[Evidence-based medicine on the relationship between Helicobacter pylori and gastroesophageal reflux disease].
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Biomedical subjects
Publications and source records attributed to Ji-yao Wang.
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OBJECTIVE: To evaluate the clinical value of serum fibrosis markers hyaluronic acid (HA), type IV collagen (CIV), type III procollagen N peptide (PIIIP) and laminin (LN) in the diagnosis of liver fibrosis. METHODS: Detection of the serum levels of these markers including HA, CIV, PIIIP, LN was carried out in 50 patients with chronic hepatitis B and 18 healthy persons. Liver biopsy was performed in all patients. The relationship between the markers and liver fibrosis stage was analyzed and the diagnostic value of the markers in liver fibrosis stage evaluated with receiver operating curve. RESULTS: The correlation between serum HA, CIV, PIIIP and histologically assessed grade of inflammatory activity was weak (r = 0.430, 0.382 and 0.300, respectively, P < 0.05). The correlation between serum HA, CIV and histologically assessed stage of liver fibrosis were moderate (r = 0.614, 0.708, respectively, P < 0.05). The increase in serum HA, CIV was correlated with the progression of liver fibrosis. Based on receiver operating curve, the value of using serum HA to differentiate patients with early cirrhosis (S4) from those without cirrhosis (S0-S3) was greater than that of serum CIV, PIIIP and LN (the areas under the curves = 0.967 vs 0.932, 0.659, 0.403), while the ability of serum CIV to predict liver fibrosis (S1-S4) was superior to that of serum HA, PIIIP and LN (areas under the curves = 0.853 vs 0.680, 0.536, 0.487). Serum LN was found to show limited changes in different pathologic grade and stage. The combined detection of HA and CIV has higher specificity than that of a single marker. CONCLUSIONS: Serum fibrosis markers can be helpful in diagnosis of liver fibrosis even in its early stage, but can not discriminate accurately the stage of fibrosis as accurately as the histological assessment. The combination of fibrosis markers is more valuable than single marker. New fibrosis markers and combination of noninvasive markers are the future trend in liver fibrosis research.
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OBJECTIVE: To evaluate the antifibrotic effect of receptor-mediated sterical stability liposome (SSL) targeting hepatic stellate cells (HSCs) and containing recombinant human interferon-alpha 1b (IFNalpha-1b) on hepatic cirrhosis. METHODS: The ligand, cyclo (RGD) with specific affinity to HSCs, was incorporated via PEG into the lipid bilayers of SSL. Forty male SD rats were randomly divided into 4 equal groups: liver fibrosis model group undergoing double ligation and cutting of the common bile duct (BDL group), BDL + IFN-SSL group, undergoing BDL and injection of IFN 50,000 IU per week via caudal vein for 4 times; IFN-RGD-SSL treatment group, undergoing BDL and injection of IFN-RGD-SSL (equal to 50,000 IU per week) via caudal vein for 4 times; and sham operation group used as control. The rats were killed 24 hours after the last injection. Their livers and serum samples were collected. Pathological changes of the liver were observed with HE and alpha-SMA immunohistochemical staining. Biochemical automatic analyzer was used to test the serum indices of liver function: ALT, AST, total bilirubin (TBIL), alkaline phosphatase, and gamma-glutamine (gamma-GT). Radioimmunoassay method was used to examine the s serum index of liver fibrosis: HA, procollagen III (PCIII), LN, and CIV. Colorimetry was used to examine the level of hydroxyl proline (Hyp). RT-PCR was used to detect the mRNA expression of type I collagen. Western blotting was used to examine the protein expression of alpha-SMA of HSC. RESULTS: Compared with the control group, liver fibrosis was seen in the other 3 groups, especially in the BDL group. In comparison with the sham operation group, the levels of serum indices of liver fibrosis, liver hydroxyl proline content, and expression of type I collagen mRNA and alpha-SMA protein in liver were significantly higher in the other groups (all P < 0.05), being significantly lower in the BDL + IFN-RGD-SSL group than in the BDL + IFN-SSL group (all P < 0.05). CONCLUSION: The receptor-mediated IFN-RGD-SSL displays good targeting antifibrotic effects on liver fibrosis.
OBJECTIVE: To investigate the binding characteristics between an artificial Arg-Gly-Asp (RGD)-containing cyclic peptide [cyclo(CGRGDSPK)] and rat hepatic stellate cells (HSC). METHODS: An artificial RGD-containing cyclic peptide was labeled with fluorescein isothiocyanate (FITC). HSCs were isolated by collagenase in situ liver recirculating and purified by density gradient centrifugation from normal rats. The cells were cultured for 5 days of primary culture (quiescent phenotype) or for 7 days of secondary culture (activated phenotype). To access the binding and uptake, HSCs were incubated with FITC-cRGD of different concentrations at 4 degree C or 37 degree C, and then the binding and uptake were investigated by flow cytometry. The location of FITC-cRGD in HSC was investigated by fluorescent microscopy. Kd and maximal binding sites per cell were calculated by radioligand binding assay (RBA) of receptors using 3H-cRGD. In the interim, FITC-cAGA was used as a peptide control devoid of any binding site. RESULTS: The binding between FITC-cRGD and HSC was saturable, time- and dose-dependent and could compete with overdosed unlabeled cRGD. The fluorescence was mainly distributed in cytoplasma, especially near the nuclei. Kd was 7.05 x 10(-9) mol/L and Bmax per cell was nearly 6.79 x 10(5). CONCLUSIONS: The results demonstrate that cRGD are specifically taken up by HSC through a receptor-mediated pathway. The information is useful for understanding the ligand-receptor interaction of HSC. FITC labeled cyclic RGD-peptides meet the standards of special ligands and FITC does not change the binding activation of cyclic RGD-peptides.
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OBJECTIVES: To investigate the role of glycyrrhizin on TGFbeta1 stimulated signaling transduction in rat hepatic stellate cells (HSCs). METHODS: The mice HSCs were isolated and cultured with or without glycyrrhizin (1 micromol/L-1000 micromol/L) in vitro after TGFbeta1 stimulation. The mRNA level of Smad2, 3, 7 were measured with RT-PCR; protein expression level of Smad2, 3, 7 and collagen I, III were analyzed with Western blot. RESULTS: TGFbeta1 increased the mRNA level and protein expression of Smad2, 3, 7 in HSC; it also increased protein expression of collagen I and III. 1 micromol/L-1000 micromol/L glycyrrhizin decreased the mRNA level and protein expression of Smad2, 3, 7; it also inhibited protein expression of collagen I and III gradually. CONCLUSION: Interventing the TGFbeta signaling pathway and decreasing the synthesis of collagen, might be involved in the anti-fibrosis mechanism of glycyrrhizin.
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OBJECTIVE: To study the effects of antisense transforming growth factor beta receptor-II (TGFbetaRII) expressing plasmid on experimental liver fibrosis. METHODS: RT-Nest-PCR and gene recombinant techniques were used to construct the rat antisense TGFbetaRII recombinant plasmid which can be expressed in eukaryotic cells. Thirty-six male SD rats were randomly distributed into five groups: 10 in experimental liver fibrosis model induced by pig-serum as disease control group; 10 in antisense TGFbetaRII transfection as treatment group; 10 in pCDNA3 transfection as treatment control group and 6 in normal control group. The recombinant plasmid and empty vector (pCDNA3) were encapsulated by glycosyl-poly-L-lysine and then transducted into rats of pig serum-induced liver fibrosis model respectively. Expression of exogenous transfected plasmid was assessed by Northern blot, RT-PCR and Western blot. We also tested ELISA of serum TGF-beta1, the contents of hepatic hydroxyproline, immunohistochemistry of type I and III collagen, and VG staining for pathological study. RESULTS: The antisense TGFbetaRII expressing plasmid could be well expressed in vivo, and could block the mRNA and protein expression of TGFbetaRII in the fibrotic liver induced by pig serum. Its expression also reduced the level of TGF-beta1 [antisense treatment group (23.16+/-3.13) ng/ml, disease control group (32.96+/-3.79) ng/ml; F=36.73, 0.01]. Compared with the disease control group, the contents of hepatic hydroxyproline [antisense treatment group (0.17+/-0.01) mg/g liver, disease control group (0.30+/-0.03) mg/g liver; F=15.48, 0.01] and the deposition of collagens type I and type III decreased in the antisense group (antisense treatment group collagen type I 650.26+/-51.51, collagen type III 661.58+/-55.28; disease control group type I 1209.44+/-116.60, collagen type III 1175.14+/-121.44; F values are 69.87, 70.46, 0.01). And its expression also improved the pathologic classification of liver fibrosis models (0.01). CONCLUSION: The results demonstrate that TGF-beta plays a key role in liver fibrogenesis and the prevention of liver fibrosis by antisense TGFbetaRII recombinant plasmid intervention may be therapeutically useful.
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OBJECTIVE: To evaluate the effectiveness and safety of mosapride on treatment of functional dyspepsia. METHODS: Randomized controlled clinical trial was conducted and patients suffered from functional dyspepsia were included. 5 mg mosapride was given three times daily for 4 weeks in the treatment group. 10 mg domperidone was given three times daily for 4 weeks as control. Changes on symptom score, gastric empty or new occurring events were included as outcomes. RESULTS: 231 patients suffered from functional dyspepsia were selected by inclusion and exclusion criteria from August 15 to Oct 22, 1999. Of these, 108 (46.8%) were males, versus 123 (53.2%) females and 118 (51.2%) in the treatment group and 113 (48.9%) as controls. 222 (96.1%) patients were followed up. Results showed that the total efficacy rates in early satiety and abdominal distension were 84.5% and 90.1% in mosapride after the 2 weeks of treatment. Mosapride seemed to be more effective in improving symptoms of belching and heartburn than that in controls (P < 0.05). In 4 weeks, the total efficacy in improving symptoms of abdominal distention and belching showed more effective in mosapride than that in controls (P < 0.05). Decrease of symptoms score was more in mosapride than that in controls (P < 0.05). Mosapride was less effective in controls in improving the gastric empty in terms of proportion (46.2% vs. 25.9%, P = 0.020) and range (46.2% vs. 24.0%, P = 0.003). Side effects would include diarrhea, constipation, headache, dizziness, insomnia, skin scare and the like. There was no significant difference between the two groups (9.6% in mosapride vs. 14.0% in controls). CONCLUSION: Mosapride was safe and effective in improving the symptoms and gastric empty of functional dyspepsia.
OBJECTIVE: To evaluate the cost-effectiveness of preventive treatment on diabetes, using metformin or acarbose among patients with impaired glucose tolerance. METHODS: Using data from diabetes prevention program (DPP) and STOP-NIDDM study, we evaluated the cost of preventing one new onset of diabetes in Shanghai, and to compare its cost with the current treatment cost. RESULTS: If metformin was used for preventive treatment as in DPP study, a total cost of 69 122.95RMB was needed for preventing one new onset of diabetes in three years period. If acarbose was used for preventive treatment as in STOP-NIDDM, then 154 116.05RMB was the cost to prevent one diabetes in 3.3 years of treatment. However, if the generic metformin was used, the total cost was only 21 666.63RMB for the 3-years treatment. Data showed that the average cost for treating diabetes per year was 9143.70RMB in Shanghai. CONCLUSION: The total cost of diabetes prevention was formidable, although generic metformin showed the trend of cost-effective. The cost of drugs took the biggest part of the total cost. To choose the cheap but effective drug for treatment might save a large part of the cost. Further clinical research concerning the prevention of complications might provide us with more information on the cost-effectiveness of preventive treatment on diabetes.
OBJECTIVE: To evaluate the efficacy and safety of oxymatrine in the treatment of chronic hepatitis B. METHODS: A multicenter randomized double-blind placebo-controlled trial was conducted. A total of 144 patients with chronic hepatitis B entered the study for 52 weeks; of them 72 received oxymatrine, and 72 received a placebo. Before and after the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reactions were observed. RESULTS: In 144 patients, 14 were dropped and excluded due to inconsistencies in the included standard. Therefore, the efficacy and safety of 130 patients were analyzed. After being treated for 52 weeks, 70.77% of the patients in the study group had a normal ALT level, and in 43.08% and 33.33% their HBV DNA and HBeAg became negative. In the placebo group, 39.68% had normal ALT level, and 12.31% and 3.33% had their HBV DNA and HBeAg become negative. The rates of complete response and partial response in the oxymatrine group were 23.08% and 58.46%, and in the placebo group they were 3.08% and 44.62%. They were significantly higher in the oxymatrine group than in the placebo group. In the oxymatrine treated patients, 12 weeks after its withdrawal, 60.00% had a normal ALT level, 41.54% and 23.33% had both HBV DNA and HBeAg negative. In the placebo group, 31.75% had a normal ALT level, 3.08% and 1.67% had both HBV DNA and HBeAg negative. The rates of complete response and partial response in the oxymatrine group were 21.54% and 47.69%, and in the placebo group they were 0 and 41.54%. They were significantly higher in the study group than in the placebo group. The adverse reaction rates of oxymatrine in the study and the placebo group were 7.69% and 6.15%, respectively, but there was no statistical significant difference between them. CONCLUSION: Oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.
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OBJECTIVE: To investigate the effects of glycyrrhizin on genes expression during the process of rat liver fibrosis. METHODS: Rat models of liver fibrosis were obtained by subcutaneous injections of CCl(4), another group were treated with both CCl(4) and glycyrrhizin. A control rat, a CCl(4) induced liver fibrosis rat and a glycyrrhizin treated rat were chosen to undergo cDNA microarray respectively. According to the results of cDNA microarray, a gene (smurf2) abnormally expressed in the liver fibrosis rat and expressed normally in the treated group was chosen to study its changes at different stages of experimental liver fibrosis by semi-quantitative RT-PCR. RESULTS: Many genes including smurf2, PTAFR, CYP2D6, FGG associated with inflammation and metabolism were identified increased expression in the CCl(4) treated group and normal expression in the glycyrrhizin group by cDNA microarray. Semi-quantitative RT-PCR showed after 1 week there were no differences of smurf2 gene expression levels among the three groups, after 2 weeks smurf2 gene expression levels decreased both in the CCl(4) group and glycyrrhizin group, after 4 weeks smurf2 gene expression levels increased in the CCl(4) group but decreased in glycyrrhizin group, after 8 weeks smurf2 gene expression levels decreased again in the CCl(4) group but increased to the normal level in the glycyrrhizin group. CONCLUSION: By cDNA microarray, we found the effects on the changes of smurf2 gene expression may contribute to the anti-fibrosis molecular mechanism of glycyrrhizin.
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