Identification of pathogenic mutant genes in seven families with primary biliary cholangitis patients by whole exome sequencing / 中华消化杂志

Objective:To screen the common low-frequency mutation sites in primary biliary cholangitis (PBC) by whole exome sequencing (WES), in order to find PBC-related new susceptibility genes.Methods:From January 2000 to December 2017, the clinical data of seven patients with PBC of three PBC families diagnosed at General Hospital of Tianjin Medical University and two healthy controls were collected. The DNA blood samples were extracted and analyzed by WES. SAMtools 1.3 software was used to detect gene single nucleotide polymorphism (SNP) and indel sites, and gene mutation sites were screened from known databases of 1000 Genome, ExAC, ESP6500 and Novo-Zhonghua gene database. Pymol V2.3.2 software was performed to simulate the three-dimensional structure of major histocompatibility complex-Ⅱ (MHC-Ⅱ), and the amino acid position corresponding to the common mutation sites among families were observed.Results:The age of first diagnosis of seven PBC patients was (61.2±10.2) years. The results of serum test of seven patients indicated that alkaline phosphatase (ALP) level was (306.9±242.5) U/L, γ-glutamyltranspeptidase (GGT) level was (121.7±85.9) U/L, alanine aminotransferase (ALT) level was (47.6±33.1) U/L, aspartate aminotransferase (AST) level was (55.7±34.1) U/L and immunoglobulin G level was (14.9±3.1) g/L. The antinuclear antibody were all cytoplasmic granule types and anti-mitochondrial antibody were all positive. Five PBC patients developed intra-abdominal lymphadenopathy; two patients had extrahepatic autoimmune diseases and the pathological results of liver biopsy of two patients both showed interface hepatitis and small bile duct lesions. Eighteen SNPs were common in three PBC families, which were located in the gene of OTOA, OBSCN and human leucocyte antigen- DRB1( HLA- DRB1). rs200988634 located in OTOA gene was a common polymorphic locus among the three families. rs746424683, rs545316651, rs553144914, rs533059830 and rs56087721 located in OBSCN caused the changes of nine amino acids of different location. There were 12 SNP variations located in HLA- DRB1 gene, which leaded to the changes of 12 amino acids of different location, among them rs16822698, rs112796209 and rs11554463 mutation induced G154A, Y152C and Y107X amino acid variation of MHC-Ⅱ beta chain, and Y107X amino acid was located in the groove region of MHC-Ⅱ binding with peptide. Conclusions:WES in PBC families is a good strategy to elucidate the candidate deleterious mutation genes OBSCN and OTOA. HLA- DRB1 which is a susceptible gene of PBC may affect MHC-Ⅱ mediated antigen presentation process by the changing amino acid sequence.

Association of health literacy and drinking behaviors among middle school students in six provinces of China / 中国学校卫生

Objective@#To explore the association between health literacy and drinking behaviors among middle school students in six provinces of China, and to provide scientific basis for the prevention and intervention of drinking behaviors.@*Methods@#From November 2015 to January 2016, 22 628 students were enrolled from Ulanqab, Shenyang, Xinxiang, Bengbu, Chongqing and Yangjiang by multistage stratified cluster sampling method. And a questionnaire survey was conducted among them to collect demographic information, health literacy and drinking behaviors. Rates on drinking behaviors were compared in students with specific characteristics. Multiple Logistic regression analyses were conducted to examine the association between health literacy and drinking behaviors.@*Results@#The proportion of ever drinking, current drinking, binge drinking, drunkenness was 60.0%(13 580), 16.8%(3 799), 5.9%(1 344) and 9.9%(2 250), respectively. After adjusting for gender, grade, family address, siblings, accommodation type, parental educational level, and self reported family income, compared to the high level health literacy, the low level health literacy was significantly associated with ever drinking (OR=1.76, 95%CI=1.62-1.91), current drinking(OR=1.37, 95%CI=1.23-1.52), binge drinking (OR=1.39, 95%CI=1.18-1.63), and drunkenness(OR=1.68, 95%CI=1.47-1.92), respectively(P<0.01).@*Conclusion@#Health literacy of middle school students was related to drinking behaviors. The occurrence of health risk behaviors such as drinking can be prevented and reduced by improving students health literacy level.

Role of intestinal barrier in the pathogenesis of autoimmune hepatitis / 中华消化杂志

Objective@#To observe and analyze the role of intestinal barrier in the pathognesis of autoimmune hepatitis (AIH), to explain the pathogenesis of AIH and to explore the intestinal based new treatment strategies.@*Methods@#A total of 14 AIH patients from January to December 2017 at Tianjin Medical University General Hospital (six patients without liver cirrhosis, and eight patients with liver cirrhosis) and 10 healthy controls were enrolled. The serum levels of D-lactic acid (D-Lac) and diamine oxidase (DAO) were detected by enzyme-linked immunosorbent assay. Real time fluorescence quantitative polymerase chain reaction was used to detect the relative expression levels of connexin (zonula occluden-1 (ZO-1), occludin), cytokines (interleukin(IL)-2, interferon(IFN)-γ, IL-4, IL-10) and Toll-like receptor 4 (TLR4) in terminal ileal tissues of each group. The relative expression of secretory immunoglobulin A (sIgA) in the terminal ileum was determined by Western blotting. Thirty BALB/c mice were selected and divided into blank control group, dextran sulfate sodium (DSS) group, concanavalin A (ConA) group, DSS+ ConA group, and DSS+ bacterium+ ConA group, with six mice in each group. The relative expression levels of ZO-1, occludin in mouse colonic tissues, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and inflammatory activity degree of liver tissues (Knodell score) of each group were measured. T-test and one-way analysis of variance were performed for statistical analysis.@*Results@#The serum D-Lac and DAO levels of AIH with liver cirrhosis group and AIH without liver cirrhosis group were both higher than those of healthy control group ((1 768.2±147.1) μg/L, (436.2±197.0) μg/L vs. (100.2±10.9) μg/L, and (11.5±2.5) U/L, (5.4±0.9) U/mL vs. (3.5±0.9) U/mL), and the levels of D-Lac and DAO of AIH with liver cirrhosis group were the highest; and the differences were statistically significant (t=5.512, 36.010, 4.088 and 9.443, F=396.958 and 46.640, all P<0.01). The relative expression levels of ZO-1 and occludin in the terminal ileal mucosa of AIH with liver cirrhosis group were lower than those of healthy control group (0.20±0.14 vs. 1.67±0.51, 0.12±0.09 vs. 0.90±0.21), and the relative expression of ZO-1 in AIH without liver cirrhosis group was lower than that in healthy control group (0.99±0.37 vs. 1.67±0.51); and the differences were statistically significant (t=8.641, 7.407 and 2.295, all P<0.05). The relative expression levels of IL-2 and IFN-γ in terminal ileal tissues of AIH with liver cirrhosis group were higher than those of healthy control group (1.11±0.43 vs. 0.24 ±0.16, and 3.50 ± 1.90 vs. 0.32±0.30), however the relative expression of sIgA in terminal ileal tissues was lower than that of healthy control group (0.506±0.024 vs. 1.081±0.102); and the differences were statistically significant (t=4.679, 3.981 and 5.493, all P<0.05). While the relative expression levels of IL-10 in AIH with liver cirrhosis group and AIH without liver cirrhosis group were lower than that in healthy control group (0.30±0.20, 0.42±0.24 vs. 0.84± 0.23), and the relative expression levels of TLR4 in ileum mucosa of the both groups were higher than that of healthy control group (8.74 ±5.13, 6.74 ±3.65 vs. 0.89 ± 0.70); and the differences were statistically significant (t=3.095, 4.816, 3.856 and 3.685, all P<0.05). The relative expression levels of ZO-1 and occludin of DSS+ ConA group were lower than those of ConA group (0.14±0.08 vs. 0.98±0.13, and 0.09±0.02 vs. 0.98±0.16), however serum ALT, AST levels and the Knodell score were all higher than those of ConA group ((5 496.67±618.83) U/L vs. (3 325.00±1 030.06) U/L, (8 825.00±1 165.35) U/L vs. (5 433.33±1 691.14) U/L, and 18.00±2.00 vs. 9.33±3.01); and the differences were statistically significant (t=13.480, 13.520, 4.227, 4.045 and -2.892, all P<0.05). The relative expression levels of ZO-1 and occludin in DSS+ bacterium+ ConA group were higher than those in DSS+ ConA group (0.46±0.08 vs. 0.14±0.08, and 0.53±0.15 vs. 0.09±0.02), while serum ALT and AST levels were lower than those of DSS+ ConA group ((4 343.33±252.16) U/L vs. (5 496.67±618.83) U/L, and (6 123.33±1 086.60) U/L vs. (8 825.00±1 165.35) U/L); and the differences were statistically significant (t=6.928, 7.122, 4.228 and 4.153, all P<0.01).@*Conclusions@#AIH patients have increased intestinal permeability and impaired intestinal barrier which is more serious in patients with liver cirrhosis than in patients without cirrhosis. The intestinal barrier injury can aggravate ConA-induced immune-mediated liver injury. While the protection and repair of intestinal barrier can alleviate immune-mediated liver injury induced by ConA.

Role of intestinal barrier in the pathogenesis of autoimmune hepatitis / 中华消化杂志

Objective:To observe and analyze the role of intestinal barrier in the pathognesis of autoimmune hepatitis (AIH), to explain the pathogenesis of AIH and to explore the intestinal based new treatment strategies.Methods:A total of 14 AIH patients from January to December 2017 at Tianjin Medical University General Hospital (six patients without liver cirrhosis, and eight patients with liver cirrhosis) and 10 healthy controls were enrolled. The serum levels of D-lactic acid (D-Lac) and diamine oxidase (DAO) were detected by enzyme-linked immunosorbent assay. Real time fluorescence quantitative polymerase chain reaction was used to detect the relative expression levels of connexin (zonula occluden-1 (ZO-1), occludin), cytokines (interleukin(IL)-2, interferon(IFN)-γ, IL-4, IL-10) and Toll-like receptor 4 (TLR4) in terminal ileal tissues of each group. The relative expression of secretory immunoglobulin A (sIgA) in the terminal ileum was determined by Western blotting. Thirty BALB/c mice were selected and divided into blank control group, dextran sulfate sodium (DSS) group, concanavalin A (ConA) group, DSS+ ConA group, and DSS+ bacterium+ ConA group, with six mice in each group. The relative expression levels of ZO-1, occludin in mouse colonic tissues, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and inflammatory activity degree of liver tissues (Knodell score) of each group were measured. T-test and one-way analysis of variance were performed for statistical analysis. Results:The serum D-Lac and DAO levels of AIH with liver cirrhosis group and AIH without liver cirrhosis group were both higher than those of healthy control group ((1 768.2±147.1) μg/L, (436.2±197.0) μg/L vs. (100.2±10.9) μg/L, and (11.5±2.5) U/L, (5.4±0.9) U/mL vs. (3.5±0.9) U/mL), and the levels of D-Lac and DAO of AIH with liver cirrhosis group were the highest; and the differences were statistically significant ( t=5.512, 36.010, 4.088 and 9.443, F=396.958 and 46.640, all P<0.01). The relative expression levels of ZO-1 and occludin in the terminal ileal mucosa of AIH with liver cirrhosis group were lower than those of healthy control group (0.20±0.14 vs. 1.67±0.51, 0.12±0.09 vs. 0.90±0.21), and the relative expression of ZO-1 in AIH without liver cirrhosis group was lower than that in healthy control group (0.99±0.37 vs. 1.67±0.51); and the differences were statistically significant ( t=8.641, 7.407 and 2.295, all P<0.05). The relative expression levels of IL-2 and IFN-γ in terminal ileal tissues of AIH with liver cirrhosis group were higher than those of healthy control group (1.11±0.43 vs. 0.24 ±0.16, and 3.50 ± 1.90 vs. 0.32±0.30), however the relative expression of sIgA in terminal ileal tissues was lower than that of healthy control group (0.506±0.024 vs. 1.081±0.102); and the differences were statistically significant ( t=4.679, 3.981 and 5.493, all P<0.05). While the relative expression levels of IL-10 in AIH with liver cirrhosis group and AIH without liver cirrhosis group were lower than that in healthy control group (0.30±0.20, 0.42±0.24 vs. 0.84± 0.23), and the relative expression levels of TLR4 in ileum mucosa of the both groups were higher than that of healthy control group (8.74 ±5.13, 6.74 ±3.65 vs. 0.89 ± 0.70); and the differences were statistically significant ( t=3.095, 4.816, 3.856 and 3.685, all P<0.05). The relative expression levels of ZO-1 and occludin of DSS+ ConA group were lower than those of ConA group (0.14±0.08 vs. 0.98±0.13, and 0.09±0.02 vs. 0.98±0.16), however serum ALT, AST levels and the Knodell score were all higher than those of ConA group ((5 496.67±618.83) U/L vs. (3 325.00±1 030.06) U/L, (8 825.00±1 165.35) U/L vs. (5 433.33±1 691.14) U/L, and 18.00±2.00 vs. 9.33±3.01); and the differences were statistically significant ( t=13.480, 13.520, 4.227, 4.045 and -2.892, all P<0.05). The relative expression levels of ZO-1 and occludin in DSS+ bacterium+ ConA group were higher than those in DSS+ ConA group (0.46±0.08 vs. 0.14±0.08, and 0.53±0.15 vs. 0.09±0.02), while serum ALT and AST levels were lower than those of DSS+ ConA group ((4 343.33±252.16) U/L vs. (5 496.67±618.83) U/L, and (6 123.33±1 086.60) U/L vs. (8 825.00±1 165.35) U/L); and the differences were statistically significant ( t=6.928, 7.122, 4.228 and 4.153, all P<0.01). Conclusions:AIH patients have increased intestinal permeability and impaired intestinal barrier which is more serious in patients with liver cirrhosis than in patients without cirrhosis. The intestinal barrier injury can aggravate ConA-induced immune-mediated liver injury. While the protection and repair of intestinal barrier can alleviate immune-mediated liver injury induced by ConA.

Characteristics of initial diagnosis in autoimmune liver disease: an 18-year, retrospective single-center study / 中华内科杂志

Objective To analyze the chorological changes of diagnosis in patients with autoimmune liver disease (AILD) and related factors for early diagnosis.Methods A total of 581 patients with age ranged from 16 to 81 were retrospectively analyzed,who were admitted to Tianjin Medical University General Hospital with AILD during January 2000 to December 2017.Age at diagnosis,diagnostic method and cirrhosis at diagnosis were compared in different groups according to admission period as 2000-2005,2006-2011,2012-2017.Results The diagnostic rate of AILD showed an upward trend during the past near two decades.The proportion of AILD patients diagnosed via health examination was increasing year by year mainly by elevated transaminases (P＜0.001).The mean age at diagnosis in our AILD patients were younger at present,especially in men (P=0.044).The proportion of cirrhosis at diagnosis was gradually reduced in three different periods respectively [77.78％(21/27),41.58％ (79/190),25.00％(91/364),P＜0.001],which were coincident in patients with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) (P＜0.001).The shrinking trend of cirrhosis at diagnosis was significantly correlated with the increasing application of health examination (r=-0.549,P＜0.001).Conclusions Extensive application of health examination expands the diagnostic rate of AILD.During the past 18 years,more young patients are diagnosed with AILD.The proportion of severe cases such as cirrhosis at diagnosis is decreasing.Screening of immunological examinations in patients with abnormal transaminases is needed and critical to the early diagnosis of asymptomatic AILD.

Receptor interacting protein serine threonine kinase 3 mediates macrophage activation and interleukin-6 production in autoimmune hepatitis / 中华消化杂志

Objective To investigate the expression level of receptor-interacting protein serine threonine kinase (RIP) 3 in macrophages/monocytes activation in autoimmune hepatitis (AIH) and its regulation on inflammatory cytokines.Methods The degree of macrophage infiltration and the expression of RIP3 in liver tissues from patients with AIH or hepatic cysts by double-immunofluorescence.After 24 hours treated with different concentrations (0,1,3,6,10 μg/mL) of lipopolysaccharide (LPS),Necrostatin-1,the specific inhibitor of RIP3 signaling pathway,and 6-thioguanine,the active metabolite of azathioprine,the expression levels of RIP1 (RIP3 upstream signal molecule),RIP3 and mixed-lineage kinase domain-like protein (MLKL,RIP3 downstream substrate) in RAW264.7 macrophages were detected by Western blotting.The expression of macrophage-associated cytokine at mRNA level of each treatment group was determined by real time quantitative polymerase chain reaction (PCR).Student's t test and sum rank test were performed for statistical analysis.Spearman analysis was performed for the correlation analysis.Results Compared with hepatic cysts adjacent liver tissues,the infiltration of CD68 positive macrophages in liver tissue of AIH patients was significantly increased (4.75 ± 0.96 vs 28.86 ± 6.23),and the difference was statistically significant (t =7.80,P＜0.05),and the expression level of RIP3 also was significantly increased (15,11 to 22 vs 0,0 to 1),and the difference was statistically significant (Z=-2.66,P＜0.05).In vitro,compared with those of control group,the expression levels of RIP1,RIP3 and MLKL stimulated by LPS at 0,1,3,6,10 μg/mL were significantly increased,and the differences were statistically significant (t=4.00,4.90,6.40,10.30;3.80,9.30,9.80,9.00;4.90,9.90,9.30 and 7.70;all P＜0.05),and were dose-dependent (r=0.91,0.86 and 0.79,all P＜0.05).Furthermore,compared with those of LPS-stimulated group,the expressions of RIP1,RIP3,MLKL of LPS+Necrostatin-1 group were significantly decreased (0.73±0.11 vs 0.47±0.13,0.60±0.07 vs 0.37 ± 0.05,0.65 ± 0.22 vs 0.38 ± 0.04,respectively),and the differences were statistically significant (t=2.60,4.50 and 2.10,all P＜0.05).And the expressions of interleukin (IL)-1β,IL-6and IL-10 at mRNA levels were also decreased (810.3±200.8 vs 463.7±118.1,1 504.4±482.7 vs 290.4±106.9,1 358.6 ± 559.2 vs 677.8 ± 297.6,respectively),and the differences were statistically significant (t=5.40,12.52,5.70,all P＜0.05).However,the expressions of IL-4 and TGF-β at mRNA levels up-regulated (0.3±0.2 vs 0.6±0.3,0.4±0.1 vs 0.9±0.4,respectively),and the differences were statistically significant (t=4.60 and 6.10,both P＜0.05).Compared with those of the LPS-stimulated group,the expressions of IL-1β,IL-6 and IL-10 at mRNA levels of LPS and 6-thiopurine stimulated group significantly down-regulated (810.3±200.8 vs 283.4±65.5,1 504.4±482.7 vs 354.4±73.8,1 358.6± 559.2 vs 625.6±336.3),and the differences were statistically significant (t=4.30,10.60 and 3.50,all P＜0.05);however,the expressions of IL-4 and TGF-β at mRNA levels significantly up-regulated (0.3±0.2 vs 0.6±0.1 and 0.4±0.1 vs 0.5±0.1),and the differences were statistically significant (t=5.20and 12.50,P＜0.05).Conclusions The regulation effects of 6-thiopurine on RIP3 signaling pathway and related cytokines are similar to those of Necrostatin-1.And the expression of RIP3 signaling protein increasing in activated macrophages of liver tissues from AIH patients is closely related to the regulation of IL-6.The RIP3 mediated inflammatory signaling pathway in macrophage may be involved in the genesis and development of AIH and may be a potential therapeutic target.

Analysis of the influence of the first stage examination of clinical practitioner qualification on the education and teaching of provincial medical univrsities / 中华医学教育探索杂志

First-period examination in empirical study of clinical medical national licensing staged examination has been implemented for two years in Binzhou Medical University (BZMU).During the examination,BZMU obtained the experience of organization,guarantee,and training,which adopted corresponding reform measures including course teaching,assessment method,incentive reward and punishment,etc.The first-period examination of staged examination is national examination of quality of education and teaching on the university,which has promoting effect to strengthen the core of the education teaching and renew the idea of teachers' teaching evaluation.It can improve the evaluation system of curriculum assessment and promote students correctly using the theoretical knowledge to clinical practice skills and improve alignment between the university and hospital.Finally,it can promote the reform and development of medical education.

Application value of immunoglobulin G4 detection in unexplained liver injuries / 中华消化杂志

Objective To investigate the expression level of immunoglobulin G (IgG)4 cells in patients previously diagnosed as unexplained liver injuries,and to analyze whether these patients could be diagnosed as immunoglobulin G4-related disease (IgG4-RD).The clinical characteristics of patients with IgG4 positive cells infiltration in liver tissues who did not met IgG4-RD diagnosis criteria were also analyzed.Methods From August 2010 to July 2016,33 patients with unexplained liver injuries even after liver biopsy were enrolled.Immunostaining of IgG and IgG4 in liver tissue slices was performed.Whether the patients met the IgG4-RD diagnosis criteria was analyzed.Also,the relation between IgG4 positive cell infiltration in liver tissues and serum parameters (alanine aminotransferase (ALT),aspartate transaminase (AST),alkaline phosphatase (ALP),γ-glutamyl transpeptadase (GGT),IgG),the classification of liver inflammation and stage of liver fibrosis were analyzed.Chi-square,Fisher exact probability method,t test and Wilcoxon rank and inspection were used for statistical analysis.Results Among 33 patients with unexplained liver injuries,average age of onset of the disease was (50.48 ± 14.52) years old.Ten patients (30.3 ％) presented with different degree of IgG4 positive cells infiltration in liver.In one patient,the IgG4 positive cell number in liver tissue was over 10/high-powered field (HPF),IgG4+ / IgG+ ratio was over 40％,the serum IgG4 increased and low density nodules in the left hepatic lobe level,which met the diagnostic criteria of IgG4-RD.Serum parameters of liver function of this patient were as follows:ALT 948 U/L,AST 658 U/L,ALP 176 U/L,GGT 197 U/L,TBil 21.5 μmol/L,DBil 10.0 μmol/L.According to whether there were IgG4 positive cells infiltration in liver tissues,33 patients were divided into IgG4 positive cells infiltration group (IgG4 positive group,10 cases) and no IgG4 positive cells infiltration group (IgG4 negative group,23 cases).The medium levels of ALT,AST,ALP and GGT in the IgG4 positive group and the IgG4 negative group were 26.0 U/L vs 31.0 U/L,28.5 U/L vs 32.0 U/L,114.0 U/L vs 77.0 U/L,65.0 U/L vs 36.0 U/L,respectively and there were no statistically significant differences (Z=-0.098,-0.216,-0.862,-0.705;all P＞0.05).The serum IgG level of the IgG4 positive group was higher than that of the IgG4 negative group (17.15 g/L vs 13.65 g/L),and the difference was statistically significant (Z=-1.776,P =0.035).Conclusions IgG4-RD may be the reason of liver injury.There are no significant differences in clinical charateristics,serum parameters and inflammation degree in liver tissue between patients with or without IgG4 positive cells infiltration.

Mediating effect of exercise on the relationship between body mass index and health-related quality of life / 中华行为医学与脑科学杂志

Objective To evaluate the effect of exercise on the relationship between body mass index (BMI) and health-related quality of life (HRQOL).Methods A total of 1 114 participants were recruited from the Physical Examination Center of two hospitals.SF-36 was used to measure HRQOL,and the classification of sports level was done according to the subjective evaluation of participants.Results The total score of HRQOL,physical component summary and mental component summary were 76.26± 16.10,75.97 ± 16.67 and 76.55± 18.33 respectively.The results of correlation analysis were as following:the positive correlation between BMI and general health (r=0.109),vitality (r=0.116),social functioning (r=0.092),role emotional (r=0.122),mental health (r =0.145) were significant (P＜ 0.01).The negative correlation between BMI and PF(r=-0.07,P=0.019)was significant.The mediation effects of exercise in was relationship between BMI and general health,vitality,mental health were significant,and the mediating effect were 5.84％,9.14％ and 6.58％.Conclusion This study demonstrates that mediation effects of the exercise are significant in some dimensions of HRQOL,but the direct influence of BMI on the HRQOL plays a leading role.And BMI is a protective factor under certain conditions.

Advances in clinical differentiation between immunological and drug-induced liver injury / 中华肝脏病杂志

The differentiation between autoimmune hepatitis (AIH) and drug-induced liver injury (DILI) is a difficult task in clinical practice. Some AIH patients had a medication history before disease onset, and some DILI patients may have positive serum antibody. In addition, these two groups of patients have similar clinical symptoms, serological examination results, and liver histopathology, which lead to the difficulties in differentiation. However, correct differential diagnosis is of great significance in making clinical treatment decisions and preventing liver cirrhosis. Therefore, it is necessary to investigate the association between immunological and drug-induced liver injury from the perspectives of pathogenesis, similarities and differences in clinical features, serological examination results, and histological changes, prospects of new biomarkers in differentiation, and the significance of hormone therapy and clinical follow-up in differential diagnosis and treatment, in order to provide a reference for clinical decision-making and research in future.

Rapid Identification and Quality Analysis of Olibanum by TGA-DTA Thermal Analysis / 世界科学技术-中医药现代化

This study was aimed to quickly identify Chinese medicine Olibanum.Thermal analysis method was used on the quality analysis of Chinese materia medica (CMM).A total of 25 batches of Olibanum on the market were collected.This study examined three important factors of temperature range,heating rate,powder mesh on the TGA and DTA thermal analysis experiments.And a method of rapid authentication of medicinal materials using TGA and DTA feature maps was built.Methods of the first-order points,connection on thermogravimetric analysis and heat enthalpy calculation were adopted in the quantitative analysis of Olibanum.The results showed that the best condition of TGA and DTA experiment on Olibanum was confirmed.The temperature range is 50-750℃.The heating rate is 20℃· min-1.The powder mesh is 100 mesh.Under these conditions,good quality goods of Olibanum,counterfeit Olibanum and adulterants of Olibanum could be distinguished through the characteristic peak (T1=447 ± 5℃,T2=549 ± 5℃,T3=350 ± 5℃),thermogravimetric analysis (TV-max,△W2+△W3) and thermal enthalpy analysis (△H).It was concluded that the TGA-DTA technology was simple.It was thought to be a rapid,accurate and simple new method for Olibanum identification and quality analysis.

Research on Toll-like Receptor 7 Agonist in Liver Diseases / 胃肠病学

As an important protein molecule for innate immunity,Toll-like receptor 7 (TLR7) is also a bridge between innate immunity and adaptive immunity.When TLR7 is activated,it can exert its effect on liver diseases through different signaling pathways.Studies on the role and application of TLR7 agonist in liver diseases are increasing in recent years.This article reviewed the research on TLR7 agonist in liver diseases.

Comparative study of dual-source CT coronary angiography and conventional coronary angiography in the diagnosis of coronary stenosis / 天津医药

Objective To determine the diagnostic accuracy of dual- source computed tomography coronary angiography (DSCT-CA) for detecting various degrees of coronary artery stenosis. Methods A total of 278 patients with coronary atherosclerotic heart disease (CHD) were selected for DSCT-CA examination. The coronary angiography (CAG) examination was carried out within 30 days in these patients. The result of CAG was used as the gold standard. The coronary artery stenosis of 50% and 75% was used as the sector. Based on the data of patients, DSCT-CA was calculated for quantitative assessment of the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of coronary stenosis for the coronary blood vessels and coronary artery segments. Kappa consistence test was used to analyze the results of two methods. Results The 50%and 75%of coronary artery stenosis was used for the sector, based on the patients, the sensitivities of DSCT-CA were 99.6% and 99.1%, specificities were 84.2%, 89.6%, diagnostic accuracies were 98.6%and 97.5%, and the Kappa values were 0.88 and 0.91. Based on coronary vessels, the sensitivities were 92.0%and 96.9%, specificities were 89.9%and 94.8%, diagnostic accuracies were 91.0%and 95.8%, and the Kappa values were 0.88 and 0.92. Based on coronary artery segments, the sensitivities were 97.3%, 96.5%, specificities were 93.3%, 98.1%, diagnostic accuracies were 94.2%and 97.9%, and the Kappa values were 0.84 and 0.91. Conclusion Based on patient’s coronary artery analysis, DSCT-CA can accurately assess the different degrees of coronary stenosis, but based on the analysis of the coronary artery segment, the false-positive results may occur in the diagnosis of DACT-CA, which suggests that DSCT-CA can partly replace the CAG, still cannot completely replace the CAG.

Summary and analysis on external quality assessment results of clinical immunology during 2009 - 2013 / 国际检验医学杂志

Objective To perform the summary and analysis on the external quality assessment(EQA) results of the clinical im‐munology during 2009 - 2013 to find out the possible problems existing in the laboratory work of the clinical immunology for con‐tinuously improve the quality of clinical immunological detections and ensuring the accuracy of clinical immunological test results . Methods The results of the external quality assessment in the clinical Immunology participating in the National Center for Clinical and Laboratory and the Guangxi Center for Clinical Laboratory during 2009 - 2013 were performed the statistical analysis and sum‐mary .Results 600 samples were detected during these 5 years .The performance was worst in 2012 ,the annual coincidence rate of the results was 98% ;and which in other 4 years was 100% ;each 1 sample of result in the two items of anti‐HCV and anti‐TP was unconformity during these 5 years ,the total coincidence rate was 98 .6% ;the total coincidence rates of HBsAg ,HBsAb ,HBeAg , HBeAb ,HBcAb and anti‐HIV were 100% .Conclusion By participating in the external quality assessment of the clinical immunolo‐gy and retrospectively analyzing the results ,the possible problems would be found and some effective improvement measures could be formulated in time for improving the quality of examinations and ensuring to provide reliable laboratory data for clinic .

Function and clinical applications of bone morphogenetic proteins in bone repair / 国际生物医学工程杂志

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-β (TGF-β) superfamily, acting as important regulators in embryogenesis and bone and cartilage formation and repair.The complexity of BMPs action has early been unveiled by generous cell and molecular biology approaches and transgenic animal studies.Genetic engineering allows for the mass production of BMPs for clinical use of bone repair, but the desirable scaffold material is also needed to ensure controlled release and maximum biological activity of BMPs at the surgical site.Currently, BMP-2 and BMP-7 have been approved by United States Food and Drug Administration for clinical therapy in long bone fracture, spinal fusion and oral and maxillofacial surgery.The results are satisfactory, but the side effects have been also widely concerned.The functions and clinical applications of BMPs in bon repair are reviewed.

Imaging and quantitative analysis of early caries using optical coherence tomography / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To explore the efficacy of optical coherence tomography (OCT) in imaging and quantitatively evaluating early enamel caries and provide experimental evidence for the clinical diagnosis of early caries.</p><p><b>METHODS</b>The smooth surface of bovine teeth showing early artificial caries and demineralization changes was scanned by an all fiber-based OCT for images and optical profiles, which were compared with images from a polarized light microscope (PLM) and mineral loss from an atomic absorption spectrometer. Data were analyzed by paired-sample t-test and Pearson correlation analysis using SPSS software.</p><p><b>RESULTS</b>The images of enamel with early caries and demineralization from OCT coincided with those from PLM. The integrated reflectivity loss in the early caries group was significantly lower than that in the demineralized group (P < 0.05), whereas no significant difference in demineralized depth was found between the two groups (P > 0.05). A linear correlation was observed between integrated reflectivity loss and mineral loss (P < 0.05).</p><p><b>CONCLUSION</b>OCT can be used to nondestructively and accurately image early caries and quantify lesion extent and degree, suggesting the extensive use of this approach in the clinical diagnosis of early caries.</p>

Exposure risk assessment of plasticizer in dietary food in Xiamen / 中华预防医学杂志

<p><b>OBJECTIVE</b>To understand the dietary consumption of residents in Xiamen and the content of phthalic acid esters (PAEs) in food, and to assess the plasticizer exposure risk of diet in Xiamen.</p><p><b>METHODS</b>The survey was conducted by stratified cluster random sampling method in Xiamen from September to October in 2010. According to the Xiamen administrative division, six neighborhood communities were selected as sampling units, then 25 families were randomly chosen from each sampling units.From the above 150 families, the permanent residents over the age of six were permitted to our study. The survey included 495 residents totally. These participants' information, such as basic personal information, physical activity levels, meal frequency and the average consumption of 33 kinds of food in 13 categories were collected using questionnaires. Thirteen categories included cereal and tubers, beans, vegetables, fungi and algae, fruits, dairy products, meat, seafood, eggs, snacks, beverages, cooking oil and spices. The height and weight of residents were measured and the average daily dietary intake was calculated. Thirty-three kinds of food in 13 categories were collected in supermarkets in Xiamen. According to the annual sales ranking, the top three-five brands of each kinds of food were selected and numbered, then two or three brands were chosen by random number table method from them; three completely individual packed samples in the same batch of each brand were detected; 243 samples were included in our study.100-500 g solid samples or 100-500 ml liquid samples were collected. The content of diethyl phthalate (DEP), dibutyl phthalate (DBP), di (2-ethylhexyl) phthalate (DEHP) in food were detected by liquid chromatography mass spectrometry, which expressed by median (minimum-maximum). The exposure dose, contribution rate and risk index of PAEs were calculated by point estimation method.</p><p><b>RESULTS</b>According to the average daily dietary intake of residents in Xiamen, the top three ones in 13 categories of food were cereal and tubers (337.16 g/d, 18.21%), vegetables (309.12 g/d, 16.69%) and fruits (213.20 g/d, 11.51%). The content of DEP, DBP or DEHP among different categories of food was significantly different (χ² values were 58.05, 50.19 and 102.10, P < 0.01). Among 13 categories of food, seafood contained the most DEP (0.090 (0.000-0.324)mg/kg); cooking oil had the most DBP (0.700(0.000-2.980) mg/kg) and DEHP (5.115(0.000-24.160) mg/kg). DEP, DBP and DEHP exposure(0.19, 4.20, 18.10 µg × kg⁻¹ ×d ⁻¹)in dietary food in Xiamen were less than the reference dose(RfD) (800, 100, 20 µg × kg⁻¹ × d⁻¹) proposed by the United States Environmental Protection Agency (EPA), and the risk indexes were 0.02%, 4.20% and 90.50%, respectively. Among 13 categories of foods, seafood was the main source of DEP dietary exposure. The exposure dose and contribution rate of DEP in seafood were 0.18 µg × kg⁻¹ × d⁻¹ and 94.74%, respectively.Vegetables were the main source of DBP and DEHP dietary exposure. The exposure dose and contribution rate of DBP and DEHP were 1.48 µg × kg⁻¹ × d⁻¹, 35.24% and 6.07 µg × kg⁻¹ × d⁻¹, 33.54%, respectively.</p><p><b>CONCLUSION</b>The food consumed by residents in Xiamen was overall in a safe state, but to some extent, there still exists DEHP exposure risk in foods.</p>

Prospective efficacy of chronic sinusitis lost to short-term follow up after nasal endoscopic surgery / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the prospective efficacy of chronic sinusitis lost to short-term follow up after nasal endoscopic surgery and the influential factors.@*METHOD@#Prospective efficacy of 153 chronic sinusitis (CRS) was evaluated . All cases were treated by nasal endoscopic surgery at least 1 year ago but lost to follow up within 3 months after surgery. The clinical data of 153 patients were analyzed, including gender, age, educational level, course of the disease, smoking and drinking history, early surgery history, allergic rhinitis (AR) history, nasal polyps, visual analogue scale (VAS) score, nasal endoscopy score, CT examination score, the endoscopic experience of surgeons, medication of intranasal glucocorticoid and nasal irrigation after surgery. Multifactor logistic regression analysis were used to analyze the data.@*RESULT@#Among 153 patient, the symptoms of 32 cases (20.9%) were completely control, while those of 74 cases (48.4% ) were partially control, and the symptoms of 47 cases (30.7%) were not controlled. The curative effect were better for CRS without nasal polyps, AR or early surgery history, with CT examination score < or = 5, operated by surgeons with experience of endoscopy surgery for more than 5 years. and treated with intranasal glucocorticoid for more than -1 weeks after surgery.@*CONCLUSION@#Postsurgery follow-up should be paid more attention to in treatment of CRS. Plans of follow up should be adjusted to patients condition. Treatment of postoperative sinus cavity should be minimized when the lesion is slight and operated properly.

The changes of carbonic anhydrase activity and its mRNA expression in rats cochlea after noise exposure / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the changes of carbonic anhydrase (CA) activity and its mRNA expression in rats cochlea after noise exposure.@*METHOD@#Twenty-four healthy Sprague Dawley rats were randomly allocated into 4 groups including 1 control group without contact of noise and 3 experimental groups exposed to a narrowband white noise of 4 kHz, 110 dB SPL 4h/d for 1 day, 1 week and 3 weeks, respectively. ABR thresholds were tested for each group at the time points described above. An immunohistochemical method was used to detect the expression of CA in the cochlea tissue. Differences in CAII mRNA expressions with and without noise exposure were examined using RT-PCR.@*RESULT@#The thresholds of ABR in noise exposed cochlea were increased compared with the control cochlea (P < 0.01). CA activity and the CAII mRNA expression in noise exposed cochlea were decreased compared with the control cochlea (P < 0.01). The increase of ABR thresholds and decreases of CA activity and the CAII mRNA expression showed a time dependent pattern as the extension of duration exposed to noise.@*CONCLUSION@#Noise exposure could downregulate the CA activity and CAII mRNA expression in the cochlea. CA was proably involved in the pathogenesis of noise-induced hearing loss.

Research progress on tumor targeting of splice variants / 中国肿瘤临床

Splice variants are transcripts that exhibit various functions or activities and are obtained from alternative splicing of precursor mRNA. An increasing number of tumor-specific splice variants are being discovered and their roles in cancer development and progression are being investigated. In this study, the expression patterns and activities of tumor-specific splice variants were charac-terized. The results suggest that a variant-specific gene therapy that targets cancer cells would be more specific and would have minimal effect on healthy tissues. Using antisense oligonucleotides, mRNA that contributed to cancer cell survival and altered splicing patterns was downregulated in a clinical trial. The results provide a new appreciation for the gene therapy of cancer. Identification of novel tu-mor-specific splice variants and constant improvement of therapeutic strategies by modifying splicing patterns can lead to the develop-ment of more effective and safer cancer therapies.