OBJECTIVE: To clarify the molecular signaling mechanism underlying the inhibitory effect of metformin on transforming growth factor-β1 (TGF-β1)-stimulated collagen I production in rat biliary fibroblasts. METHODS: Primary biliary fibroblasts were isolated under aseptic condition from 50 Sprague-Dawley rats (half male and half female), and microscopic observation identified no obvious difference in the morphology or viability of the cells from rats with different sexes or body weight. The cells were treated with TGF-β1 (10 ng/mL), Smad3 siRNA+TGF-β1, CTGF siRNA+TGF-β1, metformin (10 mmol/L)+ TGF-β1, or Compound C (10 μmol/L)+metformin+TGF-β1. The expressions of CTGF and collagen I in the treated cells were determined using ELISA kit or Western blotting; the phorsphorylated and total Smad3 and AMPK expressions were detected using immunoblotting. RESULTS: TGF-β1 time- and dose-dependently induced collagen I production in rat biliary fibroblasts. The activated AMPK by metformin dose-dependently inhibited TGF-β1-induced collagen I production. Pre-incubation of cells with the AMPK inhibitor Compound C restored the inhibitory effect of AMPK on TGF-β1-induced collagen I secretion ( < 0.01). Activation of AMPK by metformin significantly reduced TGF-β1-induced collagen I production by suppressing Smad3-driven CTGF expression ( < 0.01), and the application of Compound C reversed such changes in the fibroblasts ( < 0.01). CONCLUSIONS Metformin inhibits TGF-β1-stimulated collagen I production by activating AMPK and inhibiting Smad3- driven CTGF expression in rat biliary fibroblasts.
Animals ; Cells, Cultured ; Collagen ; Female ; Fibroblasts ; Male ; Metformin ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Smad3 Protein ; Transforming Growth Factor beta1

Objective To assess the safety and efficacy of balloon dilation of pulmonary valve stenosis with 10 F domestic balloon catheter in children ≥ 10 kg. Methods From May 2009 to June 2014, eighty-three consecutive children with weight ≥ 10 kg and age of (4.5±2.8)(ranged from 1-12) years underwent percutaneous balloon pulmonary valvoloplasty(PBPV) with 10 F domestic balloon catheter. Indication for treatment, procedural details, catheterization data, complication rate, peak-to-peak systolic gradient across the valve and pulmonary insufficiency on echocardiography were respectively analyzed. Forty-four patients were followed up 6-44 months after procedure. Results All procedures were completed successfully. The peak-to-peak systolic gradient across the pulmonary valve decreased from (67.7±26.2) mmHg to (15.4±11.6) mmHg (P < 0.01) immediately after PBPV. Two patients developed reactive infundibular spasm after dilation. They were relieved at 6 months post PBPV. No patient had severe pulmonary insufficiency, tricuspid regurgitation or reintervetion. Conclusions PBPV with 10 F domestic balloon catheter in children with weight≥10 kg is a safe and effective method.

We analyzed the whole genome coding sequence of Volvariella volvacea to study the pattern utilization of codons by Codon W 1.4.2. As results, 24 optimal codons were identified. Moreover, the frequency of codons usage was calculated by CUSP program. We compared the frequency of codons usage of V. volvacea with other organisms including 6 modal value species (Homo sapiens, Saccharomys cerevisiae, Arabidopsis thalian, Mus musculus, Danio rerio and Drosophila melanogaster) and 4 edible fungi (Coprinopsis cinerea, Agaricus bisporus, Lentinula edodes and Pleurotus ostreatus). We found that there were less differences in 3 edible fungi (excluding Pleurotus ostreatus) than 6 modal value species, comparing with the frequency of codons usage of V. volvacea. With software SPSS16.0, cluster analysis which showed differences in the size of codon bias, reflects the evolutionary relationships between species, which can be used as a reference of evolutionary relationships of species. This was the first time for analysis the codon preference among the whole coding sequences of edible fungi, serving as theoretical basis to apply genetic engineering of V. volvacea.
Agaricales ; genetics ; Animals ; Arabidopsis ; genetics ; Cluster Analysis ; Codon ; DNA, Fungal ; genetics ; Drosophila melanogaster ; genetics ; Humans ; Mice ; Saccharomyces cerevisiae ; genetics ; Software ; Volvariella ; genetics ; Zebrafish ; genetics

Objective To investigate the intra- and interobserver repeatability of coronary artery disease (CAD) diagnosis based on invasive coronary angiography (ICA) and CT coronary angiography (CTCA).Methods Two readers with comparable experience ( over 10 years) independently evaluated ICA results of 42 consecutive patients with a blind method. After 30 days,one of them reviewed the same patients again.Another two comparable-experience (over 10 years) readers evaluated the results of CTCA (prospectively ECG-triggering) from the same 42 patients in the same way.The inter-reader and intra-reader repeatability of ICA and CTCA were analyzed by performing Kappa test and calculating the percentage of the segments with agreement on stenotic degree.Using ICA as reference,the accuracy of CTCA in diagnosing CAD was studied by comparing the area under ROC. Results The Kappa between readers for ICA and CTCA were 0.91 and 0.81.Intra-reader Kappa were 0.92 and 0.83 respectively (x2 =509.4 and 432.5,all P ＜0.01 ).The percentage of the segments with agreement between readers on the degree of stenosis were 80.8％ (494/611) in ICA and 75.2％ (469/624) in CTCA ( x2 =2.75,P =0.10),and within the same reader,86.9％ (531/611)in ICA and 81.9％ (511/624) in CTCA(x2 =3.76,P =0.053).With≥ 50％narrowing as a CAD diagnosis criterion,the agreement rates for two readers were 96.6％ (590/611 ) in ICA and 94.4％ (589/624) in CTCA( x2 =3.36,P =0.07),and for the same reader,97.4％ (595/611) in ICA,95.4％ (595/624) in CTCA ( x2 =3.62,P =0.06).Using ICA as reference,two readers of CTCA results achieved a sensitivity and specificity of 84.9％ (530/624)and 98.1％ (612/624).The area under ROC was 0.94 (95％ CI 0.91-0.97).Conclusions Both ICA and CTCA demonstrate good repeatability in diagnosing CAD.The repeatability of ICA is superior to that of CTCA.A certain discrepancy exists in two readings from the same reader or two readers.

This article is report the study of the pharmacokinetics and metabolic disposition of exogenous phosphocreatine (PCr) in rats by means of an ion-pair HPLC-UV assay. PCr and its metabolite creatine (Cr) and related-ATP in rat plasma and red blood cell (RBC) were simultaneously determined. A blank plasma and RBC were initially run for baseline subtraction. Plasma and RBC samples were deproteinized with 6% PCA prior to HPLC. Following i.v. administration of PCr 500 mg x kg(-1) and 1 000 mg x kg(-1) the C-T curve could be described by the two-compartment model with t1/2beta 22.5-23.3 min, V(d) 0.956 4-0.978 6 L x kg(-1), CL 0.029 L. kg(-1) x min(-1). The Cr as PCr degraded product appeared as early as 2 min post i.v. dosing with t(max) 20 min, t1/2kappa (m) 40.6-42.7 min and f(m) 60%-76%. After po administration of PCr, the parent drug in plasma was undetectable, but the metabolite Cr was detected with t(max) 65-95 min, t1/2kappa (m) 56.0-57.7 min, metabolite-based bioavailability F(m) 55.02%-62.31%. PCr i.v. administration resulted in significant elevation of ATP level in RBC but not in plasma, the related-ATP in RBC was characterized by t(max) 68-83 min, t1/2kappa 49-52 min. In RBC no exogenous PCr was found but Cr was detected following i.v. administration of PCr, with the t(max) 120 min and t1/2k (m) 70 min for Cr. The above results indicate that PCr eliminates and bio-transforms in body very rapidly; K > K(m) confers ERL, instead of FRL, type upon the metabolic disposition of Cr. Following po administration of PCr, the degraded product Cr is absorbed but not the parent drug PCr. The formed Cr can be accounted for by most of i.v. and po PCr. Intravenous dosing leads apparently increased and sustained Cr and related-ATP concentration in RBC.

ObjectiveTo investigate reproducibility of cardiac MRI for assessment of cardiac morphology and ventricular function in selected normal Chinese Han population.MethodsTwo hundred and sixty-nine normal volunteers underwent cardiac MRI using a 1.5 T MR system.HASTE and steady state free precession imaging were performed with long and short axis images and cine mode through the ventricle with wireless vector cardiac gating.The images were reviewed by two independent observers.The dimensions of cardiac chambers and ventricular function including ejection fraction (EF),end diastolic volume( EDV),end systolic volume (ESV) and myocardial mass were evaluated.The data between male and female were compared by using two-tailed unpaired t test.Results Total imaging time was (15 ± 3 ) min.The anteroposterior diameter of the left atrium was( 2.87 ± 0.77 ) cm,the right atrial diameter perpendicular to the atrial septum was ( 3.61 ± 0.57 ) cm,the end diastolic diameter of the left ventricle was (4.97 ±0.52) cm,the end diastolic diameter of the right ventricle was (2.65 ± 0.48) cm.On the left ventricle,EF was(60.62 ±7.08)％,EDV was (115.37 ±26.71) ml,ESV was (46.02+15.72) ml and LV mass was ( 82.97± 24.03 ) g.On the right ventricle,EF was (47.73 ± 6.50 ) ％,EDV was ( 128.27 ± 32.16 )ml,ESV was (67.7 ± 21.07) ml and RV mass was (48.24 ± 13.42) g.There were no statistically significant differences in LVESV( P =0.144 ),LVEDV index ( P =0.714 ),LVESV index ( P =0.113 ),LVCI ( P =0.199),RVEF ( P =0.296 ) and RV mass ( P =0.093 ),and statistically significant differences in other cardiac parameters between male and female.Conclusion Cardiac MRI can provide useful information about cardiac function and morphology with a high level of reproducibility in normal Chinese Han population.

To evaluate the efficacy of HbA1C in diagnosing diabetes in subjects with primary hypertension.The results demonstrated that the area under the reciever operating characteristic ( ROC ) curve was 0.895,with corresponding sensitivity of 85.4％,and specificity of 82.2％,when the optimal cutpoint of HbA1C in diagnosing diabetes was 6.0％.Our study suggested that HbA1C ≥6.0％ can be used efficiently in diagnosing diabetes in patients with primary hypertension.

Objective To investigate the application of abdominal drainage after liver resection.Methods From Jan 2008 to June 2009,210 consecutively admitted patients undergoing liver resection by the same surgical team were chronologically allocated into drainage group(120)and non-drainage group (90).Patient's preoperative characteristics,operation-related factors,postoperative complications and hospital stay were compared between the two groups.Results Postoperative complications were comparable between the two groups,which was not significantly different among preoperative characteristics and operation-related factors(P>0.05).Mortality was 0.8% in drainage group and 1.1% in non-drainage group,again,the difference was not significant(X~2=0.042,P>0.05).Snrgical complications were significantly higher in drainage group than in non-drainage group,especially for abdominal infection and ascites occurrence(P<0.05).The hospital stay was significantly longer in the drainage group(13.1 ±5.2)days than the non-drainage group(11.4±5.6)days.Conclusions Postoperative abdominal drainage is not necessary for patients undergoing liver resection,furthermore,abdominal drainage increases postoperative complications.

Objective To explore the incidence and risk factors of bacterial infection after othtotopic liver transplantation (OLT). Methods Altogether 56 OLT recipients from January 2005 to October 2007 were included in the study. The incidents and the related variables of the infection were analyzed retrospectively. The related variables were evaluated using multivariate logistic regression model to identify the significant risk factors. Results Bacterial infection was confirmed in 29 recipients (51.8%). Among them, the lung infection was the most common site (53.7%). The Gram-positive cocci were 46.3%, while the Gram-negative bacilli were 53.7%. The risk factors for bacterial infection included duration of the operation and detained respirator using. Conclusion Bacterial infection is a major complication following OLT. Surveillance for the risk factors, enhancement the skill of operation, and improving the recovery of respiratory function is the key to decreasing the incidence of bacterial infection after transplantation.

Objective To study the stability of the toxicity,antigenicity and immunogenicity of Neisseria meningitidis serogroup A/C[CMCC(B)29201/29205],and to analyze the quality of the capsular polysaecharide extracted from Neisseria meningitidis.Methods The toxicity of the 3rd,5th,10th,15th,20th,25th and 30th passage of the Neisseria meningitidis was assayed in mice,and the antigenicity of each passage was measured by the tube agglutination test(TAT)and ELISA.The effect of individual 30 passages of Neisseria nveningitidis on the brain tissue and the immunogenicity of each passage were tested in mice,and the capsular polysaccharide was purified and analyzed.Resuits The LD50 of the strains CMCC(B)29201/29205 of each passage was low(≥109/ml),and all the 30 passages of the two strains had no effect on the brain tissue of the mice.The titer of each passage was 1∶320 in TAT and more than 1∶3752 in ELISA.After immunization with individual 30 passages of the Neisseria meningitidis the titers in serum bactericidal assay (SBA)were all more than 1∶32.The capsular polysaccharide purified from Neisseria meningitidis met the quality standard of the requirement.Conclusion The strains of Neisseria meningitidis serogroup A/C used in the manufacture of the meningococcal conjugate vaccine,are stable in the toxicity,antigenicity and immunogenicity.And the capsular polysaccharide has met the quality standard.