absorption and fluorescence spectra. Results showed that the reactions of the two complexes with DNA are obviously different: for [Cu(HAsp)ImH2O]SO4 x 4 H2O, it is intercalation companied by electrostatic effect, while [Cu(Asp)Im(OH)] x 4 H2O mainly cooperates with the nitrogen atom of the DNA base pair, which induces the breakage of DNA double helix. The reasons for these differences in their DNA binding modes were also discussed.

Expression of TGF-ß1/mTOR signaling pathway in pathological scar fibroblasts.

The aim of the present study was to detect the expression of the key molecules, including transforming growth factor­ß1 (TGF-ß1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) of TGF­ß1/mammalian target of rapamycin (mTOR) pathway in pathological scar fibroblasts. Immunofluorescence, reverse transcription­polymerase chain reaction (RT­PCR) and western blot analysis were used to detect the expression of the key molecules TGF­ß1, PI3K, Akt, mTOR in fibroblasts of normal skin tissue and pathological scar tissue. Immunofluorescence showed that the expression of TGF­ß1, PI3K and Akt was significantly enhanced (P<0.05) in pathological scar fibroblasts, and mainly expressed in the cell nucleus, but not in normal skin tissue or fibroblasts. RT­PCR and western blot test results revealed that the TGF­ß1, PI3K, Akt, and mTOR mRNA and protein expression in pathological scar fibroblasts were significantly higher (P<0.05) than in the normal skin tissue. Expression of the TGF­ß1/mTOR signaling pathway in pathological scar fibroblasts was significantly increased. Data suggest that this expression may be an important mechanism for pathological scar formation.

A giant and extensive solitary Peutz-Jeghers-type polyp in the antrum of stomach: Case report.

RATIONALE: A solitary Peutz-Jeghers-type polyp is a hamartomatous polyp which without either mucocutaneous pigmentation or a family history of Peutz-Jeghers syndrome (PJS). It can occur in all of the gastrointestinal tract, but it is extremely rare in the stomach. PATIENT CONCERNS: A 53-year-old man was admitted to the local hospital with left upper abdominal pain lasting 2 weeks. A gastroscopy showed a giant and extensive bulging lesion on the greater curvature and posterior and anterior walls of the gastric antrum, involving three-quarters of the gastric wall. Endoscopic ultrasonography showed a muscularis mucosa lesion. DIAGNOSES: A solitary Peutz-Jeghers-type polyp in the antrum of stomach. INTERVENTIONS: The patient underwent an endoscopic submucosal dissection (ESD). OUTCOMES: The patient recovered quickly, without any complications. LESSONS: This is the second largest gastric solitary Peutz-Jeghers-polyp reported until now, and the largest gastric solitary Peutz-Jeghers type-polyp treated by endoscope.

Triptolide Upregulates Myocardial Forkhead Helix Transcription Factor p3 Expression and Attenuates Cardiac Hypertrophy.

The forkhead/winged helix transcription factor (Fox) p3 can regulate the expression of various genes, and it has been reported that the transfer of Foxp3-positive T cells could ameliorate cardiac hypertrophy and fibrosis. Triptolide (TP) can elevate the expression of Foxp3, but its effects on cardiac hypertrophy remain unclear. In the present study, neonatal rat ventricular myocytes (NRVM) were isolated and stimulated with angiotensin II (1 µmol/L) to induce hypertrophic response. The expression of Foxp3 in NRVM was observed by using immunofluorescence assay. Fifty mice were randomly divided into five groups and received vehicle (control), isoproterenol (Iso, 5 mg/kg, s.c.), one of three doses of TP (10, 30, or 90 µg/kg, i.p.) for 14 days, respectively. The pathological morphology changes were observed after Hematoxylin and eosin, lectin and Masson's trichrome staining. The levels of serum brain natriuretic peptide (BNP) and troponin I were determined by enzyme-linked immunosorbent assay and chemiluminescence, respectively. The mRNA and protein expressions of α- myosin heavy chain (MHC), ß-MHC and Foxp3 were determined using real-time PCR and immunohistochemistry, respectively. It was shown that TP (1, 3, 10 µg/L) treatment significantly decreased cell size, mRNA and protein expression of ß-MHC, and upregulated Foxp3 expression in NRVM. TP also decreased heart weight index, left ventricular weight index and, improved myocardial injury and fibrosis; and decreased the cross-scetional area of the myocardium, serum cardiac troponin and BNP. Additionally, TP markedly reduced the mRNA and protein expression of myocardial ß-MHC and elevated the mRNA and protein expression of α-MHC and Foxp3 in a dose-dependent manner. In conclusion, TP can effectively ameliorate myocardial damage and inhibit cardiac hypertrophy, which is at least partly related to the elevation of Foxp3 expression in cardiomyocytes.

Oxidative degradation of diethyl phthalate by photochemically-enhanced Fenton reaction.

A kinetic investigation into the photo-degradation of aqueous diethyl phthalate by Fenton reagent was conducted in this study. The obtained results showed the enhancement of diethyl phthalate (DEP) decomposition by UV irradiation with the Fenton reaction. It was found that H2O2 concentration, Fe2+ concentration, and aqueous pH value were the three main factors that could significantly influence the degradation rates of DEP. The highest degradation percentage (75.8%) of DEP was observed within 120 min at pH 3 in the UV/H2O2/Fe2+ system, with original H2O2 and Fe2+ concentrations of 5.00 x 10(-4) and 1.67 x 10(-4)mol L(-1), respectively. The present study provides an effective approach to the treatment of wastewater containing DEP.

Distributions and sources of volatile chlorocarbons and bromocarbons in the Yellow Sea and East China Sea.

Six volatile halogenated organic compounds (VHOC), namely, chloroform, carbon tetrachloride, trichloroethylene, bromodichloromethane, dibromochloromethane, and bromoform, were studied in the Yellow Sea and East China Sea from April to May, 2009. The spatial variability of these VHOC was influenced by various factors, including anthropogenic inputs, biogenic production and complicated hydrographic features such as Changjiang Diluted Water, Yellow Sea Cold Water Mass, and Kuroshio Current. Diurnal study results showed that factors such as solar irradiation, biological activity, and tide affected the abundance of these VHOC. Correlation analyses revealed that bromodichloromethane was positively correlated with chlorophyll a in surface seawater. Principal component analysis suggested that chlorinated compounds like carbon tetrachloride originated from anthropogenic sources whereas brominated compounds such as bromodichloromethane originated from biogenic sources. Sources of other chlorinated and brominated compounds may not be governed by biological processes in the marine environment.