Clinical value of plasma scaffold protein SEC16A in evaluating hepatitis B-related liver cirrhosis and hepatocellular carcinoma / 中华肝脏病杂志

Objective: To investigate the clinical value of plasma scaffold protein SEC16A level and related models in the diagnosis of hepatitis B virus-related liver cirrhosis (HBV-LC) and hepatocellular carcinoma (HBV-HCC). Methods: Patients with HBV-LC and HBV-HCC and a healthy control group diagnosed by clinical, laboratory examination, imaging, and liver histopathology at the Third Hospital of Hebei Medical University between June 2017 and October 2021 were selected. Plasma SEC16A level was detected using an enzyme-linked immunosorbent assay (ELISA). Serum alpha-fetoprotein (AFP) was detected using an electrochemiluminescence instrument. SPSS 26.0 and MedCalc 15.0 statistical software were used to analyze the relationship between plasma SEC16A levels and the occurrence and development of liver cirrhosis and liver cancer. A sequential logistic regression model was used to analyze relevant factors. SEC16A was established through a joint diagnostic model. Receiver operating characteristic curve was used to evaluate the clinical efficacy of the model for liver cirrhosis and hepatocellular carcinoma diagnosis. Pearson correlation analysis was used to identify the influencing factors of novel diagnostic biomarkers. Results: A total of 60 cases of healthy controls, 60 cases of HBV-LC, and 52 cases of HBV-HCC were included. The average levels of plasma SEC16A were (7.41 ± 1.66) ng/ml, (10.26 ± 1.86) ng/ml, (12.79 ± 1.49) ng /ml, respectively, with P < 0.001. The sensitivity and specificity of SEC16A in the diagnosis of liver cirrhosis and hepatocellular carcinoma were 69.44% and 71.05%, and 89.36% and 88.89%, respectively. SEC16A, age, and AFP were independent risk factors for the occurrence of HBV-LC and HCC. SAA diagnostic cut-off values, sensitivity, and specificity were 26.21 and 31.46, 77.78% and 81.58%, and 87.23% and 97.22%, respectively. The sensitivity and specificity for HBV-HCC early diagnosis were 80.95% and 97.22%, respectively. Pearson correlation analysis showed that AFP level was positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and γ-glutamyltransferase (GGT) with P < 0.01, while the serum SEC16A level was only slightly positively correlated with ALT and AST in the liver cirrhosis group (r = 0.268 and 0.260, respectively, P < 0.05). Conclusion: Plasma SEC16A can be used as a diagnostic marker for hepatitis B-related liver cirrhosis and hepatocellular carcinoma. SEC16A, combined with age and the AFP diagnostic model with SAA, can significantly improve the rate of HBV-LC and HBV-HCC early diagnosis. Additionally, its application is helpful for the diagnosis and differential diagnosis of the progression of HBV-related diseases.

Annual Frequency in Traditional Chinese Medicine Physique, Syndrome Differentiation and Western Medicine Staging of 482 Eczema Patients / 中国实验方剂学杂志

Objective:To make statistics on the annual frequency of patients with eczema by traditional Chinese medicine (TCM) physique, syndrome differentiation, and western medicine staging based on questionnaire survey, in order to infer the distribution and characteristics of the annual frequency by different TCM physique, syndrome differentiation and western medicine stage, and provide new ideas and new methods for the prevention and treatment of Eczema. Method:According to the Dermatovenerology of Traditional Chinese Medicine edited by QU Xing, and Clinical Diagnosis and Treatment of Chinese Medicine for Dermatovenerology edited by CHEN Da-can, and Traditional Chinese Medicine for Dermology edited by YU Wen-qiu, and Physique Classification and Patient Self-Testing Table formulated by China Association of Chinese Medicine and Professor WANG Qi's nine categories of physique, the TCM Physique Classification and Patient Self-Testing Table for eczema patients and the Syndrome Differentiation and Classification Table for Eczema Patients were formulated. General conditions of 482 cases of eczema patients treated at Tianjin Academy of Traditional TCM Affiliated Hospital and their types of TCM physique, TCM syndrome differentiation, western medicine staging and annual frequency were surveyed. Result:There were significant differences in the annual frequency of patients with different physical constitutions. By single physique, Tanshi, Shire and Qiyu had more frequent occurrences every year, and Pinghe had the lowest annual frequency. There were differences in the annual occurrences among cases with different TCM syndrome types. Shire syndrome patients have more frequent annual occurrences than other types of eczema patients. There were significant differences in the annual occurrences among cases of different western medicine staging, and the annual occurrences of acute eczema were more than those of subacute and chronic eczema. Conclusion:The annual occurrences of patients with Tanshi, Shire and Qiyu physique were higher than those of other physiques. There are fewer outpatients with Pinghe physique than other physiques. The annual occurrences of Shire syndrome patients are higher than that of other types of eczema patients. The annual occurrences of acute eczema are more than those of subacute and chronic eczema. The annual occurrences of chronic eczema are less than acute and subacute eczema.

A national trauma database analysis of alcohol- associated injuries

INTRODUCTION@#Knowledge of the pattern of alcohol-associated injury (AAI) is lacking in Singapore. We aimed to determine the local demographic pattern, injury mechanism, injury severity and outcomes of AAI.@*METHODS@#Data on trauma cases presenting to emergency departments in 2012-2013 was extracted from the National Trauma Registry. Cases with missing data fields and those aged 1-15 years were excluded. Patients were classified as alcohol positive (A+) or negative (A-) based on clinical assessment. The two groups' demographics, injury mechanism, injury severity, mortality and disposition were compared. Logistic regression analysis was used to determine independent associations with mortality.@*RESULTS@#105,468 trauma cases met the inclusion criteria. 3.9% were A+ and their peak age range was 25-44 years. The A+ group had more Indian males (p 44 years and male gender as independent predictors of mortality.@*CONCLUSION@#AAI in Singapore is associated with more severe injuries and resource utilisation. Using data from the registry, 'at risk' demographic groups are identified for targeted injury prevention. However, alcohol use is not an independent predictor of mortality in trauma cases.

Research Progress in Molecular Mechanism of TCM for Protection and Treatment of Pulmonary Fibrosis / 中国中医药信息杂志

Pulmonary fibrosis is a kind of intractable disease threatening human health in the respiratory system, which heavily affects life quality of patients. The current Western medicine in clinical drug treatment still does not have significant efficacy, with adverse reactions. In recent years, TCM has shown unique advantages in pulmonary fibrosis models of animals experimental study. This article reviewed the research progress in molecular mechanism of TCM for the protection and treatment of pulmonary fibrosis, discussed its action targets, and provide references for the clinical research and treatment of pulmonary fibrosis.

Prevalence of depressive symptoms among adolescents / 预防医学

Objective To evaluate the prevalence of depressive symptoms and influencing factors among adolescents. Methods A total of 635 students aged 13 to 18 years were selected in March 2017 and were investigated with general information questionnaire, CES-D and CTQ-SF. Results 630 questionnaires are effective and the positive rate of depression was 29.84％(188/630) . The average score of CTQ was 32.15±2.98; 38.73％ of the students were disregarded and only 2.22％ of that were abused during their childhood. 40.00％ of the students had no CTQ, 1 kinds of CTQ accounted for 31.43％ , 2 kinds of CTQ accounted for 18.25％, and more than 3 CTQ accounted for 10.32％. Multivariate logistic regression analysis show that gender (OR=1.034, 95％ CI: 1.012-1.056) , parents' marital status (OR=1.124, 95％ CI: 1.087-1.162) , family atmosphere (OR=1.025, 95％ CI: 1.024-1.158) , CTQ cumulative number (ORCTQ=1=1.528, 95％ CI: 1.214-1.923; ORCTQ=2=3.067, 95％ CI: 1.325-7.102; ORCTQ≥3=10.361, 95％ CI: 3.059-35.093) were the risk factors for depression. Conclusion Gender, parents' marital status, family atmosphere and CTQ cumulative number were risk factors for depression in adolescents.

Serum C-reactive protein level in COPD patients stratified according to GOLD 2011 grading classification

Background and Objective: The Global Initiative for Chronic Obstructive Lung Disease [GOLD] 2011 grading classification has been used to evaluate the severity of patients with chronic obstructive pulmonary disease [COPD]. However, little is known about the relationship between the systemic inflammation and this classification. We aimed to study the relationship between serum CRP and the components of the GOLD 2011 grading classification

Methods: C-reactive protein [CRP] levels were measured in 391 clinically stable COPD patients and in 50 controls from June 2, 2015 to October 31, 2015 in the First Affiliated Hospital of Xiamen University. The association between CRP levels and the components of the GOLD 2011 grading classification were assessed

Results: Correlation was found with the following variables: GOLD 2011 group [0.240], age [0.227], pack year [0.136], forced expiratory volume in one second % predicted [FEV1%; -0.267], forced vital capacity % predicted [-0.210], number of acute exacerbations in the past year [0.265], number of hospitalized exacerbations in the past year [0.165], British medical Research Council dyspnoea scale [0.121], COPD assessment test score [CAT, 0.233]. Using multivariate analysis, FEV1% and CAT score manifested the strongest negative association with CRP levels

Conclusions: CRP levels differ in COPD patients among groups A-D based on GOLD 2011 grading classification. CRP levels are associated with several important clinical variables, of which FEV1% and CAT score manifested the strongest negative correlation

Study of using an individualized treatment strategy to treat patients with chronic hepatitis C / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the outcomes of chronic hepatitis C (CHC) patients treated with antiviral regimens of interferon (IFN) plus ribavirin (RBV) using individualized doses and durations.</p><p><b>METHODS</b>This study was designed as an open-label, prospective clinical trial to analyze the virological responses of 169 CHC patients who received individualized dosages of IFNa-2b or pegylated (Peg)IFNa-2a combined with RBV based on their weight ( less than 60 kg or more than or equal to 60 kg), age (less than 65 years or 65-75 years), morbid state (liver cirrhosis or not), and complications (such as heart disease, diabetes, thyroid disorder). Treatment duration was calculated using the time required to induce HCV RNA negativity. The rates of virological response and adverse effects among the different groups were compared.</p><p><b>RESULTS</b>The IFNa-2b treatment was given to 116 patients, and PegIFNa-2a was given to 53 patients. Compared to the IFNa-2b group, the PegIFNa-2a group showed significantly higher rates of complete early virological response (cEVR; 76.7% vs. 92.5%, P less than 0.05) and sustained virological response (SVR; 53.6% vs. 92.3%, P less than 0.05) among the patients who had completed their course of treatment; the rapid virological response (RVR) rate was also higher for the PegIFNa-2a group but the difference did not reach statistical significance (48.7% vs. 60.4%, P more than 0.05). Seventy-eight patients received the routine dose, and 91 patients received the low dose; there were no significant differences between these two groups for RVR (53.8% vs. 58.9%, P more than 0.05), cEVR (78.0% vs. 80.8%, P more than 0.05), or SVR (65.5% vs. 58.3%, P more than 0.05).</p><p><b>CONCLUSION</b>Use of an individualized antiviral treatment strategy designed according to the patient's baseline condition, early viral kinetics, and tolerability to adverse reactions can achieve a high rate of SVR, as well as improve the safety, prognosis, and cost-effectiveness associated with treating CHC patients.</p>

Activation of Fas/FasL and its downstream signaling pathway promotes development of alcoholic steatohepatitis and liver fibrosis in mice / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the role and mechanism of the Fas/Fas ligand (FasL) system and its downstream signaling pathway related to the progression of alcoholic steatohepatitis and liver fibrosis.</p><p><b>METHODS</b>Eighteen C57BL/6J mice were randomly divided into three groups: controls; alcoholic steatohepatitis model, given four-weeks of a 4% ethanol-containing Lieber-DeCarli liquid diet; alcoholic steatohepatitis and liver fibrosis model, given the four-week alcohol diet followed by twice weekly intraperitoneal injections of carbon tetrachloride (5% olive oil solution; 2 mL/kg dose) during the fifth to eighth weeks. Mice in the model groups were sacrificed at the end of week 4 and 8, respectively, along with control mice for comparative analyses. Liver tissue sections were evaluated for hepatocellular apoptosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The mRNA expression of Fas, FasL, cysteine aspartate-specific proteases 3 (caspase 3), and cytochrome P450 2E1 (CYP 2E1) in liver tissues was detected by reverse transcription (RT)-PCR, visualized by ethidium bromide staining, and normalized to the gray-value of GAPDH expression. The protein expression of Fas and caspase 3 were detected by western blotting (b-actin normalized), and of FasL and CYP 2E1 by immunohistochemistry staining. Intergroup differences and statistical significance were evaluated by single factor analysis of variance and the least squares difference-t test or the Kruskal-Wallis H test and the Mann-Whitney U test.</p><p><b>RESULTS</b>The number of apoptotic cells in the liver sections was significantly higher in both model groups with alcoholic steatohepatitis (vs. controls) and the amount in the alcoholic steatohepatitis plus liver fibrosis model was significantly higher than that in the model with only alcoholic steatohepatitis. In addition, activation of Fas, FasL and its downstream signaling pathway showed an increasing trend with extent of liver injury. The hepatic mRNA (by RT-PCR) and protein (by western blotting) normalized expression levels in the controls, alcoholic steatohepatitis models, and alcoholic steatohepatitis plus liver fibrosis models were, respectively: Fas mRNA: 0.50+/-0.05, 0.61+/-0.10, 0.76+/-0.03 (H=12.137, P less than 0.05), protein: 0.52+/-0.14, 0.86+/-0.10, 0.99+/-0.09 (F=12.758, P less than 0.01); FasL mRNA: 0.31+/-0.03, 0.53+/-0.02, 1.02+/-0.04 (F=153.260, P less than 0.01); caspase 3 mRNA: 0.86+/-0.11, 0.85+/-0.05, 1.33+/-0.16 (F=8.740, P less than 0.01), protein: 0.40+/-0.03, 0.69+/-0.06, 1.02+/-0.10 (F=90.785, P less than 0.01); CYP 2E1 mRNA: 0.72+/-0.14, 1.00+/-0.15, 1.30+/-0.20 (H=4.713, P less than 0.01). The changes in hepatic FasL and CYP 2E1 expression detected by immunohistochemistry were consistent with the mRNA expression.</p><p><b>CONCLUSION</b>Activation of Fas/FasL and its downstream signaling pathway, which induces hepatocellular apoptosis, contributes to the development of alcoholic steatohepatitis and liver fibrosis.</p>

Establishment of a complex alcoholic liver fibrosis mouse model and investigation of OPN and TGF-beta1 hepatic expression / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To create a convenient method to establish an alcoholic liver fibrosis model in mice and use it to explore the putative pathogenic mechanisms involving the immunomodulatory proteins osteopontin (OPN) and transforming growth factor-betal (TGF-beta1).</p><p><b>METHODS</b>Forty C57BLI6J mice were fed the Lieber-DeCarli 4% ethanol-containing liquid diet for four weeks, followed by an additional four weeks of the 4% ethanol diet combined with intraperitoneal injection of carbon tetrachloride (CC14 5% solution in olive oil; 2ml/ kg body weight, 2 times/week) to induce alcoholic liver fibrosis. Control groups (n = 6 each) included: normal diet; normal diet plus CCl4 injections; ethanol diet alone; ethanol diet plus solvent (olive oil) injections. Model establishment was monitored by sacrificing six mice at model inception (week 0), and weeks 4, 5, 6, 7, and 8 of modeling to collect liver tissues and blood for histological and biochemical analyses. Extent of hepatic steatosis, inflammation, and fibrosis was assessed by hematoxylin-eosin and Masson staining. Liver function markers, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, were tested by automated enzymatic assays. Alpha-smooth muscle actin (alpha-SMA) expression was detected by immunohistochemistry. The mRNA and protein expression of OPN and TGF-beta1 was detected by real-time quantitative reverse transcription-PCR and western blotting, respectively. Significance of differences between multiple groups was assessed by one-way ANOVA analysis followed by least significant difference t-test or Kruskal-Wallis H test followed by the Mann-Whitney U test.</p><p><b>RESULTS</b>Compared to the control groups, the group of mice administrated ethanol and CCl4 developed mild to moderate hepatic steatosis at week 4 of modeling, progressive necroinflammation and perisinusoidal and portal fibrosis from weeks 5-8, and irregular necrosis and bridging fibrosis at week 8. In addition, the model group showed progressive up-regulation of a-SMA expression in the activated hepatic stellate cells (HSCs) and fibrotic areas from weeks 5-8. Both hepatic OPN and TGF-beta1 showed significantly increasing trends in mRNA and protein expressions from weeks 5-8 (OPN mRNA: 1.83 +/- 0.25, 2.94 +/- 0.19, 3.45 +/- 0.31, and 5.99 +/- 0.17 (F= 476.27, P < 0.001); OPN protein: 0.52 +/- 0.06, 1.02 +/- 0.10, 1.52 +/- 0.11 and 1.50 +/- 0.08 (F= 298.03, P< 0.001); TGF-beta1 mRNA: 13.19 +/- 0.40, 3.31 +/- 0.28, 1.58 +/- 0.18 and 2.08 +/- 0.26 (F= 85.55, P < 0.001); TGF-P31 protein: 1.26 +/- 0.16, 0.96 +/- 0.12, 1.09 +/- 0.25 and 1.10 +/- 0.20 (F = 43.64, P < 0.001).</p><p><b>CONCLUSION</b>Feeding C57BL/6J mice the Lieber-DeCarli ethanol-containing liquid diet combined with CCl4 intraperitoneal injection is a convenient method to establish a model of alcoholic liver fibrosis within a relatively short amount of time (eight weeks). Progression of alcoholic liver fibrosis is accompanied by increased hepatic expression of OPN and TGF-beta1, which may contribute to the pathogenic mechanism of this disease and may be targets of future molecular therapies.</p>

Relation of IL-17 polymorphisms and serum levels in patients with chronic HCV infection / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the association of single nucleotide polymorphisms (SNPs) in the interleukin 17 (IL-17) gene and serum protein levels in patients with chronic hepatitis C virus (HCV) infection.</p><p><b>METHODS</b>A total of 228 patients with chronic HCV infection and 81 healthy controls were enrolled in the study. The frequencies of IL-17 rs8193036 and rs2275913 polymorphisms were detected by the TaqMan SNP genotyping assay. Serum levels of IL-17 protein were detected by ELISA. Pairwise comparisons were made by the Chi-square test, and the significance of between-group differences was assessed by the Student's t-test with P less than 0.05.</p><p><b>RESULTS</b>The patients with chronic HCV infection and the healthy controls showed similar frequencies of the rs8193036 C/T allele (x2 = 1.428, P = 0.232) and the rs2275913 A/G allele (x2 = 0.106, P = 0.744). In addition, the two groups showed similar distribution of the rs8193036 CC (chronic HCV infection: 46.49% vs. healthy controls: 41.98%), CT (45.61% vs. 44.44%) and TT (7.89% vs. 13.58%) genotypes (x2 = 2.346, P = 0.309), and of the rs2275913 AA (16.23% vs. 13.58%), AG (48.25% vs. 50.62%) and GG (35.53% vs. 35.80%) genotypes (x2 = 0.340, P = 0.844). Subgroup analysis of chronic HCV infection patients stratified according to HCV genotypes 1 and 2 showed no differences in the distribution of rs8193036 and rs2275913 alleles (x2 = 1.127, P = 0.288; x2 = 1.088, P = 0.297) and genotypes (x2 = 2.825, P = 0.246; x2 = 0.970, P = 0.616). However, the chronic HCV infection group did show significantly higher levels of serum IL-17 than the controls (97.67+/-39.68 vs. 71.60+/-19.78 pg/ml, t = 2.414, P = 0.033).</p><p><b>CONCLUSION</b>Chronic HCV infection is associated with increased serum IL-17; however, the IL-17 polymorphisms rs8193036 and rs2275913 were not associated with chronic HCV infection susceptibility in this study's Chinese cohort.</p>

Relationship between AKAP95, cyclin E1, cyclin D1, and clinicopathological parameters in lung cancer tissue / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the correlation between expression of A-kinase anchoring protein 95 (AKAP95) and protein expression of cyclin E1 and cyclin D1 in lung cancer tissue.</p><p><b>METHODS</b>Fifty-one cases of lung cancer were included in the study. The protein expression of AKAP95, cyclin E1, and cyclin D1 were measured by immunohistochemistry.</p><p><b>RESULTS</b>The protein expression of cyclin E1 in lung cancer tissues was significantly higher than that in para-cancerous tissues (positive rate: 75.56%vs 20%, P < 0.01); its expression showed no relationship with histopathological type, lymph node metastasis, and cellular differentiation (P > 0.05). The protein expression of cyclin D1 in lung cancer tissues was higher than that in para-cancerous tissues (positive rate: 69.39% vs 14.29%); its expression showed a significant relationship with histopathological type (P < 0.05). The expression of AKAP95 was correlated with the protein expression of cyclin E1 and cyclin D1 in lung cancer tissues (P < 0.01).</p><p><b>CONCLUSION</b>Cyclin E1 and cyclin D1 are highly expressed in lung cancer tissue, suggesting that they play an important role in the development and progression of lung cancer. The protein expression of cyclin E1 has no relationship with cellular differentiation, lymph node metastasis, and histopathological type of lung cancer, and the protein expression of cyclin D1 has a significant relationship with histopathological type. The expression of AKAP95 is correlated with the protein expression of cyclin E1 and cyclin D1 in lung cancer tissue.</p>

Role of the IGF-1/PI3K pathway and the molecular mechanism of Fuzhenghuayu therapy in a spontaneous recovery rat model of liver fibrosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To determine the role of IGF-1/PI3K pathway and investigate the molecular mechanism of Fuzhenghuayu (FZHY) therapy in a spontaneous recovery rat model of liver fibrosis.</p><p><b>METHODS</b>The liver fibrosis model was induced in male Wistar rats by administering 8 weeks of twice weekly CCL4 intraperitoneal injections without (untreated model) or with once daily FZHY (treated model). Normal, untreated rats served as the control group. At weeks 4, 6 and 8 (fibrosis) and 10, 12 and 14 (spontaneous recovery) after modeling initiation, effects on protein (a-SMA, IGF-1, PI3K) and mRNA (IGF-1, PI3K) expression levels were evaluated by immunohistochemistry and RT-PCR, respectively. Serum markers of liver function (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and liver cell damage (alkaline hydrolysis, HYP) were measured. Histology was performed to assess the degree of inflammation and fibrosis (Ishak scoring system).</p><p><b>RESULTS</b>In the untreated model group, progression of liver fibrosis (weeks 4, 6 and 8) was accompanied by gradual increases in inflammation, necrosis, serum ALT and AST, and hepatic expression of a-SMA protein and IGF-1 and PI3K protein and mRNA; however, during the spontaneous recovery period (weeks 10, 12 and 14) the IGF-1 and PI3K protein and mRNA levels rapidly decreased and the HYP level, Ishak score, and a-SMA hepatic expression also decreased. The FZHY-treated model group showed significantly lower fibrosis-related up-regulation of IGF-1 and PI3K protein and mRNA expression, HYP level, Ishak score, and a-SMA hepatic expression at each time point (vs. untreated model group).</p><p><b>CONCLUSION</b>The IGF-1/PI3K pathway may contribute to progression of liver fibrosis. The mechanism by which FZHY prevents liver fibrosis in a rat model may involve blocking of the IGF/PI3K pathway and inhibiting HSC activation.</p>

Peroxisome proliferator activated receptor gamma activation and overexpression prevent hepatocellular apoptosis of nutritional fibrotic steatohepatitis in mice / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To elucidate the effect of targeted gene modulation of peroxisome proliferator activated receptor gamma (PPARg) on hepatocellular apoptosis in nutritional fibrotic steatohepatitis in mice. C57BL/6J mice were fed with high fat, methionine-choline deficient (MCD) diet for 8 weeks to induce fibrotic steatohepatitis. Mice fed the MCD diet were treated with adenovirus carrying PPARg (Ad-PPARg), adenovirus-beta-galactosidase (Ad-LacZ), Ad-PPARg plus PPARg agonist rosiglitazone, or PPARg antagonist 2-chloro-5-nitro- benzanilide (GW9662), respectively. H and E stain was performed for observation of hepatocellular apoptosis, hepatic steatosis, inflammation and fibrosis in the liver sections. The expression levels of mRNA and protein of PPARg and apoptosis related genes, Fas, Fas Ligand (FasL), B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax) and cysteine-containing aspartate-specific proteases-3 (caspase-3) were detected by real-time RT-PCR and Western blot assay, respectively.</p><p><b>RESULTS</b>Mice fed with MCD diet for 8 weeks showed severe hepatic injury including steatosis, hepatocellular apoptosis, inflammatory infiltration and fibrosis, concomitancy with enhanced expression of pro-apoptosis genes, Fas, FasL, Bax and caspase-3 and increased expression of anti-apoptosis gene Bcl-2, by comparing with the control group. The mRNA expression levels of these genes were 3.59+/-0.35 vs 1.11+/-0.37, 4.37+/-1.03 vs 1.09+/-0.33, 4.27+/-0.48 vs 1.03+/-0.10, 4.93+/-0.67 vs 1.12+/-0.24 and 3.95+/-0.34 vs 1.20+/-0.19, and LSD-t values were 2.49, 3.28, 3.25, 3.80 and 2.75, as compared with the control group, P is less than 0.01; the protein expression levels were 1.96+/-0.07 vs 0.45+/-0.07, 0.53+/-0.07 vs 0.22+/-0.02, 1.32+/-0.06 vs 0.59+/-0.03, 1.51+/-0.23 vs 0.36+/-0.09 and 0.57+/-0.01 vs 0.29+/-0.01, and LSD-t values were 1.51, 0.31, 0.73, 1.14 and 0.28, P is less than 0.01. Administration of PPARg agonist rosiglitazone and/or Ad-PPARg significantly ameliorated hepatic steatosis, hepatocellular apoptosis, necro inflammation and fibrosis. These effects were associated with repressed expression of pro-apoptosis genes and up-regulated expression of anti-apoptosis gene. After rosiglitazone treatment, the mRNA expression levels were 3.78+/-0.58, 3.66+/-0.83, 3.04+/-0.37, 2.54+/-0.62 and 4.42+/-0.42, and LSD-t values were 0.18, 0.71, 1.23, 2.39 and 0.46, as compared with MCD group, the P values were 0.627, 0.241, less than 0.01, less than 0.01 and 0.278, the protein expression levels were 1.06+/-0.03, 0.30+/-0.01, 0.70+/-0.05, 1.19+/-0.30 and 0.90+/-0.01, and LSD-t values were 0.90, 0.23, 0.62, 0.31 and 0.34, the P values were less than 0.01, less than 0.01, less than 0.01, 0.122, less than 0.01. After Ad-PPARg treatment, the mRNA expression levels were 2.31+/-0.16, 2.71+/-0.23, 2.52+/-0.27, 1.79+/-0.32 and 5.97+/-0.72, and LSD-t values were 1.28, 1.66, 1.75, 3.13 and 2.02, as compared with MCD group, P is less than 0.05; the protein expression levels were 1.73+/-0.07, 0.43+/-0.04, 1.01+/-0.08, 1.31+/-0.10 and 1.56+/-0.04, and LSD-t values were 0.23, 0.10, 0.30, 0.20 and 0.99, with P values equal 0.009, 0.01, less than 0.01, 0.322 and less than 0.01.</p><p><b>CONCLUSIONS</b>This study provided evidences for the protective role of activation and overexpression of PPARg in ameliorating hepatocellular apoptosis in mice with hepatic fibrosing steatohepatitis.</p>

The role of Fas mutation on non-alcoholic steatohepatitis in mice / 中华肝脏病杂志

<p><b>OBJECTIVE</b>Our previous study indicated that the death receptor Fas played a key role on hepatocyte apoptosis in nutritional steatohepatitis in mice. This study aimed to explore whether Fas mutation accelerated hepatic steatosis and inflammatory infiltration in methionine-choline deficient (MCD) diet feeding mice.</p><p><b>METHODS</b>Mice homozygous for the lymphoproliferation spontaneous mutation (C57BL/6J-Faslpr) and wild type C57BL/6J mice were fed with MCD diet for three weeks to induce non-alcoholic steatohepatitis (NASH). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG) and total cholesterol (TC) levels were detected by an Olympus AU5400 automatic chemical analyzer. The role of Fas gene mutation on NASH was assessed by comparing the severity of hepatic steatosis and inflammation in the liver sections, the mRNA and protein expressions of hepatic inflammatory and fibrogenesis related factors, proliferating cell nuclear antigen (PCNA) and transforming growth factor beta 1 (TGFb1).</p><p><b>RESULTS</b>The serum ALT levels of the wild type and Faslpr mice fed with MCD were significant higher than that of the control mice (126.33+/-10.50 U/L vs (25.00+/-10.14) U/L, (160.33+/-48.29) U/L vs (18.33+/-9.08) U/L, with the LSD-t value 12.02, 5.08 respectively, the P value<0.001, 0.007 respectively. The serum ALT levels showed no significant difference between the Faslpr and wild type mice fed with MCD, with the LSD-t value 1.19, the P value 0.229. The serum AST, TG and TC levels showed neithere significant difference among the four groups. MCD diet induced hepatic steatosis and inflammatory infiltration in both of the wild type and Faslpr mice. Especially, severer hepatic injury was observed in Faslpr mice as compared with wild type mice. The mRNA expression levels of cell proliferation factor PCNA and fibrogenesis growth factor TGF b1 in wild type mice fed with MCD were significantly higher than that of the control mice (2.84+/-0.73, 2.77+/-0.54 vs 1.31+/-0.18, 0.89+/-0.18), with the LSD-t value 4.99, 8.08 respectively, the P value 0.001, <0.001 respectively. The mRNA expression levels of PCNA and TGFb1 in Faslpr mice fed with MCD were significantly higher than that of the Faslpr control mice and the wild type mice fed with MCD (5.57+/-1.13, 5.73+/-0.89 vs 1.04+/-0.16, 0.85+/-0.11 and 2.84+/-0.73, 2.77+/-0.54), with the LSD-t value 10.15, 13.19 and 5.33, 6.91 respectively, the P value<0.001. The protein expressions levels of PCNA and TGFb1 were concordant with the mRNA.</p><p><b>CONCLUSIONS</b>Faslpr promoted hepatic steatosis and inflammatory infiltration in mice fed with MCD diet, which might associated with excessive release of cell proliferative, inflammatory and fibrogenesis factors.</p>

The role of heme oxygenase-1 in non-alcoholic steatohepatitis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the potential role of heme oxygenase-1 on preventing non-alcoholic steatohepatitis (NASH) in mice.</p><p><b>METHODS</b>Experimental models of NASH were established by feeding male C57BL/6J mice with choline-methionine deficient diet (MCD) for four weeks. Control animals were fed with choline-methionine supplemented diet. The treatment groups were fed with MCD diet combined with HO-1 inducer hemin or inhibitor zinc protoporphyrin IX (ZnPP-IX). Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested by enzymic method with automatic biochemistry analyzer. The degree of hepatic steatosis, inflammation and fibrosis were examined under HE staining. The hepatic mRNA and protein expressions of HO-1, TNFalpha and IL-6 were analyzed by RT-PCR and Western blot respectively. MCD fed mice showed increased serum ALT and AST levels and moderate to severe hepatic steatosis with inflammatory infiltration, hepatic spot or focal necrosis, light portal and sinus hepaticus fibrosis in the liver sections, which associated with enhanced expression of HO-1, TNFalpha and IL-6 mRNA and protein (1.13+/-0.11, 1.74+/-0.05; 0.20+/-0.01, 1.92+/-0.10; 0.58+/-0.02, 2.06+/-0.05 vs 0.43+/-0.02, 0.75+/-0.05; 0.08+/-0.00, 0.59+/-0.02; 0.22+/-0.01, 0.91+/-0.02). Administration of hemin significantly decreased serum ALT and AST levels and attenuated hepatic steatosis and necroinflammation which associated with up-regulation of antioxidative gene HO-1 and down-regulation of pro-inflammatory cytokines TNFalpha and IL-6 (P < 0.01). A contrary effect on serum aminotransferase levels and liver histopathology was observed in mice injected with ZnPP-IX (P < 0.01).</p><p><b>CONCLUSIONS</b>The effect was associated with suppressed HO-1 expression and increased TNFaLPHA and IL-6 expression. The data provided a biochemical, morphological and molecular biological evidence for the protective role of HO-1 in ameliorating hepatic steatosis, necroinflammation in experimental nutritional steatohepatitis.</p>

Effects of arsenic trioxide on the autoimmunity and survival time in BXSB lupus mice / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of arsenic trioxide (ATO) on the autoimmunity and survival time in BXSB lupus mice.</p><p><b>METHODS</b>The model BXSB lupus mice were randomly divided into two groups equally, the ATO treated group and the control group, 17 in each group. Mice in the ATO group were given intraperitoneal injection of ATO at the daily dose of 0.4 mg/kg, once every other day for 105 days or 90 days, respectively, and the observation lasted for 210 days. The survival time between the two groups was compared; the serum levels of anti-dsDNA and IgG were detected by enzyme-linked immunosorbent assay (ELISA), and the interferon-gamma (IFN-gamma) mRNA expression in renal and spleen tissue were measured by reverse transcriptase polymerase chain reaction (RT-PCR) technique.</p><p><b>RESULTS</b>Till the 210th day, the total number of death was 8 in the ATO treated group and 13 in the control group, comparison between the two groups showed significantly different (chi2 = 4.20, P < 0.05). The mean OD value of serum anti-dsDNA antibody was lower in the ATO group (0.392 +/- 0.087) than that in the control group (0.566 +/- 0.080, P < 0.001). The serum level of IgG on day 105 in the ATO group was significantly lower than that in the control group and before treatment (P < 0.05). The expression of IFN-gamma mRNA in spleen tissue and renal tissue in the ATO group and the control group was 0.540 +/- 0.300 and 0.338 +/- 0.163, 2.320 +/- 0.522 and 0.588 +/- 0.104 (P < 0.05 and P < 0.01 respectively).</p><p><b>CONCLUSION</b>ATO can prolong the survival time of BXSB lupus mice, decrease the peripheral level of anti-dsDNA antibody and IgG expression, inhibit the over-expression of IFN-gamma mRNA in spleen and kidney tissues.</p>

Relationship between the activation of hepatic stellate cell and the early stage of liver fibrosis in experimental diabetic tree shrews / 基础医学与临床

Objective: To study the relationship between the activation of hepatic stellate cell(HSC) and the early stage of liver fibrosis in experimental diabetic tree shrews.Methods: Tree shrews were divided randomly into normal control group and streptozocin(STZ)-treated group.STZ-treated animals were then divided into diabetic group and STZ control group.ALT,AST,Type Ⅳ collagen(Ⅳ-C),Laminin(LN) and Hyaluronic acid(HA) were detected respectively before and after modelling.Liver biopsy was performed at the end of the experiment(8th week).All of the liver specimens were observed in light microscope and transmission electron microscope.?-smooth muscle actin(?-SMA) was detected by immunohistochemistry and computer image analysis system.Results: Early fibrosis of the liver in diabetic tree shrews can be found by both light and electron microscope.There were some ?-SMA positive HSCs,namely,activated HSCs could be observed in the liver of diabetic group but not in other two groups.The expression of ?-SMA increased significantly in the liver of diabetic group as compared with that of other two groups.In addition,the level of expression of ?-SMA was positively correlated with the collagen area density in diabetic group.Conclusion HSC may play an important role in the development and aggravation of liver fibrosis in diabetic tree shrews.

Relationship between insulin resistance and serum levels of adiponectin,leptin and erythrocyte membrane insulin receptor in patients with gestational diabetes / 中华全科医师杂志

Objectives To investigate changes in serum levels of adiponectin,leptin and erythrocyte membrane insulin receptor among patients with gestational diabetes (GDM),and to study their relation to insulin resistance.Methods Fasting plasma glucose (FPG),fasting serum insulin (FINS), serum levels of adiponeetin and leptin,indices of lipid metabolism,2 h plasma glucose during oral glucose tolerance test (2 h PG),2 h serum insulin during oral glucose tolerance test (2 h INS),as well as number of erythrocyte membrane insulin receptors with high and low appetency and its constants,were determined in 40 patients with GDM and 34 controls with normal glucose tolerance.Insulin resistance index (IRI) was calculated.Results ① Serum levels of leptin and adiponectin were (11.7?2.8) ?g/L and (7.8?1.6) ?g/L,respectively,and number of high appeteney erythrocyte membrane insulin receptor (R_1) and low appetency erythrocytemembrane insulin receptor (R_2) was (43?9) / red cell and (2297?525) / red cell,respectively.Serum level of leptin was significantly higher in those with GDM than those of normal controls (P

The relationship between insulin resistance and erythrocyte insulin receptors in patients with gout as- sociated with macroalbruminuria / 中华风湿病学杂志

Objective To investigate the relationship between insulin resistance and erythrocyte in- sulin receptors in patients with gout associated with macroalbruminuria(MAU).Methods FBG,PBG,FINS, P2hINS,CH,TG,HDL,LDL-c,UA and erythrocyte insulin receptors were determined in 44 patients with MAU,62 patients with normal MAU(NMAU).Results In MAU,the levels of FINS,TG,LDL-c and HOMA-IR were(16?4)mU/L,(2.5?0.6)retool/L,(3.2?0.5)mmol/L and 3.6~1.2 respectively.While they were(13?3) mU/L,(2.3?0.8)mmol/L,(3.0?0.5)mmol/L and 3.0~0.4 in NMAU group.The levels of FINS,TG,LDL-c and HOMA-IR were significantly higher in the MAU patients than those in NMAU patients(P

Relationship between the polymorphism of angiotensin converting enzyme gene and vascular complications in type 2 diabetes in Guangxi region / 中国实用内科杂志

Objectives To investigate the relationship between the insertion and deletion (I/D) polymorphism of human angiotensin converting enzyme (ACE) gene and the vascular complications in type 2 diabetes. Methods The I/D polymorphism of ACE gene was detected by polymerase chain reaction in 120 type 2 diabetic patients and 100 healthy controls. Results The frequency of DD genotype was significantly higher, while frequency of II genotype was lower in diabetic nephropathy patients (DN) than those in control group. The frequency of ID genotype was significantly higher, while frequency of II genotype was lower in type 2 diabetic patients with coronary heart disease (CHD), when compared to those without CHD. The frequencies of ACE genotypes in patients with diabetic retinopathy (DR) or hypertension (HP) were not different from those in control group and non-DR or non- HP patients. Conclusions ① There were relationships between the I/D polymorphism of ACE gene and DN and CHD in type 2 diabetes. ② The DD genotype and D allele of ACE gene might be as markers in predisposing DN, while II genotype and I allele as protective factors for DN in diabetes. The ID genotype might be as a marker in predisposing CHD, while II genotype as a protective factor for CHD in diabetes.③ There was no relationship between I/D polymorphism of ACE gene and HP or DR in diabetes in Guangxi region.