In recent years,clinical immunology has an increasing variety of prominent applications in the field of chronic hepatitis B infection.On one hand,the discovery and identification of the mechanisms of pathogen recognition by the innate immune system,novel immune cell subpopulations and immunoregulatory pathways further enriched the immunological pathogenesis of chronic hepatitis B.On the other hand,the development of new immunotherapy strategies aimed at reconstructing the antiviral immunity,including agonists of Toll like receptors,immune cell therapies and therapeutic vaccines,have provided several new targets for the optimization of antiviral therapy strategies and brought new opportunities for patients of chronic hepatitis B to obtain HBsAg clearance and clinical cure.

Despite different opinions on its definition and classification in the past,a consensus has gradually been reached regarding the na-ming,classification,and clinical diagnosis of liver failure.The classification of liver failure is described,and the definition and natural his-tory of severe exacerbation of hepatitis B are summarized.Antiviral treatment and artificial liver support in the early stage are beneficial for clinical outcomes and prognosis.

Objective:To investigate the expression of transforming growth factor ?1(TGF-?1) in dog mandibular distraction osteogenensis (DO). Methods: Mandibular DO model was established in 12 dogs and nonunion model in another 12 dogs, 4 dogs were used as the no-treatment control. Tissue samples were obtained 6 d,2 and 8 weeks after operation respectively.Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were used to determine the expressions of TGF-?1 in the samples.Results: TGF-?1 (ng/g) in control group was 1394.3?20.1,6 d after operation that in DO and nonunion groups was 1928.5?33.5(vs control,P

Objectives To investigate dynamic pathological features and virus distribution in the liver with a murine severe acute respiratory syndrome(SARS)model injected with murine hepati- tis virus 3(MHV-3)through trachea.As a representative of host genes,mouse fgl2(mfgl2)pro- thrombinase gene expression and its clinical significance were discussed in SARS associated liver dam- ages.Methods The Balb/cJ mice were infected with 100 PFU of MHV-3 through trachea and Balb/ cJ mice injected with saline were served as control.Survival rate,pathological features in organs and liver function were observed.Virus titers in different organs were determined on monolayer of L2 cells by a standard plaque assay.Virus distribution and cellular localization were studied by in situ hy- bridization.Both mfgl2 and fibrin expressions were examined in the liver by in situ hybridization and immunohistochemistry to investigate the role of mfgl2 in the liver impairment.Results Mice infected with MHV-3 through trachea developed multiple organs damages and died within 5 days,while all mice in control group survived with no histopathological changes.Infected liver tissues showed wide- spread cloudy swelling,prominent ballooning degeneration with mild lymphocytic infiltration in the portal area.Dot and zonal hepatocellular necrosis could be found occasionally.The lungs showed typi- cal interstitial pneumonia and hyaline membranes formation.Other histological changes also could be found in other organs examined.MHV-3 virus replication was identified in all organs observed.The liver function was injured,mfgl2 expression were evidenced mainly in the necrosis areas with fibrin deposition around the necrosis areas.Conclusions Pathological changes of the liver in this murine SARS model can mimic the liver impairment characteristics of SARS in human.In addition to the physical damage induced by the virus,the up-regulation of novel gene mfgl2 in the liver in association with fibrin deposition may play a vital role in the development of SARS associated liver damages.

Methylmalonic aciduria (MMA) is a common inherited autosomal recessive disorder resulting from defects in the enzyme methylmalonyl CoA mutase (MCM, mut complementation group) or in the synthesis of the MCM cofactor adenosylcobalamin (cbl complementation groups). The defects in the mut complementation group accounts for the largest number of patients with isolated MMA. At least 200 mutations in the MUT gene on chromosome 6p12 have been identified in MMA patients until now. This study aimed to investigate the clinical characteristics of MMA and genomic variations in the MUT gene of Chinese patients. Genomic DNA was extracted from 18 patients who were diagnosed as having isolated MMA by gas chromatography/mass spectrometry (GC-MS), and from some of their parents as well. Amplification and direct sequencing of the MUT coding regions (exon 2-13) and their adjacent intronic consensus splice sites were performed in order to identify the disease causing mutations. In this group, six novel mutations in the MUT gene, c.424A>G (p.T142A), c.786T>G (p.S262R), c.808G>C (p.G270R), c.1323_1324insA, c.1445-1G>A and c.1676+77A>C were identified. p.T142A and p.G270R were respectively detected at a heterozygous level in one patient. Two previously reported mutations, c.682C>T (p.R228X) and c.323G>A (p.R108H) were also found in this study. In addition, six previously described single nucleotide polymorphism (SNP), c.636A>G (p.K212K), c.1495G>A (p.A499T), c.1595A>G (p.H532R), c.1992G>A (p.A664A), c.2011G>A (p.V671I) and c.1677-53A>G were identified. In this study, we updated the spectrum of MUT mutations and identified the main MMA-causing mutations in Chinese MMA patients.

Objective To evaluate the safety and efficacy of endoscopic ultrasonography(EUS) guided ethanol ablation in patients with insulinoma. Methods The data of 10 patients with insulinoma trea-ted at the First Affiliated Hospital of Guangxi Medical University from December 2013 to January 2015 were prospectively analyzed. Results The patients were given EUS-guided ethanol ablation with dose of 0. 10 to 2. 00 ml(average 0. 70 ± 0. 62 ml)in pancreatic lesions for 15 times. No complications were observed dur-ing and after the procedure. The blood glucose improved after the procedure[4. 8(3. 9-5. 5)mmol/ L VS 2. 4 (1. 9-2. 5)mmol/ L,P < 0. 05]and the serum insulin level significantly decreased[83. 7(40. 1-143. 5) pmol/ L VS 177. 3(66. 5-200. 6)pmol/ L,P<0. 05]. The average hospital stay was(4. 3±1. 5)days. The patients were followed up for 6-12 months. EUS indicated that the echo of pancreatic lesions changed from high to low. CE-EUS revealed low enhancement and lack of blood supply. Conclusion EUS-guided ethanol ablation may become a promising minimally invasive treatment for insulinoma because of its safety,efficacy and low price. Trail registration Clinical Trial.gov,NCT02121366.

To study the contribution of T cell subsets in the pathogenesis of Murine hepatitis virus Type3 (MHV-3) induced chronic viral hepatitis in C3H/Hej mice, ninety C3H/Hej mice were chosen to individually receive 10 plaque forming units (PFU) of MHV-3 intraperitoneally. The changes of virus titer and pathology in liver tissue were examined by standard plaque assay and by the hematoxylin/eosin (HE) staining method from 2 days post MHV-3 infection. The ratios of T cell subsets including CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD4-CD8-, CD3+CD4+CD25+, CD3+CD4+CD25- and CD3+CD4-CD25+ T lymphocyte of total T lymphocytes in blood, spleen and liver were examined at 0, 2, 4, 6,8, 10, 12, 15, 20, 25, 30, 40 days post MHV-3 infection by flow cytosorting. We observed that the virus titer raised and showed persistent virus duplications and inflammatory changes in the livers of C3H/Hej mice from 2 days post MHV-3 infection. The double negative T cell (DN Treg cell) and CD4+CD25+ T cell ratios increased significantly from 2 days post MHV-3 infection in C3H/Hej mice, and CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD4+CD25- and CD3+CD4-CD25+ T cell ratios decreased accordingly. In conclusion, the changes of virus titer and pathology in the livers of C3H/Hej mice post MHV-3 suggest their contribution to viral persistence. Further characterizations of DN Treg cells are that infection indicates that MHV-3 could induce the chronic inflammation in livers of C3H/Hej mice.The increase of the DN Treg cell and CD4+CD25+ T cell ratios in C3H/Hej mice post MHV-3 infection suggests that DN Treg cells and CD4+CD25+ T cells may both have important suppressive immunomodulation functions in the development of chronic viral hepatitis and have important roles in the virus persistent infection. Further characterizations of DNT cell and CD4+CD25+ T cell are under investigation.

Objective To comparatively analyze the domestic and foreign sicentific product, academic impact and cooperation in toxicology from 1980 to 2015.Methods The countries, Chinese scientific research institutions and authors engaged in research of toxicology were analyzed according to the InCites-covered number of published pa-pers, cited papers and collaborations .The highly cited papers covered in Web of Sciene were analyzed by biblio-metric analysis.Results The number of papers on toxicology published by USA, Britian and Japan was greater than that published by other countries.The number of papers on toxicology published by China increased significantly and their academic level was notebly improved.Conclusion China should strengthen the subject system construc-tion, attach importance to frontier and retrospective analysis and international cooperation, speed up the develop-ment of toxicology and improve the academic level of its scientific achievements .

Aim To evaluate the analgesic effect of agmatine on inflammatory pain and its influence on the analgesic effect of morphine. To investigate whether the mechanism of analgesic effect of agmatine is related to activation of imidazoline receptor or to affect the release of endogenous glutamate and gamma-aminobutyric acid (GABA) from rat spinal cord slices. Methods The formalin test in rats was used as a long-lasting inflammatory pain model. Effects of agmatine on basal and K+ evoked release of endogenous glutamate and GABA from rat spinal cord slices were determined by high performance liquid chromatography (HPLC). Results Pretreatment with agmatine (ip or sc) inhibited the second phase of the nociceptive response of rats and potentiated the analgesic effect of morphine in phase 2, but not in phase 1. Idazoxan did not attenuate the analgesic effect of agmatine. Agmatine (1, 10, 100, 1000 ?mol?L -1 ) had no effect on the basal release of glutamate and GABA from spinal cord slices, nor did it affect the K+ (50 mmol?L -1 ) evoked release of glutamate and GABA contents. Conclusions Agmatine has an analgesic effect and enhances morphine analgesia in the second but not the first phase of formalin-induced nociception. Its analgesic effect does not likely involve imidazoline receptor. The mechanism of the analgesic effect of agmatine may not be associated with inhibiting glutamate release nor increasing the GABA content.

The noninvasive measurement of liver stiffness (LS) was evaluated by transient elastography (FibroScan) and the possible influencing factors from the patients' clinical situations including age, gender, liver inflammation represented by alanine transaminase (ALT) and total billirubin (TBIL) level, HBV replication (HBV DNA loads), portal vein pressure (portal vessel diameter, PVD), splenic thickness (SPT) and body mass index (BMI) were analyzed in patients with chronic hepatitis B (CHB). A total of 466 patients including 31 patients with acute-on-chronic liver failure (ACLF), and 435 patients with chronic hepatitis B (CHB) among which 82 patients were diagnosed with liver cirrhosis (LC) by clinical manifestations and liver B-type ultrasonic inspection were enrolled at Tongji Hospital from April to December 2009. LS was measured by a FibroScan device (EchoSens, France). Simultaneously, ALT and TBIL levels, HBV DNA loads, PVD, SPT and BMI in all patients were also tested. Forty-one healthy volunteers served as controls. The values of LS were correlated positively with ages of CHB patients and significantly higher in males than in females. In patients with BMI>28 kg/m(2) (obesity) and abnormal levels of ALT and TBIL, LS values were significantly increased as compared with those having normal levels of ALT and TBIL. The patients with ACLF had the highest LS value. Furthermore, LS values in the patients with LC were significantly higher than those in patients without LC. It is concluded that noninvasive measurement of liver fibrosis by FibroScan provides an alternative method to evaluate liver fibrosis of patients with CHB. In order to properly illustrate the stiffness value taken by transient elastography, patients' gender should be taken into consideration and it is also suggested to avoid possible influencing factors including liver inflammation (high levels of ALT and TBIL) and obesity (high BMI).