Clinical and histological features of patients with chronic hepatitis B virus infection in the grey zone.

Chronic HBV infection patients who do not conform to any of the usual immune states are regarded as 'grey zone' patients. We aimed to investigate the proportion of chronic HBV infection patients in the grey zone, and evaluate the clinical characteristics and liver pathological changes in grey zone patients. Clinical data of 1391 treatment-naive chronic HBV infection patients with liver biopsy were collected. Natural history of HBV infection was determined based on European Association for the Study of the Liver (EASL) 2017, American Association for the Study of Liver Diseases (AASLD) 2018 and Chinese 2019 guidelines for the prevention and treatment of chronic HBV infection. Significant liver histological changes and associated risk factors of normal ALT grey zone patients were analysed. According to EASL, AASLD and Chinese criteria, there were 50.0%, 28% and 37.4% chronic HBV infection patients in the grey zone. Among the 353 grey zone patients with normal ALT, 72.4% had significant liver histological changes. ALT (optimal cut-off value 25 IU/L) and HBV DNA (optimal cut-off value 18,000 IU/mL) were independent risk factors of significant liver histological abnormalities. In conclusion, a substantial proportion of grey zone patients with normal ALT have significant liver histological changes that can be predicted by levels of serum ALT and HBV DNA. These results provide guidance of antiviral treatment in grey zone patients.

Influence of physical activity at a young age and lifetime physical activity on the risks of 3 obesity-related cancers: systematic review and meta-analysis of observational studies.

CONTEXT: Excess weight has been linked to increased risks of 13 types of cancers. Physical activity is a non-nutritional modifiable lifestyle factor that is not only crucial for weight control but is also known to regulate hormones and metabolic pathways that may contribute to carcinogenesis. There is solid evidence that being physically active during middle and late adulthood lowers the risks of 3 obesity-related cancers, namely breast cancer, colon cancer, and endometrial cancer. However, the associations between physical activity at a young age (childhood, adolescence, and young adulthood; age 5 to ≤30 yr) and lifetime physical activity and the risks of breast cancer, colon cancer, and endometrial cancer are less defined. OBJECTIVE: The present systematic review and meta-analysis of observational studies was performed in accordance with the MOOSE guidelines to determine whether physical activity at a young age and lifetime physical activity may lower the risks of breast cancer, colon cancer, and endometrial cancer. DATA SOURCES: The PubMed and Web of Science databases were searched for relevant observational studies published from inception to July 2018. STUDY SELECTION: Observational studies (prospective cohort, case-cohort, nested case-control, historical cohort, and case-control) were considered relevant if they investigated the association between physical activity at a young age or lifetime physical activity and the risks of developing selected cancers. DATA EXTRACTION: A random-effects meta-analysis was performed to generate the summary relative risk (RR) with 95%CI for the highest vs the lowest category of physical activity of any type. RESULTS: Eighty publications were included in the present meta-analysis. Higher physical activity at a young age was associated with lower risks of breast cancer (RR 0.81, 95%CI 0.76, 0.87) and colon cancer (RR 0.67, 95%CI 0.50, 0.88). Similarly, lifetime physical activity was inversely associated with the risks of breast cancer (RR 0.79, 95%CI 0.72, 0.86) and colon cancer (RR 0.75, 95%CI 0.69, 0.82). For breast cancer, menopausal status did not appear to modify the observed inverse association. The benefit with respect to endometrial cancer risk reduction was only observed with higher lifetime physical activity (RR 0.77, 95%CI 0.67, 0.88), not with higher physical activity at a young age (RR 0.89, 95%CI 0.73, 1.07). CONCLUSIONS: Being physically active over a lifetime, starting from early childhood, may lower the risks of developing breast cancer, colon cancer, and endometrial cancer.

Associations Between the Knowledge of Different Food Categories and Glycemia in Chinese Adult Patients With Type 2 Diabetes.

This study aims to evaluate the levels of knowledge of different food categories and analyze the association between the levels of dietary knowledge and glycemia in Chinese adult patients with type 2 diabetes mellitus (T2DM). A cross-sectional study design was adopted. A total of 334 patients with T2DM were recruited from six hospitals from July to October 2014 in China. The Diabetes Dietary Knowledge Scale was utilized to obtain dietary knowledge. The results showed the item examining knowledge of carbohydrates received the highest score, whereas the item examining knowledge of healthy fats received the lowest score. The item "nuts" (B = -0.49; 95% confidence interval [CI] = [0.38, 0.99]) was associated with the incidence of hyperglycemia. The item "foods when hypoglycemic" (B = 0.42; 95% CI = [1.22, 2.07]) was associated with the incidence of hypoglycemia. There were different knowledge levels of different food categories in patients with T2DM, and these have implications for blood glucose control.

Population genetics, phylogenomics and hybrid speciation of Juglans in China determined from whole chloroplast genomes, transcriptomes, and genotyping-by-sequencing (GBS).

Genomic data are a powerful tool for elucidating the processes involved in the evolution and divergence of species. The speciation and phylogenetic relationships among Chinese Juglans remain unclear. Here, we used results from phylogenomic and population genetic analyses, transcriptomics, Genotyping-By-Sequencing (GBS), and whole chloroplast genomes (Cp genome) data to infer processes of lineage formation among the five native Chinese species of the walnut genus (Juglans, Juglandaceae), a widespread, economically important group. We found that the processes of isolation generated diversity during glaciations, but that the recent range expansion of J. regia, probably from multiple refugia, led to hybrid formation both within and between sections of the genus. In southern China, human dispersal of J. regia brought it into contact with J. sigillata, which we determined to be an ecotype of J. regia that is now maintained as a landrace. In northern China, walnut hybridized with a distinct lineage of J. mandshurica to form J. hopeiensis, a controversial taxon (considered threatened) that our data indicate is a horticultural variety. Comparisons among whole chloroplast genomes and nuclear transcriptome analyses provided conflicting evidence for the timing of the divergence of Chinese Juglans taxa. J. cathayensis and J. mandshurica are poorly differentiated based our genomic data. Reconstruction of Juglans evolutionary history indicate that episodes of climatic variation over the past 4.5 to 33.80 million years, associated with glacial advances and retreats and population isolation, have shaped Chinese walnut demography and evolution, even in the presence of gene flow and introgression.

Correlation between circulating miR-122 and prognosis of chronic HBV-related liver failure.

OBJECTIVE: To assess the correlation between circulating microRNA (miR)-122 level and the prognosis of chronic hepatitis B-related liver failure (CHBLF). METHODS: Serum miR-122 from CHBLF patients (n = 6) and healthy controls (n = 6) was quantified using an Exiqon locked nucleic acid microarray. Quantitative real-time polymerase chain reaction was utilized to determine serum miR-122 expression in 102 patients with different liver diseases [CHBLF (n = 58), acute hepatitis B (n = 10), chronic hepatitis B (n = 22) and hepatitis B-related cirrhosis (n = 12)] and 23 healthy controls. The correlations between miR-122 and disease stages based on prothrombin activity (PTA) and model for end-stage liver disease (MELD) scores were further analyzed. RESULTS: Microarray showed that miR-122 was significantly upregulated among 148 significantly modified miRNAs in CHBLF patients. Serum level of miR-122 in CHBLF patients was significantly upregulated at early stage based on PTA or stages I-II based on MELD score. Interestingly, there was a significant correlation between the MELD score and circulating miR-122 level in patients with an MELD score of <30 (r = 0.521, P = 0.001). Moreover, serum level of miR-122 was significantly decreased at discharge compared with that at admission as shown in the same group of CHBLF patients (P < 0.05). CONCLUSIONS: Serum level of miR-122 is correlated with the severity of liver injury at an early stage. miR-122 may be a potential biomarker for both the diagnosis at an early stage of CHBLF and the prognosis for recovery.

De novo assembly and characterization of the leaf, bud, and fruit transcriptome from the vulnerable tree Juglans mandshurica for the development of 20 new microsatellite markers using Illumina sequencing.

Manchurian walnut (Juglans mandshurica Maxim.) is a vulnerable, temperate deciduous tree valued for its wood and nut, but transcriptomic and genomic data for the species are very limited. Next generation sequencing (NGS) has made it possible to develop molecular markers for this species rapidly and efficiently. Our goal is to use transcriptome information from RNA-Seq to understand development in J. mandshurica and develop polymorphic simple sequence repeats (SSRs, microsatellites) to understand the species' population genetics. In this study, more than 47.7 million clean reads were generated using Illumina sequencing technology. De novo assembly yielded 99,869 unigenes with an average length of 747 bp. Based on sequence similarity search with known proteins, a total of 39,708 (42.32 %) genes were identified. Searching against the Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG) identified 15,903 (16.9 %) unigenes. Further, we identified and characterized 63 new transcriptome-derived microsatellite markers. By testing the markers on 4 to 14 individuals from four populations, we found that 20 were polymorphic and easily amplified. The number of alleles per locus ranged from 2 to 8. The observed and expected heterozygosity per locus ranged from 0.209 to 0.813 and 0.335 to 0.842, respectively. These twenty microsatellite markers will be useful for studies of population genetics, diversity, and genetic structure, and they will undoubtedly benefit future breeding studies of this walnut species. Moreover, the information uncovered in this research will also serve as a useful genetic resource for understanding the transcriptome and development of J. mandshurica and other Juglans species.

Identifying at-risk foot among hospitalized patients with type 2 diabetes: A cross-sectional study in one Chinese tertiary hospital.

OBJECTIVE: To investigate the prevalence of diabetic at-risk foot and its associated factors. METHODS: A total of 838 hospitalized patients with type 2 diabetes were screened for at-risk foot. Neural and vascular disorders were evaluated by assessing vibration perception thresholds and ankle brachial indexes (ABIs). After excluding 12 patients with abnormally high ABIs, remaining individuals with neural and/or vascular disorder were identified as at-risk patients and further classified into three subtypes: isolated neural disorder, isolated vascular disorder and mixed disorder. Potential associated factors were examined using Logistic regression models. RESULTS: In the final sample of 826 individuals, the prevalence of diabetic at-risk foot was 30.6%. Among all at-risk patients, isolated neural disorders (69.6%) were more common than mixed (16.2%) or isolated vascular disorders (14.2%). Isolated neural and vascular disorders shared specific risk factors, including age per 20-year increment (odds ratio [95% CI], 3.73 [2.59-5.37] and 4.01 [1.98-8.11]), diabetic duration ≥10 years (1.69 [1.13-2.54] and 3.29 [1.49-7.24]) and systolic blood pressure ≥140 mmHg (1.96 [1.31-2.93] and 2.90 [1.38-6.10]) respectively. In addition, isolated neural disorders were associated with a heavy smoking history (95%CI 2.69 [1.15-6.31]), increased high-sensitivity C-reactive protein levels (95%CI 1.30 [1.04-1.62]) and mild obesity (95%CI 0.49 [0.20-1.24]). Isolated vascular disorders were linked with decreased high density lipoprotein (HDL) cholesterol levels (95%CI 3.42 [1.31-8.96]) and increased triglycerides levels (95%CI 2.74 [1.26-5.97]). CONCLUSIONS: Diabetic at-risk foot is epidemic among hospitalized patients with type 2 diabetes. Aging, long-term diabetes, hypertension, smoking, inflammatory response and dyslipidemia may be associated with the prevalence of diabetic at-risk foot.

IL28B genetic variations are associated with treatment response of patients with chronic hepatitis C in a Chinese Han population.

OBJECTIVES: This study aimed to investigate the association between interleukin 28B (IL28B) single nucleotide polymorphisms (SNPs) and sustained virological response (SVR) in Chinese Han patients with chronic hepatitis C (CHC) and to analyze the correlations between IL28B SNPs and their personal, virological and clinical characteristics. METHODS: Altogether 631 Chinese Han individuals, including 297 CHC patients treated with pegylated interferon α plus ribavirin, 14 spontaneous responders to hepatitis C virus (HCV) and 320 healthy controls were enrolled in the study. Two main SNPs of IL28B, rs12979860 and rs8099917, were genotyped using an SNaPshot Multiplex Assay. Associations between IL28B, treatment outcomes and the patients' characteristics were assessed by multivariate logistic regression. RESULTS: The proportion of individuals with the rs12979860 CC or rs8099917 TT genotype was similar in the healthy controls and the CHC patients, although all spontaneous responders presented with both genotypes. Patients with IL28B genotypes had a significantly high rate of rapid virological response (RVR) and SVR. Multivariate analysis revealed that the IL28B SNP rs12979860 CC genotype, being aged <40 years and having a non-genotype 1 (G1) were independent predictors for SVR. The rs12979860 CC genotype and rs8099917 TT genotypes were predictors for RVR. The rs12979860 CC and rs8099917 TT genotypes were more prevalent in patients with a non-G1 genotype than those with G1 genotype. CONCLUSIONS: IL28B rs12979860 CC genotype is a significant predictor for SVR and RVR in Chinese Han patients with CHC. Non-G1 HCV genotype is associated with favourable IL28B genotypes.

[Effects of oral antiviral agents on long-term outcomes of treatment-naive patients with HBV-related decompensated cirrhosis: a retrospective cohort study].

OBJECTIVE: To evaluate the efficacy of nucleos(t)ide analogues (NA) treatment and to assess the long-term outcomes, including survival, liver function improvement and virologic response, in patients with decompensated cirrhosis due to hepatitis B virus (HBV) infection. METHODS: Patients with Child-Turcotte-Pugh (CTP) scores more than or equal to 7, who had been treated with either lamivudine or other agents, but who were free of co-infection with other hepatitis virus were enrolled between January 2005 and December 2009. The study participants were subgrouped according to the antiviral drugs received or model for endstage liver disease (MELD) score for comparative analyses.Additionally, the 19 patients who were treated with NA for more than 5 years were investigated for changes in biochemical and virological indices, before and after the antiviral treatment. RESULTS: A total of 166 patients (125 males; 89 e-negative) and 52 untreated healthy patients (as control) were analyzed.The cohort of patients receiving antiviral therapy had significantly better 5-year actuarial survival than the untreated patients (74.1% vs.34.9%, P less than 0.001). For patients with MELD score more than or equal to 18, actuarial survival was not significantly different between the two groups (P=0.073). CONCLUSION: Antiviral therapy significantly increases survival and improves the clinical long-term outcome of patients with HBV-induced decompensated cirrhosis.Antiviral treatment should be initiated at an early stage to maximize benefit in the improvement of clinical status.

Study on female sexual dysfunction in type 2 diabetic Chinese women.

OBJECTIVE: To investigate the female sexual dysfunction (FSD) in type 2 diabetes patients, by comparing the sexual function between type 2 diabetic women and non-diabetic women with Female Sexual Function Index (FSFI). METHODS: 115 type 2 diabetic women and 107 age-matched non-diabetes women were enrolled with similar backgrounds. Their sexual functions were evaluated with FSFI. Metabolic parameters such as body mass index, blood lipid profile, hemoglobin A1C, plasma glucose were also collected. RESULTS: Total score of FSFI of the type 2 diabetic women were significantly lower than that of the non-diabetic controls (18.27±8.96 vs. 23.02±5.78, P=0.000). Scores of the FSFI domains (desire, arousal, lubrication, orgasm, satisfaction, pain) of the type 2 diabetic group were also lower than those of the control group. According to the FSD criterion (FSFI<25) available in China, the percentage of FSD in the type 2 diabetic group was significantly higher than that of the control group (79.2%vs. 55.0%, P<0.001). These trends seemed more prominent in pre-menopause subgroups. The logistic regression analysis indicated that age and diabetes were independent risk factors of FSD. Body Mass Index (BMI) also had influence in the diabetes group. CONCLUSION: Findings from this study showed that there are more FDS in Chinese type 2 diabetic women than in their non-diabetic counterparts, especially in pre-menopause participants.

Distribution of hepatitis C virus genotypes in Chinese patients with chronic hepatitis C: correlation with patients' characteristics and clinical parameters.

OBJECTIVE: This study aimed to explore the most up-to-date distribution of hepatitis C virus (HCV) genotypes in China, especially the association between HCV genotypes and patients' characteristics and clinical parameters. METHODS: Sera from 483 HCV antibody-positive patients were genotyped using a HCV genotyping chip assay. The distribution of HCV genotypes, clinical parameters, modes of transmission and duration of infection were determined and the relationships among these parameters were analyzed. RESULTS: A total of 424 patients were successfully genotyped. HCV genotypes 1, 2, 3 and 6 were found with a constituent ratio of 72.1%, 12.3%, 10.6% and 5.0%, respectively, in which subtypes 1b (69.1%), 2a (11.6%) and 3a (7.5%) were prevalent. The mean age of patients with genotype 1 and 2 was significantly elder than those with genotype 3 and 6 (P < 0.05). The distribution of HCV genotypes in relation to the mode of HCV transmission was remarkable (P < 0.001). Transfusion of blood and blood products was the main mode of transmission. Most genotype 1 infection (53.1%) was found in the group with a duration of HCV infection of 10-20 years. Genotype 1b was independently associated with age (P = 0.001) and mode of HCV transmission (P = 0.007). CONCLUSIONS: The main HCV subtype was genotype 1b in Chinese patients. The prevalence of HCV genotypes was correlated with age and the mode of HCV transmission. Genotype 3a and 6 may become an increasing threat in the future.

Effects of CpG-ODNs on phenotype and function of monocyte-derived dendritic cells in chronic hepatitis B.

AIM: To study the effects of synthetic nonmethylated CpG-containing oligodeoxynucleotides (CpG-ODNs), either alone or combined with recombinant Hepatitis B surface antigen (HBsAg) polypeptide, on the phenotype, function, and intracellular signaling pathways of monocyte-derived dendritic cells (DCs) in patients with chronic hepatitis B (CHB). METHODS: Peripheral blood monocytes isolated from CHB patients and healthy volunteers were induced to be dendritic cells by recombinant human granulocyte-monocyte colony stimulating factor and interleukin-4. The DCs were then treated with CpG-ODNs, CpG-ODNs/HBsAg, or tumor necrosis factor (TNF)-α for 18 h. The expression of surface molecules including HLA-DR, CD86, and CD1a in DCs were detected by flow cytometry, and the expression of signal transducers and activators of transcription (STAT1, 3, 4, 5, 6) and suppressors of cell signaling (SOCS1, 3) were determined by Western blotting assay. In addition, the capacity of DCs to stimulate allogeneic T lymphocytes and the amount of IL-12p70 released from DCs were measured. RESULTS: In the DCs derived from patients with CHB, treatment with TNF-α, CpG-ODNs, or CpG-ODNs/HBsAg, as compared to the vector control, significantly increased the expression of HLA-DR, stimulated the release of IL-12p70, and enhanced the capacity of DCs to stimulate allogenic T lymphocytes. The expressions of STAT1/4/6 and SOCS1/3, but not STAT3/5, were upregulated by TNF-α, CpG-ODNs, and CpG-ODNs/HBsAg. In addition, the expression of CD1a was upregulated only in the presence of both CpG-ODNs and HBsAg. CONCLUSION: The treatment with CpG-ODNs, either alone or combined with HBsAg, has a remarkable stimulatory effect on the impaired phenotype and function of DCs in CHB, possibly by regulating the expression of STAT1, 4, 6 and SOCS1, 3.

[Viral factors influencing histological changes of HBeAg-negative chronic hepatitis B patients with persistently normal serum ALT levels].

OBJECTIVE: To investigate the correlation between viral factors and liver histological changes of HBeAg-negative chronic hepatitis B patients with persistently normal serum ALT levels (PNAL). METHODS: HBV DNA level, HBV genotype, basal core promoter (BCP) and precore mutation were examined in 52 HBeAg-negative chronic hepatitis B patients with PNAL (defined as normal ALT measured on at least 3 occasions in the intervals of about two months over a period of 12 months or more prior to the biopsy). RESULTS: Subjects with both BCP and precore mutations had significantly higher HBV DNA levels than those without mutations [(4.9+/-1.4) vs (4.1+/-1.1) log(10)copies/ml, t = 2.308, P < 0.05]. A higher proportion of patients with histological activity index (HAI) > or = to 4 was found in patients with both mutations (32.1% vs 16.7%) than in patients without mutation, however, the proportion of patients with histological activity index (HAI) > or = to 3 in patients with mutations was not significantly different from that in patients without mutations (14.3% vs. 12.5%, x(2)=0.000, P > 0.05). In patients without precore or BCP mutations, there was a strong positive correlation between viral load and liver inflammation as well as fibrosis (precore: r=0.626, 0.592, P < 0.01; BCP: r=0.730, 0.641, P < 0.01). In patients without both mutations, HBV DNA has shown a high accuracy for predecting fibrosis (F > or = 3) (AUC = 0.905, 95% CI: 0.771-1.039, P < 0.05) with the cutoff value of 4.5 log(10) copies/ml (sensitivity = 1.000, specificity = 0.778, PPV = 42.9%, NPV = 100.0%). Results of both genotypes and mutations were successfully obtained in 40 samples with HBV DNA is > or = to 10(4) copies/ml. The higher viral load was observed in the patients with genotype B than genotype C (5.1 vs 4.3 log(10)copies/ml, t = 2.059, P < 0.05), but no difference was seen of liver pathologic changes between these two genotypes. CONCLUSIONS: Virus harboring both BCP and precore mutants has the higher replication level than wild type virus. 32.1% and 14.3% of the patients with both mutations have moderate or severe inflammation and fibrosis. There was a strong positive correlation between viral load and liver histological changes in patients without precore or BCP mutations, and viral load shows a high accuracy for predecting significant fibrosis (F > or = 3).

[Effect of silencing connective tissue growth factor on rat liver fibrosis and the accumulation of extracellular matrix].

OBJECTIVE: To investigate the anti-fibrogenesis property of intraportal vein injection of small interfering RNA targeting connective tissue growth factor (CTGF) in a rat model of liver fibrosis and its effect on the accumulation of extracellular matrix (ECM). METHODS: Thirty male rats were randomly divided into five groups. Some rats received CCl4 subcutaneously every three days for 6 consecutive weeks, and in the meantime they also received either siRNA targeting CTGF (preventive group), saline (model group) or siRNA (siRNA control group) by intraportal vein injections. Other rats received CCl4 by subcutaneous injection for 2 weeks, followed by CCl4 and CTGF siRNA intraportal vein injection for 4 more weeks (as treatment group). The expressions of CTGF and type I and III collagen genes were detected by means of reverse transcription-polymerase chain reaction (RT-PCR) and/or Western blot respectively. Hepatic histology was evaluated by HE and Sirius red stained sections. The collagen staining areas were measured quantitatively using a computer-aided manipulator with slight modifications. Serum procollagen type III and hyaluronic acid were determined by radioimmunoassay. RESULTS: Six weeks after CCl4 injection, prominent upregulation of gene expressions of CTGF, type I and III collagen, and laminin in saline or siRNA-treated rat livers were observed. The expressions of CTGF at mRNA and protein level and type I and III collagen at mRNA level were markedly reduced in rats with CTGF siRNA treated for four or six weeks. Expressions of CTGF at mRNA and protein levels decreased by 76%+/-8%, 80%+/-3% (F = 68.630) and 95%+/-2%, 93%+/-3% (F = 21.234, P < 0.01); type I and III collagen and laminin at mRNA levels decreased by 74%+/-8%, 78%+/-8%, 31%+/-7% and 57%+/-6%, 59%+/-10%, 43%+/-9% (F = 24.219, 16.315, 9.716, P < 0.01) compared with rats in the model group at 72 h. The CTGF siRNA treatment markedly reduced serum levels of procollagen type III and hyaluronic acid and the degrees of liver fibrosis. CONCLUSION: Intraportal vein siRNA injection targeting CTGF could significantly inhibit CTGF gene expression in rats, thereby attenuating liver fibrosis by reducing ECM accumulation.

[Effects of CpG-ODN combined with HBsAg on the phenotype, function and the activity of NF-kappa B and AP-1 of monocyte-derived dendritic cells in chronic hepatitis B patients].

OBJECTIVE: To investigate the effect of synthetic non-methylated CpG-ODN combined with recombined HBsAg on the phenotype, function and the expression level of nucleic transcription factor NF-kappa B (NF-kB) and AP-1 of monocyte-derived dendritic cells (DC) in patients with chronic hepatitis B (CHB). METHODS: Purified monocytes were isolated from the peripheral blood of CHB patients and healthy volunteers and cultured with human granulocyte-monocyte colony stimulating factor added together with interleukin-4. On the fifth day of culture, CpG-ODN, HBsAg and other reagents, such as TNF alpha and PBS, were added to the medium, and 18 hours later cells were collected for the detection of surface molecules (HLA-DR/CD86/CD1a). IL-12p70 levels in the supernatant and stimulating capacity to allogenic T lymphocytes were detected. The nucleic proteins of NF-kB and AP-1 in DC were extracted and purified for the gel shift assay. RESULTS: Compared with those of the PBS group, the expression rates of HLA-DR of DC treated with CpG-ODN and/or HBsAg were obviously increased. Both the IL-12p70 level and the stimulating capacity of DC to allogenic T lymphocytes in mixed lymphocyte reaction increased significantly in the CpG-ODN group and in the CpG-ODN/HBsAg combination group (P less than 0.01 and 0.05, respectively). The expression rates of CD1a were raised only in the CpG-ODN/HBsAg combination group. Three kinds of immunological adjuvants, TNF alpha, CpG-ODN and CpG-ODN/HBsAg enhanced the expression of nucleic NF-kB and inhibited the expression of AP-1 in DC. CONCLUSION: CpG-ODN, like TNF alpha, has remarkable stimulatory effect on the impaired phenotype and function of monocyte-derived DC in patients with CHB; CpG-ODN and HBsAg have a synergetic effect in increasing the antigen presenting function. The regulating ability of CpG-ODN and TNF alpha on the expression levels of NF-kB and AP-1 might be one of the mechanisms of their immunostimulatory effects on DC of the CHB patients.

[Caspase-12 expression and activation in the pathogenesis of acute hepatic failure induced by lipopolysaccharide and D-galactosamine].

OBJECTIVE: To study the role of caspase-12 expression on hepatocyte apoptosis in an experimental model of acute hepatic failure (AHF). METHODS: A mouse experimental model of AHF was developed by intraperitoneal injection of lipopolysaccharide (LPS) and D-galactosamine (D-Gal). Hepatocyte apoptosis was examined by DNA agarose gel and liver pathology. Caspase-12 mRNA expression in liver was detected by reverse transcriptase PCR (RT-PCR) method. The expression of caspase-12, GRP78 proteins in livers was determined by Western blot. RESULTS: Caspase-12 mRNA expression in the livers increased significantly from 5 to 7 hours after administration of LPS and D-Gal. Typical manifestation of hepatocyte apoptosis appeared at 5 hours after the drug administration. After 5 hours the level of serum ALT and AST were remarkably increased, and they reached the peak at 7 hours. The expression of procaspase-12 protein decreased obviously at 7 hours. Seven hours after the drug administration, hepatocyte apoptosis and necrosis both started. The marker of endoplasmic reticulum (ER) stress, Bip/GRP78 was activated during the development of hepatocyte apoptosis. The level of Bip/GRP78 protein was gradually increased at 5 hours after the drug induction. CONCLUSION: Hepatocyte apoptosis plays an important role in the pathogenesis of AHF. Caspase-12 induced ER stress involves in hepatocyte apoptosis. It suggests that inhibition of caspase-12 activation might be a potential strategy in the treatment of AHF in the future.