PubMed Health⌕ Search

Biomedical subjects

Bei Han

Publications and source records attributed to Bei Han.

6 recordsLinked to original sources

Sequential treatment with lamivudine and interferon-alpha monotherapies in hepatitis B e antigen-negative Chinese patients and its suppression of lamivudine-resistant mutations.

OBJECTIVES: To assess the efficacy of sequential treatment with lamivudine and interferon-alpha monotherapies in Chinese patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. METHODS: One hundred and sixty-two patients with HBeAg-negative chronic hepatitis B were included in this study. Ninety-eight were treated with lamivudine alone (100 mg per day) for 48 weeks (group B). Sixty-four were treated with lamivudine alone (100 mg per day) for 20 weeks, then combined with interferon-alpha-2b (5 million units three times per week) for 4 weeks and then treated for another 24 weeks with interferon-alpha-2b alone (5 million units three times per week) (group A). All patients were followed for an additional 24 weeks. RESULTS: After 48 weeks of treatment, the percentage of patients with normalization of alanine aminotransferase (ALT) levels or hepatitis B virus (HBV) DNA levels below 1000 copies/mL was not significantly different between the lamivudine monotherapy group (55.10% and 55.10%, respectively) and the sequential treatment group (59.36% and 56.25%, respectively). The percentage of patients with normalized ALT levels was significantly higher in group A (53%) than in group B (36%) at week 72 (P<0.05). The percentage of patients with lamivudine-resistant mutations was significantly higher with lamivudine monotherapy (22.45%) than with sequential therapy (P<0.05). CONCLUSIONS: Sequential treatment of chronic hepatitis B with lamivudine and interferon-alpha monotherapies is as effective as lamivudine-alone treatment in Chinese patients. However, sequential treatment can significantly suppress the emergence of lamivudine-resistant mutations.

Adult↗

Detection of YMDD mutants using universal template real-time PCR.

AIM: To establish a rapid and accurate method for the detection of lamivudine-resistant mutations in hepatitis B virus and monitor of lamivudine resistance during lamivudine treatment in patients with chronic hepatitis B virus infection. METHODS: We established a real-time PCR method using a universal template and TaqMan probe to detect YMDD mutants. Variants of YVDD and YIDD were tested by individual reactions (reaction V and reaction I) and total hepatitis B viruses were detected in another reaction for control (reaction C). Results were determined by deltaCt < 3.5 (deltaCt = Ct of reaction V or I - Ct of reaction C). Clones of the HBV polymerase gene containing different YMDD mutations were tested. Serum samples from 163 lamivudine-treated patients with chronic hepatitis B virus infection were detected using this method and the results were confirmed by DNA sequencing. RESULTS: As many as 1000 copies per milliliter of wide-type plasmid were detected and nonspecific priming was excluded. In the 163 samples from patients treated with lamivudine, lamivudine-resistant mutations were detected in 51 samples. CONCLUSION: This universal real-time PCR is a rapid and accurate method for quantification of YMDD mutants of HBV virus in lamivudine-treated patients and can be used to monitor lamivudine-resistant mutations before and during lamivudine therapy.

Antiviral Agents↗

[Molecular genetic analysis of congenital lipoid adrenal hyperplasia].

OBJECTIVE: Congenital lipoid adrenal hyperplasia (CLAH) is an autosomal recessive inherited disorder, characterized by deficiency of adrenal and gonadal steroid hormones. Recent studies have shown that mutations in the gene for steroidogenic acute regulatory protein (StAR) cause this most severe genetic disorder in steroid hormone biosynthesis. StAR is a mitochondrial protein promotes cholesterol transfer from outer mitochondrial membrane to the inner mitochondrial membrane, where the cholesterol serves as a substrate for P450scc and initiates steroidogenesis. So far, more than 30 different mutations in the StAR gene have been found in the patients with CLAH from various ethnic groups. None of CLAH patients in the Chinese population has been previously reported. In the present study we analyzed the StAR gene in a Chinese patient with CLAH. METHODS: The patient who was a 19-yr-old phenotypic female, has a 46, XY karyotype. Endocrinological evaluation was performed. Genomic DNA samples were abstracted from the bloods of the patient and his parents. Polymerase chain reaction (PCR), direct DNA sequencing, family analysis and restriction enzyme digestion analysis were used to detect and confirm the mutations of StAR gene. RESULTS: Endocrine evaluation of the patient showed extremely elevated basal concentrations of serum ACTH and gonadotropin and minimal concentration of gonadal steroids. An ACTH stimulation test indicated basal serum dehydroepiandrosterone and 17-hydroxyprogesterone were lower than normal detectable range and had no obvious increase after the ACTH stimulation. Automatic sequencing of 7 exons of the StAR gene with the polymerase chain reaction products of the genomic DNA revealed compound heterozygous for a novel nonsense mutation Q77X in exon 3 and the frameshift mutation 838delA in exon 6. The father carried Q77X mutation and the mother carried 838delA mutation. The restriction enzyme site of the Q77X mutation was examined by endonucleotidase BfaI. Furthermore, this mutation was not found in a series of 20 alleles of normal individuals. CONCLUSION: Q77X is the novel mutation found in the patient with CLAH. Q77X and 838delA compound mutations could inactivate the StAR function and give rise to clinically manifest CLAH. This case is the first Chinese patient with CLAH identified by molecular genetic analysis. DNA-based analysis of StAR gene will be helpful for the diagnosis of CLAH.

Adrenal Hyperplasia, Congenital↗

[Expression of green fluorescent protein vector by promoter sequence of CYP21 gene and CYP21P gene].

After amplification of PCR fragment of -770 bp(-)-1 bp in promoters of CYP21 gene and CYP21P gene respectively, the CMV promoter was cut off from pEGFP-N1, the vectors were constructed, in which contained promoter areas in CYP21 gene (pCYP21) and CYP21P gene (pCYP21P). All pCYP21, pCYP21P, pEGFP-N1(positive control) and negative control were transfected respectively into steroidogenic Y1 cell line, and were observed by inverted fluorescent microscopy and laser confocal microscopy. After transient transfection, the cells placed on inverted fluorescent microscopy. The appearance of GFP expression observed is as follows: pEGFP-N1 at 3 hours; pCYP21 at 7 hours. However, neither pCYP21P nor negative control expressed GFP. Laser confocal microscopy showed that pEGFP-N1 and pCYP21 produced GFP. pEGFP-N1 is stronger than pCYP21, but none of pCYP21P and negative control expressed GFP. Different distribution of GFP in Y1 cell could be seen of pEGFP-N1 and pCYP21, and the intensity of GFP in nucleus is stronger than cytoplasm. Our results further conform that there is a significantly difference of GFP expression in Y1 cell line by promoters of CYP21 and CYP21P.

Animals↗

[Double stranded RNA (RNA interference RNAi) in different creatures].

Double stranded RNA could degrade mRNA of target gene. It is a useful way for studying gene function. It is used widely in different creatures,such as Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Zebrafish, Mouse. This review is mainly related to the application of dsRNA in recent years.

English Abstract↗